Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data is for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. It is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, and response to hypoxia via HIF1A targets (↑in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cells, B cell, and NF-kB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

The ability to express and recognize emotion via facial expressions is well known to change with age. The present study investigated the differences in the facial recognition and facial expression of the elderly (n = 57) and the young (n = 115) and measure how each group uses different facial muscles for each emotion with Facial Action Coding System (FACS). In facial recognition task, the elderly did not recognize facial expressions better than young people and reported stronger feelings of fear and sad from photographs. In making facial expression task, the elderly rated all their facial expressions as stronger than the younger, but in fact, they expressed strong expressions in fear and anger. Furthermore, the elderly used more muscles in the lower face when making facial expressions than younger people. These results help to understand better how the facial recognition and expression of the elderly change, and show that the elderly do not effectively execute the top-down processing concerning facial expression.

Obesity is a problem in the last decades since the development of different technologies forced the submission of a faster pace of life, resulting in nutrition style changes. In turn, domestic pigs are an excellent animal model in recognition of adiposity-related processes, corresponding to the size of individual organs, the distribution of body fat in the organism, and similar metabolism. The present study applied the next-generation sequencing method to identify adipose tissue (AT) transcriptomic signals related to increased fat content by identifying differentially expressed genes (DEGs), included long-non coding RNA molecules. The Freiburg RNA tool was applied to recognise predicting hybridisation energy of RNA-RNA interactions. The results indicated several long non-coding RNAs (lncRNAs) whose expression was significantly positively or negatively associated with fat deposition. lncRNAs play an essential role in regulating gene expression by sponging miRNA, binding transcripts, facilitating translation, or coding other smaller RNA regulatory elements. In the pig fat tissue of obese group, increased expression of lncRNAs corresponding to human MALAT1 was observed that previously recognised in the obesity-related context. Moreover, hybridisation energy analyses pinpointed numerous potential interactions between identified differentially expressed lncRNAs, and obesity-related genes and miRNAs expressed in AT.

Few-layer graphene oxide (GO) has shown none or very weak cytotoxicity and anti-proliferative effects in a wide range of cell lines such as glyoma cells and human skin HaCaT cells, in concentrations up to 100 µg/mL However, multi-layer GO has been hardly explored in the biomedical field. Thus, multi-layer GO was examined here in human keratinocyte HaCaT cells treated with different concentrations ranging from 0.01 to 150 µg/mL during different periods of times (3, 12 and 24 hours). The results of this study showed a time-concentration dependence with two non-cytotoxic concentrations (0.01 and 0.05 µg/mL) and a median effective concentration value of 4.087 µg/mL at 24 hours of GO exposure. Contrary to what has been reported for few-layer GO, cell proliferation of the HaCaT cells in contact with the multi-layer GO at 0.01 μg/mL showed identical proliferative activity compared to an epidermal growth factor (1.6-fold greater than the control group) after 96 hours. The effects of the multi-layer GO on the expression of 13 genes (SOD1, CAT, MMP1, TGFB1, GPX1, FN1, HAS2, LAMB1, LUM, CDH1, COL4A1, FBN and VCAN) at the non-cytotoxic concentrations of GO in the HaCaT cells were analyzed after 24 hours. Thus, the lowest non-cytotoxic GO concentration was able to up-regulate the CAT, TGFB1, FN1 and CDH1 genes, which confirms the great potential of multi-layer GO in the biomedical field.

Abstract: Bacillus subtilis fmb60, which has broad-spectrum antimicrobial activities was isolated from plant straw compost. A hybrid NRPS/PKS cluster was screened from the genome. Sixteen secondary metabolites produced by the gene cluster were isolated and identified using LC-HRMS and NMR. Three lipoamides D–F (1-3) and two amicoumacin derivatives, amicoumacins D, E (4, 5), were identified, and are reported here for the first time. Lipoamides D–F exhibited strong antibacterial activities against harmful foodborne bacteria, with the MIC ranging from 6.25 to 25 µg/mL. Amicoumacin E scavenged 38.8% of ABTS+ radicals at 1 mg/mL. Direct cloning and heterologous expression of the NRPS/PKS and ace gene cluster identified its importance for the biosynthesis of amicoumacins. This study demonstrated that there is a high potential for biocontrol utilization of B. subtilis fmb60, and genome mining for clusters of secondary metabolites of B. subtilis fmb60 has revealed a greater biosynthetic potential for the production of novel natural products than previously anticipated.

The expression microarray technique was performed to investigate the differences in gene expression between Czech Large White pigs and wild boars in the longissimus lumborum et thoracis and biceps femoris muscle tissues. The NREP gene (neuronal regeneration related protein homolog) was selected for detailed study as an expressional and functional candidate gene. NREP plays a role in the transformation of neural, muscle and fibroblast cells and in smooth muscle myogenesis. Quantitative real-time PCR results confirmed that the porcine NREP gene was expressed in both skeletal muscles and significantly overexpressed in Czech Large White pigs compared to wild boars (P < 0.05). We identified 9 polymorphic sites in genomic DNA of NREP gene. Six of these polymorphisms were in complete linkage disequilibrium and therefore only 4 polymorphisms were informative. Associations of these 4 polymorphisms (HF571253:g.103G>A, HF571253:g.134G>A, HF571253:g.179T>C and HF571253:g.402_409delT) with meat performance traits were assessed in Czech Large White pigs. New polymorphisms in NREP gene were significantly associated with parameters of daily weight gain, lean meat and backfat thickness in Czech Large White pigs. Our primary study suggested that porcine NREP may play an important role in skeletal muscle growth, fat metabolism and meat performance traits.

Angelica decursiva is one of the lending traditional Chinese medicinal plants producing coumarins. Notably, several studies have focused on the biosynthesis and not the qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction) study of coumarins. This qRT-PCR technique has been extensively used to investigate gene expression levels in plants and the selection of reference genes which plays a crucial role in standardizing the data form the qRT-PCR analysis. In our study, 11 candidate reference genes were selected from the existing transcriptome data of Angelica decursiva. Here, four different types of statistical algorithms (geNorm, NormFinder, BestKeeper, and Delta Ct) were used to calculate and evaluate the stability of gene expression under different external treatments. Subsequently, RefFinder analysis was used to determine the geometric average of each candidate gene ranking, and to perform comprehensive index ranking. The obtained results showed that among all the 11 candidate reference genes, SAND family protein (SAND), protein phosphatase 2A gene (PP2A), and polypyrimidine tract-binding protein (PTBP) were the most stable reference genes, where Nuclear cap binding protein 2 (NCBP2), TIP41-like protein (TIP41), and Beta-6-tubulin (TUBA) were the least stable genes. To the best of our knowledge, this work is the first to evaluate the stability of reference genes in the Angelica decursiva which has provided an important foundation on the use of qRT-PCR for an accurate and far-reaching gene expression analysis in this medicinal plant.

Long non-coding RNA (lncRNA) can regulate several aspects of gene expression, being associated with complex phenotypes in humans and livestock species. In taurine beef cattle, recent evidence points to the involvement of lncRNA in feed efficiency (FE), a proxy for increased productivity and sustainability. Here, we hypothesized specific regulatory roles of lncRNA in FE of indicine cattle. Using RNA-Seq data from liver, muscle, hypothalamus, pituitary and adrenal gland from Nellore bulls with divergent FE, we submitted new transcripts to a series of filters to confidently predict lncRNA. Then, we identified lncRNA that were differentially expressed (DE) and/or key regulators of FE. Finally, we explored lncRNA genomic location and interactions with miRNA and mRNA to infer potential function. We were able to identify 126 relevant lncRNA for FE in Bos indicus, some with high homology to previously identified lncRNA in Bos taurus and some possible specific regulators of FE in indicine cattle. Moreover, lncRNA identified here were linked to previously described mechanisms related to FE in hypothalamus-pituitary-adrenal axis and are expected to help elucidate this complex phenotype. This study contributes to expanding the catalogue of lncRNA, particularly in indicine cattle, and identifies candidates for further studies in animal selection and management.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Cysteine cathepsins, a class of proteinaceous enzymes, regulate a wide variety of metabolic processes in human including protein breakdown and turnover and immune functions. Eleven cysteine cathepsins have been identified so far and a wide array of studies related to identifying their specific functions, regulation and distribution patterns in tissues have been conducted. However, in recent past, the association of cysteine cathepsins in occurrence and progression of cancers have been identified and this has caused unrest in scientists triggering them to investigate the physiology, biochemical pathways and interactions of these cathepsins in cancer metastasis and therefore has become a noteworthy topic of intensive research. This review focusses and collects together the published work on molecular functional and structural characterization studies that have been done so far on in vitro expression of genes encoding for cysteine cathepsins in the Escherichia coli bacterial expression system. Accordingly, it was found out that all cathepsins except for cathepsins K, C, H, X and W have been expressed this way and the majority of them were found to be expressed in E. coli BL21(DE3) pLysS expression host via pET3 expression vector. In addition, it was also noted that in most of the expression studies, the substrate that was used to validate the enzymatic activity of the recombinant enzyme that was produced was a cysteine residue along with a benzyloxy-carbonyl salt. Through this review, the authors suggest that there is a very high need that all cysteine cathepsins need to be characterized both structurally and functionally on a molecular platform to better understand their interactions including the biochemical pathways. It is also momentous that the mass production of the recombinant forms of these enzymes are facilitated via expression in such bacterial expression systems and in turn, would also provide a strong platform for the development and progression of studies related to human physiology including oncological studies such as cancer metastasis. Moreover, as per biochemical features of the enzymes that could be identified, the production of efficient inhibitors or inducers as per the necessity to improve health and promote wellbeing among the mankind could be facilitated.

Obesity is a universal health concern that can lead to serious diseases. The side effects of synthetic anti-obesity drugs necessitate the finding of suitable natural/herbal alternatives. Mother nature offers a wide range of plants with medicinal properties that include crude extracts and isolated compounds which are effective for controlling and reducing weight gain. Obesity was induced in 60, 3-week-old male ICR mice, using high-fat diet (60% dietary energy from fat) for 16-week. The mice were divided at random into six groups with 10 mice: mice fed with high-fat diet (HFD) only, mice fed normal diet only (NC), and orlistat at 15.9 mg/kg (HFD+Orlistat), and mice in three other high-fat diet groups treated with methanolic leaf extract of Clinacanthus nutans (MECN) at 500, 1000 and 1500 mg/kg. After 21-day of the treatment, MECN significantly reduced (P<0.05) the body weight, visceral fat and muscle saturated fatty acid compositions. There was also significant downregulation of HSL, PPAR α and PPAR γ and SCD genes expressions in the obese mice treated with 1500 mg/kg MECN compared to the HFD group. Therefore, MECN is a potentially useful natural supplement for alleviating obesity and obesity-mediated metabolic diseases.

Molecular classifications of colorectal cancer (CRC) are benefitting cancer research by providing insights into subtype-specific disease prognosis and better therapeutic intervention. So far different conventional DNA markers such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), chromosomal instability (CIN), and BRAF and KRAS mutations have been used to classify CRC patients but have not shown promising prognostic values. Here, for the first time, we show classification of CRC tumors from Saudi Arabian patients based on gene expression profile (GEP). An existing method of CRC subtyping has been applied to the GEP of tumors from Saudi CRC patients. Survival analysis was carried out on predicted CRC subtypes. In-silico functional analyses were conducted on the gene signature used for subtype prediction. The predicted subtypes showed distinct but statistically insignificant overall survival distribution (log-rank test, p = 0.069). Comparison of predicted subtypes in Saudi CRC patients with that of the French one showed significant dissimilarity in the two populations (Chi-square test, p = 0.0091). Functional analyses of the gene signature used for subtyping suggest their association with “cancer” and “gastrointestinal diseases”. Most of the signature genes were found differentially expressed in CRC tumors compared to adjacent normal tissues. Such a classification framework might help improve the treatment of colorectal cancer patients.

Nine crossbred finishing barrows randomly assigned to 3 dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient, lysine-adequate, or lysine-excess diet for 5 weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. A total of 674 transcripts were differentially expressed (P ≤ 0.05); 60 out of 131 transcripts (P ≤ 0.01) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA, (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA, (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA, and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA, and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA.

