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ARTICLE | doi:10.20944/preprints202306.0357.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Cardiomyopathy; myosin RLC; myosin ELC; N-terminal protein modification, S15D-RLC phosphomimetic, super-relaxed state (SRX); Tg mice
Online: 5 June 2023 (16:43:56 CEST)
This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for the mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in myosin essential (ELC) or regulatory (RLC) light chains. S15D-RLC phosphomimetic was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared to those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM=treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.
ARTICLE | doi:10.20944/preprints202306.0310.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: exercise training; aortic stenosis; heart failure; isolated papillary muscle; isolated cardiomyocyte; calcium handling.
Online: 5 June 2023 (10:47:28 CEST)
Aerobic exercise training (AET) has been used in the management of heart disease. AET may, totally or partially, restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis. The objective of this study was to evaluate the effects of AET on calcium handling and cardiac function in rats with heart failure due to aortic stenosis. Wistar rats were distributed into two groups: control (Sham; n= 61) and aortic stenosis (AoS; n= 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. Echocardiogram, isolated papillary muscle, and isolated cardiomyocyte analyzed cardiac function. During isolated papillary muscle assay and isolated cardimyocyte was evaluated Ca2+. The expression of regulatory proteins of diastolic Ca2+ was analyzed via Western Blot. AET attenuated the diastolic dysfunction and benefited the systolic function. AoS-ET animals presented better response to post-rest contraction, and SERCA2a and L-type Ca2+ channels blocked than the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented alteration in the protein expression of the SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity, improved the cellular Ca2+ influx mechanism, and increased myofilament responsiveness to Ca2+, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with aortic stenosis and heart failure.
Fri, 2 June 2023
BRIEF REPORT | doi:10.20944/preprints202306.0164.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: biofilms; bioelectric effect; electrolysis; plaque index; gingival index
Online: 2 June 2023 (09:48:55 CEST)
Bioelectric effect is known as combinatorial biofilm treatment with low dose of antibiotics with small electricity. When external electric field or current are applied, biofilms can be affected by the electrostatic force, non-uniform distribution of essential electrolytes, induction of low activity of enzyme, and increase of permeability of biofilms. In this work, we have focused on the reduction of applied electric power consumption that could avoid water electrolysis which was one of major challenges for biomedical applications. We have developed a new type of electrical signal that enhances the efficacy of biofilm removal. The results show combination of alternating and direct current remove biofilm effectively without causing electrolysis. We further developed an oral healthcare device as a bioelectric toothbrush and tested in dental clinic. The results demonstrated 75% reduction of gingivitis. In addition, we have tested a mimicked air conditioner biofilms that are root causes of aerobic hygiene infection. The result demonstrates 81.8% increased biofilm removal. In conclusion, a new bioelectric technology has been developed and demonstrated the biofilm removal efficacy without the electrolysis.
Thu, 1 June 2023
ARTICLE | doi:10.20944/preprints202306.0031.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: cancer; pancreatic cancer; CWA; APTT; sTF/FIXa; thrombin time
Online: 1 June 2023 (04:53:42 CEST)
Background: The patients with cancer, especially pancreas cancer, are frequently associated with thrombosis which is one of causes for poor outcome, and hypercoagulability exists in cancer patients. Hypercoagulability is considered to be caused by thrombin burst. Methods: Activated partial thromboplastin time (APTT), small amount of tissue factor induced FIX activation (sTF/FIXa) assays and thrombin time (TT) using clot waveform analysis (CWA) were performed in 138 patients with malignant neoplasm including pancreas cancer and 66 non-cancer patients. Results: Thrombosis was frequently associated in pancreas cancer and was observed in stage I. CWA-APTT showed that the peak times and heights were markedly long and heigh, respectively, in cancer patients, and the peak times were significantly longer in pancreas cancer patients than benign pancreas diseases, and the 1st DPH was significantly higher in pancreas cancers than other cancers or benign pancreas diseases. CWA-sTF/FIXa showed that the peak times and heights were longer and higher, respectively, in patients with cancer than those without cancers, and that the 1st DPH was significantly higher in pancreas cancers than in other cancers. CWA-TT showed that the peak times were significantly shorter in cancer patients than in healthy volunteers and that the peak heights were significantly higher in cancer than in benign pancreas diseases. Conclusions: Cancer patients including pancreas cancer were frequently associated with thrombosis due to hypercoagulability with thrombin burst detected by CWA.
REVIEW | doi:10.20944/preprints202306.0009.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: endometrium; endometriosis; epithelial-mesenchymal transition; EMT; claudins; keratins
Online: 1 June 2023 (03:10:51 CEST)
In the pathogenesis of endometriosis, the differences between the eutopic and ectopic endometrium as well as between the eutopic endometrium with and without endometriosis are repeatedly pointed out. Various mechanisms have been suggested to explain these changes among them epithelial-mesenchymal transition (EMT). Recently, we suggested based on immunohistochemical data that most of the changes occur after and not before implantation of endometrial cells into ectopic locations. Furthermore, the subtle changes between eutopic endometrium with and without endometriosis and maintenance of epithelial cell-to cell contacts only suggest a partial EMT. In this study, we have re-analyzed the mRNA expression array data of eutopic and ectopic endometrium with respect to expression changes and EMT. Especially, we found that the similarity between eutopic endometrium with and without endometriosis is extremely high (~99.1%). In contrast, eutopic endometrium compared to ectopic endometrium only shows an overall similarity of ~95.3%. Analysis of some EMT-associated genes revealed small differences in the mRNA expression levels of some members of the claudin family. The array data suggest that the changes in eutopic endometrium at the beginning of the disease are quite subtle and that the majority of differences occur after implantation into ectopic locations.
Wed, 31 May 2023
ARTICLE | doi:10.20944/preprints202305.2231.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Lobosphaera; attached cultivation; antibiotics; bioremoval, arachidonic acid
Online: 31 May 2023 (11:00:11 CEST)
Pharmaceuticals including antibiotics are among hazardous micropollutants (HMP) of the environment. Incomplete degradation of the HMP leads to their persistence in water bodies causing a plethora of deleterious effects. Conventional wastewater treatment cannot remove HMP completely, and a promising alternative is comprised by biotechnologies based on microalgae. The use of immobilized microalgae in environmental biotechnology is advantageous since immobilized cultures allow recycling of the microalgal cells, support higher cell densities, and boost tolerance of microalgae to stresses including HMP. Here we report on a comparative study of HMP (exemplified by the antibiotic ceftriaxone) removal by suspended and chitosan-immobilized cells of Lobosphaera sp. IPPAS C-2047 unialgal culture. We also monitored the dynamics of photosynthetic pigments content and the physiological condition of the cells as reflected by the activity of their photosynthetic apparatus. Special attention was paid to the changes in the accumulation of valuable arachidonic acid (C20:4). In addition to this, we followed the changes in the culture microbiome induced the antibiotic exposure. Collectively, our results showed that both suspended and immobilized cultures took up ceftriaxone from the culture medium. In the case of immobilized culture, a significant amount of the antibiotic was adsorbed on the chitosan carrier itself. The dynamics of the taxonomic composition of the microbiome of the microalgae was more shifted by the immobilization on the chitosan than by exposure to 20 mg/L of ceftriaxone. The possibility and limitations of the using of chitosan-immobilized Lobosphaera sp. IPPAS C-2047 for HMP removal coupled with the production of valuable long-chain polyunsaturated fatty acids is discussed.
Tue, 30 May 2023
ARTICLE | doi:10.20944/preprints202305.2031.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Kpètè Kpètè; microbiological contaminant; Enterobacteria; resistance genes; Staphylococcus spp
Online: 30 May 2023 (04:02:20 CEST)
This study aimed to determine the pathogenicity of the bacteria isolated and characterized from the kpètè kpètè used to produce two fermented beers in Benin. Species were identified by specific biochemical tests such as catalase, coagulase, and API 20 E. Antibiotic sensitivity was tested according to the French Society of Microbiology Antibiogram Committee. The crystal violet microplate technique and conventional PCR evaluated biofilm production to identify genes encoding virulence and macrolide resistance. Our data shows that Kpètè Kpètè used to produce beers are contaminated by Enterobacteriaceae species (Klebsiella terrigena, Enterobacter aerogens, Providencia rettgeri, Chryseomonas luteola, Serratia rubidae, and Enterobacter cloacae) and Staphylococcus spp. These multidrug-resistant strains can produce biofilms with a strong predominance of Enterobacter aerogens, Klebsiella terrigena (100%), and Staphylococcus spp (60%). Enterobacter cloacae (4%) and Coagulase negative Staphylococcus (5.55%) harbor the macrolide resistance gene. For other strains, these genes were not detected. Foods contaminated with bacteria resistant to antibiotics and carrying a virulence gene could constitute a potential public health problem. There is a need to increase awareness campaigns on hygiene rules in preparing and selling these traditional beers.
