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Life Sciences, Molecular Biology; Kummerowia striata; anti-oxidant activity; melanin synthesis; p-coumaric acid; quercetin
Online: 21 June 2018 (14:44:02 CEST)
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Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.
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Life Sciences, Immunology; T-regulatory cells, immune regulation, Foxp3, PPARγ, autoimmune diabetes, NOD mouse, Thiazolidinediones, ciglitazone.
Online: 21 June 2018 (13:42:18 CEST)
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Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e thiazolidinedione (TZD) class of drugs on Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and NOR mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independant mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies.
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Life Sciences, Other; hepatic injury; sealants; metalloproteinases; inflammatory response; wound healing
Online: 21 June 2018 (06:15:23 CEST)
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Sealants and adhesives are used in the repair and preservation of damaged solid organs. This study examines the matrix metalloproteinases (MMP) activity in the healing of liver injuries treated with two biological adhesives (Tachosil® and GelitaSpon®) as well as that of a new elastic cyanoacrylate (Adhflex®). Methods. We induced in 90 male rats hepatic lesions using a Stiefel biopsy punch in the liver. Wound healing was assessed 2, 6, and 18 days after injury by quantifying MMP1, 2, 8, 9, and 13 tissue levels. The histopathological repair was evaluated by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and CD31, CD68 immunohistochemical marker. The three sealants used supported complete healing of liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong inflammatory reaction at the beginning of healing. Results. All the MMPs measured disclosed higher values at an early stage of the healing process in animals treated with Adhflex® and Tachosil, the expression of for MMP2 and MMP9 being significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not negatively influence the histological healing process of hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered a suitable treatment option.
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Life Sciences, Genetics; pigs; genetics; marbling; IMF %, GWAS
Online: 21 June 2018 (04:47:15 CEST)
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We examined the amount of marbling and tested the genome of boars from 5 breeds of Duroc, Iberian, Lacombe, Berkshire and Pietrian that were commercially available for a swine herd in Canada. The marbling was ranked according to the amount of intramuscular fat % obtained in loin chops consisting of the longissimus dorsi muscle. The genetics were analysed by genome wide association study using 80,000 single nuclear polymorphism (SNP) microarrays. Our samples had pork that achieved > 7 % IMF from 110kg animals. Meta-analysis revealed SNP markers that were associated with the highest marbled pork chops on chromosomes 5, 7, and 16. Using the susScr 11.1 map, we determined that the nearest genes were SSNP, Rh glycoprotein and EGFLAM. We tested a sub-population of Duroc sired animals and found a different set of markers close to GRLB and KCNJ3 on chromosomes 8 and 15. Based on our sample, we can achieve pork with good marbling from animals conventionally raised to standard market weights of 110kg. The choice of a good marbling line of pig is not necessarily breed specific.
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Life Sciences, Genetics; Alzheimer’s disease; Parkinson’s disease; Genetic testing; bioethics
Online: 21 June 2018 (04:38:35 CEST)
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Over the last decade, advances in our understanding about the genetic architecture of complex traits and common diseases, have increased our ability to perform susceptibility genetic testing for diseases in asymptomatic individuals. These technological developments raise complex ethical, legal and social considerations. Here we discuss a series of ethical issues associated with susceptibility genetic testing for Alzheimer's and Parkinson's disease. These include, amongst others, informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. As knowledge of the genetic basis of these diseases continues growing, and as genetic testing becomes more widespread, we anticipate that it will become increasingly important for scientists and clinicians to engage in the conversation about the ethical, social and policy implications of these technologies.
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Life Sciences, Cell & Developmental Biology; cerebral ischemia, blood brain barrier, endothelial cells, impaired mitochondria, neurovascular unit, regenerative medicine, stem cell therapy, transfer of healthy mitochondria, vasculature
Online: 19 June 2018 (14:27:25 CEST)
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Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.
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Life Sciences, Virology; Crimean-Congo hemorrhagic fever virus; Crimean-Congo hemorrhagic fever; Hyalomma marginatum; human cutaneous immune response; Langerhans cells; dermal dendritic cells; tick-borne virus; tick-virus-host interface
Online: 19 June 2018 (11:50:54 CEST)
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Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.
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Life Sciences, Microbiology; urine; resistance; antibiotic; nitrofurantoin; Mozambique
Online: 19 June 2018 (10:33:14 CEST)
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Urinary tract infections are a major cause of morbidity and mortality in Mozambique. They are sometimes treated empirically with nitrofurantoin. However, little is known about this antibiotic’s performance and bacterial resistance in the country. This study analyzed the results of nitrofurantoin sensitivity tests requested in the Central Hospital of Maputo during 2012 and 2013. As result, 181 samples were tested and most cases (66.9%) showed absolute sensitivity but there were considerable cases of resistance (29.8%). Morganella morganii was the only bacteria presenting no absolute or intermediate resistance. The sensitivity was also high in the case of Escherichia coli (90%) and Gram-negative bacteria (66.7%). Serratia marcescens was mostly resistant (64.3%). The remaining bacteria showed inconclusive results. Thus they shall be subjected to a sensitivity test before prescription. Factors such as seasonality, patients’ sex and urine transparency did not seem to be reliable indicators of microbial resistance in the urine. Yet, a longer time span (over 5 years) might be sufficient for the sensitivity profile to change.
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Life Sciences, Molecular Biology; ovarian cancer; cancer stem cells; signaling, chemoresistance, metastasis
Online: 15 June 2018 (15:14:22 CEST)
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Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons personalized approaches may be necessary for effective treatment and cure. Understanding the molecular mechanisms that contribute to tumor metastasis and chemoresistance are essential to improve survival rates. One favored model for tumor metastasis and chemoresistance is the cancer stem cell (CSC) model. CSCs are cells with enhanced self-renewal properties that are enriched following chemotherapy. Elimination of this cell population is thought to be a mechanism to increase therapeutic response. Therefore, accurate identification of stem cell populations that are most clinically relevant is necessary. While many CSC identifiers (ALDH, OCT4, CD133, and side population) have been established, it is still not clear which population(s) will be most beneficial to targeted in patients. Therefore, there is a critical need to characterize CSCs with reliable markers and find their weaknesses that will make the CSCs amenable to therapy. Many signaling pathways are implicated for their roles in CSC initiation and maintenance. Therapeutically targeting pathways needed for CSC initiation or maintenance may be an effective way of treating HGS ovarian cancer patients. In conclusion, the prognosis for HGS ovarian cancer may be improved by combining CSC phenotyping with targeted therapies for pathways involved in CSC maintenance.
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Life Sciences, Biotechnology; lignocellulosic biomass; laccases; peroxidases; green biochemical; acidophilic microbes
Online: 15 June 2018 (05:51:17 CEST)
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The processing of fossil fuels is the major environmental issue today which should be lessen. Biomass is gaining much interest these days as an alternate to energy generation. Lignocellulosic biomass (cellulose, hemicellulose and lignin) is abundant and has been used for a variety of purposes. Among them, the lignin polymer having phenyl-propanoid subunits linked together through C-C bonds or ether linkages, can produce numerous chemicals. It can be depolymerized by microbial activity together with certain enzymes (laccases and peroxidases). Both acetic acid and formic acid production by certain fungi contribute significantly to lignin depolymerization. Natural organic acids production by fungi has many key roles in nature that are strictly dependent upon organic acid producing fungus type. Fungal enzymatic conversion of lignocellulosic is beneficial over other physiochemical processes. Laccases, the copper containing proteins oxidize a broad spectrum of inorganic as well as organic compounds but most specifically phenolic compounds by radical catalyzed mechanism. Similarly, lignin peroxidases (LiP), the heme containing proteins perform a vital part in oxidizing a wide variety of aromatic compounds with H2O2. Lignin depolymerization yields value-added compounds, the important ones are BTX (Benzene, Xylene and Toluene) and phenols as well as certain polymers like polyurethane and carbon fibers. Thus, this review will provide a concept that biological modifications of lignin using acidophilic microbes can generate certain value added and environment friendly chemicals.
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Life Sciences, Molecular Biology; Clostridium botulinum; botulinum neurotoxin; serotype F; subtype; VAMP-2; synaptobrevin; Zn2+ protease
Online: 15 June 2018 (05:32:49 CEST)
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In the recent past about 40 botulinum neurotoxin (BoNT) subtypes belonging to serotypes A, B, E, and F pathogenic to humans were identified among hundreds of independent isolates. BoNTs are the etiological factors of botulism and represent potential bioweapons, but are also recognized pharmaceuticals for efficient counteraction of hyperactive nerve terminals in a variety of human diseases. The detailed biochemical characterization of subtypes as the basis for development of suitable countermeasures and possible novel therapeutic applications is lagging behind the increase in new subtypes. Here we report the primary structure of a ninth subtype of BoNT/F. Its amino acid sequence diverges by at least 8.4% at the holotoxin and 13.4% on the enzymatic domain level from all other known BoNT/F subtypes. We found that BoNT/F9 shares the scissile Q58/K59 bond in its substrate vesicle associated membrane protein 2 with the prototype BoNT/F1. Comparative biochemical analyses of four BoNT/F enzymatic domains showed that the catalytic efficiencies decrease in the order F1 > F7 > F9 > F6 and vary by up to factor eight. KM values increase in the order F1 > F9 > F6 ≈ F7, whereas kcat decreases in the order F7 > F1 > F9 > F6. Comparative substrate scanning mutagenesis studies revealed a unique pattern of crucial substrate residues for each subtype. Based upon structural coordinates of F1 bound to an inhibitor polypeptide the mutational analyses suggest different substrate interactions in the substrate binding channel of each subtype.
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Life Sciences, Virology; adenovirus; oncolytic; targeting; virotherapy; cancer; αvβ6 integrin; immunotherapy; tropism
Online: 15 June 2018 (05:14:24 CEST)
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The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability. As well characterised clinical and experimental agents, we have detailed knowledge of adenoviruses’ mechanisms of pathogenicity, supported by detailed virological studies and in vivo interactions. In this review we highlight the strides made in the engineering of bespoke adenoviral vectors to specifically infect, replicate within, and destroy tumour cells. We discuss how mutations in genes regulating adenoviral replication after cell entry can be used to restrict replication to the tumour, and summarise how detailed knowledge of viral capsid interactions enable rational modification to eliminate native tropisms, and simultaneously promote active uptake by cancerous tissues. We argue that these designer-viruses, exploiting the viruses natural mechanisms and regulated at every level of replication, represent the ideal platforms for local overexpression of therapeutic transgenes such as immunomodulatory agents. Where T-Vec has paved the way, Ad-based vectors now follow. The era of designer oncolytic virotherapies looks decidedly as though it will soon become a reality.
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Life Sciences, Biochemistry; hepcidin-25; copper; nickel; ATCUN motif; metal complex; MS; NMR structure; metal peptide, metalloprotein; metallopeptide, isomerization, racemization, purity, reference material
Online: 14 June 2018 (11:33:21 CEST)
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Hepcidin-25 was identified as the main iron regulator in the human body by binding to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as ATCUN (amino terminal Cu(II)- and Ni(II)- binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the formed complex of hepcidin-25 with copper could reveal insights into its biological role. The present work is mainly focused on the study of the metal-bound form of hepcidin-25, which could be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25, which was achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry MS/MS, high resolution mass spectrometry HRMS) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a 3D model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.
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Life Sciences, Genetics; genetic architecture; Africa; GWAS; health disparities
Online: 13 June 2018 (11:17:04 CEST)
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Human genetic studies have long been vastly Eurocentric, raising a key question about the generalizability of these study findings to other populations. Because humans originated in Africa, these populations retain more genetic diversity, and yet individuals of African descent have been tremendously underrepresented in genetic studies. The diversity in Africa affords ample opportunities to improve fine-mapping resolution for associated loci, discover novel genetic associations with phenotypes, build more generalizable genetic risk prediction models, and better understand the genetic architecture of complex traits and diseases subject to varying environmental pressures. Thus, it is both ethically and scientifically imperative that geneticists globally surmount challenges that have limited progress in African genetic studies to date while meaningfully including African investigators, as greater inclusivity and enhanced research capacity affords enormous opportunities to accelerate genomic discoveries that translate more effectively to all populations. We review the advantages and challenges of studying the genetic architecture of complex traits and diseases in Africa. For example, with greater genetic diversity comes greater ancestral heterogeneity; this higher level of understudied diversity can yield novel genetic findings, but some methods that assume homogeneous population structure and work well in European populations may work less well in the presence of greater diversity and heterogeneity in African populations. Consequently, we advocate for methodological development that will accelerate studies important for all populations, especially those currently underrepresented in genetics.