In this manuscript we use an exactly solvable stochastic binary model for regulation of gene expression to analyse the dynamics of response to a treatment aiming to modulate the number of transcripts of RKIP gene. We demonstrate the usefulness of our method simulating three treatment scenarios aiming to reestablish RKIP gene expression dynamics towards pre-cancerous state: i. to increase the promoter’s ON state duration; ii. to increase the mRNAs’ synthesis rate; iii. to increase both rates. We show that the pre-treatment kinetic rates of ON and OFF promoter switching speeds and mRNA synthesis and degradation will affect the heterogeneity and time for treatment response. Hence, we present a strategy for reducing drug dosage by simultaneously targeting multiple kinetic rates. That enables a reduction of treatment response time and heterogeneity which in principle diminishes the chances of emergence of resistance to treatment. This approach may be useful for inferring kinetic constants related to expression of antimetastatic genes or oncogenes and on the design of multi-drug therapeutic strategies targeting master regulatory genes.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (version 2.0) contains increased 24,145 predicted genes from previous version (24317 genes) with a higher BUSCO value of 96.9%. 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjust genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserve their original des ignations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using newly obtained transcriptome data with the revised gene prediction model. This improved annotation of cucumber genome will provide essential and accurate resources for studies in cucumber.

This study was conducted with the objective of investigating the enrichment of weaned piglet diets with organic selenium (proteinate selenium) and inorganic selenium (sodium selenite) with two addition levels (0.15 and 0.30 mg/kg). A total of 40 piglets (20 castrated males and 20 females) weaned at 28 days of age with an average initial weight of 6.60±1.06 kg were used. The treatments were: Control diet (Control diet); Selenium-enriched control diet proteinate with 0.15 mg/kg of selenium added (SeOrg-0.15); Selenium-enriched control diet proteinate with 0.30 mg/kg of selenium added (SeOrg-0.30); Control diet enriched with sodium selenite with 0.15 mg/kg of selenium added (SeInorg-0.15); and Control diet enriched with sodium selenite with 0.30 mg/kg of selenium added (SeInorg-0.30). The presence of selenium in the control diet came from the ingredients and the mineral supplement. The following data were analyzed: productive performance; digestibility of nutrients and energy; morphometry and intestinal integrity; serum biochemical parameters; and gene expression of selenoproteins in intestinal epithelium and liver tissue of piglets. The SeOrg-0.30 treatment caused a reduction (P

The epigenetic mechanism of DNA methylation is essential for regulating gene expression and adaptation in plants, especially when exposed to various environmental stressors such as drought, heat, and nutrient availability. The impact of these stressors can lead to alterations in DNA methylation patterns and gene expression, which this study aims to investigate. Specifically, we are interested in understanding how DNA methylation plays a role in controlling the expression of stress-response genes, as well as genes involved in plant growth and development. To accomplish this, we are analyzing the changes in DNA methylation patterns and gene expression in response to different stressors like drought and heat. Our research findings suggest that DNA methylation is a vital regulator of plant adaptation to environmental stress, and we hope to gain further insight into these mechanisms by identifying genes that exhibit differential expression in response to stress and analyzing their DNA methylation status. This study offers valuable insights into the development of crops that can thrive under changing climate conditions.

Phase change refers to the process of maturation and transition from the juvenile to the adult stage. In response to this shift, certain species like chestnut lose the ability to form adventitious roots, thereby hindering the successful micropropagation of adult plants. While auxin is the main hormone involved in adventitious root formation, other hormones, such as ethylene, are also thought to play a role in its induction and development. In this study, experiments were carried out to determine the effects of ethylene on the induction and growth of adventitious roots. The analysis was performed in two types of chestnut microshoots derived from the same tree, a juvenile-like line with high rooting ability derived from basal shoots (P2BS) and a line derived from crown branches (P2CR) with low rooting responses. By means of the application of compounds to modify ethylene content or inhibit its signalling, the potential involvement of this hormone in the in-duction of adventitious roots was analyzed. Our results show that ethylene can modify the rooting competence of mature shoots, while the response in juvenile material was barely affected. To further characterize the molecular reasons underlying this maturation-derived shift in behaviour, specific gene expression analyses were developed. Findings suggest that several mechanisms, including ethylene signalling, auxin transport and epigenetic modifications, relate to the modu-lation of the rooting ability of mature chestnut microshoots and their recalcitrant behaviour.

Tandemly organized rRNA genes are the typical example of a multigene family, where individual members evolve coordinately within but independently between species due to gene conversion and unequal crossing over. More frequently, in eukaryotic species with an inter-species hybrid origin, expression of unhomogenized rRNA genes from one progenitor is epigenetically silenced because of nucleolus dominance, and distinct rRNA genes may lose functionality and evolve faster. Interestingly, we obtained unusual ribosomal gene sequences from Oryza species that showed great diversity and did not appear in the present rice genomic sequence. The diversity of rDNA sequences indicated that the homogenization in rice is incomplete and explains the introgression of distinct rRNA gene families into ancestral rice genome before speciation and continent separation. The divergent large subunit (LSU) ribosomal genes are expressed, some of them differentially, depending on the N-fertilization of plants. Detection of differential transcripts of the rRNA genes suggested that rRNA gene families are not functionally equivalent. Phylogenetic analysis assigned Oryza species branching order to monocots, and monocot lineages probably have the same ecological origin by molecular clock calculation. Therefore, our results suggested that the geographical distances of continents separation cause barriers to the gene flow and homogenization among Oryza species which requires further explanation,

Plastid-encoded RNA polymerase (PEP) forms a multisubunit complex in operating chloroplasts, where PEP subunits and a sigma factor are tightly associated with 12 additional nuclear-encoded proteins. Mutants with disrupted genes encoding PEP-associated proteins (PAPs) provide unique tools for deciphering mutual relationships among phytohormones. A block of chloroplast biogenesis in Arabidopsis pap mutants specifying highly altered metabolism in white tissues induced dramatic fluctuations in the content of major phytohormones and their metabolic genes, whereas hormone signaling circuits mostly remained functional. Reprogramming of the expression of biosynthetic and metabolic genes contributed to a greatly increased content of salicylic acid (SA) and a concomitant decrease in 1-aminocyclopropane-1-carboxylic acid (ACC) and oxophytodienoic acid (OPDA), precursors of ethylene and jasmonic acid, respectively, in parallel to reduced levels of abscisic acid (ABA). The lack of differences in the free levels of indole-3-acetic acid (IAA) between the pap mutants and wild-type plants was accompanied by fluctuations in the contents of IAA precursors and conjugated forms as well as multilayered changes in the expression of IAA metabolic genes. Along with cytokinin (CK) overproduction, all of these compensatory changes aim to balance plant growth and defense systems to ensure viability under highly modulated conditions.

Leucyl-aminopeptidase (LAP), an important metallopeptidase, hydrolyses amino acid residues from the N-terminal of polypeptides and proteins, acting preferentially on the peptide bond formed by N- terminus leucine. A new leucyl-aminopeptidase was found in Bacillus cereus CZ. Its gene (bclap) contained a 1485 bp ORF encoding 494 amino acids with a molecular weight of 54 kDa. The bcLAP protein was successfully expressed in E. coli BL21(DE3). Optimal activity is obtained at pH 9.0 and 58°C. The bcLAP displays a moderate thermostability and an alkaline pH adaptation range. Enzymatic activity is dramatically enhanced by Ni2+. EDTA significantly inhibits the enzymatic activity, and bestatin and SDS also show strong inhibition. The three-dimensional model of bcLAP monomer and homohexamer is simulated by Phyre2 server and SWISS-MODEL server. The docking of bestatin, Leu-Trp, Asp-Trp and Ala-Ala-Gly to bcLAP is performed using AutoDock4.2.5 , respectively. Molecular docking results show that the residues Lys260, Asp265, Lys272, Asp283, Asp342, Glu344, Arg346, Gly372, His437 are involved in the hydrogen bonding with the ligands and zinc ions. There may be two nucleophilic catalytic mechanisms in bcLAP, one involving His 437 or Arg346 and the other involving His437 and Arg346. The bcLAP can hydrolyse the peptide bonds in Leu-Trp, Leu-Trp and Ala-Ala-Gly.

Cytological diagnosis of pleural mesothelioma (PM) is controversial even using ancillary markers (BAP1, MTAP and CDKN2A). Here, we aimed to prospectively validate a previously developed 117-gene expression panel for the differential cytological diagnosis of epithelioid, biphasic PM and mesothelial hyperplasia. Seventy-seven pleural effusions were classified using the 117-gene expression levels (NanoString system). Sixty-eight cases were also screened for ancillary markers. The performance of both gene panel and ancillary markers was evaluated using ROC metrics. A score using the top consistently deregulated genes between epithelioid and biphasic PM was built to subtype malignant effusions. The panel alone reached a diagnostic accuracy (0.89) comparable to the best marker combination (BAP1 plus MTAP: 0.88). Ancillary tests missed 8 PMs, seven of which were correctly classified by the panel. The score built by averaging the expression levels of MSLN, CLDN15 and CFB showed an accuracy of 0.80 in subtyping epithelioid and biphasic effusions. The 117-gene panel is effective for PM cytological diagnosis of epithelioid and biphasic PM. This tool can be complementary to ancillary markers, reducing invasive procedures and allowing an earlier diagnosis. Finally, the possibility to subtype PM on effusions strengthens the panel role in PM diagnosis and management.

Sporothrix brasiliensis is the most pathogenic species, responsible for the Brazilian cat-transmitted sporotrichosis hyperendemics. In this scenario, investigation of pathogen-host interaction can provide relevant information for future treatment strategies. To this end, the invertebrate Galleria mellonella has proven to be a suitable alternative to evaluate the virulence of pathogenic fungi since the insect immune system is similar to the mammalian innate immune response. The aim of this work was to investigate phenotypic and molecular aspects of the immune response of G. mellonella throughout the S. brasiliensis infection. Hemocyte density and the evolution of the fungal load were evaluated. In parallel, RT- qPCR expression analysis of genes encoding antimicrobial peptides (Gallerimycin and Galiomycin) and stress management genes (C7 Contig 15362 and C8 Contig 1910) was conducted. Fungal load and hemocyte densities were proportionally increasing simultaneously to the deleterious morphological events and larvae mortality. Gallerimycin, C7 Contig 15362, and C8 Contig 19101 genes were positively regulated (p&lt;0.05) at distinct moments of S. brasiliensis infection, characterizing a time-dependent and alternately modulated profile. Galiomycin gene expression remained unchanged. Our results contribute to the future proposal of potential alternative pathways to treat and, consequently, control S. brasiliensis zoonosis, a major public Health in Latin America.

Cerebral palsy (CP) is the most common movement disorder in children with a prevalence rang-ing from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraple-gic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased ex-pression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetra-plegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Never-theless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

The achievement of reproductive competence in male mammals is dependent on the testis. Goat testis’ development and spermatogenesis involve physiological events with high complexity. In the current work, 6 testes were respectively collected from immature, sexually mature and physically mature Qianbei Ma goats (1, 6 and 12 months old, respectively). RNA-Seq was carried out to reveal changes in testis mRNA expression levels in Qianbei Ma goats at various developmental stages, and gene expression profiling at different ages was established. Totally 18 libraries were established for screening genes and pathways associated with testis development and spermatogenic processes. Totally 9,724 upregulated and 4,153 downregulated genes were identified between immature (I) and sexually mature (S) testes; 7 upregulated and 3 downregulated genes were detected between sexually mature (S) and physically mature (P) testes, and approximately 4% of genes were alternately spliced between the I and S groups. Selected genes were verified by qRT-PCR, in agreement with sequencing data indicating their reliability. Those genes have critical functions in various developmental stages of goat testicular development and spermatogenesis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to evaluate differentially expressed genes (DEGs). GO analysis suggested DEGs were involved in “reproduction process”, “channel activity” and “cell periphery part” between I and S, and in “ion transport process”, “channel activity” and “transporter complex part” between S and P. KEGG analysis indicated that pathways such as “glycerolipid metabolism”, “steroid hormone biosynthesis” and “MAPK signaling pathway” may be involved in testis development and spermatogenesis. Genes including IGF1, TGFB1, TGFBR1 and EGFR may regulate the development of the testis from immature to sexually mature, which may be key candidate genes for the development of goat testis. These findings provide novel insights into goat testicular development and spermatogenesis.