Mon, 29 May 2023
ARTICLE | doi:10.20944/preprints202305.2008.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: endogenously produced methane; reactive oxygen species; methyl radicals; dimethyl sulfoxide; methyl donors; stable carbon and hydrogen isotope labelling; oxidative stress; antioxidant defense system
Online: 29 May 2023 (10:27:42 CEST)
Methane (CH4), produced endogenously in animals and plants, has recently been suggested to play a role in cellular physiology, potentially influencing the signaling pathways and regulatory mechanisms involved in nitrosative and oxidative stress responses. In addition, it has been proposed that supplementation of CH4 to organisms may be beneficial for the treatment of several diseases, including ischemia, reperfusion injury, and inflammation. However, it is still unclear if and how CH4 is produced in mammalian cells without the help of microorganisms, and how CH4 might be involved in physiological processes in humans. In this study, we provide first proof of the principle that CH4 is formed non-microbially in the human body by applying isotopically labeled methylated sulfur compounds, such as dimethyl sulfoxide (DMSO) and methionine, as carbon precursors to confirm cellular CH4 formation. A volunteer applied isotopically labeled (2H and 13C) DMSO on the skin, orally, and to blood samples. Monitoring of stable isotope values of CH4 convincingly showed the conversion of the methyl groups, as isotopically labeled CH4 was formed during all experiments. Based on these results, we consider several hypotheses about endogenously formed CH4 in humans, including physiological aspects and stress responses involving reactive oxygen species (ROS). While further and broader validation studies are needed, the results may unambiguously serve as a proof of concept for the endoge-nous formation of CH4 in humans by a radical-driven process. Furthermore, these results might encourage follow up studies to decipher the potential physiological role of CH4 and its bioactiv-ity in humans in more detail. Of particular importance is the potential to monitor CH4 as an ox-idative stress biomarker if the observed large variability of CH4 in breath air is an indicator for physiological stress responses and immune reactions. Finally, the potential role of DMSO as a radical scavenger to counteract oxidative stress caused by ROS might be considered in the health sciences. DMSO has already been investigated for many years, but its potential positive role for medical use remained highly uncertain.
ARTICLE | doi:10.20944/preprints202305.1964.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: 3D printing; silver nanoparticles; titanium dioxide; hydrogels; antimicrobial activity
Online: 29 May 2023 (04:41:53 CEST)
Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO2) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young’s modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus Aureus and Pseudomonas Aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram– bacteria of AgNPs and TiO2 agents embedded in the CH or ALG macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/ml). The biocompatibility of chitosan was widely demonstrated by cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/ml concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with AgNPs concentration of 100 µg/ml. In conclusions, the 3D printed dressings here developed own the features to be cheap, highly defined, easy to be manufactured and further applied in personalized antimicrobial medicine applications.
Fri, 26 May 2023
ARTICLE | doi:10.20944/preprints202305.1881.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Euphorbia ingens; Anticancer; Antiproliferative; Prostate Cancer; Network Pharmacology; Phyto-chemicals; Mechanism of action; Molecular targets
Online: 26 May 2023 (07:46:44 CEST)
Euphorbia ingens is traditionally used to treat and manage cancer in Ambeere community of Embu County in Kenya. Whilst research has demonstrated the bioactivities of E. ingens including antimicrobial, antitubercular and antifungal activities, scientific validation of its anticancer properties is limited. This study evaluated the antiproliferative potentials of E. ingens on human prostate cancer cell line (DU-145). The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was used to assess the antiproliferative activity, chemical constituents were analysed by qualitative colour method and Gas Chromatography-Mass Spectrometry analysis. At the same time, the investigation of putative molecular targets and mechanisms of action of E. ingens was done through network pharmacological analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was carried out to validate the network predictions of putative targets. Our result showed E. ingens ethyl acetate inhibited DU-145 growth (IC50 of 9.71 ± 0.4 µg/ml) with a high selectivity index of 8.26. There was the presence of phenols, terpenoids, flavonoids, tannins, sterols, and saponins; additional 18 compounds were identified by the GC-MS approach. ESR1, IL6, MMP9, CDK2, MAP2K1, AR, PRKCD, CDK1, CDC25B, and JAK2 were indicated as key targets of E. ingens against prostate cancer with the PI3K-AKT, MAPK, and p53 signalling pathways identified as the most probable mechanisms of action. There was significant downregulation of AR and BCL2, and upregulation of p53 and caspase-3 in E. ingens-treated DU-145 cells compared to 0.2 % DMSO negative control. Our results suggest that E. ingens has phytochemical compounds efficacious at inhibiting the proliferation of DU-145 cells; therefore, the plant can be considered a potential source of compounds that may be used to manage and treat prostate cancer; however, further in vivo evaluations are needed.
ARTICLE | doi:10.20944/preprints202305.1819.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Fucus vesiculosus; proteomics; metabolomics; NPC1; Caco-2 cell line
Online: 26 May 2023 (02:46:45 CEST)
High blood cholesterol levels are one of the main risks for atherosclerotic disease. A purified aqueous extract of Fucus vesiculosus, characterized as rich in phlorotannins and peptides, was described as having the capacity to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells metabolites and proteins was analysed, aiming to expand the knowledge about its mode of action targeting cholesterol metabolism, in particular exogenous cholesterol absorption and transport. Caco-2 cells differentiated into enterocytes were exposed to the purified aqueous extract of F. vesiculosus and analysed by undirected metabolomics and proteomics. The results of the metabolomic analysis showed only statistically significant differences in glutathione content of the cells exposed to the extract relatively to the control cells, with a decreased glutathione expression in exposed cells. The proteomic analysis showed an increased expression for cells exposed to the extract of NPC1, an important protein known to be involved in cholesterol transport. To extent of our knowledge this is the first study using untargeted metabolomics and proteomic analysis to study the effect of F. vesiculosus on differentiated Caco-2 cells, which aims to provide some insight about the molecular mechanism of extract compounds on intestinal cells.
Wed, 24 May 2023
REVIEW | doi:10.20944/preprints202305.1708.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Cytoplasmic membrane homeostasis; Pathogenicity; Pathogenic fungi; Membrane lipid metabolism; Membrane curvature; Transmembrane protein; Cell wall components; Cytoskeleton; Growth and development; Host infection
Online: 24 May 2023 (10:38:22 CEST)
The cytoplasmic membrane is the fundamental component of all living cells, which participates in various physiological processes, such as material exchange, stress response, cell recognition, signal transduction, cellular immunity, apoptosis, pathogenicity, etc. The normal function of a cytoplasmic membrane requires stable organization of transmembrane protein-lipid microdomains, transmembrane protein-cell wall microdomains, and cytoskeleton-transmembrane protein microdomains. Here, we review the mechanisms and functions of various membrane lipid components, fatty acid content and saturation, membrane curvature, and cell wall and cytoskeleton in plasma membrane homeostasis affecting the pathogenicity of pathogenic fungi. Pathogenic fungi maintains plasma membrane homeostasis and contributes to fungal virulence by maintaining plasma membrane assembly, structural and functional integrity of pathogenic fungi at various stages of cell development through interactions among lipid components of cytoplasmic membranes, transmembrane proteins, cytoskeleton and cell wall components, etc.
ARTICLE | doi:10.20944/preprints202305.1698.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Cancer; Aggressiveness; Mitochondria; Acadvl; Fatty acid beta oxidation; Biomarker; Proteomics; Malignant mesothelioma
Online: 24 May 2023 (05:06:41 CEST)
Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.
Tue, 23 May 2023
ARTICLE | doi:10.20944/preprints202305.1642.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: melanoma 1; keyword 2; leukemia 3; medicinal plants 4; anthracene 5; caspase 6
Online: 23 May 2023 (10:44:52 CEST)
Cancer is a complex disease, considered a major public health problem worldwide. Among the types of cancer, melanoma, and leukemias present high mortality rates in Brazil and worldwide. Currently, conventional cytotoxic treatments cause severe side effects by the non-selectivity between normal cells and cancer cells. Therefore, molecules of natural origin with more efficient anticancer properties and that present fewer adverse effects are of extreme importance for cancer therapy and improvement in patients’ quality of life. This study isolated, identified, and characterized the chemical structure of a new anthraquinone present in the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by NMR. Subsequently, their cytotoxic activity was evaluated by the MTT method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. By flow cytometry technique, the apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2'-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2'-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and CA+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed-cell death pathways induced by 2'-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2'-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.