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Life Sciences, Other; Aryl hydrocarbon receptor; Chloracne; Dioxin; Nuclear factor-erythroid 2-related factor-2; heme oxygenase-1; Yusho
Online: 13 June 2018 (10:29:35 CEST)
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Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.
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Jacqueline Donoghue,
Lauren Kerr,
Naomi Alexander,
Sameer Greenall,
Anthony Longano,
Nicholas Gottardo,
Rong Wang,
Viviane Tabar,
Timothy Adams,
Paul Mischel,
Terrance Johns
Life Sciences, Cell & Developmental Biology; GBM, EGFR, ERBB4, prognosis, therapy
Online: 12 June 2018 (14:51:34 CEST)
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Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ERBB4 is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples. Using immunohistochemistry, we characterized the localization of total and phosphorylated ERBB4 (p-ERBB4) and EGFR protein in archived GBM samples and assessed their association with patient survival. Furthermore, we evaluated the effect of ERBB4 phosphorylation on angiogenesis and tumorigenicity in GBM xenograft models. Total ERBB4 mRNA was significantly lower in GBM than NNB samples, with the JM-a and CYT-2 variants predominating. ERBB4 protein was ubiquitously expressed in GBM but was not associated with patient survival. However, high p-ERBB4 in 11% of archived GBM samples, independent of p-EGFR, was associated with shorter patient survival (12.0±3.2 months) than was no p-ERBB4 (22.5±9.5 months). Increased ERBB4 activation was also associated with increased proliferation, angiogenesis, tumorigenicity and reduced sensitivity to anti-EGFR treatment in xenograft models. Despite low ERBB4 mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.
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Life Sciences, Endocrinology & Metabolomics; aronia; ginseng; mushroom; pancreatectomy; type 2 diabetes; gut microbiome; insulin secretion
Online: 12 June 2018 (13:01:30 CEST)
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The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.
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Life Sciences, Biotechnology; β4-galactosyltransferase 4; transcriptional mechanism; sensor cells; colon cancer; drug screening
Online: 12 June 2018 (12:51:07 CEST)
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The increased expression of β4-galactosyltransferase (β4GalT) 4 was closely associated with poor prognosis of colon cancer. Recently, we showed that the expression of the β4GalT4 gene is regulated by the 0.17 kb core promoter region containing one binding site for Specificity protein 1 (Sp1). To develop a novel screening method for anti-colon cancer drugs, two sensor cell lines having the luciferase gene under the control of two β4GalT4 gene promoters that differed in length were established from SW480 human colon cancer cells. The hGT4-0.17-sensor cells possessed the luciferase reporter driven by the 0.17 kb promoter, while the hGT4-0.3-sensor cells possessed the luciferase reporter driven by the 0.3 kb promoter containing one binding site each for colon cancer-related transcription factors including activator protein 2, E2F, caudal-related homeobox transcription factors, and Runt-related transcription factors besides Sp1. Upon treatment with mitogen-activated protein kinase inhibitor U0126, the promoter activities of the hGT4-0.3-sensor cells decreased significantly, while those of the hGT4-0.17-sensor cells unchanged. These results suggest that the responsiveness to U0126 differs between two sensor cell lines due to the different regulation of the luciferase reporters. This study provides the novel screening method for anti-colon cancer drugs by the combination of two sensor cell lines.
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Life Sciences, Genetics; rare disease; functional genomics; genetic variant validation
Online: 12 June 2018 (12:36:08 CEST)
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Many insights into human disease have been built on experimental results in Drosophila, and research in fruit flies is often justified on the basis of its predictive value for questions related to human health. Additionally, there is now a growing recognition of the value of Drosophila for the study of rare human genetic diseases, either as a means of validating the causative nature of a candidate genetic variant found in patients, or as a means of obtaining functional information about a novel disease-linked gene when there is little known about it. For these reasons, funders in the US, Europe, and Canada have launched targeted programs to link human geneticists working on discovering new rare disease loci with researchers who work on the counterpart genes in Drosophila and other model organisms. Several of these initiatives are described here, as are a number of output publications that validate this new approach.
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Life Sciences, Molecular Biology; SIRT6, Diabetes, Gluconeogenesis, Cancer, Aging, Heart Disease, Pharmacological SIRT6 Inhibitor, Cardiac Hypertrophy, Tumorigenesis, Neurodegeneration, Neurodegenerative Diseases, AD
Online: 11 June 2018 (16:29:11 CEST)
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SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.
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Life Sciences, Molecular Biology; miR-29a; cholestasis; apoptosis; ER stress; toll like receptors; epigenetics
Online: 11 June 2018 (14:03:48 CEST)
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Both fibrosis and cirrhosis of the liver are the end results of most kinds of chronic liver damage and present a common but difficult clinical challenge throughout the world. The inhibition of the fibrogenic, proliferative, and migratory effects of hepatic stellate cells (HSCs) has become an experimental therapy for preventing and even reversing hepatic fibrosis. Furthermore, a complete understanding of the function of non-coding RNA-mediated epigenetic mechanisms in HSC activation may improve our perception of liver fibrosis pathogenesis. This review focuses on an evolving view of molecular mechanisms in which HSC activation by miR-29a signaling may moderate their profibrogenic phenotype, thus supporting the use of miR-29a agonists as a potential therapy for treating liver fibrosis in the future.
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Life Sciences, Other; thin composite hollow fiber; water treatment; water vapor separation; dehydration of alcohols; pervaporation
Online: 11 June 2018 (04:47:30 CEST)
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Nowadays asymmetric thin film composite (TFC) polymeric hollow fiber (HF) membranes are extensively used in industrial gas/vapor separations, water treatment etc. There are numerous advantages to use hollow fibers such as: low energy requirements, simplicity of operation, and high specificity. In the present article we discuss the progress made during the past decade in the preparation of the HF substrate and preparation/modification of the thin selective layer. Their applications in water treatment, dehydration of alcohols via pervaporation and gas/vapor separation are also demonstrated.
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Simone Pippa,
Cecilia Mannironi,
Valerio Licursi,
Luca Bombardi,
Gianni Colotti,
Enrico Cundari,
Adriano Mollica,
Antonio Coluccia,
Valentina Naccarato,
Giuseppe La Regina,
Romano Silvestri,
Rodolfo Negri
Life Sciences, Molecular Biology; histone demethylase inhibitors; DNA damage; epigenetic drugs; breast cancer
Online: 8 June 2018 (12:29:10 CEST)
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Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are over-expressed in different kinds of cancer, including breast, prostate and bladder carcinoma, with positive effects on cancer proliferation and chemo-resistance. For these reasons, these enzymes are potential therapeutic cancer targets. Methods: In the present study, we analyzed the effects of three different inhibitors of KDM5 enzymes in MCF-7 breast cancer cells over-expressing JARID1B. In particular we tested H3K4 demethylation (western blot); target gene transcription (RNAseq and real time PCR); radio-sensitivity (citoxicity and clonogenic assays) and damage accumulation (kinetics of H2AX phosphorylation). Results: we show that two compounds with completely different chemical structure can selectively inhibit KDM5 enzymes and that both compounds are capable of increasing sensitivity of breast cancer cells to ionizing radiation and H2AX phosphorylation. Conclusions: These findings confirm the involvement of H3K4 specific demethylases in DNA damage signaling and repair and suggest new strategies for the therapeutic use of their inhibitors.
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Life Sciences, Immunology; colitis disease; Eucheuma cottonii; inflammatory cytokines; red seaweed
Online: 7 June 2018 (12:22:21 CEST)
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This study aims to determine the protective effects of red seaweed Eucheuma cottonii (EC) ethanol extract on acute colitis disease in mice. Male BALB/c mice used for acute colitis disease model by induced 2.5% (w/v) of dextran sulfate sodium (DSS) for 7 days for all groups, except control group. The DSS-induced mice then treated by three different doses of EC extracts (0.35, 0.70, 1.75 g/kg body weight), curcumin (as a positive control, 0.10 g/kg), and a group was orally only by water. In 8th day, the mice sacrificed and collected the blood, then measured the body weight, colon weight, and colon length. Disease activity index (DAI), pro-inflammatory such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, as well as IL-10 as anti-inflammatory were measured. The results showed that after treatment for 7 days, EC extract protected the weight loss and decreased the colon weight per length ratio. In addition, EC extract also decreased the pro-inflammatory cytokines expression in serum and increased the IL-10. Moreover, EC extract protected the colonic tissue damage. According to this results, the EC ethanol extract might be can used for the treatment of colitis disease.
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Life Sciences, Immunology; CCR6; CCL20; TH17; Treg, inflammation; multiple organs; health and disease
Online: 7 June 2018 (08:49:51 CEST)
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Chemokine C-C receptor 6 (CCR6) and its exclusive ligand CCL20 is an extremely important chemokine receptor-ligand pair which controls cell migration and immune induction during inflammatory disease. Not many scientific studies have been undertaken to study its immune mechanisms in detail, but its unique contribution to steady state cell chemotaxis in upholding immune tolerance and regulating immune homeostasis during inflammation is evident in multiple organ systems, including lung, liver, kidney, skin, brain, eye, joints, gonads and the gut in the human body. The role of CCR6 is constitutively expressed as a series of much debilitating severe inflammatory and autoimmune diseases, HIV and cancer metastasis. CD4+ T cells, the central organizers of adaptive immunity, are stringently mobilized by the CCR6/CCL20 axis also induced by cytokines and a host of other factors in a carefully executed immune modulation scenario, to bring about a delicate balance between pro-inflammatory TH17 cells and regulatory Treg cells. Although the exact immune regulatory role is not elucidated yet, CCR6/CCL20 axis is implicated as a front runner which determines the polarization of TH17 and Treg cells and consequently the resolution or progression of many debilitating disorders. This review therefore aims at emphasizing the pleiotropic significance of the chemokines CCR6 and CCL20 in immunologic function in multiple organ systems thereby hoping to accentuate its value in future therapeutic modalities.
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Life Sciences, Other; Neuroscience; basal ganglia; cortical layers; cerebellum; habenula; inhibition; predictions; dopamine; serotonin; acetylcholine; opioids; mirror neurons; place cells; language; imagery; working memory
Online: 7 June 2018 (06:02:29 CEST)
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Understanding brain function is one of the most important open problems in science today. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain’s capacities. Brain function is managed by a response (R) process that is structurally similar to the immune response, and shows anatomical and molecular specificity. Different R process stages utilize different cortical layers, hippocampus fields, basal ganglia paths, GABAergic interneurons, cerebellum paths, and molecular agents such as dopamine, serotonin and opioids. We show how the R process supports hierarchical action sequences, language and thought. The theory is supported by a large body of experimental evidence in many modalities, and accounts for virtually all of the major facts known about the brain at the system level.
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Life Sciences, Biochemistry; BMI, Food Preference, Working Pattern and coronary heart (CHD disease in the southern region of Bangladesh.
Online: 6 June 2018 (16:09:59 CEST)
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Background: In present study focused on to detect the effect of BMI, food preference, and working pattern on coronary heart disease aged between (30-80) years old male and female in southern region of Bangladesh. Methods: Data were collected by questionnaires on the basis of sex, age, BMI, physical activity, hypertension, family history, food preferences, lipid profile test, smoking habit and presence or absence of other disease like diabetes. All data were analyzed statistically. Results: A total of 240 respondents of male and female diagnosed by coronary heart disease were selected randomly to collected data. Among them male were 188 and 52 were female. This study also indicates that increased body weight, hypertension, smoking, sedentary life style related factors, including poor dietary habits, excess saturated and trans fat, high salt intake, and low-level physical activity may be important as well and family history of cardiac diseases are influential risk factors for CHD. Most of patients’ affected by excessive overweight; 60.1 % male and 61.5 % female were suffer from diabetics which proved that Diabetic is often liable to affect CHD; 62.2 % male and 65.4 % female respondents gain heart disease from family; On the contrary the rate of CHD affected male were 73.40 % who were involved in normal physical activity level; 56.9 % male do smoke all time; Conclusion: This study demonstrates that increasing body weight, physical inactivity, unhealthy eating habits or food preferences, poor lifestyle is correlated with CHD and males are more vulnerable to CHD than females.