In this paper, an analytical form of the Unit Step Function (or Heaviside Step function) is presented. This important function constitutes a fundamental concept of Operational Calculus and is also involved in many other fields of applied and engineering mathematics. In particular, Heaviside Step Function is performed in a very simple manner by the use of a finite number of standard operations, as the summation of six inverse tangent functions. The novelty of this work when compared with other analytical expressions, is that the proposed exact formula contains two arbitrary single - valued continuous functions which satisfy only one restriction. In addition, the proposed representation is not exhibited in terms of miscellaneous special functions, e.g. Bessel functions, Beta function, Logistic function. Besides, it is neither the limit of a function, nor the limit of a sequence of functions with point – wise or uniform convergence. Hence, this formula may be much more practical, flexible and useful in the computational procedures which are inserted into Operational Calculus techniques and other engineering practices.

Antarctica is the continent with the lowest local human impact, yet it is still vulnerable to contaminants coming from external sources. Emerging pollutants, like PFAS, pose an increasing threat to this environment and therefore require more in-depth investigations to understand their environmental fate and biological impacts. The present study, part of the AntaGPS project, focuses on expression analysis at the transcriptional level of genes coding for 4 antioxidant enzymes (sod1, sod2, gpx1, gpx4) in different organs of an Antarctic fish species, Trematomus newnesi. The kidney showed a higher level of expression than the liver of wildlife specimens. The mRNA levels were also assessed in fish exposed to 1.5 μg/L of PFOA for 10 days. In the liver, the treatment induced an increase in gene expression for all the considered enzymes, while in the kidney it induced a general decrease. The obtained results constitute a starting point for using the expression of antioxidant enzymes as biomarkers, both of oxidative stress and exposure to PFAS, in future biomonitoring campaigns in the Antarctic marine environment.

An increasing ecological phase-shift from coral dominated reefs to macroalgae dominated reefs as a result of anthropogenic impacts, such as eutrophication, sedimentation, and overfishing, has been observed in many reef systems around the world. Ocean warming is a universal threat to both corals and macroalgae, which may alter the outcome of competition between them. Therefore, in order to explore the effects of indirect and direct exposure to macroalgae on the physiological, biochemical, and genetic expression of corals at elevated temperature, the coral Acroproa hyacinthus and highly invasive green algae Caulerpa taxifolia have been chosen. Physiologically, the results exhibited that distinguish from control and direct contact treatments, the density and chlorophyll a content of zooxanthella decreased by 53.1% and 71.2% respectively, when coral indirect contacted with algae at ambient temperature (27°C). Besides, enzyme activities of superoxide dismutase (SOD) and catalase (CAT) in coral tissue were enhanced by interacting with algae. After an increase of 3°C, the density and chlorophyll a content of zooxanthella reduced by 84.4% and 93.8% respectively, whereas the enzmy activities of SOD and CAT increased by 2.3 and 3.1-fold. However, only the zooxanthellae density and pigment content decreased when C.taxifolia co-culture with A.hyacinthus at 30°C. Molecularly, different from the control group, the differentially expressed genes (DEGs) such as Rab family, ATG family and Casp7 were significantly enriched in endocytosis, autophagy and apoptosis pathways , regardless whether A.hyacinthus was indirect or indirect exposure to C.taxifolia at 27°C. Under thermal stress without algae interaction, the DEGs were significantly enriched in microbial immune signal transduction pathways, such as Toll-like receptor signaling pathway and TNF signaling pathway, while multiple cellular immunity (IFI47, TRAF family) and oxidative stress (CAT, SODC, HSP70) genes were up-regulated. Inversely, compared with corals without interaction with algae at 30°C, the DEGs of corals interacted with C.taxifolia at 30°C, were remarkably enriched in apoptosis, NOD-like receptor signaling pathway, including the transcription factors such as Casp family, TRAF family. In conclusion, the density and chlorophyll a content of zooxanthella remained a fading tendency induced by macroalgae at ambient temperature. The oxidative stress and immune response levels of coral has been elevated at 30°C, but macroalgae alleviated the negative effects triggered by thermal stress.

Standard cell culture is routinely performed at supraphysiological oxygen concentrations (~18% O2). Conversely, oxygen levels in most tissues range from 1%–6% (physioxia). Such hyperoxic conditions can alter reactive oxygen species (ROS) production, energy metabolism, mitochondrial network dynamics, and response to drugs and hormones. The aim of this project was to investigate the transcriptional response to different oxygen levels and whether it is similar across cell lines, or cell-line specific. Using RNA-seq, we performed differential gene expression and functional enrichment analyses in four human cancer cell lines, LNCaP, Huh-7, PC-3, and SH-SY5Y cultured at either 5% or 18% oxygen for 14 days. We found that oxygen levels affected transcript abundance of hundreds of genes, with the affected genes having little overlap between cell lines. Functional enrichment analysis also revealed different processes and pathways being affected in each cell line. Interestingly, we found that the top differentially expressed genes are involved in cancer biology. Further, we observed several hypoxia-inducible factor (HIF) targets upregulated at 5% oxygen, suggesting a role of HIF at physiological oxygen conditions. Finally, oxygen strongly induced transcription of mitochondrial genes in most cell lines, in a cell-type specific manner too. We conclude that cellular response to oxygen is widely cell-type specific, emphasizing the importance of maintaining physioxia in cell culture.

Nuclear lamins are type V intermediate filament proteins that form a filamentous meshwork beneath the inner nuclear membrane. Additionally, a sub-population of A-type and B-type lamins is localized in the nuclear interior. The nuclear lamina protects the nucleus from mechanical stress and mediates nucleo-cytoskeletal coupling. Lamins form a scaffold that partially tethers chromatin at the nuclear envelope. The nuclear lamina also stabilizes protein-protein interactions involved in gene regulation and DNA repair. The lamin-based protein sub-complexes are implicated in both nuclear and cytoskeletal organization, the mechanical stability of the nucleus, genome organization, transcriptional regulation, genome stability, and cellular differentiation. Here we review recent research in the field of nuclear lamins and their role in modulating various nuclear processes and their impact on cell function.

Plant sulfite oxidase )SO( is a molybdo-enzyme responsible for the oxidation of excess SO₂/sulfite into non-toxic sulfate. The effect of toxic sulfite level on leaves and fruits was studied in tomato plants with different SO expression levels: wild-type (WT), SO overexpression (OE) and SO RNA interference (Ri) plants. Leaf discs and ripe fruit of plants lacking SO were more susceptible, whereas SO OE plants were more resistant as revealed by remaining chlorophyll content and tissue damage levels. Application of molybdenum further enhanced the tolerance of leaf discs to sulfite by enhancing SO activity in SO OE lines, but not in WT or Ri plants. Notably, incubation with tungsten, the molybdenum antagonist, overturned the effect of molybdenum spray in SO OE plants, revealed by remaining chlorophyll content and SO activity. The results indicate that SO determines, in tomato leaves and ripe fruits, the resistance to toxic sulfite and the application of molybdenum enhances sulfite resistance in OE plants by increasing SO activity. The results suggest that overexpressing SO mechanism can be employed in agriculture with or without molybdenum application, for the development of more tolerate crops and vegetables to higher concentrations of sulfite/SO₂ containing postharvest treatments.

Multiple unique environmental factors such as space radiation and microgravity (µG) pose a serious threat to human gene stability during space travel. Recently, we reported that simultaneous exposure of human fibroblasts to simulated µG and radiation results in more chromosomal aberrations than in cells exposed to radiation alone. However, the mechanisms behind this remain unknown. The purpose of this study was thus to obtain comprehensive data on gene expression using a 3D clinostat synchronized to a carbon (C)-ion or X-ray irradiation system. Human fibroblasts (1BR-hTERT) were maintained under standing or rotating conditions for 3 or 24 h after synchronized C-ion or X-ray irradiation at 1 Gy as part of a total culture time of 2 days. Among 57,773 genes analyzed with RNA sequencing, we focused particularly on the expression of 82 cell cycle-related genes after exposure to the radiation and simulated µG. The expression of cell cycle-suppressing genes (ABL1 and CDKN1A) decreased and that of cell cycle-promoting genes (MKI67, KPNA2, CCNB1, STMN1, and MCM4) increased after C-ion irradiation under µG. The cell cycle may pass through the G1/S and G2 checkpoints with DNA damage due to the combined effects of C-ions and µG, suggesting that increased genomic instability might occur in space.

Local cryotherapy is widely used as a treatment for sports-related skeletal muscle injury. However, its molecular mechanisms are unknown. To clarify these mechanisms, in this study, we applied one to three 15-min cold stimulations at 4 °C to various cell lines (in vitro), the tibialis anterior (TA) muscle (ex vivo), and mouse limbs (in vivo). In the in vitro assay, cAMP response element-binding protein 1 (CREB1) was markedly phosphorylated (as pCREB1) and CREB-binding protein (CBP) was recruited to pCREB-1 in response to two or three cold stimulations. In a reporter assay with the cAMP-responsive element, the signals significantly increased after two to three cold stimulations at 4 °C. In the ex vivo study, CREB-targeting genes were significantly upregulated following two or three cold stimulations. The in vivo experiment disclosed that cold stimulation of a mouse limb for 9 days significantly increased mitochondrial DNA copy number and upregulated genes such as Pgc-1α involved in mitochondrial biogenesis. The foregoing results suggest that local cryotherapy increases CREB transcription and upregulates CREB-targeting genes in a manner dependent on cold stimulation frequency and duration. This information may serve as an impetus for further investigations into local cryotherapy as a treatment for sports-related skeletal muscle trauma.

Herein, we evaluated the electrophoretic deposition of nanohydroxyapatite/superhydrophilic multiwalled carbon nanotube composites (nHAp/MWCNT) onto stainless steel biomedical alloys for applications in bone tissue engineering. First, nHAp/MWCNT composites were dispersed into 0.042 mol L⁻¹ of Ca(NO₃)₂·4H₂O + 0.025 mol L⁻¹ NH₄H₂PO₄ electrolytes (pH = 4.8) at two different concentrations. Next, a voltage of −2 V was applied using 316L stainless steel as a working electrode and (0.27 cm²), a high-purity platinum coil wire as the auxiliary electrode, and an Ag/AgCl(3 M) electrode was used as the reference electrode. The nHAp/MWCNT composites were characterized by transmission electron microscopy. The deposited nHAp and nHAp/MWCNT films were characterized by profilometry, scanning electron microscopy, X-Ray diffractometry and Raman spectroscopy. Human osteoblast cells were cultivated with the different materials, and in vitro cytotoxicity was evaluated using lactate dehydrogenase (LDH) assay. The osteogenesis process was evaluated by mRNA levels of the three genes that are directly related to bone repair: Alkaline Phosphatase, Osteopontin and Osteocalcin. We showed that rough, crystalline apatite thin films containing phases of nHAp were successfully deposited onto 316L stainless steel alloys. Also, we noticed that nHAp/MWCNT thin films deposited onto 316L stainless steel alloys upregulated the expression of important genes related to bone mineralization and maturation. Our results strongly support the possibility of this new alternative to modify the surface of metallic biomedical alloys to promote bone tissue regeneration.

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.

The comprehensibility of good predictive models learned from high-dimensional gene expression data is attractive because it can lead to biomarker discovery. Several good classifiers provide comparable predictive performance but differ in their abilities to summarize the observed data. We extend a Bayesian Rule Learning (BRL-GSS) algorithm, previously shown to be a significantly better predictor than other classical approaches in this domain. It searches a space of Bayesian networks using a decision tree representation of its parameters with global constraints, and infers a set of IF-THEN rules. The number of parameters and therefore the number of rules are combinatorial to the number of predictor variables in the model. We relax these global constraints to a more generalizable local structure (BRL-LSS). BRL-LSS entails more parsimonious set of rules because it does not have to generate all combinatorial rules. The search space of local structures is much richer than the space of global structures. We design the BRL-LSS with the same worst-case time-complexity as BRL-GSS while exploring a richer and more complex model space. We measure predictive performance using Area Under the ROC curve (AUC) and Accuracy. We measure model parsimony performance by noting the average number of rules and variables needed to describe the observed data. We evaluate the predictive and parsimony performance of BRL-GSS, BRL-LSS and the state-of-the-art C4.5 decision tree algorithm, across 10-fold cross-validation using ten microarray gene-expression diagnostic datasets. In these experiments, we observe that BRL-LSS is similar to BRL-GSS in terms of predictive performance, while generating a much more parsimonious set of rules to explain the same observed data. BRL-LSS also needs fewer variables than C4.5 to explain the data with similar predictive performance. We also conduct a feasibility study to demonstrate the general applicability of our BRL methods on the newer RNA sequencing gene-expression data.