ARTICLE | doi:10.20944/preprints202305.1613.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Origanum onites L.; natural products; liposomes; antioxidant activity; mice
Online: 23 May 2023 (08:09:49 CEST)
In the present study the effects of Origanum onites L. extract and essential oil of O. onites L. on the antioxidant status of the liver and brain of mice were investigated. Due to certain disadvantages of essential oils, such as poor solubility, high volatility, sensitivity to UV light and heat, formulation of liposomes with Oregano essentials (OE) was optimized and used in this study. The results demonstrated that the best composition of the lipid carriers and Oregano essentials were conducted in terms of the PDI, mean particle size and EE. The LE4 formulation contained Lipoid S100 of 45 mg, Lipoid S75 of 45 mg and 90 mg of EO. The administration of O. onites L. extract to mice for 21 days significantly decreased glutathione (GSH) level in the liver and brain of mouse as well as malondialdehyde (MDA) concentration in the liver. In the brain of mice MDA level significantly increased after this extract consumption. Whereas liposomes with OE significantly decreased GSH concentration in mouse brain and MDA concentration in mouse liver but increased (p>0.05) GSH level in liver and MDA concentration in brain of mice compared with the control group. It was investigated that both, O. onites L. extract as well as liposomes with OE of this plant material make changes in the antioxidant status in the liver and brain of mice.
Fri, 19 May 2023
REVIEW | doi:10.20944/preprints202305.1357.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: ROS; TRP; inflammation
Online: 19 May 2023 (02:09:34 CEST)
The channels from the superfamily of transient receptor potential (TRP) activated by reactive oxygen species (ROS) are defined as redox channels. Those with the best exposure of the cysteine residues and hence the most sensitive to oxidative stress are TRPC4, TRPC5, TRPV1, TRPV4, and TRPA1, while others, such as TRPM2 and TRPM7 are indirectly activated by ROS. Activation by ROS has different effects on the tumorigenic process: some TRP channels may, upon activation, stimulate proliferation, apoptosis, or migration of cancer cells, while others inhibit these processes, depending on the cancer type, tumoral microenvironment and finally on the methods used for evaluation. Therefore, the use of these polymodal proteins as therapeutic targets is still an unmet need, despite their draggability and modulation by simple and mostly unharmful compounds. In this review, we intend to create some cellular models of the interaction between oxidative stress, TRP channels, and inflammation. Although the crosstalk between the three actors is rather theoretical, we intended to gather the recently published data and proposed pathways of cancer inhibition using modulators of TRP proteins, hoping that the experimental data corroborated with clinical information may finally bring the results from the bench to the bedside.
Thu, 18 May 2023
ARTICLE | doi:10.20944/preprints202305.1351.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Euterpe oleracea Mart; Polyphenols; Apoptosis; Autophagy; Annexin A2
Online: 18 May 2023 (14:41:35 CEST)
Açaí, Euterpe oleracea Mart. is a native plant from the Amazonian and is rich in several phyto-chemicals with anti-tumor activities. The aim was to analyze the effects of açaí seed oil on colo-rectal adenocarcinoma (ADC) cells. In vitro analyses were performed on CACO-2, HCT-116, and HT-29 cell lines. The strains were treated with açaí seed oil for 24, 48, and 72 h, and cell viability, death, and morphology were analyzed. Molecular docking was performed to evaluate the inter-action between the major compounds in açaí seed oil and Annexin A2. The viability assay showed the cytotoxic effect of the oil in colorectal adenocarcinoma cells. Acai seed oil induced increased apoptosis in CACO-2 and HCT-116 cells and interfered with the cell cycle. Western blotting showed increased expression of LC3-B, suggestive of autophagy, and annexin A2, an apoptosis regulatory protein. Molecular docking confirmed the interaction of major fatty acids with annexin A2, suggesting a role of açaí seed oil in modulating annexin A2 expression in these cancer cell lines. Our results suggest the antitumor potential of açaí seed oil in colorectal adeno-carcinoma cells and contribute to the development of an active drug from a known natural product.
ARTICLE | doi:10.20944/preprints202305.1304.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: drug resistance; cisplatin; arsenic; tumor microenvironment; microRNA; molecular pathway network
Online: 18 May 2023 (08:41:46 CEST)
To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.
COMMUNICATION | doi:10.20944/preprints202305.1298.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Mass spectrometry; RAS; ACE; ACE2; CPN; bradykinin; hypertension; cardiovascular disease; antihypertensiva; ACE inhibitors; angiotensin receptor blockers; bradykinin; neuropeptide re-porter assay
Online: 18 May 2023 (08:13:10 CEST)
(1) Background: Co-morbidities such as hypertension and cardiovascular disease are major risk factors for severe COVID-19. The renin-angiotensin-system (RAS) is critically involved in their pathophysiology and is counterbalanced by both angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and the kallikrein-kinin-system (KKS). Considerable research interest with respect to COVID-19 treatment is, thus, currently directed towards the components of these systems. In an earlier study, we noticed significantly reduced carboxypeptidase N (CPN, KKS member) activity and partially excessive angiotensin-converting enzyme (ACE, RAS member) activity in the sera of both hospitalized (HoP) COVID-19 patients and a sub-group of covalescent patients, while in the majority of the probands recovering from the disease these values had returned to normal. The data had been obtained using bradykinin (BK) as a reporter peptide, which is a target of both CPN and ACE, and they were supplemented by serum proteomics of the same patient cohort. We hypothesized that the data could be indicative of Long COVID, which had not been fully appreciated at the time of our study.; (2) Methods: The data were re-evaluated in the light of Long COVID. The recent literature on the RAS in COVID-19, antihypertensiva, and Long COVID was briefly reviewed.; (3) Results: While the levels of the BK serum degradation products should return to normal concentrations during convalescence, this was not true for some patients. This could be due to persisting liver problems, because CPN is synthesized there, but also to a dysregulated RAS. This was not reflected in the levels of selected RAS/KKS serum proteins like angiotensinogen (AGT), although AGT correlated with disease severity in HoP. However, standard tests in routine patient care in Long COVID often come back normal, and it may be that BK degradation is specific in some pathophysiologies. Moreover, the HoP group was sub-divided based on the serum protein profiles and COVID-19 severity.; (4) Conclusions: We point out two insights: 1) Sensitive technology such as omics methods might provide unexpected significant differences within the pre-defined patient groups of a clinical study. Those can only be explored, if the cohorts are large enough and properly matched with respect to the parameters known beforehand (e.g., age, gender, co-morbidities). 2) Results of the BK-reporter serum protease activity assay could be indicative of persisting liver problems and/or potentially of Long COVID. Clinical studies are required to test this hypothesis.
REVIEW | doi:10.20944/preprints202305.1293.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: spatial proteomics; spatial resolution; temporal resolution; super-resolution microscopy; fluorescence microscopy,
Online: 18 May 2023 (07:54:20 CEST)
Dawn of the omics revolution in biological sciences meant that we seek to understand more and in greater detail the molecular constituents of cells and biological systems. While we have gained significant insights from conventional omics tools, we now seek to understand the spatial dimensions of the data where subcellular localisation may impact on cellular physiology and phenotype. This review paper seeks to address current questions in the new field of image-based spatial proteomics as well as outline future challenges of the field. At first glance, spatial proteomics offers enormous potential to expand our understanding of different cell types in different disease and cell states. But limitations in types of fluorophores and issues with spectral overlap significantly hampers the practical implementation of the technique. On the other hand, while we have super-resolution microscopy techniques such as STED, PALM and STORM able to achieve 10 to 20 nm spatial resolution in single molecule localisation, problems with slow image acquisition limits high temporal resolution tracking of multiple protein targets in live cell imaging. Hence, the field of spatial proteomics is a mix of promises and challenges where we could image, in multi-colour, upwards of 10 well-chosen proteins that could inform on the molecular mechanisms of selected biological processes, but, at present, the method could not tackle larger scale questions. In essence, current implementation of image-based spatial proteomics is useful, but it is unable to fulfil the mission of large-scale projects such as the Human Protein Atlas or Human Cell Atlas. Future challenges in the field includes the development of more fluorophores (especially photoswitchable and photoactivable ones) for single molecule localisation microscopy, as well as seeking to improve temporal resolutions to the sub-millisecond range.