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Life Sciences, Molecular Biology; feed-forward loop (FFL); cAMP receptor protein (CRP); transcriptional factor (TF).
Online: 6 June 2018 (16:00:56 CEST)
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The feed-forward loop (FFL) is an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs like araBAD and araFGH operons and adapt to fluctuating environmental nutrients thus enhancing the survivability of E. coli. Although computational simulations have been used to explore the potential functionality of FFLs, a comprehensive study of the functions of all structural types based on in vivo data is lacking. Also, the regulatory role of CRP-mediated feed-forward loops (CRP-FFLs) remain unclear to date. Using EcoCyc and RegulonDB, we identified 393 CRP-FFLs in the E. coli. Dose-response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, that were further divided into five functional groups. Microarray and reported regulatory relationships identified 202 CRP-FFLs which were directly regulated by CRP in these eight types of FFLs. Interestingly, 30% (147/482) of genes were directly regulated by CRP and CRP-regulated TFs, indicating that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs.
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Life Sciences, Molecular Biology; long noncoding RNA; MALAT1; UCA1; NRON; Z probe; colorectal cancer; pancreatic cancer; breast cancer
Online: 6 June 2018 (13:05:30 CEST)
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Formalin-Fixed Paraffin Embedded (FFPE) tissues are a valuable resource in studying different markers and mechanistic molecules (protein, DNA and RNA) in order to understand the etiology of different cancers as well as many other diseases. Degradation and modification of RNA is the major challenge in utilizing FFPE tissue samples in medical research. Recently, non-protein coding transcripts long non-coding RNAs (lncRNAs), have gained significant attention due to their important biological actions and potential involvement in cancer. There is no validated method except qRTPCR or RNAseq to evaluate and study lncRNA expression. We have standardized and are reporting a sensitive Z probe based in situ hybridization method to identify, localize and quantitate lncRNA in FFPE tissues. This assay is sensitive to single transcript and localizes lncRNA in individual cells within tumor. We have characterized a tumor suppressor lncRNA-NRON (non coding repressor of NFAT), which is scarcely expressed, a moderately expressed oncogeneic lncRNA UCA1 (urothelial cancer associated 1), and a highly studied and expressed lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript1) in different cancers. High MALAT1 staining was found in colorectal, breast and pancreatic cancer. MALAT1 expression increased with the progression of the stage in colorectal cancer and invasiveness in breast cancer.
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Life Sciences, Biotechnology; wastewater treatment; microbial fuel cells; bioenergy
Online: 6 June 2018 (05:38:03 CEST)
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Microbial Fuel Cells (MFCs) representing a promising technology for the extract of energy and resources through wastewater and it also offer an economic solution to the problem of environment effluent and energy crisis in near future. The advance device is rather appealing, due its potential benefits, its practical application is, however hindered by several drawbacks, such an internally competing microbial reaction, and low power generation. This report is an endeavor to address various design connected to the MFCs application to wastewater treatment, in particular cost effective bioelectricity from waste water are reviewed and discussed with a multidisciplinary approach. The conclusions drawn herein can be of practical interest to all new researchers dealing with effluent wastewater treatment using MFCs.
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Life Sciences, Immunology; adipose-derived mesenchymal stem cells; intraperitoneal therapy; biodistribution; efficacy; colitis
Online: 5 June 2018 (11:33:18 CEST)
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Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. It is described that the immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless the route of administration used, the inflammation conditions and the MHC context. These observations arise the question as to whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the `responder´ mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial to achieve an optimal modulation of inflammation.
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Life Sciences, Virology; cophylogeny; granulovirus; host shifts; Lepidoptera; mPTP; multitrophic interactions; niche conservatism; nucleopolyhedrovirus; phylogenetics; resource tracking; species delimitation
Online: 5 June 2018 (06:32:44 CEST)
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The Baculoviridae, a family of insect-specific large DNA viruses, is widely used in both biotechnology and biological control. Its applied value stems from millions of years of evolution influenced by interactions with their hosts and the environment. To understand how ecological interactions, have shaped baculovirus diversification, we reconstructed a robust molecular phylogeny using 217 complete genomes and ~580 isolates for which at least one of four lepidopteran core genes was available. We then used a phylogenetic-concept-based approach (mPTP) to delimit 165 baculovirus species, including 38 species derived from new genetic data. Phylogenetic optimization of ecological characters revealed a general pattern of host conservatism punctuated by occasional shifts between closely related hosts and major shifts between lepidopteran superfamilies. Moreover, we found significant phylogenetic conservatism between baculoviruses and the type of plant growth (woody or herbaceous) associated with their insect hosts. In addition, we found that colonization of new ecological niches sometimes led to viral radiation. These macroevolutionary patterns show that besides selection during the infection process, baculovirus diversification was influenced by tritrophic interactions, explained by their persistence on plants and interactions in the midgut during horizontal transmission. This complete eco-evolutionary framework highlights the potential innovations that could still be harnessed from the diversity of baculoviruses.
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Life Sciences, Other; Alzheimer’s Dementia; anaerobic neurotoxicity; inflammation; neuronal apoptosis; Non-REM Sleep
Online: 4 June 2018 (13:16:46 CEST)
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Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).
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Life Sciences, Virology; varicella-zoster virus; latency; reactivation; sensory ganglia; VZV latency-associated transcript; open reading frame 63; RNA-sequencing; epigenetics; immunity
Online: 4 June 2018 (11:49:09 CEST)
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Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, the lack of suitable in vitro models to study VZV latency have seriously hampered molecular studies of viral latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and have redefined our understanding of VZV latency and factors that initiate reactivation. Together, these findings pave the way for a new era of research that may finally unravel the precise molecular mechanisms that govern latency. In this review, we will summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies.
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Life Sciences, Microbiology; fruit juice; debre markos; hygiene; microbial safety
Online: 4 June 2018 (09:56:33 CEST)
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Improperly prepared fresh fruit and vegetable juices are recognized as an emerging cause of food borne illnesses. Therefore, this study was aimed at evaluating the microbiological safety of fresh fruit juices marketed in Debre-Markos town and their hygienic conditions of preparations. Thirty six fruit juices samples were collected from 6 cafés and restaurants of Debre-Markos town and analyzed for total aerobic viable bacterial count (TAVBC), total staphylococcal count (TSC), aerobic spore forming bacterial count (ASFBC), total coliform count (TCC), fecal coliform count (FCC), yeast and mould count (YMC). The spread plate method was used for the isolation of microorganisms on appropriate selective media. All isolates were characterized following standard methods. Bacterial and fungal species were isolated following standard methods. Questionnaires were distributed for 30 juice makers to obtain preliminary information on hygienic and safety practices of fruit juice makers. Results show that the mean TAVBC, ASFBC, TSC, yeast and mold, TCC and FCC of mango were 2.2±0.48x106,0.13±0.04x105 ,0.004x105 ,1.1±0.2x106 ,0.15±0.05x105,5.7±3.73x104 and 0.06±0.04x104 cfu/ml respectively. The mean of TAVBC, ASFBC, TSC, YMC, TCC, and FCC of avocado juice were 3.6±0.6x106, 0.08±0.02x105, 0.27±0.07x105, 1.2±0.4x106, 0.02±0.01x105, 6.46±3.7x104, and 0.2±0.1x104 cfu/ml respectively. The bacterial isolates were identified as Staphylococcus aureus, Escherichia coli, Klebsiella spp. Bacillus cereus, Enterobacter spp., Enterococcous spp., Streptococcus spp., and Serratia spp. while the identities of the fungal isolates were Fusarium spp., Mucor spp. and Saccharomyces cerevisiae. The results also showed that the microbial loads of most of the fruit juices were higher than the specifications set for fruit juices sold in the Gulf region and other parts of the world. Most venders obtained fruit from the open market and all juice makers lacked special training in food hygiene and safety. Therefore, regular training and health education on food hygiene and safety is recommended for juice handlers to improve the quality of fresh fruit juices in the study area.
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Life Sciences, Molecular Biology; molecular dynamics simulation; 17β-estradiol; DNA-aptamer; GROMACS; modeling
Online: 4 June 2018 (08:42:47 CEST)
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Micro pollutants such as 17β-Estradiol (E2) have been detected in low concentrations in different water resources and their negative effects on the environment and organisms are observed. In this study, a previously described 35-mer E2-specific aptamer was used to investigate the underlying binding characteristics between E2 and the aptamer through an MD simulation in an aqueous medium. There is no 3D structure information for this aptamer, so it was modeled using coarse-grained modeling method. The E2 ligand was positioned inside the potential binding area of the aptamer structure, the underlying complex was used for an 25 ns MD simulation, and the interactions were examined by an interaction profiler tool for each time step. The E2-specific bases of the aptamer had presumably dominant roles in the binding of E2 in terms of the different interaction types. We identified the specific bases within the interior loop of the aptamer and we also demonstrate the influence of oftentimes underestimated water-mediated hydrogen bonds. The study contributes to the understanding of the behavior of ligands binding through aptamer structure in an aqueous solution. The developed workflow allows to generate and examine further appealing ligand aptamer complexes.
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Life Sciences, Biochemistry; Trypanosoma cruzi; benznidazole; resistance; quantum mechanics; molecular mechanics
Online: 1 June 2018 (10:22:17 CEST)
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The Chagas disease (CD) is an endemic infectious disease in a large part of Latin America. This disease is characterized by the fact of being caused by the parasite Trypanosoma cruzi. Some symptoms of this disease are cardiopathies and gastrointestinal problems. Therefore, the commonly used treatment consists of nitro drugs such as benznidazole and nifurtimox, which target the nitroreductase enzyme that docks to the coenzyme flavin mononucleotide (FMN) and an oxidation-reduction reaction is generated. From this reaction, the nitro chemical function of benznidazole and nifurtimox is reduced to amine. This amine in turn interacts with the parasite´s DNA. In vitro tests experimentally help in the study of the parasite resistance to the drug benznidazole. This fact could explain how nonsynonymous mutations in the nitroreductase (NTR) enzyme do not allow the anchorage of the FMN coenzyme and as a consequence the parasite susceptibility to benznidazole decreases as the drug cannot be reduced. The structural relations from the hybrid Quantum Mechanics-Molecular Mechanics (QM/MM) allow to detect the small changes generated in the system, considering a charge distribution associated with the structure, angle changes, interaction distances, potential surface calculations between the wildtype enzyme and the mutation found.
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Life Sciences, Immunology; influenza; serum; IgG; humoral antibody; original antigenic sin; hemagglutinin
Online: 31 May 2018 (10:51:16 CEST)
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The first exposure to influenza is thought to impact subsequent immune responses later in life. The consequences of this can be seen during influenza epidemics and pandemics with differences in morbidity and mortality for different birth cohorts. With the development of new universal vaccines there is need for better understanding of how vaccine responses are affected by early exposures to influenza viruses. In this analysis of hemagglutination inhibition (HI) antibody responses in two cohorts of military personnel we noticed differences related to birth year. These data suggest that HI antibody production, in response to influenza vaccination, is affected by influenza activity in the years following birth. The magnitude of this antibody response is associated with, among other factors, the influenza strain that circulated following birth.
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Life Sciences, Biotechnology; monoclonal antibody; immunoglobulin G; glycosylation; Chinese hamster ovary; perfusion cell culture; continuous biomanufacturing
Online: 30 May 2018 (16:52:12 CEST)
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A critical quality attribute of therapeutic monoclonal antibodies (mAbs) is the terminal sugar molecules of the N-linked glycan attached to the fragment crystalizable (Fc) region. There exists naturally-occurring heterogeneity in the N-linked glycan structure of mAbs, and such heterogeneity has a significant influence on the clinical safety and efficacy of mAb drugs. We previously proposed a constraint-based modeling method called glycosylation flux analysis (GFA) to characterize the rates (fluxes) of intracellular glycosylation reactions and applied the method to examine the N-linked glycosylation of immunoglobulin G (IgG) in fed-batch Chinese hamster ovary (CHO) fed-batch cultivations. In this work, we significantly improved the computational efficiency of the GFA, and employed the method to analyze the glycosylation of IgG in continuous perfusion CHO cultivations. Perfusion cell cultures have several advantages over the traditional (fed-)batch operation, including higher productivity per unit volume of reactor and more consistent product quality. The GFA showed that as in the fed-batch cultivation, the dynamical changes of IgG glycan heterogeneity in the perfusion culture are mainly attributed to alterations in the galactosylation flux activity. Furthermore, a regression analysis of the galactosylation flux activity using random forest regression linked the dynamics of galactosylation activity with the cell-specific productivity of IgG and the extracellular ammonia concentration.