Contrary to previous belief, mutation frequency also depends on how essential a gene is. Mutation frequency is substantially lower in the coding regions of essential genes and higher in less essential genes. Even though the mutation bias based on gene essentiality is incapable of invalidating Darwinism, this bias certainly added a rather unsubtle obstacle to it by contradicting a paradigm that was widely held: that mutations are random in the sense of being independent of their function for the organism. The reason this bias occurs is currently unknown. Here, I present the theoretical solution of why genetic mutations also depend on whether the gene is more or less essential. My theory is that each gene or epigene has its own level of resistance to entropic elevation, something directly proportional to the frequency of its expression. The more a gene is expressed, the higher is its resistance to entropic elevation and vice versa. For genetic information to be conserved instead of suffering mutation, a relevant factor is also the frequency of its expression. The energy expenditure directed to a gene of current utility engenders resistance to entropic elevation of the information encoded in that gene, as energy enables not only the existence of information but also its conservation. My theory—which is based on fundamental physics and contains predictions that can be empirically tested—solves a crucial problem in evolutionary biology and genetics; if I am right, I will have established a biological law. Finally, my aim here is also to provide a substantial advance in knowledge about the relationship between information, genetics, and thermodynamics.

Acetamiprid is a broad-spectrum neonicotinoid insecticide used in agriculture to control aphids. While recent studies have documented resistance to acetamiprid in several aphid species, the underlying mechanisms are still not fully understood. In this study, we analyzed the transcriptome and metatranscriptome of a laboratory strain of the pea aphid, Acyrthosiphon pisum (Harris, 1776), with reduced susceptibility to acetamiprid after nine generations of exposure to identify candidate genes and the microbiome involved in the adaptation process. Sequencing of the transcriptome of both selected (RS) and non-selected (SS) strains allowed the identification of 14858 genes and 4938 new transcripts. Most of the differentially expressed genes were associated with catalytic activities and metabolic pathways involving carbon and fatty acids. Specifically, the alcohol-forming fatty acyl-CoA reductase (FAR) and acyl-CoA synthetase (ACSF2), both involved in the synthesis of epidermal wax layer components, were significantly upregulated in RS, suggesting that adaptation to acetamiprid involves the synthesis of a thicker protective layer. Metatranscriptomic analysis revealed subtle shifts in the microbiome of RS. These results contribute to a deeper understanding of acetamiprid adaptation by the pea aphid and provide new insights for aphid control strategies.

Europium is one of the most reactive lanthanides and humans use it in many different applica-tions, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) were obtained and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothi-oneins and/or displace essential cations of these proteins during their homeostasis function. Both lipid metabolism (lipid droplets that fuse with europium-containing vacuoles) and au-tophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella Sativa, has been extensively researched for its anti-cancer properties across various human cancers. Yet, its specific anticancer mechanisms and pathways in glioblastoma remain to be elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 µM and 5 µM TQ concentrations. However, at 25 µM and 50 µM, TQ significantly reduced cell viability in a dose-dependent manner. We identified 1548 DEGs at 25 µM TQ (684 upregulated, 864 downregulated) and 2797 DEGs at 50 µM TQ (1528 upregulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5), while modulating Wnt signaling and upregulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anticancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.

Carotid intima-media thickness (CIMT) is a surrogate indicator for atherosclerosis and has been shown to predict cardiovascular risk in multiple large studies. Identifying and characterizing molecular markers for carotid atheroma plaque formation can be critical for early intervention and prevention of atherosclerosis. This study performed transcription factor (TF) network analysis of transcriptomic data focusing on two TF genes, ZNF385D, HAND2, whose polymorphisms reportedly associate with carotid atherosclerosis. Gene expression data were measured from pieces of carotid endarterectomy of hypertensive patients each paired with one sample of distant macroscopically intact tissue. TF networks were reconstructed for ZNF385D and HAND2 and their association with carotid atheroma progression examined using gene-set enrichment analysis with high statistical significance (p<6.95e-7) suggesting involvement of expression quantitative loci (eQTL). Examination of the regulation and correlation patterns suggests high clinical and interventional impacts of the two TF genes on impairing carotid atheroma plaque formation and preventing carotid atherosclerosis.

Trichothecene mycotoxin T-2 toxin is an important environmental pollutant and poses a global threat to human and animal health. T-2 toxin could induce nephrotoxicity, however, the precise molecular mechanism remains unclear. In this study, the mice were intraperitoneally administrated with a single dose of 2 mg/kg T-2 toxin. The kidney function and ultrastructural observation were also assessed and found T-2 toxin exposure could cause kidney damage. Transmission electron microscopy showed a significant swelling and vacuolization of the mitochondria of renal cell. A total of 1122, 58, and 391 differential expression genes (DEGs) that were predominantly expressed in kidney tissues at 1 d, 3 d, and 7 d after T-2 toxin exposure, respectively. Early transcriptomic changes at 1 d after exposure were down-regulation of DEGs involved in the cell cycle, p53 signaling pathway, and cellular senescence, while up-regulation of DEGs referred to the ribosome pathway. The temporal variations in gene expression pattern in T-2 toxin exposure in mice kidney were presented and cellular metabolism was disturbed at the exposure recovery period with 7 d. In conclusion, this study, for the first time, provided a comprehensive comparative transcriptomic analysis of gene regulation in T-2 toxin exposure-induced nephrotoxicity at different temporal periods and explored the nephrotoxicity mechanism of T-2 toxin at the mRNA level.

Anthracnose, caused by the fungus Colletotrichum lindemuthianum, poses a significant and widespread threat to the common bean crop. The use of plant genetic resistance has proven to be the most effective strategy for managing anthracnose disease. The Amendoim Cavalo (AC) Andean cultivar has resistance against multiple races of C. lindemuthianum, which is conferred by the Co-AC gene. Fine mapping of this resistance gene to common bean chromosome Pv01 enabled the identification of Phvul.001G244300, Phvul.001G244400, and Phvul.001G244500 candidate genes for further validation. In this study, we assessed the relative expression of Co-AC candidate genes, as well as other putative genes in vicinity of this locus and known resistance genes, in the AC cultivar following inoculation with the race 73 of C. lindemuthianum. Gene expression analysis revealed significantly higher expression levels of Phvul.001G244500. Notably, Phvul.001G244500 encodes a putative Basic Helix-Loop-Helix transcription factor, suggesting its involvement in the regulation of defense responses. Furthermore, we observed a significant modulation of the expression of defense related genes PR1a, PR1b, and PR2, in a time-course experiment. These findings contribute to the development of improved strategies for breeding anthracnose-resistant common bean cultivars, thereby mitigating the impact of this pathogen on crop yields and ensuring sustainable bean production.

Xaa-Pro dipeptidase (XPD, EC 3.4.13.9; also known as prolidase) catalyzes the hydrolysis of iminopeptide bond in the trans Xaa-Pro dipeptides (Xaa represents any amino acid except proline), which makes it find wide applications in food, medical and environmental protection fields. In the present study, a novel Xaa-Pro dipeptidase from Aspergillus phoenicis ATCC 14332 (ApXPD) was molecularly and biochemically characterized. Reclassification based on phylogenetic analysis and version 12.5 MEROPS database showed that this enzyme was the only fungal XPD in the unassigned subfamily which shared the highest sequence similarity with Xanthomonas campestris prolidase but not with that from the more related fungal species A. niudulans. As compared with other prolidases, ApXPD also contained an N-terminal tail (residues 81-89) and an additional region (PAPARLREKL), and used a different arginine residue for dipeptide selectivity. After heterologous expression and partial purification, recombinant ApXPD was highly active and stable over the alkaline range from 8.5 to 10.0, with a maximum activity at pH 9.0 and more than 80% activity retained after 1-h incubation at pHs of 8.5-10.0 (55oC). It also had an apparent optimum temperature of 55oC and remained stable at 20-30oC. Moreover, this enzyme was a cobalt dependent prolidase that only cleaved dipeptides Lys-Pro, Gly-Pro and Ala-Pro rather than other dipeptides, tripeptides and tetrapeptides. All these distinct features make A. phoenicis ATCC 14332 XPD unique among currently known prolidases, thus defining a novel Xaa-Pro dipeptidase subfamily.

Excess weight, which is seen as the background cause of most diseases, is gradually becoming the most important problem in the world. The cafeteria diet is robust diet that mimics the western diet and provides rapid weight gain associated with the obesity, diabetes, and cancer. The relationship between obesity and cancer is well known. For this reason, it is of great importance to reveal the first molecular and metabolic alterations that occur before entering the obesity process with any factor to understand the pathology of many diseases and to treat them in the early period. The beneficial effects of probiotics are attributed to their metabolite content with antioxidant properties or the postbiotic metabolites produced by them. In this study, the effects of different dietary practices on the hepatic antioxidant system of rats in developmental period were investigated by real-time PCR, enzyme activity measurements, and quantitative measurements of metabolites. After all, it was observed that CAF caused serious impairments by affecting the hepatic antioxidant system at gene and protein levels, and these impairments were relatively reversed with SCD Probiotics supplementation. In addition, regardless of the CAF diet, the regulatory effect of SCD Probiotics supplementation on the hepatic antioxidant system is remarkable.

In the tissue regeneration field, stem cell transplantation and the control of their differentiation represent a promising therapeutic strategy. The second aspect can be achieved using electrical stimulation. This study aims to characterize the effect of a microsecond electrical stimulation on MSCs and iNSCs, in the context of the RISEUP FET-OPEN project (n. 964562) that seeks to control these cells differentiation for the spinal cord injury treatments. Here, the effect of a specific microsecond electric pulses stimulation, characterized by bipolar pulses of 100 µs + 100 µs, delivered for 30 minutes at an intensity of 250 V/cm, on i) cell proliferation, ii) cell cycle, iii) gene expression and iv) apoptosis was evaluated. Results show that the stimulation does not affect cell proliferation, cell cycle, and apoptosis, but induced some variations in gene expression, in particular in EGR1, FOS, and POU5F1. These ob-servations led us to deeply investigate the cell proliferation until 72h from the stimulation observing an increase in the iNSCs. The main outcome of this study is that the chosen stimulation protocol is safe and not toxic for MSCs and iNSCs. The observed variations in the gene expression need to be deeply investigated to assess the molecular mechanisms involved.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

Introduction: congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of urinary collecting system, known as hydronephrosis or ureterohy-dronephrosis. Mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin 11 and TGFβ levels in obstructed ureteral tissue. The aim of the study is to investigate expression of fibrosis related genes in obstructive and normal ureteral tissue. Material and methods: it is a monocentric study in which nineteen patients were selected prospec-tively. 17 patients of which underwent Hynes-Anderson pyeloplasty due to the PUJO, 2 patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO) and 6 patients were chosen for control group: 5 underwent nephrectomies due to the kidney tumor and 1- upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR to evaluate the relative expres-sion of Tgfb1, Mmp1, Timp1, Pai1, Ctgf and Vegfa was performed. Expression levels of Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and Wilcoxon rank-sum test was performed to determine statistical significance of the differences. Results: significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, Pai1 was found. Discussion and conclusions: These findings suggest that tissue fibrosis similar to other tissues and organs is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF ex-pression is indicative of developmental origin of obstruction.