Wed, 17 May 2023
REVIEW | doi:10.20944/preprints202305.1258.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: acute myeloid leukemia; genetic classification; mutational profiling; transcriptome analysis; prognostic stratification; clonal evolution
Online: 17 May 2023 (14:36:39 CEST)
The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. AML with mutated Nucleophosmin1 (NPM1-mut) is the largest of the genetically defined groups, involving about 30% of adult AMLs and is currently recognized as a distinct entity in the actual AML classifications. NPM1-mut AML usually occurs in de novo AML and is associated predominantly with a normal karyotype and relatively favorable prognosis. However, NPM1-mut AMLs are genetically, transcriptionally, and phenotypically heterogeneous. Furthermore, NPM1-mut is a clinically heterogenous group. Recent studies have in part clarified the consistent heterogeneities of these AMLs and have strongly supported the need for an additional stratification aiming to improve the therapeutic response of the different subgroups of NPM1-mut AML patients.
Tue, 16 May 2023
ARTICLE | doi:10.20944/preprints202305.1124.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: docking; binding free energy; pharmacophore; KPLS; QSAR; alkylhydrazide; histone deacetylases (HDAC)
Online: 16 May 2023 (08:26:45 CEST)
Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.
REVIEW | doi:10.20944/preprints202305.1106.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: photothermal-antimicrobials; antibacterial mechanisms; anti-biofilm; wound healing
Online: 16 May 2023 (05:40:58 CEST)
Rapid developing antimicrobial resistance due to broad antibiotic utilisation in healthcare and food industries and the non-availability of novel antibiotics represents one of the most critical public health issues worldwide. The current advances in nanotechnology allow new materials to address drug-resistant bacterial infections in specific, focused and biologically safe ways. The unique physicochemical properties, biocompatibility, and wide range of adaptability of nanomaterials that exhibit photothermal capability can be employed to develop the next generation of photothermally induced controllable hyperthermia as antibacterial nanoplatforms. Here, we review the current state-of-the-art in different functional classes of photothermal antibacterial nanomaterials and the strategies to optimise antimicrobial efficiency. The recent achievements and trends in developing photothermally active nanostructures, including plasmonic metals, semiconductor, carbon-based, and organic photothermal polymers, and antibacterial mechanisms of action, including anti-multidrug resistant bacteria and biofilms removal, will be discussed. Insights into mechanisms of the photothermal effect and various factors influencing photothermal antimicrobial performance, emphasising the structure–performance relationship, are discussed. We will examine the photothermal agents’ functionalisation for specific bacteria, effects of near-infrared light irradiation spectrum, or active photothermal materials for multimodal synergistic-based therapies to minimise side effects and maintain low cost. Most relevant applications are presented, such as anti-biofilm formation, biofilm penetration or ablation, and nanomaterial-based infected wound therapy. Practical antibacterial applications employing the photothermal antimicrobial agents, alone or in synergistic combination with other nanomaterials, are considered. Existing challenges and limitations in photothermal antimicrobial therapy and future perspectives are presented from the structure, function, safety, and clinical potential points of view.
Mon, 15 May 2023
ARTICLE | doi:10.20944/preprints202305.1028.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: ozonated sunflower oil, OSO; antioxidant; dyslipidemia; high-cholesterol diet, HCD; zebrafish; zebrafish embryo; carboxymethyllysine, CML
Online: 15 May 2023 (10:42:45 CEST)
Ozonated sunflower oil (OSO) is well known functional oil with its antioxidant, antimi-crobial, anti-allergic, and skin-moisturizing properties. However, studies on the effects of OSO on high-cholesterol diet (HCD)-induced metabolic disorders have been scarce. In the current study, we aimed to determine the anti-inflammatory effects of OSO on lipid me-tabolism in adult hypercholesterolemic zebrafish and its embryo. Microinjection of OSO (final 2%, 10 nL) into zebrafish embryos under presence of carboxymethyllysine (CML, 500 ng) protected acute embryo death upto 61% survival, while sunflower oil (final 2%) showed much less protection around 42% survival. The microinjection of OSO was more effective than SO to inhibit reactive oxygen species (ROS) production and apoptosis in the CML induced embryo toxicity. Intraperitoneal injection of OSO under presence of CML protected acute death from CML-induced neurotoxicity with improved hepatic inflamma-tion, less detection of ROS and interleukin (IL)-6, and lowering blood total cholesterol (TC) and triglyceride (TG), while SO-injected group did not protect the CML-toxicity. Long-term supplementation of OSO (final 20%, wt/wt) with HCD for 6 months resulted higher sur-vivability than HCD alone group or HCD+SO group (final 20%, wt/wt) with significant lowering of plasma TC and TG levels. The HCD+OSO group showed the least hepatic in-flammation, fatty liver change, ROS, and IL-6 production. In conclusion, short-term treat-ment of OSO by injection exhibited potent anti-inflammatory activity against acute neuro-toxicity of CML in zebrafish and its embryo. Long-term supplementation of OSO in diet also revealed the highest survivability and blood lipid-lowering effect through potent an-ti-oxidant and anti-inflammatory activity.
ARTICLE | doi:10.20944/preprints202305.0987.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Maximum Entropy; species distribution model; ground validation; endemic; tree-frog; Protected Area; Biodiversity Hotspot
Online: 15 May 2023 (07:19:47 CEST)
Conservation of tropical endemic amphibians largely suffers from Wallacean shortfall, a gap to which predictive species distribution models have contributed significantly to bridge by delineating probable distribution and the underlying suitable habitat within their distributional range. However, rarely is a prediction model ground-truthed to evaluate their predictive performance. Here we present a species distribution modeling approach using maximum entropy algorithm corrected for smaller sample size, in guiding explorative surveys aimed at optimizing survey effort and discovering unrecorded populations of Zhangixalus suffry, a rhacophorid tree-frog endemic to the northeastern part of the Indian subcontinent along with the factors limiting their distribution. With only 16 established historical locality data to model for (after spatial thinning to reduce autocorrelation) and a set of environmental predictors (climatic, topographic, and landscape composition), our model prediction enabled the successful discovery of seven new population records from unreported landscapes, extending its southernmost distributional limit over a considerable distance. The final composite distribution model combining all the locality records (n=23) predicted similar core areas of suitable habitat consistent with the known geographic distribution of the species but showed poor representation under existing coverage of Protected Area (PA) network in the Region with only 7% representation of suitable habitat under protection. Habitat suitability of a site was significantly governed by factors related to precipitation (precipitation seasonality and precipitation of the warmest quarter) and topographic factors that can influence it (elevation and aspect). This corroborates with the known ecology of Rhacophorid frogs, especially concerning their seasonal explosive reproductive strategy and foam nest-building behavior.Through this study, we propose explorative surveys guided by species distribution models to expedite unknown population discovery of rare, tropical endemic amphibians and using such taxa as surrogates in identifying conservation priority zones that can be directly applied to reserve design and conservation and management planning.
Fri, 12 May 2023
REVIEW | doi:10.20944/preprints202305.0893.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: lncRNAs; non-coding RNAs; lung cancer; metastasis; biomarkers; therapy resistance
Online: 12 May 2023 (05:24:56 CEST)
Long non-coding RNAs (LncRNAs) are mRNA-like molecules that do not encode for proteins and that are longer than 200 nucleotides. LncRNAs play important biological roles in normal cell physiology and organism development. Therefore, deregulation of their activities is involved in disease processes such as cancer. Lung cancer is the leading cause of cancer-related deaths due to late stage at diagnosis, distant metastasis, and high rates of therapeutic failure. LncRNAs are emerging as important molecules in lung cancer for their oncogenic or tumor suppressive functions. LncRNAs are highly stable in circulation, presenting an opportunity for use as non-invasive and early-stage cancer diagnostic tools. Here, we summarize latest works providing in vivo evidence available for LncRNAs role in cancer development, therapy-induced resistance, and their potential as biomarkers for diagnosis and prognosis, with a focus on lung cancer. Additionally, we discuss current therapeutic approaches to target LncRNAs. The evidence discussed here strongly suggests that investigation of LncRNAs in lung cancer in addition to protein-coding genes will provide a holistic view of molecular mechanisms of cancer initiation, development, and progression, and could open a new avenue for cancer treatment.
ARTICLE | doi:10.20944/preprints202305.0881.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Climate change; livestock farmers; rural livelihoods; climate education.