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Life Sciences, Other; coefficient of variation; correlation; factor; jenny; principal components analysis
Online: 30 May 2018 (06:14:46 CEST)
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Colostrum is a natural product, issued by both mammals and humans in first week of lactation. Among different species, donkey colostrum is considered as having, besides a valuable composition in nutrients and immune factors, an outstanding similitude with human colostrum. In this context, and taking into account the scarcity of available data concerning the interaction between climate factors and colostrum quality, a trial was conducted aiming to identify the possible influence of environmental factors on donkey colostrum nutritional traits. A stock of 16 jennies from 2 farms located in the County of Cluj, during a 7 days postpartum period was analyzed. During experimental period the daily temperature, humidity, and wind velocity data were collected. Strong positive correlations may be reported between fat and lactose, and fat and protein respectively, while moderate to strong correlation is emphasized between lactose and protein content of donkey colostrum. Testing the influence of environmental temperature, relative humidity, and wind velocity influence upon nutritional content of donkey colostrum, results the neglectable influence of the wind velocity, the negative influence of the heat stress upon all studied colostrum components, and complex influence of relative humidity, which has positive influence on fat and lactose increase when it increases, while its increase has negative influence on protein content of donkey colostrum.
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János Sándor,
Anita Pálinkás,
Ferenc Vincze,
Valéria Sipos,
Nóra Kovács,
Tibor Jenei,
Zsófia Falusi,
László Pál,
László Kőrösi,
Magor Papp,
Róza Ádány
Life Sciences, Other; primary health care; workforce crisis; general practitioner vacancy; aging of general practitioners; premature mortality
Online: 30 May 2018 (05:47:53 CEST)
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The workforce crisis of primary care is reflected in the increasing number of general medical practices (GMP) with vacant general practitioner (GP) position, and the GPs’ ageing. Our study aimed to describe the association between this crisis and premature mortality. Age-sex-standardized mortality for 18-64 years old adults were calculated for all Hungarian GMPs annually in the period from 2006 to 2014. The relationship of premature mortality with GPs’ age and vacant GP position were evaluated by standardized linear regression controlled for list size, urbanization, geographical location, clients’ education, and type of the GMP. The clients’ education was the strongest protective factor (beta=-0175; p<0.001), followed by urban residence (beta=-0.149; p<0.001), and the bigger list size (beta1601-2000=-0.054; p<0.001; beta2001-X=-0.096; p<0.001). The geographical localization influenced significantly also the risk. Although, GMP with a GP aged older than 65 years (beta=0; p=0.995) did not affected the risk, GP vacancy was associated with higher risk (beta=0.010; p=0.033), but the corresponding number of attributable cases was 23.54 for 9 years. The vacant GP position is associated with significant but hardly detectable increased risk of premature mortality without considerable public health importance. Nevertheless, employment of GPs aged more than 65 does not impose premature mortality risk elevation.
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Life Sciences, Virology; bacteriophage; Tevenvirinae; radiolabeling; genomic map; 2-D polyacrylamide gel electrophoresis; NEPHGE-SDS PAGE
Online: 29 May 2018 (08:31:59 CEST)
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The mechanisms by which bacteriophage T4 converts the metabolism of its E. coli host to one dedicated to progeny phage production was the subject of decades of intense research in many labs from the 1950’s through the 1980’s. At this point, a wide range of phages are starting to be used therapeutically and in many other applications and also the range of available phage sequence data is skyrocketing. It is thus important to re-explore the extensive available data about the intricacies of the T4 infection process as summarized here, expand it to looking much more broadly at other genera of phages, and explore phage infections using newly-available modern techniques and a range of appropriate environmental conditions.
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Life Sciences, Other; silver nanoparticles; nanosilver; endocytosis; oxidative stress; reactive oxygen species; inflammation; wound healing; hypoxia; mitochondria; endoplasmic reticulum stress; unfolded protein response; autophagy; apoptosis; angiogenesis; epigenetics; genotoxicity; cancer; anti-cancer
Online: 28 May 2018 (15:51:12 CEST)
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Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.
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Life Sciences, Other; microbiota; kynurenine pathway; serotonin; inflammation; gut motility
Online: 28 May 2018 (12:48:11 CEST)
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The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.
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Life Sciences, Cell & Developmental Biology; Rho; Rhotekin; PDZ domain; SH3 domain
Online: 28 May 2018 (10:20:19 CEST)
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Rhotekin is an effector protein for small GTPase Rho. This protein consists of a Rho binding domain (RBD), a pleckstrin homology (PH) domain, proline-rich regions and a C-terminal PDZ-binding motif. We and other groups have identified various binding partners for Rhotekin and proposed their possible physiological roles. However, functions of Rhotekin per se are largely unknown and information about its physiological roles are fragmentary. In this review, we summarize known features of Rhotekin in neuronal tissues and cancer cells. We also describe characteristics of binding partners for Rhotekin and predicted roles of their interaction.
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Life Sciences, Molecular Biology; codons value; numerical paradigm; reflection symmetry; contiguity
Online: 28 May 2018 (05:59:23 CEST)
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To understand the degeneracy, symmetry and code-amino acid assignments in the standard genetic code system, theoretical approach is tested based on allotting numerical values to each nucleotide base of DNA and generated the concept of numerical values of codons. When codon values are calculated according to the numerical values of their each nucleotide base, a significant association among the codon values of each amino acid is observed and a map is constructed according to their values of each codon. This map is named as the numerical paradigm of the genetic code. Through the numerical paradigm, reflection symmetry is discovered present in the structure of genetic code system. Every amino acid has its codons values in a contiguous manner and some codons of each amino acid possess identical numerical values, even those codons are distributed randomly in the standard genetic code table, such as leucine, serine, arginine, and stop codons. However, the chemical evolution of codon-amino acid assignment patterns is remained ambiguous, after numerical study of standard and alternative codes, its concluded that assignment of codons-amino acids patterns in genetic code system possesses contiguous and identical numerical codon values.
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Life Sciences, Microbiology; anaerobic digestion; Co-digestion; CSTR; BMP-test; Illumina sequencing; T-RFLP; glycoside hydrolase families 5 and 48
Online: 27 May 2018 (12:53:51 CEST)
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This study investigated whether biogas reactor performance, including microbial community development, in response to a change in substrate composition is influenced by initial inoculum source. Test reactors were first started with two different inocula and operated with the same grass-manure mixture for more than 120 days. These reactors initially showed great differences depending on inoculum source, but eventually showed similar performance and overall microbial community structure. At the start of the present experiment, the substrate was complemented with milled feed wheat, added all at once or divided into two portions. The starting hypothesis was that process performance depends on initial inoculum source and microbial diversity, and thus that reactor performance is influenced by the feeding regime. In response to the substrate change, all reactors showed increases and decreases in volumetric and specific methane production, respectively. However, specific methane yield and development of the microbial community showed differences related to initial inoculum source, confirming the hypothesis. The different feeding strategies had however only minor effects on process performance and overall community structure, but still induced differences in the cellulose-degrading community and in cellulose degradation.
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Life Sciences, Microbiology; Scoprion Venoms; Hos Defence Peptides; antimicrobial activity; antibiofilm activity; synergism; bacterial resistance
Online: 25 May 2018 (09:26:11 CEST)
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Current research in the field of antimicrobials is focused on the development of novel antibiotics and antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host Defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they share unique characteristics suitable for antimicrobial activity including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that was identified through molecular cloning from the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against different strains of Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displaying significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was designed from the naturally occurring scorpion venom host defense peptide. The design strategy depended on modifying the amino acid sequence of the parent peptide in order to increase its net positive charge, percentage helicity and optimize other physico-chemical parameters involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 displayed potent and selective in vitro antimicrobial activities against a wide range of MDR Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics displayed a synergistic mode of action which resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. These effective concentrations were associated with negligible toxicities on mammalian cells. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics may be pursued as a potential novel treatment strategy against MDR and biofilm forming bacteria.
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Life Sciences, Cell & Developmental Biology; TGF-β; cancer; immunosuppression; TAK1; mechanobiology; extracellular matrix; tensegrity; DNA damage
Online: 25 May 2018 (08:37:53 CEST)
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TGF-β signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix remodeling. In this article, we will review how TAK1 activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we will discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development will be critical in designing therapeutics which inhibit tumor progression while bolstering the immune response.
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Life Sciences, Immunology; PPARgamma first trimester placenta; decidual macrophages; miscarriage
Online: 24 May 2018 (13:24:08 CEST)
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PPARgamma belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARgamma is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPARgamma under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion & 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPARgamma. Expression changes were evaluated by immunohistochemistry and RT-PCR in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using CD68 as marker for macrophages. The intermediate villous trophoblast revealed a significantly lower PPARgamma expression in spontaneous and recurrent abortion. Maternal macrophages express PPARgamma. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPARgamma only in very few cases. PPARgamma is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPARgamma in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.
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Life Sciences, Molecular Biology; abies beshanzuensis; ITS variation; structure; molecular phylogeny
Online: 24 May 2018 (10:40:55 CEST)
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Abies beshanzuensis, an extremely endangered species, attracts serious concerns on genetic diversity recovery and population protection. However, little genetic information was known about it till now. In this study, intra-/intergenomic ITS variation, secondary structure, and molecular phylogeny of A.beshanzuensis were determined by nrDNA-ITS marker, and results indicated that, ITS region featured rich polymorphism in ITS1 and highly conservative in 5.8S/ITS2 among intra-/inter-genome, implying rich genetic diversities and the occurrence of non-concerted evolution in ITS region. Predicated 5.8S structure possessed Helices-Loops with 3 motifs (M1/M2/M3) and 5 helices B4-B8, and ITS2 could form conservative Clover-like structure with 5 ribotypes, manifesting genetically structural generalities and individualities. Thirteen ITS pseudogenes were also identified from 76 samples (or clones). Molecular phylogeny revealed that, A.beshanzuensis shared genetically closer relationships with A.fanjingshanensis, A.chensiensis, A.yuanbaoshanensis among genus Abies. The available original data provided rich genetic information on ITS sequence, structure and molecular phylogeny of A.beshanzuensis, which not only updated the databases of ITS sequences as well as secondary structures essential for phylogenetic reference and DNA barcoding analyses, but also contributed to deep exploration of population diversities, origin and evolution as well theoretical direction for population recovery and protection of A.beshanzuensis.
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Life Sciences, Biochemistry; LC-QQQ; liquid chromatography; triple quadrupole; vitamin D; 25(OH)D; plants; algae
Online: 24 May 2018 (09:27:21 CEST)
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Vitamin D has previously been quantified in some plants and algae, particularly in leaves of the Solanaceae family. We measured the vitamin D content of Australian native food plants and Australian-grown edible seaweed. Using liquid chromatography with triple quadrupole mass spectrometry, 13 samples (including leaf, fruit and seed) were analysed in duplicate for vitamin D2, vitamin D3, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3. Five samples contained vitamin D2: raw wattleseed (Acacia victoriae) (0.03 µg/100 g dry weight (DW)); fresh and dried lemon myrtle (Backhousia citriodora) leaves (0.03 and 0.24 µg/100 g DW, respectively); dried leaves and berries of Tasmanian mountain pepper (Tasmannia lanceolata) (0.67 and 0.05 µg/100 g DW, respectively). Fresh kombu (Lessonia corrugata) contained vitamin D3 (0.01 µg/100 g DW). Detected amounts were low; however, it is possible that exposure to ultraviolet radiation may increase the vitamin D content of plants and algae if vitamin D precursors are present.