It has been previously shown that aldehyde dehydrogenase (ALDH) family member ALDH1A1 has a significant association with acute myeloid leukemia (AML) patient risk group classification, and that AML cells lacking ALDH1A1 expression can be readily killed by chemotherapy. In the past, however, a redundancy between the activities of subgroup members of the ALDH family has hampered conclusive evidence for addressing the role of specific ALDH genes. We here describe the bioinformatics evaluation of all nineteen member genes of the ALDH family as prospective actionable targets for the development of methods aimed to improve AML treatment. We implicate ALDH1A1 in the development of recurrent AML, and we show that from the nineteen members of the ALDH family, ALDH1A1 and ALDH2 have the strongest association with AML patient risk group classification. Furthermore, we discover that the sum of the expression values for RNA from the genes ALDH1A1 and ALDH2 has a stronger association with AML patient risk group classification and survival than either one gene alone. In conclusion, we identify ALDH1A1 and ALDH2 as prospective actionable targets for the treatment of AML in high risk patients. Substances that inhibit both enzymatic activities can constitute potentially effective pharmaceutics.

miRNAs are major regulators of eukaryotic gene expression, host immunity, and play an important role in the inflammation-mediated pathways in periodontal disease (PD) pathogenesis. Expanding our previous observation with the global miRNA profiling using partial human mouth microbes and lack of in vivo studies involving oral spirochete Treponema denticola induced miRNAs, this study was designed to delineate the global miRNA expression kinetics during progression of periodontitis in mice infected with T. denticola by using NanoString nCounter® miRNA panels. All the T. denticola-infected male and female mice at 8- and 16 weeks demonstrated bacterial colonization (100%) on the gingival surface, and an increase in alveolar bone resorption (p &lt; 0.0001). A total of 70 miRNAs with at least 1.0-fold differential expression/regulation (DE) miRNAs (26 upregulated and 44 downregulated) were identified. nCounter miRNA expression profiling identified 13 upregulated miRNAs (e.g. miR-133a, miR-378) and 25 downregulated miRNAs (e.g. miR-375, miR-34b-5p) in T. denticola-infected mice mandibles during 8-weeks infection whereas 13 upregulated miRNAs (e.g. miR-486, miR-126-5p) and 19 downregulated miRNAs (miR-2135, miR-142-3p) were observed during 16- weeks of infection. One miRNA (miR-126-5p) showed significant difference between 8-and 16-weeks of infection. Interestingly, miR-126-5p has been presented as a potential biomarker in patients with periodontitis and coronary artery disease. Among the 13 upregulated miRNAs, miR-486, miR-126-3p, miR-126-5p were reported in human gingival plaques samples with periodontitis. KEGG analysis revealed various functional pathways of DE miRNAs such as bacterial invasion of epithelial cells, Ras signaling, Fc gamma R- mediated phagocytosis, osteoclast differentiation, adherens signaling and ubiquitin mediated proteolysis. This is the first study of DE miRNAs in mice mandibles at different time-points of T. denticola infection and the combination of three specific miRNAs miR-486, miR-126-3p, miR-126-5p may serve as an invasive biomarker of T. denticola in PD. These miRNAs may have significant role in PD pathogenesis and establishes a link between miRNA, periodontitis, and systemic diseases.

In China, the demand for rabbit meat is also increasing, and the production for rabbit meat is important. However, the underlying mechanisms of regulate skeletal muscle growth and development in rabbits remain unclear. The purpose of this study was to identify candidate genes related to skeletal muscle growth in rabbits and explore their potential regulatory mechanisms. RNA-seq technique was used to compare the differences of skeletal muscle transcriptome in Fujian white rabbits at different developmental stages (day 20 and 26 of embryos and birth 1, 30 and 60-day-olds) with a total of 25 individual selected. A total of 9737 DEGs that were acquired from the five groups were annotated into three ontologies of the GO database: biological process (BP), cell component (CC), and molecular function (MF). For KEGG analysis, there are 8249 genes were enriched in 1148 pathways, of which 67 pathways were significantly enriched, mainly in Hypertrophic cardiomyopathy (HCM), the PPAR signaling pathway, MAPK signaling pathway. Among all comparison groups, SE was the most abundant AS event. Real-time PCR verified that the expression patterns of differential genes were consistent with the transcriptome sequencing results. These results will provide a molecular regulation mechanism of muscle growth and development in Fujian white rabbits, and should serve an important theoretical basis for improving meat performance and growth rate of Chinese local meat rabbit breeds.

Hemoglobin switch from fetal (HbF) to adult (HbA) has been studied intensively as an essential model for gene’s expression regulation, but also as a beneficial therapeutic approach for β-hemoglobinopathies, towards the objective of reactivating HbF. Transcription factor LRF (Leukemia/lymphoma-related), encoded from ZBTB7A gene has been implicated in fetal hemoglobin silencing, though has a wide range of functions that have not been fully clarified. We thus established LRF/ZBTB7A-overexpressing and ZBTB7A-knockdown K562 (human erythroleukemia cell line) clones and hemoglobin production was evaluated pre- and post-induction. Related effects on the process of hemoglobin switch from fetal to adult were also assessed. Transgenic K562 clones were further developed and studied under the influence of epigenetic chromatin regulators, such as DNA methyl transferase 3 (DNMT3) and Histone Deacetylase 1 (HDAC1), to evaluate LRF’s potential disturbance upon aberrant epigenetic background and provide valuable information of the preferable epigenetic frame, in which LRF unfolds its action on the β-type globin’s expression. ChIP-seq analysis demonstrated that LRF binds το γ-globin genes (HBG2/1) and apparently associates BCL11A for their silencing, but also, during erythropoiesis induction LRF binds BGLT3 gene promoting BGLT3-lncRNA production through the γ-δ intergenic region of β-type globin’s locus, triggering the transcriptional events from γ- to β-globin switch.

Emotion recognition defined as identifying human emotion and is directly related to different fields such as human-computer interfaces, human emotional processing, irrational analysis, medical diagnostics, data-driven animation, human-robot communi- cation and many more. The purpose of this study is to propose a new facial emotional recognition model using convolutional neural network. Our proposed model, “ConvNet”, detects seven specific emotions from image data including anger, disgust, fear, happiness, neutrality, sadness, and surprise. This research focuses on the model’s training accuracy in a short number of epoch which the authors can develop a real-time schema that can easily fit the model and sense emotions. Furthermore, this work focuses on the mental or emotional stuff of a man or woman using the behavioral aspects. To complete the training of the CNN network model, we use the FER2013 databases, and we test the system’s success by identifying facial expressions in the real-time. ConvNet consists of four layers of convolution together with two fully connected layers. The experimental results show that the ConvNet is able to achieve 96% training accuracy which is much better than current existing models. ConvNet also achieved validation accuracy of 65% to 70% (considering different datasets used for experiments), resulting in a higher classification accuracy compared to other existing models. We also made all the materials publicly accessible for the research community at: https://github.com/Tanoy004/Emotion-recognition-through-CNN.

The excellent properties of nanomaterials have been confirmed in many fields, but the effects on plants are still unclear. In this study, we have found that bismuth vanadium promoted the growth of taproots and the development of lateral roots, increased the roots activity by regulating the expression of polyamine or hormone-related genes and reducing the accumulation of reactive oxygen species in Arabisdopsis thaliana. Meantime, BV had higher antimicrobial effect than that of graphene oxide (GO). These results showed us a new perspective possibility of nanomaterials assisting the development of plants and crops, which is expected to become one of the ways to solve the problem of controlling and promoting the development of plants and crops.

Inorganic polyphosphate (polyP) is an important factor of stress tolerance in microbial cells. In yeast, the major enzyme of polyP biosynthesis is Vtc4, a subunit of the vacuole transporter chaperone (VTC) complex. In this study, we demonstrated that Vtc4 knockout in Saccharomyces cerevisiae not only decreased polyP content but also caused shifts in the composition of the intracellular polyP pool and changed the stress tolerance profile. In the mutant S. cerevisiae, the level of short-chain acid-soluble polyPs was decreased nearly 10-fold, whereas that of longer acid-insoluble polyPs was decreased only 2-fold, suggesting the existence of other enzymes compensating the production of long-chain polyPs. The Δvtc4 mutant showed inhibition of Mg2+-dependent phosphate uptake and decreased resistance to alkaline stress but increased tolerance to oxidation and heavy metal ions, especially Mn2+. Quantitative PCR revealed the upregulation of the DDR2 gene implicated in multiple stress responses and downregulation of PHO84 encoding a phosphate and Mn2+ transporter, which could account for the effects on phosphate uptake and Mn2+-related stress response in the Δvtc4 mutant. Our study indicates that short-chain polyPs, plays an important role in the regulation of stress response in yeast.

Selection of biologically relevant genes from high dimensional expression data is a key research problem in gene expression genomics. Most of the available gene selection methods are either based on relevancy or redundancy measure, which are usually adjudged through post selection classification accuracy. Through these methods the ranking of genes was done on a single high-dimensional expression data, which leads to the selection of spuriously associated and redundant genes. Hence, we developed a statistical approach through combining Support Vector Machine with Maximum Relevance and Minimum Redundancy under a sound statistical setup for the selection of biologically relevant genes. Here, the genes are selected through statistical significance values computed using a non-parametric test statistic under a bootstrap based subject sampling model. Further, a systematic and rigorous evaluation of the proposed approach with nine existing competitive methods was carried on six different real crop gene expression datasets. This performance analysis was carried out under three comparison settings, i.e. subject classification, biological relevant criteria based on quantitative trait loci, and gene ontology. Our analytical results showed that the proposed approach selects genes that are more biologically relevant as compared to the existing methods. Moreover, the proposed approach was also found to be better with respect to the competitive existing methods. The proposed statistical approach provides a framework for combining filter, and wrapper methods of gene selection.

MicroRNAs are used as biomarkers for classification of cancer subtypes since certain miRNAs are differentially expressed in normal and patient samples. Moreover, miRNAs target mRNAs and can heavily influence Gene Expressions. Thus, deregulation of miRNAs is linked to various disorders. Thus, miRNAs can be used for prognosis and developing personalized health solutions for patients. Given the importance of miRNAs, there has been substantial work done in the field. In this paper, recent works in the field of using miRNAs expressions of patients were considered. A total of 20 papers were surveyed which utilized feature selection ensembles, fuzzy logic as well as deep learning. 10 papers have been reported which offer insight into how miRNAs can be utilized for subtype-specific or generalized cancer diagnosis.

COVID-19 manifests regarding extreme acute respiratory conditions caused by a novel beta coronavirus (SARS-CoV-2) which is reported to be the seventh coronavirus to infect humans. Like other SARS-CoVs it has a large positive-stranded RNA genome. But specific furin site in the spike protein, mutation prone and phylogenetically mess Orf1ab separates SARS-CoV-2 from other RNA viruses. Since, the outbreak (February - March 2020) which originated in China, researchers, scientists, and medical professionals are inspecting all possible facts from every possible aspect including its replication, detection, and prevention strategies. This led to the prompt identification of its basic biology, genome characterization, structural based functional information of proteins, and strategies to prevent its spread. Due to the rapid mutation rate, the functional characterization of a few proteins is still lagging. This review summarizes the recent updates on the basic molecular biology of SARS-CoV-2 and prevention strategies undertaken worldwide to tackle COVID-19. This recent information can be implemented for the development and designing of therapeutics against SARS-CoV-2.

One of the typical forms of linear matrix expressions (linear matrix-valued functions) is given by $A + B_1X_1C_1 + \cdots + B_kX_kC_k$, where $X_1, \ldots, X_k$ are independent variable matrices of appropriate sizes, which include almost all matrices with unknown entries as its special cases. The domain of the matrix expression is defined to be all possible values of the matrix expressions with respect to $X_1, \ldots, X_k$. I this article, we approach some problems on the relationships between the domains of two linear matrix expressions by means of the block matrix method (BMM), the matrix rank method (MRM), and the matrix equation method (MEM). As application, we discuss some topics on the relationships among general solutions of some linear matrix equations and their reduced equations.

In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

We assessed the growth performance, physiological traits, and gene expressions in steers fed with dietary rumen-protected L-tryptophan (RPT) under cold environment. Eight Korean native steers were assigned to two dietary groups, no RPT (Control) and RPT (0.1% RPT supplementation on a dry matter basis), 6 wks. Maximum and minimum temperatures throughout the experiment were 6.7°C and -7.0°C, respectively. Supplementation of 0.1% RPT to a total mixed ration did not increase body weight but had positive effects of elevating average daily gain (ADG) and reducing the feed conversion ratio (FCR) at day 27 and 48. Metabolic parameter showed higher glucose level (at day 27) in the 0.1% RPT group compared to the control group. Real-time PCR analysis showed no significant differences in the expression of muscle (MYF6, MyoD, and Desmin) metabolism genes between the two groups, whereas the expression of fat (PPARγ, C/EBPα, and FABP4) metabolism genes was lower in the 0.1% RPT group than in the control group. Thus, we demonstrate that long-term (6 wks) dietary supplementation of 0.1% RPT was beneficial owing to enhanced growth performance by increasing ADG and glucose level, decreasing FCR, and maintaining homeostasis in immune responses in beef steers during cold environment.