Online: 12 May 2023 (04:33:58 CEST)
Climate change mainly affects production and consumption systems, such as: food, livelihoods, production (e.g., reduced milk production), water, and land use. The role of local knowledge has been recognized as important for decision-making under changing circumstances. This study was conducted in the northern part of the Ecuadorian Andes using a sample of 170 dairy-cattle-producing households. The objectives were: i) to characterize the rural livelihoods of dairy cattle farmers, ii) to evaluate access to climate information and perceptions of climate change, and iii) to determine the relationship between livelihoods and perceptions of climate change. Significant differences were identified between the groups evaluated in relation to the dairy farmers’ livelihoods. In addition, 85.29% of the respondents mentioned that climate information is important, but 67.83% do not trust the sources of information. It was found that there is a significant relationship between the level of education and age with the variables of climate change perceptions. This combined knowledge allows people to promote agri-environmental and educational policies to achieve climate literacy at a rural level.
Thu, 11 May 2023
ARTICLE | doi:10.20944/preprints202305.0838.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Down syndrome [DS]; microbiome; dysbiosis; antibiotics; tetracycline; penicillin
Online: 11 May 2023 (10:04:00 CEST)
Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations the role of nutrients, vitamins, and in general, the foodborne associated background as part of the events leading ultimately to chromosome nondisjunction has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes, the possible association of DS development with maternal gut microbiota should require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa and hence, we might find associations between the use of different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N=30). Utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the prevalence of people living with DS estimated for 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.
ARTICLE | doi:10.20944/preprints202305.0787.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: entomophilous plants; phenophases; honeybee; climate change
Online: 11 May 2023 (04:47:30 CEST)
Changes in the dates of phenological phases of plants and insects reflect changes in climate. The aim of the study was to determine the phenological patterns and interrelationships of spring-flowering entomophilous plants (Corylus avellana L., Alnus incana Moench., Tussilago farfara L., Salix caprea L., Acer platanoides L., Taraxacum officinale L., Prunus L., Malus domestica Mill.) and the honey bee (Apis mellifera L.) in response to climate change. The research was carried out at Vokė Branch of the Institute of Agriculture, Lithuanian Research Centre for Agriculture and Forestry, using data from phenological observations during 1961–2020. The results of the studies showed that over a 60-year period, a trend towards earlier dates of all phenological events studied was observed. Significant and larger-scale changes occurred starting from the decade 1981–1990. Throughout the entire study period, with the exception of one decade, the dates of honeybee emergence on flowers correlated reliably with the dates of entomophilous plant phenophases. Due to the advance of plants phenophase dates the synchrony with honeybee emergence dates changes however, these changes had a positive effect on the foraging conditions of overwintering honeybees.
Wed, 10 May 2023
ARTICLE | doi:10.20944/preprints202305.0739.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: biomining; bioleaching; astrobiology; A. ferrooxidans; acidophiles; space biology; bibliometric network analysis
Online: 10 May 2023 (10:38:03 CEST)
Our understanding of the diversity of life on our planet and the possibility of finding or sustaining life elsewhere in the universe plays a central role in supporting human space settling and exploration. Astrobiology and its outcomes require a multidisciplinary and comprehensive approach, in which the microbial, geological, chemical, astronomical, and physical domains of research are interlinked. An example of the applications of astrobiology and space microbiology is the use of extremophiles for in-situ resource utilization through biomining and bioleaching. To better understand the multidisciplinary research landscape in this area, we have quantitatively reviewed the global scientific literature on astrobiology with a focus on biomining and bioleaching through bibliometric network analysis, investigating patterns and trends in its development over time. The network analysis of the keywords co-occurrence highlights different connecting and overlapping clusters, illustrating the multidisciplinary character of astrobiology. Temporal analyses show a recent focus on topics related to microbiology and geomicrobiology, emphasizing the role that these fields will play in future astrobiology research. In conclusion, astrobiology, biomining, and bioleaching research are timely responding to the identification of these techniques as tools for biotechnological applications, expected to play a crucial role in long-term human space exploration.
ARTICLE | doi:10.20944/preprints202305.0680.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Nonalcoholic Fatty Liver Disease; Golden Tomato; Red Tomato; Lepr; NFH4a; GK; lipid homeo-stasis; steatosis
Online: 10 May 2023 (04:01:08 CEST)
Abstract: Nonalcoholic fatty liver disease, characterized by the lipid accumulation within hepatocytes exceeding 5% of liver weight, is strictly related to metabolic disorders and to obesity and diabetes and represents a health emergency worldwide. Being not available any standard therapy for NAFLD, a key role is ascribed to lifestyle intervention including phytonutrient intake to prevent NAFLD development and progression. We have used a rat model of NAFLD to evaluate the effect of dietary supplementation with red tomato and golden tomato, patented mix of fruit with different degrees of ripeness, particularly rich in naringenin and chlorogenic acid, after steatosis development. We have assessed the ef-fects on body weight, metabolic profile, and hepatic steatosis and a correlation between the amelioration of all the parameters and the liver gene expression was evidenced. We found that the genes mainly up regulated by tomatoes administration were HNF4, Lepr and GK, able to condition metabolic homeostasis. Our results suggest that there is a role for red and golden tomatoes, dietary intake as a nutraceutical approach of NAFLD prevention and therapy.
Tue, 9 May 2023
REVIEW | doi:10.20944/preprints202305.0665.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: carbon monoxide; hemoglobin; carboxyhemoglobin; glutathione; antioxidant
Online: 9 May 2023 (13:36:14 CEST)
Carbon monoxide (CO) is a cytoprotective endogenous gas that is ubiquitously produced by the stress response enzyme heme-oxygenase. Being a gas, CO rapidly diffuses through tissues and binds to hemoglobin (Hb) increasing carboxyhemoglobin (COHb) levels. COHb can be formed in the erythrocytes or in plasma from cell-free Hb. Herein, it is discussed whether endogenous COHb is or is not an innocuous and inevitable metabolic waste product and it is hypothesized that COHb has a biological role. In the present review literature data is presented to support this hypothesis based on two main premises: (i) there is no direct correlation between COHb levels and CO toxicity; and (ii) COHb seems to have a direct cytoprotective and antioxidant role in erythrocytes and in hemorrhagic models in vivo. Moreover, CO is also antioxidant by generating COHb, which protects against the pro-oxidant damaging effects of cell free Hb. Up to now COHb has been considered as a sink for both exogenous and endogenous CO generated during CO intoxication or heme metabolism, respectively. Hallmarking COHb as an important molecule with a biological (and eventually beneficial) role is a turning point on CO Biology research, namely in CO intoxication and CO cytoprotection.
ARTICLE | doi:10.20944/preprints202305.0653.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: GDF15; Orthodontic tooth movement; Periodontal ligament fibroblasts; Osteoblast differentiation; Mechanobiological response; Inflammation; Osteoclast Activation
Online: 9 May 2023 (12:33:14 CEST)
Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including the regulation of local inflammation and activation of further bone-remodeling cells. Previous studies suggested the growth differentiation factor 15 (GDF15) as important pro-inflammatory regulator during the PdLFs mechanoresponse. However, the precise mechanism remains to be clarified, as GDF15 may act both intracrine and by receptor binding, potentially also in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we detected an altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLFs differentiation and their mechanoresponse.
REVIEW | doi:10.20944/preprints202305.0643.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Acute Wounds; Cellular Infiltrate; Chronic Wounds; Keloids; Scars
Online: 9 May 2023 (11:06:05 CEST)
Abstract: The purpose of this review is to summarize recent knowledge on the main processes that occur during wound healing, including the responses of various cell types and the molecular mechanisms involved. Particular attention is also dedicated to new therapies often involved in the resolution of wounds, whether acute or chronic. Awareness of these dynamics is important for the various professional figures who are confronted with these kinds of problem daily. However, the study of the healing mechanisms has yet to be defined in detail, in fact there are alterations of variously coordinated events which lead to a delayed resolution or, as in the case of keloids, to pathological states consisting in the excessive formation of scars with consequences yet to be seen. to define. Therefore, it is necessary to know the most feasible approaches and the most effective therapies.