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Life Sciences, Molecular Biology; fibrillin; cucumber; genome-wide; gene expression; high light stress
Online: 24 May 2018 (05:24:00 CEST)
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Fibrillin (FBN) is a plastid lipid-associated protein found in photosynthetic organisms from cyanobacteria to plants. In this study, 10 CsaFBN genes were identified in genomic DNA sequences of cucumber (Chinese long and Gy14) through database searches using the conserved domain of FBN and the 14 FBN genes of Arabidopsis. Phylogenetic analysis of CsaFBN protein sequences showed that there was no counterpart of Arabidopsis and rice FBN5 in the cucumber genome. FBN5 is essential for growth in Arabidopsis and rice; its absence in cucumber may be because of incomplete genome sequences or that another FBN carries out its functions. Among the 10 CsaFBN genes, CsaFBN1 and CsaFBN9 were the most divergent in terms of nucleotide sequences. Most of the CsaFBN genes were expressed in the leaf, stem, and fruit. CsaFBN4 showed the highest mRNA expression levels in various tissues, followed by CsaFBN6, CsaFBN1, and CsaFBN9. High-light stress combined with low temperature decreased photosynthetic efficiency and highly induced transcript levels of CsaFBN1, CsaFBN6, and CsaFBN11, which decreased after 24 h treatment. Transcript levels of the other seven genes were changed only slightly. This result suggests that CsaFBN1, CsaFBN6, and CsaFBN11 may be involved in photoprotection under high-light conditions at low temperature.
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Life Sciences, Immunology; crotoxin; macrophages; neutrophils; inflammation; ATP; reactive oxygen and nitrogen species; cytokines; co-culture model
Online: 23 May 2018 (09:12:45 CEST)
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Crotoxin (CTX), the predominant toxin in Crotalus durissus terrificus snake venom (CdtV), has anti-inflammatory and immunomodulatory effects. Despite its inhibitory action on neutrophil migration and phagocytosis, CTX does not directly affect the production of reactive oxygen species (ROS) by the neutrophils. In contrast, it enhances the generation of reactive oxygen and nitrogen intermediates by macrophages. Given the importance of macrophage-neutrophil interactions in innate antimicrobial defense, the aim of this study was to investigate the effect of CTX on neutrophil ROS production and killing activity, either through CTX-treated macrophage co-culture or conditioned medium of CTX-treated macrophages. The results showed an important modulatory action of CTX on the neutrophil function as well as neutrophil-macrophage interactions, as demonstrated by the increased production of hydrogen peroxide, hypochlorous acid, nitric oxide and TNF-α, along with the increased fungicidal activity of neutrophils.
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Life Sciences, Other; phytochemical; heavy metals; flavoured alcoholic beverages; herbal extract
Online: 23 May 2018 (05:15:55 CEST)
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There is proliferation of alcoholic beverages flavoured with herbal-extracts perceived to have medicinal values. Information on the phytochemical and heavy metal contents of these products is scarce. This study assessed the phytochemical properties and heavy metal contents of herbal-extract flavoured alcoholic beverages in major motor parks in Ibadan, Nigeria. The phytochemical properties of the beverages were determined in triplicate using standard methods while the heavy metal contents were assessed using atomic absorption spectrophotometry. Data were analyzed using descriptive statistics and means were compared using ANOVA at p<0.05. The pH range of the beverages was 3.28-6.57 and the alcohol content was 34.0-51.5%. Detected major phytochemicals and concentration ranges were phytic acid (0.72-2.37 mg/g), alkaloids (0.42-4.11 mg/g), flavonoids (0.22-3.64 mg rutin equivalents/g), total phenols (1.13-3.66 mg gallic acid equivalents/g), anthraquinones ((0.74-1.93 mg/g) and triterpenoids (0.74-1.93 mg/g). The phytochemical contents were within the acceptable limits while the heavy metals were: Pb (2.13-4.70 mg/L), Cd (0.06-0.07 mg/L), Co (0.12-0.23 mg/L), Zn (0.14-0.40 mg/L) and Fe (0.72-4.22 mg/L); all except Pb and Cd were within permissible limits. The herbal-extract flavoured alcoholic beverages contain beneficial phytochemicals and traces of heavy metals. Safety awareness of these products for improved consumers’ health would be of public health importance.
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Life Sciences, Other; Drosophila, dopamine, serotonin, neurodegeneration, neurotransmitter transporters, vesicular monoamine transporters
Online: 22 May 2018 (14:05:40 CEST)
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The brain of Drosophila melanogaster is comprised of some 100,00 neurons, 127 and 80 of which are dopaminergic and serotonergic, respectively. Their activity regulates behavioral functions equivalent to those in mammals, e.g. motor activity, reward and aversion, memory formation, feeding, sexual appetite etc. Mammalian dopaminergic and serotonergic neurons are known to be heterogeneous. They differ in their projections and in their gene expression profile. A sophisticated genetic tool box is available, which allows for targeting virtually any gene with amazing precision in Drosophila melanogaster. Similarly, Drosophila genes can be replaced by their human orthologs including disease-associated alleles. Finally, genetic manipulation can be restricted to single fly neurons. This has allowed for addressing the role of individual neurons in circuits, which determine attraction and aversion, sleep and arousal, odor preference etc. Flies harboring mutated human orthologs provide models, which can be interrogated to understand the effect of the mutant protein on cell fate and neuronal connectivity. These models are also useful for proof-of-concept studies to examine the corrective action of therapeutic strategies. Finally, experiments in Drosophila can be readily scaled up to an extent, which allows for drug screening with reasonably high throughput.
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Life Sciences, Cell & Developmental Biology; glial bridge; ctgfa; Fgf signaling; MAPK signaling; shh; slit2/3; Wnt signaling; genetic compensation; glial bridge cycle; spinal cord regeneration; termination signal; central nervous system; peripheral nervous system; zebrafish
Online: 22 May 2018 (12:09:09 CEST)
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Zebrafish have been found to be the premier model organism in biological and biomedical research, specifically offering many advantages in developmental biology and genetics. This unique aquatic species has been found to have the capacity to regenerate their spinal cord after injury. However, the complete molecular and cellular mechanisms behind glial bridge formation in the central and peripheral nervous systems upon glial cell injury remains unclear. This review paper focuses on the molecular mechanisms and cellular processes that underlie spinal cord regeneration in four initial phases: proliferation and initial migration; migration and differentiation; glial bridge formation; and remodeling. We propose that within these four phases the cellular mechanisms that underlie spinal cord regeneration each express a terminating signal that aborts one step of the process and initiates the next. Specifically, future studies would be devoted to investigate transmitting signals in the spinal cord injury micro-environment in hope to contribute to the understanding of underlying cellular mechanisms by connecting each process of spinal cord regeneration in zebrafish.
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Life Sciences, Virology; virus; metagenomic; RNAi; host-range; picornavirales; drosophila
Online: 21 May 2018 (13:18:23 CEST)
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Metagenomic sequencing has led to a recent and rapid expansion in the animal virome. It has uncovered a multitude of new virus lineages from under-sampled host lineages, including many that break up long branches among previously known clades, and many with genomes that display unexpected sizes and structures. Although there are challenges to inferring the existence of a virus from a virus-like sequence, the analysis of nucleic acid (including small RNAs) and sequence data can give us considerable confidence in the absence of an isolate. As a consequence, this period of ‘molecular natural history’ is helping to reshape our views of deep virus evolution. Nevertheless, there is a limit to what metagenomic discovery alone can tell us, and some open questions will require experimental isolates.
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Life Sciences, Endocrinology & Metabolomics; Implantation failure; Bisphenol A; 4-tert-octylphenol; calcium channel
Online: 18 May 2018 (07:38:04 CEST)
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Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.
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Life Sciences, Other; renovascular hypertension; chronic kidney disease; oxidative stress; fibrosis; (S)-2,9-dihydroxy-1,10-dimethoxy-aporphine
Online: 17 May 2018 (07:50:15 CEST)
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Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.
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Life Sciences, Microbiology; Elaeagnus rhamnoides butanol extracts; phenolic; non-polar fractions; anti-virulence; properties
Online: 16 May 2018 (08:02:13 CEST)
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Butanol extracts from leaves, twigs and fruits of Elaeagnus rhamnoides (L.) A. Nelson (sea buckthorn, SBT) were fractionated into phenolic and non-polar lipid components. Their chemical composition was analyzed using the Thermo Ultimate 3000RS chromatographic system, equipped with a diode array detector, a corona-charged aerosol detector, and coupled with a (Q-TOF) mass spectrometer. Assuming that an effect on natural microbiotaand host epithelial cells needs to be assessed, regardless of the purpose of using SBT formulations in vivo, the MIC/MBC/MFC of the fractions and reference phytocompounds were screened involving 17 species of Gram-positive and Gram-negative bacteria and Candida species. The impact of the fractions (subMIC) on the important in vivo persistence properties of S. aureus and C. albicans strains was evaluated. Tests for adhesion and biofilm formation on an abiotic surface and the surfaces conditioned with fibrinogen, collagen, plasma or artificial saliva showed the inhibitory activity of the fractions. The effects on FITC-labeled staphylococci adhesion to fibroblasts (HFF-1) and epithelial cells (Caco-2), and on fungal morphogenesis, indicated that SBT extracts have high anti-virulence potential. Cytotoxicity tests (MTT-reduction) on the standard fibroblast cell line showed variable biological safety of the fractions depending on their composition and concentration.
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Life Sciences, Microbiology; Streptomyces; polyketides; secondary metabolite; polyketide synthases (PKSs)
Online: 15 May 2018 (08:58:00 CEST)
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Polyketides are large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks and sponges. Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of polyketides producers. Some examples of polyketides produced by Streptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in Streptomyces that responsible for producing polyketides. This paper focuses on biosynthesis of polyketides in Streptomyces with three structurally different types of PKSs.
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Life Sciences, Molecular Biology; Vezf1; angiogenesis; vascular biology; endothelial cells; MSS31, tube formation, small molecule inhibitors computational modeling.
Online: 15 May 2018 (08:08:15 CEST)
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Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.
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Life Sciences, Immunology; antibody; Isotype IgA; Pertuzumab; allosteric; biologics; constant region; variable region
Online: 15 May 2018 (07:51:15 CEST)
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Therapeutics antibodies have increasingly shifted the paradigm of disease treatments, from small molecules to biologics, especially in cancer therapy. Despite the increasing number of antibody candidates, much remains unknown about the antibody and how its various regions interact. In fact, the constant region can govern effects that might be useful in reducing the unwanted consequences resulted from systemic circulation. For this reason, apart from the commonly used IgG isotypes, IgA antibodies are promising therapeutics drugs, given its localized mucosal effects. While the antibody Fc effector cell activity has been well explored, recent research has shown evidences that the constant region of the antibody can also influence antigen binding, challenging the conventional idea of region-specific antibody functions. To further investigate this, we analyzed the IgA antibody constant and its allosteric effects onto the antigen binding regions, using recombinant Pertuzumab IgA1 and IgA2 variants. We found mutations in the C-region to reduce Her2 binding, and our computational structural analysis showed that such allosteric communications were highly dependent on the antibody hinge, providing the evidence to consider antibodies as a whole protein rather than a sum of functional regions.
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Life Sciences, Genetics; advanced therapy; aggressive; antisocial; behavior; MAOA
Online: 14 May 2018 (10:46:26 CEST)
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Antisocial behavior is a behavior disorder inherited according to the inheritance of X-linked chromosome. This disorder derives from mutations in the MAOA gene. One of the mutations results in the MAOA-L allele activity. The MAOA-L allele activity can cause antisocial behavior in both healthy and unhealthy people. Antisocial behavior from healthy males can originate from maltreatment during childhood. Currently, MAOA inhibitor can reverse antisocial behavior to normal behavior in animal models. However, this disorder cannot be treated permanently; to treat it permanently in the future, technologies such as CRISPR/Cas9, iPSCs and ssODN are required. These technologies have succeeded to correct erroneous segments in the F8 gene and F9 gene. Both genes occupy the X chromosome. The MAOA gene also occupies the X chromosome. Therefore, it is reasonable to state that CRISPR/Cas9 and iPSCs technique for instance can be beneficial tools to edit the MAOA gene to treat antisocial behavior. CRISPR/Cas9 can be used in combination with iPSCs or ssODN for instance. This combination can greatly help the permanent healing of antisocial behavioral disorders.