Suppressors of cytokine signaling (SOCS) influence cytokine and growth factor signaling by negatively regulating the JAK-STAT pathway. This maintains homeostasis during host immune response. However, functional characterization of SOCS family members in invertebrates is limited. In this study, we discovered the Type-I subfamily of the SOCS genes in the mealworm beetle, T. molitor. The full-length ORFs of TmSOCS5, TmSOCS6, and TmSOCS7 consisted of 1,389, 897 and 1,458 nucleotides, encoding polypeptides of 462, 297 and 485 amino acids, respectively, The C-terminal region of TmSOCS was highly conserved in the SH2 and SOCS box domains. Phylogenetic analysis revealed that the three SOCS genes clustered within the same sub-family and the highest amino acid identity was with the Tribolium castaneum SOCS genes (TcSOCS). While the expression of TmSOCS5 and TmSOCS6 was low in larval, pupal, and adult stages of the insect, TmSOCS7 showed higher expression. The expression of TmSOCS5 and TmSOCS6 was higher in larval hemocytes and adult ovary. The microbes expressed the three TmSOCS genes to varying degrees. C. albicans elicited the strongest response in the host with highest 15-fold expression in TmSOCS7 3 h post-inoculation. Collectively, these data suggest that the Type I TmSOCS could play a role in eliciting host immunity.

Poliovirus 2A protease (PV2Apro) plays a vital role in viral replication and down-regulation of host cell protein synthesis. In order to understand more concerning PV2Apro, the protein was over-expressed in bacteria following amplification using sense and antisense primers and cloning in pET15b. Several expression hosts were tested and BL21 (DE3) pLysS cells gave the best expression of PV2Apro with minimal unwanted protein expression following IPTG induction. The 2Apro protein was purified to homogeneity using column chromatography, its solubility determined and its molecular weight and composition determined by MALDI-TOF mass spectrometry. The protease was found in the insoluble fraction and the purified protein had a slightly lower molecular weight than predicted. Moreover, three dimensional structure was modelled using template 1z8r with 58% identity and validated using ramachandran plot. Results revealed that most of the residues lie in favoured and allowed regions. These findings could help in a better understanding of PV2Apro structure and inhibition thus, highlighting potential targets for antiviral drug development.

Single-level Principal Components Analysis (PCA) and multi-level PCA (mPCA) methods are applied here to a set of (2D frontal) facial images from a group of 80 Finnish subjects (34 male; 46 female) with two different facial expressions (smiling and neutral) per subject. Inspection of eigenvalues gives insight into the importance of different factors affecting shapes, including: biological sex, facial expression (neutral versus smiling), and all other variations. Biological sex and facial expression are shown to be reflected in those components at appropriate levels of the mPCA model. Dynamic 3D shape data for all phases of a smile made up a second dataset sampled from 60 adult British subjects (31 male; 29 female). Modes of variation reflected the act of smiling at the correct level of the mPCA model. Seven phases of the dynamic smiles are identified: rest pre-smile, onset 1 (acceleration), onset 2 (deceleration), apex, offset 1 (acceleration), offset 2 (deceleration), and rest post-smile. A clear cycle is observed in standardized scores at an appropriate level for mPCA and in single-level PCA. mPCA can be used to study static shapes and images, as well as dynamic changes in shape. It gave us much insight into the question “what’s in a smile?”

Although wheat is a staple food for most of human population, some of its components trigger adverse reactions. Among wheat components, the alpha-amylase/trypsin inhibitors (ATI) are important triggers of several allergies and activators of innate immunity. ATI are a group of exogenous protease inhibitors and include several polypeptides. The three ATI polypeptides named CM3, CM16 and 0.28 are considered major allergens, and might also play a role in other common wheat-related pathologies, such as Non Celiac Wheat Sensitivity and even Celiac Disease. On this basis, we pointed to obtain high amounts of them in purity and evaluating their allergenicity potential. We thus isolated the mRNA corresponding to the three ATI genes CM3, CM16 and 0.28 from 28 days post-anthesis wheat kernels and the corresponding cDNAs were used for heterologous expression in Pichia pastoris. The three purified proteins were tested in degranulation assay against human sera of patients with food allergy to wheat. A large range of degranulation values was observed for each protein according to the sera tested. All the three purified proteins CM3, CM16 and 0.28 were active as allergens because able to induce basophils degranulation on wheat allergic patients’ sera, but the highest values of β-hexosaminidase release were observed for CM3 protein.

Burning Man is probably the most famous art festival in the world. What started as a bonfire ritual for a small group of friends held on San Francisco beach in 1986, has evolved into an iconic event. Held annually for one week before the Labor Day weekend, the festival attracts over 60,000 participants each year and yields over $8 million in tickets and contributions.This preprint reveals some preliminary results from the economic analysis of Burning Man that is based on the unique data from over 500 surveys collected during several Burning Man events between 2012 and 2018.The paper’s main findings demonstrate that Burning Man is not some hippie get-together with lots of booze and drugs. Instead, it is a lucrative and exclusive event that is attended by bright, wealthy and well-educated people, both from the United States and abroad. A typical Burner is a 32-old childless male with a college degree and an average annual income above $100,000 who attended Burning Man at least two times before and who spends between $5,000 and $6,000 on tickets, fares, gear, and supplies.

Data generation using high throughput technologies has led to the accumulation of diverse types of molecular data.These data have different types (discrete,real,string etc.) and occur in various formats and sizes. Datasets including gene expression, miRNA expression, protein-DNA binding data (ChIP-Seq/ChIP-ChIP), mutation data(copy number variation, single nucleotide polymorphisms), GO annotations, protein-protein interaction and disease-gene association data are some of the commonly used genomic datasets to study biological processes. Each of them provides a unique, complementary and partly independent view of the genome and hence embed essential information about their regulatory mechanisms. In order to understand the functions of genes, proteins and analyze mechanisms arising out of their interactions, information provided by each of these datasets individually may not be sufficient. Therefore integrating these multi-omic data and inferring regulatory interactions from the integrated dataset provides a system level biological insights in predicting gene functions and their phenotypic outcomes. To study genome functionality through interaction networks, different methods have been proposed for collective mining of information from an integrated dataset. We survey here data integration approaches using state-of-the-art techniques such as network integration, Bayesian networks, regularized regression (LASSO) and multiple kernel learning methods.

In the paper, the authors nd a new closed expression for the Fibonacci polynomials and, consequently, for the Fibonacci numbers, in terms of a tridiagonal determinant.

In the paper, by a very simple approach, the author establishes an expression in terms of a lower Hessenberg determinant for the Euler polynomials. By the determinantal expression, the author finds a recurrence relation for the Euler polynomials. By the way, the author derives the corresponding expression and recurrence relation for the Euler numbers.

Background: Capsaicinoid are a group of compounds and widely used in the food, medical, and pharmaceutical industries. Capsaicinoid are unique synthesized and accumulated in the pepper fruits. MeJA can enhance the capsaicinoid production. Temporal and spatial expression of capsaicinoid biosynthetic genes are helpful to understand the molecular mechnism of capsaicinoid biosynthesis in the fruits of pepper. Although some of the capsaicinoid biosynthetic genes in pepper have been identified, the expression of these genes at different developing stages of fruit has not been systemically investigated, and little is known about the molecular basis of MeJA inducing capsaicinoid biosynthesis. Results: HPLC study revealed that the capsaicinoid accumulation in the developing fruit of pepper initially appeared at 24 DAP (day after pollination), was actively development at 36 DAP and peaked at 48 DAP. 11 genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the CaCS was unique expressed in placenta and the other 10 genes were expressed in all selected tissues and 9 of 11 genes (except CaCa4H and CaCa3H) were strongly expressed in placenta tissue. Spatial expression analysis demostrated that the 11 gene could be collectively grouped into four categories based on the patterns of relative expression of the genes during fruit development. Category I has 2 and they displayed a bell-shaped expression pattern with the peak expression at 24 DAP, Category II contains 5 genes and expression of the 5 genes was constantly increased from 0 to 36 DAP and peaked at 36 DAP. Category III comprises of 2 genes and both genes reached the peak at 48 DAP. Category IV consists of 2 genes and they showed a high expression at 36 and 48 DAF, but unexpressed from 0 to 12 DAP. The gene expressions of the 11 genes were up-regulated by MeJA. 3 genes showed a high expression at 24 h; 4 genes reached the peak at 12 h; the top expression were observed at 18 h; The last one, CaACYase, achieved the highest level at 8 h. Conclusion: The biosynthesis of capsaicinoid in pepper fruit is developmentally regulated. The expression of the majority of capsaicinoid biosynthetic genes is highly consistent with the development accumulation of capsaicinoid in pepper fruit. These results not only provide the initial information on spatial and temporal expression of capsaicinoid biosynthetic genes in pepper developing fruit, but are also valuable to identify the MeJA-induced genes for capsaicinoid biosynthesis and accumulation during pepper fruit development.

Background: The commonly known assumption that combinations of several herbs in one formulation can have better efficacy due to additive or synergistic effects has not been systematically studied despite some evidence supporting the synergy concept. Study aim: The study aimed to reveal the molecular interactions in situ of host cells in response to the intervention of BHP and justify the benefits of implementing BHP in clinical practice. Results: This overview provides the results of recent clinical and network pharmacology studies of botanical herbal preparations (BHP) of Rhodiola with other plants, including Ashwagandha, Green Tea, Eleutherococcus, Schisandra, Eleutherococcus, Leuzea, Caffeine, Cordyceps, Gingko, Black Cohosh, saffron, and L-carnosine. Conclusions: The most important finding from network pharmacology studies of BHP was the evidence supporting the synergistic interaction of BHP ingredients, revealing unexpected new pharmacological activities unique and specific to the new BHP. Some studies show the superior efficacy of BHP compared with mono-drugs. At the same time, some a priori-designed combinations can fail, presumably due to antagonistic interactions and crosstalk between molecular targets within molecular networks involved in the cellular and overall response of organisms on the intervention. Network pharmacology studies help predict the results of studies to discover new indications and unpredicted adverse events.

Coilia nasus is a typical anadromous migratory fish in the lower reaches of the Yangtze River. Every year, C. nasus cluster offshore and swim upstream along the Yangtze River into the tributaries and lakes in the middle and lower reaches of the Yangtze River to breed. In this study, female C. nasus collected as the subjects from Chongming section in Shanghai, Taizhou section in Jiangsu and Anqing section in Anhui. The ovaries were used for examining in tissue sections and researching of gene expression including follicle stimulating hormone receptor (fshr), luteinizing hormone receptors (lr), kisspeptin-1 (kiss1) and forkhead box l2 (foxl2) related to the reproductive development, and the estrogen (estradiol, E2) and progesterone (17α,20β-dihydroxy-4-pregenen-3-one, 17α,20β-DHP) were also analyzed in serum levels. The results showed that, first, the growth period of oocytes was small in stage II of ovarian development, in which both E2, 17α,20β-DHP levels and gene expression were low. Then, in stage Ⅲ, the growth period of oocytes were become large, as well as the yolk granules and oil droplets began to appear. Simultaneously, E2 and expression of kiss1 and foxl2 were significantly elevated. Finally, stage Ⅳ was the period of large accumulation of nutrients in oocytes, and 17α,20β-DHP level and expression of fshr and lhr were significantly elevated. The results have enriched the theoretical study of ovarian development in the natural population of C. nasus, supplemented the biological basis of C. nasus reproduction, and scientifically supported the study of C. nasus population ecology and resource conservation.