Mon, 8 May 2023
ARTICLE | doi:10.20944/preprints202305.0528.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Botanicals; Sitophilus zeamais; Maize; Storage; Synthetic Pesticide; Pest; Efficacy
Online: 8 May 2023 (10:56:25 CEST)
The objective of this study was to compare the effect of different botanical powders and synthetic chemical in controlling Sitophilus zeamais in stored maize. A laboratory experiment was done to assess three botanicals, Zingiber officinale, Moringa oleifera, Xylopia aethiopica, in controlling the S. zeamais. The results of this study demonstrated the active potentials of these plant products as plant-derived insecticides against maize weevil. The synthetic chemical used showed both higher weevil mortality and higher grain loss than the botanicals (P< 0.05). The Botanicals also showed significance difference in the mortality rate (P < 0.05) as Z. officinale recorded the highest mortality rate (5.66%) while X. aethiopica recorded the lowest mortality rate (3.66%). The control attained the highest grain damage (7.33%) while amongst the botanicals, the highest was found in Z. officinale (7.33%) and lowest was on M. oliefera (5.33%). The exit holes made by the weevils at the end of the experiment were highest (2.66) in M. oliefera whereas lowest was recorded on X. aethiopica (1.00). Z. officinale, X. aethiopica and M. oleifera were efficacious against S. zeamais instead of synthetic chemical insecticides that have environmental health hazards and they can be used in integrated pest management by farmers and foods merchants. Therefore, since these botanicals have no any adverse effects on the seeds and safe to the environment, they are recommended for future usage in storage grains to control of S. zeamais.
ARTICLE | doi:10.20944/preprints202305.0495.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: rosebud extract; Pretty Velvet; polyphenol; antioxidation; anti-inflammation; nitric oxide; prostaglandin E2
Online: 8 May 2023 (09:37:16 CEST)
Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury, pain, as well as acute and chronic diseases. Since long-term uses of steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly-crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) were found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E2 (PGE2) production. In an air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells including neutrophils, monocytes and lymphocytes, and tumor necrosis factor-α and interleukin-1β concentrations, as achieved with dexamethasone (a steroid). Notably, PVRE also inhibited PGE2, similar to dexamethasone and indomethacin (an NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS ― NO and COX-2 ― PG pathways, and that PVRE could be a promising anti-inflammatory material for diverse issue injuries.
ARTICLE | doi:10.20944/preprints202305.0436.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: HIV; HCV; Health Literacy; HIV Knowledge; HCV Knowledge; Viral Infections
Online: 8 May 2023 (03:50:33 CEST)
The Infectious and Tropical Diseases Department of University of Brescia organized free rapid screening tests for HIV and HCV as part of the Fast Track City commitment. A cross-sectional study was conducted, consisting of an anonymous, multiple-choice questionnaire that was administered to individuals who underwent the screening or consultation. The study aimed to compare knowledge and attitudes towards HIV and HCV between age groups (18-40 vs. >40) and sexual orientations (heterosexual vs. LGBTQ+). Overall, 333 questionnaires were completed. Individuals over the age of 40 and those who identified as heterosexual had the lowest level of knowledge about HIV transmission (7.9% and 30% respectively), undetectable=untransmittable (19.7% and 39.4% respectively) and PrEP (9.2% and 18.2% respectively). They were also less willing to cohabit with people with HIV (PLHIV). Only 9.6% of the population demonstrated high levels of knowledge for both HIV and HCV. People over the age of 40 had the largest gaps in knowledge and would benefit the most from educational and prevention interventions.
Sat, 6 May 2023
ARTICLE | doi:10.20944/preprints202305.0422.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: shell nacre; ormocer; bone void filling cement; bone defects
Online: 6 May 2023 (10:57:53 CEST)
Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research on using shell nacre as cement with improved physico-chemical properties. To address this, the current study aimed to develop a chemical curable com-posite shell nacre cement (SNC) using shell nacre powder and an organically modified ceramic resin shell nacre containing ladder-structured siloxane methacrylate (SNLSM). Different amounts of shell nacre (24, 48, and 72 weight(wt)%) were added to the SNLSM resin matrix and the effect on the physicochemical properties of the cement was studied. The composite shell nacre cement SNC 72 containing 72 wt% shell nacre exhibited significantly higher mechanical properties (com-pressive strength >100 MPa, flexural strength > 35 MPa) and low linear polymerization shrinkage (0.4%) than other compositions. SNC 72 was radiopaque and the exotherm generated during the curing of the cement was minimal. Direct contact of cured SNC 72 with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the results of the study proved that the composite SNC 72 would be a promising candidate for bone defect management.
Fri, 5 May 2023
COMMUNICATION | doi:10.20944/preprints202305.0314.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: liquid profiling; plasma; methylation; mSHOX2; mPTGER4
Online: 5 May 2023 (07:23:15 CEST)
Notwithstanding the fact that there is some improvement for an earlier detection of patients with lung cancer, the majority of them still present with a late-stage disease at the time of diagnosis. Next to the most frequently used factors affecting the prognosis of lung cancer patients (stage, performance and age) the recent application of biomarkers obtained by liquid profiling gained more acceptance. In our study we aimed to answer these questions: i) is the quantification of free-circulating methylated PTGER4 and SHOX2 plasma DNA an useful method for the therapy monitoring and is this also possible for patients treated with different therapy regimens?, and ii) is this approach possible when blood drawing tubes are used which allow for a delayed processing of blood samples? Baseline values for mPTGER4 and mSHOX2 do not allow for a clear discrimination between different response groups. In contrast the combination of the methylation values for both genes show a clear difference between responders vs non-responders at the time of re-staging. Additionally, blood drawing into tubes stabilizing the sample give researchers more flexibility.
REVIEW | doi:10.20944/preprints202212.0272.v2
Subject: Biology And Life Sciences, Life Sciences Keywords: Apiaceae plants; traditional use; phytochemistry; bolting and flowering; controlling approaches
Online: 5 May 2023 (05:47:46 CEST)
Apiaceae plants have been widely used as traditional Chinese medicines (TCMs) for the treatment of removing dampness, relieving superficies, and dispelling cold, etc. In order to exploit the potential application and improve the yield and quality of Apiaceae medicinal plants (AMPs), The traditional use, phytochemistry, modern pharmacological use, effect of bolting and flowering (BF), and approaches for controlling the BF were summarized. Currently, about 228 AMPs have been recorded as TCMs with 6 medicinal parts, 72 traditional uses, 62 modern pharmacological uses, and 5 main kinds of metabolites. Three effect degrees (i.e., significantly affected, affected to some extent, and no significantly affected) could be classed based on the yield and quality. The BF of individual plants (e.g., Angelica sinensis) could be effectively controlled by the standard cultivation techniques, while the mechanism of BF has not been systemically revealed. This review will provide useful references for the reasonable exploration and high-quality production of AMPs.
Thu, 4 May 2023
REVIEW | doi:10.20944/preprints202305.0223.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: bioluminescence; fungi; mushroom; Japan
Online: 4 May 2023 (08:01:04 CEST)
Luminous fungi have long attracted public attention in Japan, from old folklore and fiction to current tourism, children’s toys, games and picture books. At present, 25 species of luminous fungi have been discovered in Japan, which correspond to approximately one-fourth of the globally recognized species. This species richness is arguably thanks to the abundant presence of mycophiles looking to find new mushroom species and the tradition of night-time activities, such as firefly watching, in Japan. Bioluminescence, a field of bioscience focused on luminous organisms, has long been studied by many Japanese researchers, including the biochemistry and chemistry of luminous fungi. A Japanese Nobel Prize winner, Osamu Shimomura (1928-2018), has primarily focused on the bioluminescence system of luminous fungi in the latter part of his life, and the total elucidation of the mechanism was finally accomplished by an international research team with representatives from Russia, Brazil, and Japan in 2018. In this review, we focused on multiple aspects related to luminous fungi of Japan, including myth, taxonomy, and modern sciences.
ARTICLE | doi:10.20944/preprints202305.0203.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Cryptococcus neoformans; Sexual reproduction; F-box protein Fbp1; AICAR transformylase/IMP cyclohydrolase, Ade16
Online: 4 May 2023 (05:46:43 CEST)
F-box protein is a key protein of the SCF E3 ubiquitin ligase complex, responsible for substrate recognition and degradation through specific interactions. Previous studies have shown that F-box proteins play crucial roles in Cryptococcus sexual reproduction. However, the molecular mechanism by which F-box proteins regulate sexual reproduction in C. neoformans is unclear. In the study, we discovered the AICAR transformylase/IMP cyclohydrolase Ade16 as a substrate of Fbp1. Through protein interaction, protein stability, and in vivo ubiquitination experiments, we demonstrated that Ade16 is a substrate for Fbp1. To examine the role of ADE16 in C. neoformans, we constructed the iADE16 strains and ADE16OE strains to analyze the function of Ade16. Our results revealed that the iADE16 strains had a smaller capsule and showed growth defects under NaCl, while the ADE16OE strains were sensitive to SDS but not to Congo red, which is consistent with the stress phenotype of the fbp1Δ strains, indicating that the intracellular protein expression level after ADE16 overexpression was similar to that after FBP1 deletion. Interestingly, although iADE16 strains can produce basidiospores normally, ADE16OE strains can produce mating mycelia but not basidiospores after mating, which is consistent with the fbp1Δmutant strains, suggesting that Fbp1 is likely to regulate the sexual reproduction of C. neoformans through the modulation of Ade16. Fungal nuclei development assay showed that the nuclei of the ADE16OE strains failed to fuse in the bilateral mating, indicating that Ade16 plays a crucial role in the regulation of meiosis during mating. In summary, our findings have revealed a new determinant factor involved in fungal development related to the post-translational regulation of AICAR transformylase/IMP cyclohydrolase.