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Life Sciences, Cell & Developmental Biology; BMP; TGF-β; signaling; sex; chromosomes; XIST; genomic imprinting; hormones; fibrosis
Online: 11 May 2018 (09:49:48 CEST)
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Crosstalk between the BMP and TGF-β signaling pathways regulates many complex developmental processes from the earliest stages of embryogenesis throughout adult life. In many situations, the two signaling pathways act reciprocally. For example, TGF-β signaling is generally pro-fibrotic whereas BMP signaling is anti-fibrotic and pro-calcific. Sex-specific differences occur in many diseases including cardiovascular pathologies. Differing ratios of fibrosis and calcification in stenotic valves suggests that BMP/TGF-β signaling may vary in men and women. In this review, we focus on the current understanding of the interplay between sex and BMP/TGF-β signaling and pose several unanswered questions.
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Life Sciences, Genetics; complex loci; autoimmune diseases
Online: 10 May 2018 (08:18:44 CEST)
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Although genome-wide association studies (GWAS) have identified several hundred loci associated with autoimmune diseases, their mechanistic insights are still poorly understood. The human genome is more complex than common single nucleotide polymorphisms (SNPs) that are interrogated by GWAS arrays. Some structural variants such as insertions-deletions, copy number variations, and minisatellites that are not very well tagged by SNPs cannot be fully explored by GWAS. Therefore, it is possible that some of these loci may have large effects on autoimmune disease risk. In addition, other layers of regulations such as gene-gene interactions, epigenetic-determinants, gene and environmental interactions also contribute to the heritability of autoimmune diseases. This review focuses on discussing why studying these elements may allow us to gain a more comprehensive understanding of the aetiology of complex autoimmune traits.
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Life Sciences, Biochemistry; carbonic anhydrase, enzyme inhibition, metalloenzymes, amino acid, glaucoma, tumors
Online: 9 May 2018 (13:55:15 CEST)
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Carbonic Anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life kingdoms, classified into seven genetically different families (α-θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or the progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) are used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.
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Life Sciences, Molecular Biology; citrus breeding; diversity; genetic similarity; Lime; molecular markers; PCR
Online: 9 May 2018 (11:05:37 CEST)
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Acid lime [Citrus aurantifolia (Christm.) Swingle] is a fruit crop, enriched with high commercial value and is cultivated in 60 out of 75 districts representing all geographical landscapes of Nepal. Lack of high yielding cultivars is probably one of the main reason for its extremely reduced productivity which warrants a deep understanding of genetic diversity in existing germplasm. Hereby, we aim to access the genetic diversity of acid lime germplasm cultivated at 3-different ecological gradients of eastern Nepal employing PCR-based Inter-Simple Sequence Repeats markers (ISSR). Altogether, 21 polymorphic ISSR markers were used to assess the genetic diversity in 60 acid lime cultivars sampled from different geographical locations. Analysis of binary data matrix was performed on the basis of bands obtained, scoring of the data was done accordingly, and principal coordinate analysis and phenogram were constructed using different computer algorithms. ISSR profiling yielded 234 amplicons, of which 87.18% were found to be polymorphic. The number of amplified fragments ranged from 7-18 with amplicon size ranging from 250-3200 bp. The NTSYS based Cluster analysis using UPGMA algorithm taking Dice Similarity coefficient separated 60 accessions into 2-major and 3-minor clusters. The genetic diversity analysis revealed the highest for Terai and the lowest for High-hill zone. Cluster I comprised of accessions from High-hill and Mid-hill regions revealing the close genetic relationship, whereas cluster II comprised of accessions from all three agro-ecological zones and the exotic varieties. Furthermore, our results revealed the accessions harvested from different geographical gradients were not genetically distinct, but highest diversity was observed in Terai accessions in comparison to the regions belonging to the High and Mid-hills. Thus, our data indicate that the ISSR provides a better option for evaluating the genetic diversity of Nepalese Acid Lime cultivars and furnished significant information, assisting parental selection in current and future breeding programs and germplasm conservation which ultimately may help to provide a technological breakthrough for the farmers of the developing country like Nepal.
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Life Sciences, Other; neuroscience; thalamus; basal ganglia; cortical layers; hippocampus; cerebellum; habenula; claustrum; amygdala; inhibition; predictions; automaticity; dopamine; serotonin; acetylcholine; opioids; oxytocin; crh; glucocorticoids; cannabinoids; orexin; melanin-concentrating hormone; mirror neuron; place cells; grid cells; language; imagery; working memory; attention; consciousness; emotions
Online: 9 May 2018 (05:35:51 CEST)
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Understanding brain function is one of the most important problems in human history. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain's capacities, including motor control, functional states, language, and thinking. Brain function is managed by a well-defined response (R) process that is generally similar to the process underlying the immune system. The R process is strongly reflected in the brain's anatomy, physiology, and external interactions. Different R process stages are supported by distinct excitatory networks located in different cortical layers, hippocampal fields, and bagal ganglia paths, by distinct coordination networks comprised of GABAergic interneurons, and by distinct molecular agents. The roles of norepinephrine, serotonin, dopamine and acetylcholine is to promote the alert, planning, goal-setting and execution R process modes, respectively. Opioids and oxytocin promote termination by success, failure, fight or run, while glucocorticoids and cannabinoids suppress acute responses to protect cells. The R process has two instances occurring at different time scales. The millisecond-scale Quax process implements the execution of hierarchical sequences of movements and thoughts, in which the selection of the next action is determined via interaction between top-down predictions and sensory inputs. The slower Need process controls the satisfaction of internal and external needs. The theory differs from the existing standard accounts in many of the major topics (e.g., the basal ganglia, dopamine, language), and shows how cognition results from biological processes.
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Life Sciences, Microbiology; propolis; Candida spp., biofilm; resistance; synergism
Online: 8 May 2018 (05:58:33 CEST)
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The aim of our work was to check if one of the products of natural origin, namely honey bee propolis may be an alternative or supplement to currently used antifungal agents. The activity of 50 ethanolic extracts of propolis (EEPs), harvested in Polish apiaries, was tested on a group of 69 clinical isolates of C. albicans. Most of the EEPs showed satisfactory activity, with minimum fungicidal concentrations (MFC) mainly in the range of 0.08-1.25% (v/v). Eradication of biofilm from polystyrene microtitration plates in 50% (MBEC50) required concentrations in the range of 0.04% (v/v) to more than 1.25% (v/v). High activity was also observed in eradication of biofilm formed by C. glabrata and C. krusei on the surfaces of PVC and silicone catheters. EEPs at subinhibitory concentrations inhibited yeast-to-mycelia morphological transformation of C. albicans in liquid medium and mycelial growth on solid medium. A synergistic effect was observed for the action of EEPs in combination with fluconazole (FLU) and voriconazole (VOR) against C. albicans. In the presence of EEP at concentration as low as 0.02%, the MICs of FLU and VOR were 256 to 32 times lower in comparison to those of the drug alone. Evidences for the fungal cell membrane as the most probable target of EEPs are presented.
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Life Sciences, Virology; tail tubular protein B; bacteriophage; biofilm; exopolysaccharide; hydrolytic activity
Online: 8 May 2018 (05:36:01 CEST)
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Background: Dual function tail tubular proteins (TTP) belonging to the lytic bacteriophages are the interesting group of biologically active enzymes. Surprisingly, apart from their structural function, they are also polysaccharide hydrolyzes destroying bacterial extracellular components. One of the representatives of this group is TTPB from Klebsiella pneumoniae phage – KP32. TTPB hydrolyzes exopolysaccharide (EPS) of Klebsiella pneumoniae and Enterococcus faecalis strain. This depolymerizing feature was associated with the activity to prevent bacterial biofilm formation. TTPB can inhibit biofilm formation by K. pneumoniae, Enterobacter cloacae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa strains. Moreover, synergistic activity with antibiotic action has been observed, most likely due to depolymerases’ facilitation of contact of antibiotic with bacterial cells. Methods: TTPB was overexpressed in E coli system, purified and tested towards the bacterial strains using agar overlay method. The hydrolytic activity of TTPB was performed using EPSs of K. pneumoniae PCM2713 and E. cloacae ATCC 13047 as the substrates. Next, we determined the reducing sugar (RS) levels in the TTPB/EPS mixtures, regarding the RS amount obtained after acidic hydrolysis. The antibiofilm activity of TTPB has been set down on bacterial biofilm using a biochemical method. Finally, we have demonstrated the synergistic activity of TTPB with kanamycin. Results: For the first time, the hydrolytic activity of TTPB towards bacterial EPSs has been shown. TTPB releases about a half of the whole RS amount of EPSs belonging to K. pneumoniae PCM 2713 and E. cloacae ATCC 13047 strains. 1.12 µM of the phage protein reduces biofilm of both strains by over 60%. Destroying the bacterial biofilm the phage protein improves the antibiotic action increasing kanamycin effectiveness up to four times.
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Life Sciences, Microbiology; Mucorales; phylogeny; rare fungi; undiscovered taxa
Online: 7 May 2018 (10:29:56 CEST)
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The order Mucorales, the largest in number of species within the Mucoromycotina, comprises typically fast-growing saprotrophic fungi. During a study of the fungal diversity of undiscovered taxa in Korea, two novel mucoralean strains, CNUFC-GWD3-9 and CNUFC-EGF1-4, were isolated from specific habitats including freshwater and fecal samples, respectively, in Korea. On the basis of their morphological characteristics and sequence analyses of internal transcribed spacer (ITS) and large subunit (LSU) of 28S ribosomal DNA regions, the CNUFC-GWD3-9 and CNUFC-EGF1-4 isolates were confirmed to be Gilbertella persicaria and Pilobolus crystallinus, respectively. It is ecologically, pathologically and mycologically significant to find such rare zygomycetous fungi in such specific habitats.
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Life Sciences, Virology; yellow fever virus; Flavivirus; vector-borne transmission, emergence
Online: 7 May 2018 (05:19:50 CEST)
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The recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America has sparked renewed interest in this infamous arboviral disease. YFV had been a human plague for centuries prior to the identification of its urban transmission vector, the Aedes aegypti mosquito species, and the development of an efficient live-attenuated vaccine, the YF-17D strain. The combination of vector-control measures and vaccination campaigns drastically reduced YFV incidence in humans on many occasions, but the virus never ceased to circulate in the forest, through its sylvatic invertebrate vector(s) and vertebrate host(s). Outbreaks recently reported in Central Africa (2015-2016) and Brazil (since late 2016), reached considerable proportions in terms of spatial distribution and total numbers of cases, with multiple exports, including to China. In turn, questions regarding the likeliness of occurrence of large urban YFV outbreaks in the Americas or of a successful import of YFV to Asia are currently resurfacing. This two-part review describes the current state of knowledge and gaps regarding the molecular biology and transmission dynamics of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.
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Life Sciences, Other; maize; organic; water
Online: 5 May 2018 (10:33:45 CEST)
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The aggravating threat for today’s agriculture is provision of food security to ever-escalating eating mouths utilizing scarce resources. Water scarcity is restraining humans to produce more from drops of water in place of gallons. Root is present at soil-plant interface and is main water extractor for plant. Its growth pattern varies as soil moisture conditions fluctuates. Present pot study consisting of two factors i.e. organic substrates (Farm manure, Poultry Manure and Molasses) and different water stress levels (50, 75, 100 and 125% of AWCs) using maize as test crop to assess their impact on different growth parameters (especially root growth). The experiment was conducted using CRD under factorial arrangement. Root length (44.55 cm), root fresh & dry biomass (71.10 g and 24.30 g), root diameter (1.73 mm), root volume (0.24 cm3) and root length density (7.4 × 10−3 cm cm−3) were observed in farm manure treated pots at 75% AWC that was statistically indistinguishable from all other treatments at same water level and 100% water availability but eloquently greater than plants of all treatments at 50% and 125% available water contents. Shoot length, dry and fresh weights were observed greater in plants having 100% available moistures, that were at par with 75% water treated plants. Comparing treatments for all of the parameters in multivariate cluster analysis it was concluded that 75% available water contents produce almost similar to 100% along with the benefit of water security.
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Life Sciences, Biophysics; cryo-electron microscopy; air-water interface; conformational heterogeneity; focus gradient; radiation damage
Online: 3 May 2018 (11:08:20 CEST)
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With forty years of developments, bio-macromolecule cryo-electron microscopy has met its revolution of resolution and is playing a very important role in structural biology study. According to different specimen states, cryo-electron microscopy (cryo-EM) involves three specific techniques, single particle analysis (SPA), electron tomography and sub-tomogram averaging, and electron diffraction. All these three techniques have not realized their full potentials of solving structures of bio-macromolecules and therefore need to be developed in the future. In this review, the current existing bottlenecks of cryo-EM SPA are discussed with theoretical analysis, which includes air-water interface during specimen cryo-vitrification, bio-macromolecular conformational heterogeneity, focus gradient within thick specimen, and electron radiation damage. Besides, potential solutions of these bottlenecks are proposed and discussed, which are worthy of further investigations in the future.