Flax seed is one of the richest plant sources of linolenic acid (LIN) and also contains unsaturated linoleic acid (LIO) and oleic acid (OLE). Stearoyl-ACP desaturases (SAD) and fatty acid desaturases (FAD) play a key role in the synthesis of flax fatty acids (FA). We sequenced flax seed transcriptomes at the 3, 7, 14, 21, and 28 day after flowering (DAF) for ten flax varieties with different oil FA compositions grown under three temperature/watering conditions. Expression levels of 25 genes of SAD, FAD2, and FAD3 families were evaluated. FAD3b, FAD3a, FAD2b-2, SAD3-1, SAD2-1, SAD2-2, SAD3-2, FAD2a-1, and FAD2a-2 had the highest expression levels, which changed significantly during seed development. These genes probably play a key role in the FA synthesis in flax seeds. High temperature and insufficient watering shifted the maximum expression levels of the FAD and SAD genes to earlier development stages, while the opposite trend was observed for low temperature and excessive watering. Differences in FAD and SAD expression profiles under different growth conditions could contribute to the FA composition of linseed oil. Stop codons in the FAD3a gene, resulting in reduced LIN content, decreased the level of the FAD3a transcript. Some difference in reaching the maximum expression level during seed development was observed between 1) SAD3-1, SAD3-2, and FAD2b-2 and 2) SAD2-1, SAD2-2, FAD2a-1, FAD2a-2, FAD3a, and FAD3b. These groups possibly contribute somewhat differently to the synthesis of FA at different development stages.

Background: This study, conducted in October 2017 at two Canadian universities, aimed to explore the relationships between gender expression, protective coping strategies, alcohol saliency, and high-risk alcohol use. Methods: Validated scales were employed to assess these variables using survey data. Multivariate analyses were conducted to investigate the associations between these factors and high-risk drinking. Results: The study revealed significant associations between high-risk drinking and androgynous gender roles (OR=1.58, 95% CI: 1.19-2.10) as well as among self-reported males (OR=2.21; 95% CI: 1.77-2.75). Additionally, protective behavioral strategies were inversely related to high-risk drinking (OR=0.95; 95% CI: 0.94-0.96), while higher alcohol saliency exhibited a positive correlation with high-risk drinking (OR=1.12; 95% CI: 1.11-1.14). Conclusions: These findings underscore the importance of considering gender, alcohol saliency beliefs, and protective behavioral strategies in the development and refinement of interventions aimed at reducing high-risk alcohol use on Canadian campuses.

Cancer metastasis accounts for approximately 90% of cancer deaths, and elucidating markers in metastasis is the first step in its prevention. To characterize metastasis marker genes of breast cancer (MGs), XGBoost models that classify metastasis status were trained with gene expression profiles from TCGA. Then, a metastasis score (MS) was assigned to each gene by calculating the inner product between the feature importance and AUC performance of the models. As a result, the 54, 202, and 357 genes with the highest MS were characterized as MGs by empirical P-value cutoffs of 0.001, 0.005, and 0.01, respectively. The three sets of MGs were compared with those from existing metastasis marker databases, which provided significant results in most comparisons. We noticed that the set of MGs with the median EP cutoff showed better performance than the other two sets, suggesting the importance of the cutoff used in determining MGs. They were also significantly enriched in biological processes associated to breast cancer metastasis. The MGs that could not be identified by statistical analysis (e.g., GOLM1, ELAVL1, UBP1, and AZGP1) as well as the MGs with the highest MS (e.g., ZNF676, FAM163B, LDOC2, IRF1, and STK40) were verified via the literature. Additionally, we checked how close the MGs are located to each other in the protein–protein interaction networks. We expect that the characterized markers will help understand and prevent breast cancer metastasis.

The Shisa family is a type of single-transmembrane adaptor proteins containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine Shisa subfamily genes have been proposed in most vertebrates; however, some of them might be species-specific. The number of Shisa genes present in zebrafish remains unclear. The purpose of this study was to investigate the evolutionary relationships among Shisa family genes in zebrafish (TU strain) using phylogenetic and syntenic analyses. The function of shisa-2 was preliminarily examined via CRISPR/Cas13d-mediated knockdown. Following identification in zebrafish,10 Shisa family genes, namely shisa-1, 2, 3, 4, 5, 6, 7, 8, 9a, and 9b, were classified into three main clades and six subclades. Their encoding proteins contained a cysteine-rich N-terminal domain and a proline-rich C-terminal region containing different motifs. A specific syntenic block containing atp8a2 and shisa-2 was observed to be conserved across all species. Furthermore, all these genes were found to be expressed during embryogenesis. shisa-2 was expressed in the presomitic mesoderm, somites, and so on. shisa-2 was identified as a regulator of the expression of the somite formation marker mesp-ab. Overall, our study provides new insights into the evolution of Shisa family genes and the control of shisa-2 over the convergent extension cells of somatic precursors in zebrafish.

Expressive clinical terminologies are of utmost importance for achieving an semantically interoperable data exchange and reuse in healthcare. SNOMED CT, widely respected as the most comprehensive terminology in medicine, provides formal concept definitions based on description logic which not only allows for advanced querying of SNOMED CT-coded data but also for flexibly augmenting its 350,000 concepts. This ability for postcoordination largely increases the expressivity of the terminology but correlates with an intrinsic complexity. Complicated by the current lack of tooling support, postcoordination is widely either ignored or applied in an error-prone way. To help facilitate the adoption of postcoordination, we implemented a web application that guides through the creation of Postcoordinated expressions (PCEs) while ensuring the adherence to syntactic and semantic constraints. Our approach was largely facilitated by making use of the extensive SNOMED CT specifications as well as advanced HL7 FHIR Terminology Services. Qualitative evaluations confirmed the usability of the developed application and the correctness of PCEs created with it.

Hypoxia represents one of the key factors that stimulate the growth of leukemic cells in their niche. Leukemic cells in hypoxia are forced to reprogram their original transcriptome, miRNome, and metabolome. How the coupling of miRNAs/mRNAs helps to maintain or progress the leukemic status is still not fully described. MicroRNAs (miRNAs) regulate practically all biological processes within cells and play a crucial role in leukemia development/progression. Here we worked with the human cell line MEC-1 (human chronic lymphocytic leukemia (CLL)) where we deleted mature miR-155 by CRISPR/Cas9. MEC-1 cells in hypoxia showed a higher proliferation rate with a relatively low level of apoptosis. Interestingly, miR-155 deficiency decreased the proliferation rate in both, normoxia and hypoxia. Besides common hypoxia-related genes (HIF1α, EGLN1, VHL, HK1, and HK2), we also measured, genes for glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). Surprisingly, only SLC2A3 (GLUT3) showed significant overexpression in hypoxia conditions in miR-155 deficient MEC-1cells which points to the possible novel target of miR-155 in CLL. Increased glucose uptake and decreased lactate support our hypothesis that miR-155 deficiency and hypoxia transform cell metabolism. To conclude, miR-155 deficiency and hypoxia-impaired glucose metabolism stimulate GLUT3 in CLL cells.

Micro-expression (ME) is one of the key psychological stress reactions. It is a modest, spontaneous facial mechanism. ME has significant applicability in a variety of psychologically-related sectors because to its precision and unpredictability with regard to psychological manifestations. Nevertheless, the current Micro-expression recognition (MER) algorithms have poor accuracy and a limited quantity of ME data, and this study issue has not been thoroughly investigated. Therefore, we present an approach for deep learning based on a Spatio-temporal capsule network (STCP-Net). STCP-Net has four components: a jitter reduction module, a differential feature extraction module, an STCP module, and a fully linked layer. The first two modules are aimed to extract diversifying differential features more precisely and to limit the influence of head jitter. The STCP module is used to extract Spatio-temporal features layer by layer, taking the temporal and geographical connection between features into account. This research runs sufficient trials using the Leave One Subject Out (LOSO) methodology for cross-validation using the CASMEII dataset. The conclusion and analysis demonstrate that the algorithm is innovative and efficient.

Sulfate transporters (SULTRs) are responsible for the uptake of the sulfate (SO42−) ions in the rhizosphere by the roots and their distribution in plant organs. In this study, SULTR family members in the genome of the two oilseed crops, Camelina sativa, and Brassica napus, were identified and characterized based on their sequence structure, duplication events, phylogenetic relationships, phosphorylation sites, and expression levels. Herein, 36 and 45 putative SULTR genes were recognized from the genome of C. sativa, and B. napus, respectively. SULTR proteins were predicted as basophilic proteins with low hydrophilicity in both studied species. According to phylogenetic relationships, we divided SULTRs into five groups, in which SULTRs 3 showed highest variation. Besides, several duplication events were observed between SULTRs. The first duplication event was predicted approximately five million years ago between three SULTRs 3.1 in C. sativa. Two subunits were indicated in the 3D structure of SULTRs that the active binding sites differed between C. sativa and B. napus. According to available RNA-seq data, SULTRs showed diverse expression in tissues and response to stimuli. SULTRs 3 showed an expression in all tissues. SULTRs 3.1 were more upregulated in response to abiotic stresses in C. sativa, while SULTRs 3.3, and SULTRs 2.1 showed an upregulation in B. napus. Furthermore, SULTRs 3 and SULTRs 4.1 showed an upregulation in response to biotic stresses in B. napus. Based on the distribution of cis-regulatory elements in the promoter region, we speculated that SULTRs might be controlled by phytohormones such as ABA, and MeJA. Therefore, it seems that SULTR genes in C. sativa have been more influenced by evolutionary processes and have acquired more diversity.

Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its response to therapy is the identification of driver mutations. The introduction of gene expression profiling (GEP) in MM was an important step in elucidating the molecular heterogeneity of MM and its clinical relevance. Since some mutations in myeloma occur in non-coding regions, studies based on the analysis of mRNA provide more comprehensive information on the oncogenic pathways and mechanisms relevant to MM biology. In this review, we discuss the role of gene expression profiling in understanding the biology of multiple myeloma together with the clinical manifestation of the disease, as well as its impact on treatment decisions and future directions.

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major "rare" ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10-4 to 10-18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10-6 M to 10-18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10-4 M. Network pharmacology analyses of genes expression profiles using Ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

The upregulated expression of thyrosine kinase AXL has been reported in several hematologic and solid human tumors including gastric, breast, colorectal, prostate, and ovarian cancers. Thus, AXL can potentially serve as a diagnostic and prognostic biomarker for various cancers. This paper reports the first-ever use of loop-mediated isothermal amplification (LAMP) of the AXL gene as a diagnostic method for ovarian cancer. We demonstrated simple instrumentation toward a point-of-care device to perform LAMP. This paper also reports the first-ever use of core-shell beads as a microreactor to perform LAMP as an attempt to promote environmentally friendly laboratory practices.

Neural networks models are mostly represented by oriented graphs where only the components, constitutive elements of the graph, are transcribed into mathematical xpression. Indeed, accurate knowledge of the full expression of the model is required in certain situations such as selecting among several reference models, the one that best fits the available data or comparing the explanatory and predictive performance of an established model with respect to some reference models. In this paper, we establish a formalism of the mathematical expression for multilayer perceptron neural network in a general framework, MLP-p-n-q, with p, n and q natural integers and show its restriction to cases where one has a hidden layer and multivariate outputs (MLP-p-1-q), and then a single output (MLP-p-1-1). Then, we give some specific cases of the most commonly used models. An application case is presented in the context of solving a nonlinear regression problem.

The most prevalent Ca2+-buffer proteins (CaBPs: parvalbumin—PV; calbindin—CaB; calretinin—CaR) are widely expressed by various neurons throughout the brain, including the retinal ganglion cells (RGCs). Even though their retinal expression has been extensively studied, a coherent assessment of topographical variations is missing. To examine this, we performed immunohistochemistry (IHC) in the mouse retina. We found variability in the expression levels and cell numbers for CaR, with stronger and more numerous labels in the dorso-central area. CaBP+ cells contributed to RGCs with all soma sizes, indicating heterogeneity. We separated 4-9 RGC clusters in each area based on expression levels and soma sizes. Besides the overall high variety in cluster number and size, the peripheral half of the temporal retina showed the greatest cluster number, indicating a better separation of RGC subtypes there. Multiple labels showed that 39% of the RGCs showed positivity for a single CaBP, 30% expressed two CaBPs, 25% showed no CaBP expression and 6% expressed all three proteins. Finally, we observed an inverse relation between CaB and CaR expression levels in CaB/CaR dually- and CaB/CaR/PV triple labeled RGCs, suggesting a mutual complementary function.