REVIEW | doi:10.20944/preprints202305.0188.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: blood-based biomarkers; clotting; inflammation; postmortem; vascular biomarkers
Online: 4 May 2023 (04:25:54 CEST)
Many assets of clinical medicine, such as clinical chemistry and diagnostic imaging, make clinical diagnosis outstanding compared to postmortem diagnosis. An assessment of functional status certainly has priority over the postmortem, cross-sectional use of diagnostic tests and laboratory equipment. In addition, the cost of these tools is sometimes steep, and their use does not always fit into a reasonable cost–benefit ratio. However, sometimes postmortem observations, such as inflammation, pulmonary edema, or infiltration and cerebral swelling, cannot be explained without implementing immunohistochemical markers for postmortem diagnosis. Introducing blood-based biomarkers in postmortem care could significantly reduce the rates of inconclusive postmortems and discrepancies in autopsy findings and clinical diagnoses. This is particularly relevant in the scope of vascular pathology, considering the great burden of vascular diseases in overall mortality. Expanding traditional autopsy with blood-based (circulating) biomarkers to avoid invasive postmortem examination would have cultural, religious, and potential economic advantages. All of the target molecules are discussed in the context of the process they up-regulate or down-regulate and which turns out to be the final cause of death. Ultimately, it is evident that further studies are needed to provide concrete validation for a combination of markers on a specific case order to reach a postmortem diagnosis with or without clinical records.
Wed, 3 May 2023
ARTICLE | doi:10.20944/preprints202305.0152.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: heat stress; air temperature; humidity; wind; heat wave; electrical fan; index
Online: 3 May 2023 (12:52:02 CEST)
Increasing wind speed alleviates physiological heat strain, however, health policies have advised against using ventilators or fans under heat wave conditions with air temperatures above the typical skin temperature of 35 °C. Recent research, mostly with sedentary participants, suggests mitigating effects of wind at even higher temperatures depending on the humidity level. Our study aimed at exploring and quantifying, whether such results are transferable to moderate exercise levels, and whether the Universal Thermal Climate Index UTCI reproduces those effects. We measured heart rates, core and skin temperatures and sweat rates in 198 laboratory experiments completed by five young, semi-nude, heat-acclimated, moderately exercising males walking the treadmill with 4 km/h on the level for three hours under widely varying temperature-humidity combinations and two wind conditions. We quantified the cooling effect of increasing wind speed from 0.3 to 2 m/s by fitting generalized additive models predicting the physiological heat stress responses depending on ambient temperature, humidity and wind speed. We then compared the observed wind effects to the assessment performed by UTCI. Increasing wind speed lowered physiological heat strain for air temperatures below 35 °C, but also for higher temperatures with humidity levels above 2 kPa water vapour pressure concerning heart rate and core temperature, and 3 kPa concerning skin temperature and sweat rate, respectively. UTCI assessment of wind effects correlated positively with the observed changes in physiological responses, showing the closest agreement (r=0.9) for skin temperature and sweat rate, where wind is known for elevating the relevant convective and evaporative heat transfer. These results demonstrate the potential of UTCI for adequately assessing sustainable strategies for heat stress mitigation involving fans or ventilators depending on temperature and humidity for moderately exercising individuals.
Sun, 30 April 2023
ARTICLE | doi:10.20944/preprints202304.1257.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Ceratocystis; hybridization; PCR RFLP
Online: 30 April 2023 (04:34:04 CEST)
Hybridization is recognized as a notable driver of evolution and adaptation, which closely related species may exploit in the form incomplete reproductive barriers. Three closely related species of Ceratocystis (i.e., C. fimbriata, C. manginecans and C. eucalypticola) previously have been shown to hybridize by mating naturally occurring self-sterile strains with an unusual laboratory-generated sterile isolate type, which could have impacted conclusions regarding the prevalence of hybridization and inheritance of mitochondria. In the current study we investigated whether interspecific crosses between fertile isolates of these three species are possible, and if so how mitochondria are inherited by the progeny. For this purpose, a PCR-RFLP method and a mitochondrial DNA-specific PCR technique were custom-made and applied in a novel approach of typing complete ascospore drops collected from the fruiting bodies in each cross to distinguish between self-fertilizations and potential hybridization. These markers showed hybridization between C. fimbriata and C. eucalypticola and between C. fimbriata and C. manginecans, while no hybridization was detected in the crosses involving C. manginecans and C. eucalypticola. In both sets of hybrid progeny, we detected biparental inheritance of mitochondria. This study was the first to successfully produce hybrids from a cross involving self-fertile isolates of Ceratocystis, and also provided the first direct evidence of biparental mitochondrial inheritance in the Ceratocystidaceae. This work lays the foundation for further research focused on investigating the role of hybridization in the speciation of Ceratocystis species, and if mitochondrial conflict could have influenced the process.
Sat, 29 April 2023
ARTICLE | doi:10.20944/preprints202304.1207.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Malaria; Amazon biome; INLA; Land use/cover interactions; Bird and amphibian rich-ness-endemics; Landscape composition; Biological diversity; Spatio-temporal modeling
Online: 29 April 2023 (04:29:50 CEST)
Malaria is a prevalent disease in several tropical and subtropical regions, including Brazil, where remains a significant public health concern. Despite control efforts, reintroduction of endemics in areas without cases for decades poses a challenge. To assess factors influencing ma-laria risk, regional outbreak cluster analysis and a spatio-temporal models were developed for the Brazilian Amazon, incorporating climate, land use/cover interactions, endemic bird, and amphibian richness. Results showed that amphibian, bird richness and endemism correlated with a reduction in malaria risk. Presence of forest had a positive effect on risk, but it depended on its juxtaposition with anthropic land uses. Biodiversity and landscape composition, rather than forest formation presence alone, modulated malaria risk in the period. Areas with low en-demic species diversity and high human activity, predominantly anthropogenic landscapes posed high malaria risk. This study underscores the importance of considering the broader eco-logical context in malaria control efforts.
Fri, 28 April 2023
COMMUNICATION | doi:10.20944/preprints202304.1121.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Atlantic Goliath Grouper; Epinephelus itajara; extinction; overfishing; marine protected areas; monitoring
Online: 28 April 2023 (05:18:39 CEST)
The Atlantic Goliath Grouper Epinephelus itajara (Lichtenstein, 1822) is thought to occur on both sides of the Atlantic, from the Carolinas (USA) to Brazil in the western Atlantic, and from North Senegal to North Angola off West Africa in the eastern Atlantic. While there are fairly good data on their distribution in the western Atlantic, genetic verification of species status, confirmed occurrences, population status, fishing reports, and trade data are almost non-existent off West Africa. Part of the problem is that tropical West African countries lack a network of marine reserves that might protect this species. Add to this destruction of mangrove forests and other coastal habitats on which the species depends when in the post-larval and juvenile stages coupled heavy pollution and intense overfishing and it becomes clear that their survival is deeply threatened. The focus of this paper is to describe all of the known historical data and examine all current data to better evaluate their present status.