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Life Sciences, Microbiology; finger millet; mycorrhiza; drought; ROS; antioxidant
Online: 3 May 2018 (09:38:17 CEST)
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Under abiotic stress conditions, arbuscular mycorrhizal (AM) fungi help plants by improving nutrient and water uptake. Finger millet is an arid crop having soils with poor water holding capacity. Therefore, it is difficult for the plants to obtain water and mineral nutrients from the soil to sustain life. To understand the role of mycorrhizal symbiosis in water and mineral up-take from the soil, we studied the role of Rhizophagus intraradices colonization and its beneficial role for drought stress tolerance in finger millet seedling. Under severe drought stress condition, AM inoculation led to the significant increase in plant growth (7%), phosphorus, and chlorophyll content (29%). Also, the level of osmolytes including proline and soluble sugars were found in higher quantities in AM inoculated seedlings under drought stress. Under water stress, the lipid peroxidation in leaves of mycorrhized seedlings was reduced by 29%. The flavonoid content of roots in AM colonized seedlings was found 16% higher compared to the control, whereas the leaves were accumulated more phenol. Compared to the control, ascorbate level was found to be 25% higher in leaf tissue of AM inoculated seedlings. Moreover, glutathione (GSH) level was increased in mycorrhiza inoculated seedlings with a maximum increment of 182% under severe stress. The results demonstrated that AM provided drought tolerance to the finger millet seedlings through a stronger root system, greater photosynthetic efficiency, a more efficient antioxidant system and improved osmoregulation.
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Life Sciences, Microbiology; antioxidant system; cell wall integrity; chemosensitization; end point; fungi; small molecule
Online: 3 May 2018 (08:32:40 CEST)
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Filamentous fungi such as Aspergillus spp. are opportunistic pathogens, which cause highly invasive infections, especially in immunocompromised individuals. Control of such fungal pathogens is increasingly problematic due to the small number of effective drugs available for treatment. Moreover, the increased incidence of fungal resistance to antifungal agents makes this problem a global human health issue. The cell wall integrity system of fungi is the target of antimycotic drugs echinocandins, such as caspofungin (CAS). However, echinocandins cannot completely inhibit the growth of filamentous fungal pathogens, which results in survival/escape of fungi during treatment. Chemosensitization was developed as an alternative intervention strategy, where co-application of CAS with the intervention catalyst octyl gallate (OG; chemosensitizer) greatly enhanced CAS efficacy, thus achieved ≥ 99.9% elimination of filamentous fungi in vitro. Based on hypersensitive responses of Aspergillus antioxidant mutants to OG, it is hypothesized that, besides destabilizing cell wall integrity, the redox-active characteristic of OG may further debilitate fungal antioxidant system.
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Life Sciences, Other; Cancer; energetic metabolism; transcription factor
Online: 2 May 2018 (12:27:44 CEST)
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Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.
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Life Sciences, Molecular Biology; Fusarium head blight; deoxynivalenol; cytotoxicity; Caenorhabditis elegans; RNAseq
Online: 29 April 2018 (10:40:16 CEST)
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Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. that causes Fusarium head blight (FHB) disease in cereal crops. Ingestion of food contaminated with DON poses serious human health complications. However, the DON cytotoxicity has been mostly deduced from animal studies. In this study, we used the nematode Caenorhabditis elegans (C. elegans) as a tractable animal model to dissect the toxic effect of DON. Our results indicate that DON reduces the fecundity and lifespan of C. elegans. The real-time RT-PCR analysis showed that DON upregulates innate immunity-related genes including C17H12.8 and K08D8.5 encoding PMK-1 (mitogen activated protein kinase-1)-regulated immune effectors, and F35E12.5 encoding a CUB-like domain-containing protein. Furthermore, our RNAseq data demonstrate that out of ~ 17,000 C. elegans genes, 313 are upregulated and 166 were downregulated by DON treatment. Among the DON-upregulated genes, several are ugt genes encoding UDP-glucuronosyl transferase (UGTs) which are known to be involved in chemical detoxification. The three upregulated genes, F52F10.4 (oac-32), C10H11.6 (ugt-26) and C10H11.4 (ugt-28) encoding the O-acyltransferase homolog, UGT26 and UGT 28, respectively, are shown to contribute to DON tolerance by RNAi bacterial feeding experiment. The results of this study provide insights to the targets of DON cytotoxicity and potential mitigation measures.
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Life Sciences, Microbiology; Parkinson’s disease; gut microbiome; neurodegenerative diseases; microbiota-gut-brain-axis
Online: 28 April 2018 (12:09:20 CEST)
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In the last years evidence has emerged that neurodegenerative diseases (NDs) are strongly associated with the microbiome composition in the gut. Parkinson’s disease (PD) is the most intensively studied neurodegenerative disease in this context. In this review, we performed a systematic evaluation of published literature comparing changes in colonic microbiome in PD to the ones observed in other NDs including Alzheimer’s Disease (AD), Multiple system atrophy (MSA), Multiple sclerosis (MS), Neuromyelitis optica (NMO) and Amyotrophic lateral sclerosis (ALS). To warrant comparability of different studies, only human case-control studies were included. Several studies showed an increase of Lactobacillus, Bifidobacterium, Verrucomicrobiaceae and Akkermansia in PD. A decrease in PD was observed of Faecalibacterium spp., Coprococcus spp., Blautia spp., Prevotella spp. and Prevotellaceae. On low taxonomic resolution, like phylum level, the changes are not disease specific and inconsistent. However, on higher taxonomic resolution like genus or species level, a minor overlap was observed between PD and MSA, both alpha synucleinopathies. We show that a methodical standardization of sample collection and analysis is necessary for ensuring the reproducibility and comparability of data. We also provide the evidence, that assessing the microbiota composition at high taxonomic resolution, reveals changes in relative abundance, that may be specific or characteristic for one disease, or a disease-group and might evolve discriminative power. The interactions between bacterial species and strains and moreover the co-abundances must be more deeply investigated before assumptions of the effects of specific bacteria on the host can be made with certainty.
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Life Sciences, Biophysics; origin of life; origins of life; mechanical energy; work; mica; biotite; Muscovite; wet/dry cycles; clay
Online: 26 April 2018 (10:34:06 CEST)
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Mechanical forces are prevalent in living cells. This may be because mechanical forces and mechanical energy preceded chemical energy at life’s origins. Mechanical energy is more readily available in non-living systems than the various other forms of energy used by living systems. Two possible prebiotic environments that might have provided mechanical forces are hot springs that experience wet/dry cycles and mica sheets as they move, open and shut, as heat pumps or in response to water movements.
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Life Sciences, Molecular Biology; myocardial infarction; heart attack; gene set enrichment analysis; protein-protein interaction network; bioinformatics; systems biology; in silico study
Online: 26 April 2018 (10:22:31 CEST)
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Myocardial infarction, more commonly known as heart attack, is a huge health problem around the world. It is a result of inadequate blood supply to certain parts of the heart and death of heart muscle cells in that region. Although it has been around for a long time, newer and newer ways of probing myocardial infarction is being followed. Bioinformatics and Systems Biology are relatively recent fields to try to give new insights into myocardial infarction. Following the footsteps of others, this in silico study has tried to chime in on the investigation into myocardial infarction. The study began with the gene expression omnibus dataset uploaded to the NCBI from a whole-genome gene expression analysis carried out at Mayo Clinic in Rochester, Minnesota. From the dataset, differentially expressed genes following first-time myocardial infarction were identified and classified into up-regulated and down-regulated ones. Gene Set Enrichment Analysis (GSEA) was carried out on the up-regulated genes which were statistically significant and corresponded with the NCBI generated annotations. Protein-Protein Interaction Network for these genes was constructed. GSEA revealed 5 transcription factors, 5 microRNAs and 3 pathways significantly associated with them. From the Protein-Protein Interaction Network, 6 key proteins (hub nodes) have been identified. These 6 proteins may open a new window of opportunity for the discovery/design of new drugs for mitigating the damage caused by myocardial infarction.
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Life Sciences, Genetics; GSEA; cocaine; addiction; enrichment analysis; bioinformatics; in silico research
Online: 24 April 2018 (08:46:31 CEST)
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Cocaine addiction is a global health problem that causes substantial damage to the health of addicted individuals around the world. Dopamine synthesizing neurons in the brain play a vital role in the addiction to cocaine. But the underlying molecular mechanisms that help cocaine exert its addictive effect have not been very well understood. Bioinformatics can be a useful tool in the attempt to broaden our understanding in this area. In the present study, Gene Set Enrichment Analysis (GSEA) was carried out on the upregulated genes from a dataset of Dopamine synthesizing neurons of post-mortem human brain of cocaine addicts. As a result of this analysis, 3 miRNAs have been identified as having significant influence on transcription of the upregulated genes. These 3 miRNAs hold therapeutic potential for the treatment of cocaine addiction.
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Life Sciences, Biophysics; peptide; self-assembly; molecular dynamics; peptergency; beta structure
Online: 23 April 2018 (11:27:51 CEST)
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By manipulating the various physico-chemical properties of amino acids, design of peptides with specific self-assembling properties has been emerging since more than a decade. In this context, short peptides possessing detergent properties (so-called “peptergents”) have been developed to self-assemble into well-ordered nanostructures that can stabilize membrane proteins for crystallization. In this study, the peptide with “peptergency” properties, called ADA8 extensively described by Zhang et al., is studied by molecular dynamics for its self-assembling properties in different conditions. In water, it spontaneously forms beta sheets with a β barrel-like structure. We next simulated the interaction of this peptide with a membrane protein, the bacteriorhodopsin, in the presence or absence of a micelle of dodecylphosphocholine. According to the literature, the peptergent ADA8 is thought to generate a belt of β structures around the hydrophobic helical domain that could help stabilize purified membrane proteins. Molecular dynamics is here used to challenge this view and to provide further molecular details for the replacement of detergent molecules around the protein. To our best knowledge, this is the first molecular mechanism proposed for ''peptergency''. In addition, our calculation approach should serve as a predicting tool for the design of beta peptergent with diverse amphipathic properties.
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Life Sciences, Virology; Betaflexiviridae; blackcurrant; blackcurrant virus A; characterization; detection
Online: 23 April 2018 (10:37:14 CEST)
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A novel virus with distinct genome features was discovered by high throughput sequencing in a symptomatic blackcurrant plant. The virus tentatively named as blackcurrant virus A (BCVA) has distinct genome organization and molecular features bridging genera in the order Tymovirales. The genome consists of 7106 nucleotides excluding the poly(A) tail. Five open reading frames were identified with the first encoding a putative viral replicase with methyl transferase (MTR), AlkB, helicase and RNA dependent RNA polymerase (RdRp) domains. The other four putative proteins exhibit no significant homology to other virus proteins. The genome organization downstream of the replicase resembles that of members of the order Tymovirales with an unconventional triple gene block (TGB) movement protein arrangement. Phylogenetic analysis using replicase conserved motifs loosely placed BCVA within the Betaflexiviridae whereas it was evolutionarily distant to existing members of the family when using the putative TGBp 1-like and coat protein sequences. Our analysis strongly suggests that BCVA is a novel virus that should be classified as a species in a new genus in the Betaflexiviridae or a new family in the order Tymovirales.
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Life Sciences, Biotechnology; designed consortium; textile effluents; biological induction; azo dyes
Online: 20 April 2018 (11:25:43 CEST)
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The potential of biological consortia designed for laccase production and dye treatment is discussed in this review. The poor yields in laccase production and low efficiency in dye decolorization of monoculture-based treatments has encouraged the use of designed biological consortia. A consortium is a system where the growth of two or more organisms, chosen to improve a particular bioprocess, is induced in the same medium. Chemical and natural mediators are being replaced by consortia for the production of laccases because, in addition to being less toxic, they induce new enzyme isoforms and lead to high laccase yields. On the other hand, consortia act synergistically in the decolorization of azo dyes through the enzymes they produce, so overall degradation is improved. Designed consortia are an attractive alternative still in development that could provide new biotechnological tools for the treatment of textile effluents.