A lot of research studies have been surveyed the completed genomes of prokaryotic and eukaryotic and focused on the correlation between the percentage of microsatellite sequences in completed genomes and the whole size of the organism genomes. There are fewer studies made in repetitive sequences otherwise simple sequence repeats or long tandem repeats of virus genomes. simple sequence repeats (SSRs) are the most important regions for recombination and moving repeats blocks from site to another site in the genomes. A tool was programmed and designed by visual basic 6.0 to find the long tandem repeats in DNA sequences of the small genomes. The tool named “Repeater Finder Regular Expression”, (RFRE) Version 1.0, 2016. The tool was utilized to discover different pattern of long tandem repeats (LTR) motifs on the completed genomes of human corona virus strains by using a joined regular expression language. In this study, a twenty-nine accession numbers of human coronavirus completed genomes, (hku1) strains were retrieved from the Genbank. The researcher can write a different regular expression patterns and joined regular expression patterns through the designed tool to search and find a specific motif of nucleotide sequences inside the complete genomes. The RFRE tool searched and found three different total lengths of a perfect long tandem repeats (240bp, 300bp and 480bp). A Dot plot gave a picture view for the long tandem repeat sequences in the completed genome sequence (KF430201.1) of human coronavirus. The genomic dot plot tool YASS was used as a genomic similarity searching tool to check for the uninterrupted repeats and confirm the sensitivity of the (RFRE) tool. To identify the recombination site in the genomes of human coronavirus the RAT tool was applied to find the recombination sites between the completed genomes of human corona viruses .The RAT tool recognized the recombination site in the nucleotide position (3012) and at the same time this recombination site position (3012) was also recognized as a beginning position of a long tandem repeat. A precise motif was predicted from the translated repeats of Human Corona Virus which found by PRATT tool. There was a relationship between the total length of long tandem repeats and genome size of Human Corona Virus and the correlation value R² was equal to (0,451). In conclusion, this study presented the importance of finding the long tandem repeats of human coronavirus and gives a relationship between the completed genome size of human coronavirus types and long tandem repeats. The nucleotide position (3012) was a hot spot site for a recombination among the complete genomes of human coronavirus and also identified as a repetitive site in the genomes of human corona virus (hku1). The repeats in human coronavirus (hku1) were predicated to be a main major role of virus evolution.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

Abstract: Brassinosteroids (BR) are essential plant hormones that play a crucial role in regulating plant growth and development, as well as their resistance to abiotic and biotic stresses, including pathogen infections. In the context of plant im-munity, BR influence various processes such as the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the re-inforcement of the plant cell structure. The aim of work is understand the role of BR in plant defense against abiotic and biotic stresses. BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, contributing to increased plant resistance to abiotic stresses. The study discusses various mechanisms of BR action on plant immunity, including the regulation of gene expression related to defense, activation of the plant defense system, in-teraction with other plant hormones, regulation of water and salt balance, and influence on photosynthetic processes. In the context of plant immunity, BR influence various processes, including the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the reinforcement of the plant cell structure. Additionally, BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, con-tributing to increased plant resistance to abiotic and biotic stresses. The paper emphasizes the importance of further research on the role and mechanisms of action of BR in plant immunity, which may contribute to the development of more effective strategies for the use of BR in agriculture, horticulture, and plant protection.

Apple red flesh coloration is a result of the performance of biochemical pathway involved in the biosynthesis of anthocyanins and anthocyanidins. Based on apple genome analysis, high number of regulatory genes, mainly transcription factors such as MYB, which are components of regulatory complex MYB-bHLH-WD40, and several structural genes (PAL, 4CL, CHS, CHI, F3H, DFR, ANS, UFGT) involved in anthocyanin biosynthesis have been identified so far. In this study, we investigated previously unrecognized genes involved in the constitution of red-flesh apple phenotype. These genes could be concerned as molecular markers for early selection of new apple cultivars. Based on comparative transcriptome analysis of apples with different fruit flesh coloration, we successfully identified and characterized ten genes from plant hormone transduction pathway of: auxin (GH3); cytokinins (B-ARR); gibberellins (DELLA); abscisic acid (SnRK2 and ABF); brassinosteroids (BRI1, BZR1 and TCH4); jasmonic acid (MYC2); and salicylic acid (NPR1). In presented studies an analysis of their expression profiles was performed in immature and ripe fruits of red-fleshed cultivars. Generally, we have uncovered, the set of the novel genes, mediating regulation of the abscisic acid, salicylic acid, cytokinins and jasmonic acid signaling and preliminarily described their role in anthocyanin biosynthesis, accumulation and degradation. Their expression was not characterized in apple fruits so far. Presented study, allowed to underline the relationship of genes from hormone signal transduction pathway with UFGT gene, directly responsible for anthocyanin color transformation as well as confirmed their crucial role of plant hormone regulation and anthocyanin accumulation during apple fruit ripening.

Background: Galectin-3 (Gal-3) overexpression is associated with fibroblastic proliferation and the production of collagen, resulting in increased cardiac fibrosis and remodelling. Aim of the study was to investigate on the expression of Gal-3 in hypertrophic hearts. We examined 19 surgical specimens taken from interventricular septum of 8 patients with Tetralogy of Fallot, 4 patients with aortic valve stenosis, 1 cardiac explant affected from dilated cardiomyopathy, and 6 myocardial biopsies of patients submitted to heart transplantation. Methods: All the samples were routinely processed, stained with Hematoxylin-Eosin, Trichromic stain and elastic fiber stain and selected by having the morphological features of myocardial hy-pertrophy: myocytolysis, nuclear pleomorphism, interstitial fibrosis. Results: At immunohistochemistry, myocardial fibers showed cytoplasmic expression of Gal-3 in the 4 patients with aortic valve stenosis (diffuse in 3 and mild in 1), in the 1 patient with cardiac explant (mild) and in the 4/6 transplanted hearts (mild and focal in 3 and diffuse in 1). The 8 patients affected from Tetralogy of Fallot and 2 patients with transplanted hearts resulted negative. Conclusions: The results agreed with the hypothesis that Gal-3 may play a role in cardiac hyper-trophy; its expression in myocardial fibers is not related with the morphological aspects as suggested by the absence in pediatric cases. The presence in myocardial biopsies taken from transplanted hearts would suggest a possible role in predicting clinical outcome of such patients.

Suppressors of cytokine signaling (SOCS) genes are essential negative regulators that modulate cytokine signaling and play key roles in numerous biological processes, including immune responses. In this study, we cloned the complementary DNA (cDNA) sequences of two SOCS genes, designated as LvSOCS6 and LvSOCS7, from the white-leg shrimp, Litopenaeus vannamei. LvSOCS6 encoded a polypeptide of 463 amino acids (aa), spanning 1,392 base pairs (bp), while LvSOCS7 encodes a significantly larger polypeptide of 955 aa, encompassing 2,868 bp. Both LvSOCS proteins exhibited conserved domains associated with SOCS, including a centralized Src homology 2 (SH2) domain and a C-terminal SOCS box. Phylogenetic analysis revealed that the deduced aa sequences of LvSOCS6 and LvSOCS7 cluster within the invertebrate type I SOCS family, indicating their evolutionary relatedness. Tissue distribution analysis demonstrated ubiquitous expression of both LvSOCS genes across all examined tissues, with LvSOCS6 showing heightened expression in the gills and LvSOCS7 exhibiting a remarkable preference for the gills and stomach. Notably, mRNA expression patterns of LvSOCS genes following LPS and poly (I:C) stimulations exhibit significant upregulations, while PGN stimulation yields incongruous results across the experimented tissues. Interestingly, concurrent with the diminished expression of LvSOCS6 and LvSOCS7, there is a significant elevation in mRNA expression levels of LvSTAT, a vital component of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. These findings shed light on the potential involvement of the newly discovered type I SOCS genes in regulating the JAK/STAT pathway and assuming pivotal roles in orchestrating the innate immune responses in L. vannamei defense mechanisms.

Oil-tea (Camellia oleifera) is a woody oil crop whose nectar includes galactose derivatives that are toxic to honey bees. Interestingly, some mining bees of the genus Andrena can entirely live on nectar (and pollen) of oil tea and are able to metabolize these galactose derivatives. We present the first next-generation genomes for five and one Andrena species that are respectively specialized and non-specialized oil-tea pollinators, and combining with published genomes of six other Andrena species which did not visit oil-tea, we performed molecular evolution analyses on genes involved in metabolism of galactose derivatives. Six genes (NAGA, NAGA-like, galM, galK, galT, and galE) involved in galactose derivatives metabolism were identified in the five oil-tea specialized species, but only five (with the exception of NAGA-like) were discovered in the other Andrena species. Molecular evolution analyses revealed that NAGA-like, galK and galT in oil-tea specialized species appeared under positive selection. RNASeq analyses showed that NAGA-like, galK, and galT were significantly up-regulated in the specialized pollinator A. camellia compared to the non-specialized pollinator A. chekiangensis. Our study demonstrated that the genes NAGA-like, galK, and galT had played an important role in the evolutionary adaptation of the oil-tea specialized Andrena species.

Meiotic crossovers/chiasmata are not randomly distributed and strictly controlled. The mechanisms behind COs patterning remain largely unknown. In many species COs predominantly occur in the distal 2/3 of the chromosome arm and suppression of COs is observed in the proximal regions. The exceptions are some species, among which Allium fistulosum has strictly localized COs in the proximal region. The ability to manipulate the COs localization can be useful for onion breeding. We investigated the factors that may contribute to the pattern of COs in two closely related onion species A. cepa and A. fistulosum, which differ significantly in the localization of chiasmata, and their F1 diploid and triploid hybrids in pollen mother cells. We demonstrate a significant shift in the COs localization to the distal and interstitial region in F1 triploid hybrid, which has a complete diploid set of A. fistulosum chromosomes and haploid set of A. cepa chromosomes. This observation points to a possible genetic control of COs distribution. We did not find the differences in the assembly and disassembly of ASY1 and ZYP1 between A. cepa and A. fistulosum while the difference between parental species and their hybrids was observed. In diploid F1 hybrids at pachytene the chromosome pairing delay marked by ASY1 was revealed. Immunolocalization of MLH1, a marker for class I of the interference-dependent COs, and MUS81, a marker for class II of the interference-free COs, and mlh1/mus81 gene expression profiling in different stages of meiosis showed a spatiotemporal asymmetry among A. cepa, A. fistulosum and their diploid and triploid F1 hybrids. Our results support the hypothesis of genetic control of CO distribution as one of the players that affect meiotic recombination and exchange of genomic material.

There is evidence of constitutional rank in Chile, and not only a sectoral rank, to estimate that the regulation of digital media is in an initial and insufficient phase to properly protect information pluralism as political pluralism. The study aims to investigate the forms of concentration, such as the communicational flow of digital media, to determine the opportunities and information defects of these media due to regulatory deficiencies in this sector. Data collection will be carried out through a qualitative and quantitative methodology. The prospect of the imminent constituent process in Chile provides the opportunity to the evaluate the possibilities to propose changes not only at the legislative level but also at the constitutional level, which are likely to benefit freedom of expression with greater guarantees to such as the pluralism of digital media. The latter also means assessing the relevance of enshrining the right to communication in the future.

Shock waves, as used in medicine, can induce cell permeabilization, genetically transforming filamentous fungi; however, little is known on the interaction of shock waves with the cell wall. Because of this, the selection of parameters has been empirical. We studied the influence of shock waves on the germination of Aspergillus niger, to understand their effect on the modulation of four genes related to the growth of conidia. Parameters were varied in the range reported in protocols for genetic transformation. Vials containing conidia in suspension were exposed to either 50, 100 or 200 single-pulse or tandem shock waves, with different peak pressures (approximately 42, 66 and 83 MPa). In the tandem mode, three delays were tested. To equalize the total energy, the number of tandem “events” was halved compared to the number of single-pulse shock waves. Our results demonstrate that shock waves do not generate severe cellular effects on the viability and germination of A. niger conidia. Nevertheless, increase in the aggressiveness of the treatment induced a modification in the four genes tested. Scanning electron microscopy revealed significant changes to the cell wall of the conidia. Under optimized conditions, shock waves could be used for several biotechnological applications, surpassing conventional techniques.

Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse Foot and Mouth Disease (FMD) Virus (FMDV) strains. Among seven distinct serotypes, only serotype O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse subtypes of FMDV serotype O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for FMDV serotypes O and A circulating in Bangladesh and surrounding territories.