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Life Sciences, Biotechnology; hepatic injury; sealants; metalloproteinases; inflammatory response; wound healing
Online: 20 April 2018 (11:14:49 CEST)
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Background. Adhesives and sealants can be used to repair and preserve solid damaged organs. This study explores the activity of different matrix metalloproteinases (MMP) during the healing of liver injuries treated with two biological adhesives (Tachosil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex®). Methods. Liver traumatic injuries were experimentally induced in 90 male Wistar rats using a Stiefel biopsy punch in the liver. Wound healing was evaluated 2, 6, and 18 days after injury by determining MMP1, 2, 8, 9, and 13 expression. The histopathological repair was assessed by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining. The three sealants used supported complete healing of the liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong initial inflammatory reaction. Results. All the MMPs measured disclosed higher values at early stage of the healing process in animals treated with Adhflex® and Tachosil, being the expression of for MMP2 and MMP9 significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not influence negatively the histological healing process of the hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered as a suitable treatment option.
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Life Sciences, Biotechnology; sterol glycosyltransferase; O-methyltransferase; Streptomyces avermitilis MA-4680; biotransformation; Cholesterol-3-O-β-D-glucoside; GC-MS
Online: 19 April 2018 (09:31:06 CEST)
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A sterol glycosyltransferases (SGT) gene (sav7185; accession number NP_828361) was isolated from Streptomyces avermitilis MA-4680. The full-length gene consists of 1284 nucleotides and encodes 427 amino acids with a calculated mass of 46.05 kDa. The gene was then cloned in pET28a vector and heterologously expressed in Escherichia coli BL21 (DE3) and was used for the biotransformation of cholesterol. This SGT protein showed favorable activity towards cholesterol tested in this study. Further, we tested the conversion of cholesterol to its methoxide using another Streptomyces O-methyltransferase (accession number KF420279). This O-methyltransferase (OMT) SpOMT2884, originating from Streptomyces peucetius ATCC 27952, was cloned, expressed, and applied for the production of methylated derivative. The GC-MS analysis confirmed the conversion of cholesterol into cholesterol-3-O-β-D-glucoside and a novel cholesterol-3-O-methoxide. Hence, these Streptomyces SGT and OMT could find applications for the derivatization of pharmaceutically significant sterols.
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Life Sciences, Biochemistry; Non-small cell lung cancer; Lambertianic acid; Apoptosis; TRAIL; XIAP; NF-B
Online: 18 April 2018 (15:25:10 CEST)
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Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.
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Life Sciences, Biochemistry; axon guidance; DRS; HGPPS; CFEOM3; in silico; systems biology; PPI network
Online: 18 April 2018 (08:23:58 CEST)
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Axon guidance is a crucial process for growth of the central and peripheral nervous systems. In this study, 3 axon guidance related disorders, namely- Duane Retraction Syndrome (DRS) , Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) and Congenital fibrosis of the extraocular muscles type 3 (CFEOM3) were studied using various Systems Biology tools to identify the genes and proteins involved with them to get a better idea about the underlying molecular mechanisms including the regulatory mechanisms. Based on the analyses carried out, 7 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with DRS, HGPPS and CFEOM3 associated genes. From the PPI network, 3 have been identified as hub proteins- DRD2, UBC and CUL3.
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Life Sciences, Biotechnology; bone graft, resorbable barrier, sinus lift, heterologous cortical lamina
Online: 16 April 2018 (13:53:55 CEST)
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Abstract A variety of surgical techniques have been developed to reconstruct the posterior maxilla when bone volume is insufficient. A barrier membrane or bone window pushed inside the sinus cavity as the ‘‘roof’’ of the sinus cavity for preserve the space and help bone. The heterologous cortical lamina is used for the mechanical support, without any grafting material, of sinus membranes resulting in only bone tissue formation and not mixed with the graft.
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Life Sciences, Microbiology; drug resistance; Candida albicans; Candida glabrata; Galenia africana; fluconazole; broth microdilution; checkerboard; sensititre
Online: 13 April 2018 (03:49:28 CEST)
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Candida infections have increased in recent years and are causing serious public health concern. In addition, Candida species are becoming resistant to numerous antifungal drugs. It is for this reason that alternative treatment options are being explored, using medicinal plants, to curb this trend of drug resistance. The aim of this study was to evaluate the anti-Candida activity of an ethanolic extract of Galenia africana (G. africana) alone and particularly in combination with fluconazole (FLC) against Candida albicans and Candida glabrata. The anti-Candida activity was evaluated using various techniques. The minimum inhibitory concentration (MIC) of the extract was 6.25 mg/ml for both Candida strains. After combining with FLC, G. africana exerted a strong synergistic effect against C. albicans and an indifferent effect against C. glabrata when interpreted by the fractional inhibitory concentration index (FICI) (0.36 and 1.002 for C. albicans and C. glabrata, respectively). Microscopic analysis revealed cell damage and decrease in cell size after G. africana treatment. Collectively, these results suggested that G. africana possessed antifungal activities against the Candida strains and a synergistic effect with FLC. Cell damage observed possibly contributed to this synergistic effect. This provides new information for the development of new antifungal agents.
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Life Sciences, Other; Wuchereria bancrofti antigen, lyophilization, dried blood spots, freeze-drying
Online: 12 April 2018 (16:18:09 CEST)
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Antigen-based rapid diagnostic tests for Lymphatic filariasis do not come with quality control (QC) materials, and research and disease control programmes rely on stored positive plasma samples. This study was undertaken to evaluate the use of freeze-dried Wuchereria bancrofti antigen positive plasma samples to serve as QC materials for LF RDTs. 10 well characterized W. bancrofti positive samples were lyophilized and stored at 4°C, 28°C and 40°C. The samples were evaluated using the Filaria Test Strips before lyophilization and after one and three (3) months of storage. The sensitivity and stability of the lyophilized samples were evaluated. The results revealed a loss of sensitivity and stability with increasing temperature and duration of storage. The results are further discussed in terms of the use of Dried Blood Spot (DBS) in diagnostics studies on LF requiring quantitative assessments, and the need for thoughtful DBS preparation and storage.
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Life Sciences, Other; electronic nose; nanowire gas sensors; food quality control; Parmigiano Reggiano; multivariate data analysis; artificial neural network
Online: 12 April 2018 (06:25:29 CEST)
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Parmigiano Reggiano cheese is one of the most appreciated and consumed food worldwide, especially in Italy, for its high content of nutrients and for its taste. However, these characteristics make this product subject to counterfeiting in different forms. In this study, a novel method based on an electronic nose has been developed in order to investigate the potentiality of this tool to distinguish rind percentage in grated Parmigiano Reggiano packages that should be lower than 18%. Different samples in terms of percentage, seasoning and rind working process were considered to tackle the problem at 360°. In parallel, GC-MS technique was used to give a name to the compounds that characterize Parmigiano and to relate them with sensors responses. Data analysis consisted of two stages: multivariate analysis (PLS) and classification made in a hierarchical way with PLS-DA ad ANNs. Results are promising in terms of correct classification of the samples. The classification rate is higher for ANNs than PLS-DA, reaching also 100% values.
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Cristiana Zanetti,
Angelo Gallina,
Alessia Fabbri,
Sofia Parisi,
Angela Palermo,
Katia Fecchi,
Zaira Boussadia,
Maria Carollo,
Mario Falchi,
Luca Pasquini,
Maria Luisa Fiani,
Massimo Sargiacomo
Life Sciences, Cell & Developmental Biology; Cholera toxin; exosomes; endocytic pathway; Caveolin-1; GM1 ganglioside
Online: 12 April 2018 (05:58:31 CEST)
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Here we first report, how cholera toxin (CT) A subunit (CTA), the bacterial enzyme moiety responsible of cell signaling alteration, can take over the exosomal pathway, spread extracellularly and be transmitted in a cell population. A first evidence for long-term transmission of CT toxic effect via extracellular vesicles was obtained in CHO cells. To follow CT intracellular route towards exosome secretion we adopted a strategy apt to convert multivesicular body (MVB) derived exosomes in traceable fluorescent vectors. CT treated Me665 cells, a human melanoma cell line highly expressing caveolin-1 (Cav-1) and GM1, were used to purify and characterize fluorescent exosomes. Our results clearly show association of CT with exosomes together with typical exosomal markers and the HSP90 and PDI molecules, the required membrane translocation elements of CTA to the cytoplasm. Confocal microscopy proved direct CT containing fluorescent exo transfer into CHO cells coupled with the morphological cell change characteristic of CT action. Moreover, direct assessment of cAMP levels in Me665 cells treated with CT containing exo showed an efficient induction of cAMP increase comparable with CT alone. From our results, we can infer that CT can exploit exosome-mediated cell communication to target and extend its pathophysiological action throughout cell tissues.
Preprint
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Life Sciences, Other; mycobacterium ulcerans; animal reservoir; transmission
Online: 11 April 2018 (13:54:56 CEST)
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Mycobacterium ulcerans is the causative agent of the Buruli ulcer, also known, in Australia, as Daintree ulcer or Bairnsdale ulcer. This destructive skin disease is characterized by extensive and painless necrosis of the skin and soft tissue with the formation of large ulcers, commonly on the leg or arm. To date, 33 countries with tropical, subtropical and temperate climates in Africa, the Americas, Asia and the Western Pacific have reported cases of Buruli Ulcer. The disease is rarely fatal, although it may lead to permanent disability and/ or disfigurement if not treated appropriately or in time. It is the third most common mycobacterial infection in the world after tuberculosis and leprosy. The precise mode of transmission of M. ulcerans is yet to be elucidated. Nevertheless, it is possible that the mode of transmission varies with different geographical areas and epidemiological settings. The knowledge about the possible route of transmission and potential animal reservoir of M. ulcerans is poorly understood and still remains patchy. We conducted a systematic review with selected key words on PubMed and INFORMIT databases to aggregate available published data on animal reservoirs of M. ulcerans. After certain inclusion and exclusion criteria, a total of 17 studies were included in the review. A variety of animals, e.g rodents, shrews, possums (ringtail and brush tail), horses, dogs, alpacas, koalas and Indian flap-shelled turtles have been recorded as being infected with M. ulcerans around the world. The majority of studies included in this review identified animal reservoirs, either aquatic or terrestrial, as predisposing for the emergence and reemergence of M. ulcerans infection. Taken together, the selected studies in this systematic review and discussed so far, it is clear that exotic wildlife, aquatic animals and native mammals play a significant role as reservoirs for M. ulcerans.
Preprint
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Sean M. Evans,
Haley E. Adcox,
Lauren VieBrock,
Ryan S. Green,
Alison Luce-Fedrow,
Suschsmita Chattopadhyay,
Ju Jiang,
Richard T. Marconi,
Daniel Paris,
Allen L. Richards,
Jason A. Carlyon
Life Sciences, Microbiology; scrub typhus; Orientia tsutsugamushi; Rickettsia; Rickettsiales; outer membrane protein A; Anaplasma
Online: 11 April 2018 (08:13:04 CEST)
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Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium, Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative real-time PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly protective scrub typhus vaccine.
Preprint
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Life Sciences, Genetics; genetic code, alphabet, unitary matrix, dyadic shift, decomposition, spectral presentation, fractal, tensor product, quantum informatics
Online: 10 April 2018 (16:20:14 CEST)
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Information molecules of DNA and RNA should obey principles of quantum mechanics where unitary operators in form of unitary matrices have key meanings. Unitary matrices are the basis of calculations in quantum computers. This article presents some author's results, which show that matrix forms of the representation of structured systems of molecular-genetic alphabets can be considered as sets of sparse unitary matrices related with phenomenologic features of the degeneracy of the genetic code. These sparse unitary matrices have orthogonal systems of functions in their rows and columns. A complementarity exists among some unitary genetic matrices in relation each other. Decompositions of numeric genetic matrices into sets of sparse unitary matrices are connected with the logical operation of modulo-2 addition used in quantum computers as well. Tensor (or Kronecker) families of unitary genetic matrices with their fractal-like properties are also considered. The described results are discussed in the frame of development of quantum-information approaches for modeling genetic systems.
Preprint
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Life Sciences, Other; metabolic syndrome; inflammation; index; Korea
Online: 10 April 2018 (09:50:20 CEST)
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Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.