Thu, 27 April 2023
ARTICLE | doi:10.20944/preprints202304.1073.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: cell mixture; deconvolution; immune cells; blood cells; cancer cells; gene signature; bioinformatics
Online: 27 April 2023 (10:34:59 CEST)
In the last two decades many detailed full transcriptomic studies on complex biological samples have been published and included in large gene expression repositories. These studies primarily provide bulk expression signal for each sample, including multiple cell-types mixed within the global signal. The cellular heterogeneity in these mixtures does not allow the activity of specific genes in specific cell types to be identified. Therefore, inferring relative cellular composition is a very powerful tool to achieve a more accurate molecular profiling of complex biological samples. In recent decades, computational techniques have been developed to solve this problem by applying cell deconvolution methods, designed to decompose cell mixtures into their cellular components and calculate the relative proportions of these elements. Some of them, only calculate the cell proportions (supervised methods), while other deconvolution algorithms can also identify the gene signatures specific for each cell type (unsupervised methods). In these work, five deconvolution methods (CIBERSORT, FARDEEP, DECONICA, LINSEED and ABIS) were implemented and used to analyze blood and immune cells, and also cancer cells, in complex mixture samples (using three bulk expression datasets). Our study provides three analytical tools (corrplots, cell-signature plots and bar-mixture plots) that allow a thorough comparative analysis of the cell mixture data. The work indicates that CIBERSORT is a robust method optimized for the identification of immune cell-types, but not as efficient in the identification of cancer cells. We also observed that LINSEED is a very powerful unsupervised method that provides precise and specific gene signatures for each of the five main immune cell-types analyzed: neutrophils and monocytes (in the myeloid lineage), B-cells, NK cells and T-cells (in the lymphoid lineage).
ARTICLE | doi:10.20944/preprints202304.1067.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Progressive Multifocal Encephalopathy (PML); JC Polyomavirus; VP1 protein; Immunoinformatics; molecular dynamics simulation
Online: 27 April 2023 (10:02:21 CEST)
The JC polyomavirus virus (JCPyV) affects more than 80% of the human population in their early life stage. It mainly affects immunocompromised individuals where virus replication in oligodendrocytes and astrocytes may lead to fatal progressive multifocal encephalopathy (PML). Virus protein 1 (VP1) is one of the major structural proteins of the viral capsid, responsible for keeping the virus alive in the gastrointestinal and urinary tracts. VP1 is often targeted for antiviral drug and vaccine development. Similarly, this study implied immunoinformatics and molecular dynamics simulation-based approaches to design a multi-epitope subunit vaccine targeting JCPyV. The VP1 protein epitopic sequences, which are highly conserved, were used to build the vaccine. This designed vaccine includes two adjuvants, five HTL epitopes, six CTL epitopes, and two linear BCL epitopes to stimulate cellular, humoral, and innate immune responses against JCPyV. Furthermore, molecular docking and molecular dynamics simulation (100ns) studies were used to examine the interaction and stability of the vaccine protein with TLR4. Trajectory analysis showed that the vaccine and TLR4 receptor form a stable complex with the vaccine protein. Overall, this study contributed to the path of vaccine development against JCPyV and may prevent PML from happening. However, this study needs experimental validation to conclude our findings.
ARTICLE | doi:10.20944/preprints202304.1057.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: genetic polymorphism; ACE1 rs4646994; lung cancer; pulmonary nodules
Online: 27 April 2023 (07:47:55 CEST)
Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodule were eventually diagnosed as benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule.Methods: This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract plasm DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by chi-square test, logistic regression analysis and cross analysis. Results: The results showed that the DD genotype of ACE1 rs4646994 may increase the risk of lung cancer in patients with pulmonary nodules, and this correlation was more significant in the female subgroup. In the age stratification analysis, it was found that the risk of lung cancer was significantly increased in the DD genotype of ACE1 rs4646994 in the older subgroup (> 45 years). In addition, the possibility of EGFR mutation in lung adenocarcinoma patients with ACE1 rs4646994 DD genotype was lower than that of II or ID genotype carriers. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.
ARTICLE | doi:10.20944/preprints202304.1028.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Radiofrequency electromagnetic field; DNA methylation; Neuroblastoma; LINE-1; Alu; ribosomal DNA
Online: 27 April 2023 (04:12:45 CEST)
A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.
Mon, 24 April 2023
ARTICLE | doi:10.20944/preprints202304.0855.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: transfer RNA-derived small RNAs; pathological cardiac hypertrophy; small RNA sequencing; biomarkers
Online: 24 April 2023 (11:01:16 CEST)
Background: It remains unclear whether transfer RNA-derived small RNAs (tsRNAs) play a role in pathological cardiac hypertrophy (PCH). We aimed to clarify the expression profile of tsRNAs and disclose their relationship to the clinical phenotype of PCH and the putative role. Methods: Small RNA sequencing was performed in the plasma of PCH patients and healthy volunteers. In a larger sample size and angiotensin Ⅱ (Ang II)-stimulated H9c2 cells, the data were validated by real-time qPCR. The atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were examined in Ang II-stimulated H9c2 cells. The role of tsRNAs in the pathogenesis of PCH was explored by bioinformatics analysis. Results: A total of 4185 differentially expressed tsRNAs were identified, of which 4 and 5 tsRNAs were observed to be significantly differentially upregulated and downregulated expressed. Of the 5 down-regulated tsRNAs, 4 of them were verified to be significantly down-regulated in the larger sample group, among which tRF-30-3JVIJMRPFQ5D, tRF-16-R29P4PE, tRF-21-NB8PLML3E, and tRF-21-SWRYVMMV0 had areas under the curve to diagnose concentric hypertrophy. The 4 down-regulated tsRNAs were negatively correlated with left ventricular posterior wall dimensions in PCH patients (r=-0.4227; r=-0.4517; r=-0.5567; r=-0.4223). The levels of ANP and BNP as well as cell size were decreased in Ang II-stimulated H9c2 cells with 21-NB8PLML3E mimic transfection. Bioinformatics analysis revealed that the target genes of tRF-21-NB8PLML3E were mainly enriched in the metabolic pathway and involved in the regulation of ribosomes. Conclusion: The plasma tsRNAs tRF-21-NB8PLML3E might be considered biomarkers in patients with PCH with early screening potential.
TECHNICAL NOTE | doi:10.20944/preprints202304.0815.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: biosafety; biorisk; biosecurity; biosecurity engagement program; bioterrorism; CBRNE; cooperative threat reduction; homemade explosives; southeast Asia; sustainability; toxins
Online: 24 April 2023 (03:57:39 CEST)
Various species of plants, bacteria, fungi, insects, invertebrates, and vertebrate animals produce unique small molecules, peptides, or proteins (biomolecules) for their defensive purposes. These biomolecules, also known as toxins, are poisonous (toxic) to humans and could be misused due to relatively easy accessibility and affordability. Toxins are not contagious and replicative; their effect or symptoms depend on their concentration (dose), which can take hours to days after exposure. Furthermore, for nefarious actors, preparing low-effort homemade explosives (HMEs) using household items or easily accessible chemical precursors is not difficult. To mitigate the biosecurity risks, biological scientists, law enforcement investigators, and public health response professionals should be aware of the new threats and challenges posed by low-effort toxins and HMEs. The chemical and biological investigation, evidence, and countermeasures training program was aimed at preparing biological scientists, law enforcement investigators, and public health representatives to mitigate the biosecurity risks from low-effort toxins and HMEs. The tailor-made eight-day training program containing lectures, round table discussions, immersion scenarios, practical exercises, practical assessment, and tabletop exercises helped participants to understand and close their skill gaps. The training also covered various elements associated with chemical, biological, radiological, nuclear, and explosive (CBRNE) threats from nefarious individuals and groups. Some highlights of the training are reported in this report.
Sun, 23 April 2023
ARTICLE | doi:10.20944/preprints202304.0797.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Heart failure; Malnutrition; Exercise; Amino-acids; mTOR; Deptor
Online: 23 April 2023 (08:45:26 CEST)
Malnutrition, clinically evident primarily with sarcopenia, is present in more than 50% of CHF patients and is an independent factor of morbidity and mortality. Several pathophysiological mechanisms, such as reduced appetite, metabolic imbalance and altered protein synthesis/degradation rate, due to the blood increase of hypercatabolic molecules, have been proposed to explain this phenomenon. Nutritional supplementation with proteins, amino acids and vitamins have all been used to treat malnutrition, acting through mTOR stimulation. However, the success and efficacy of these procedures are often contradictory and not conclusive. Interestingly, data on exercise training show that exercise reduces mortality and increase functional capacity, although it also increases energy expenditure and nitrogen providing substrate needs. Therefore, this paper discusses the molecular mechanisms of integrated nutritional approaches that would stimulate metabolic anabolic pathways. Pivotal in our opinion, is the relationship between exercise and Deptor, a subunit of the mTOR complex. Consequently, we propose a combination of personalized and integrate nutritional supplementation as well as exercise to treat malnutrition and related anthropometric and functional CHF-related disorders.
Thu, 20 April 2023
REVIEW | doi:10.20944/preprints202304.0478.v2
Subject: Biology And Life Sciences, Life Sciences Keywords: isocitrate dehydrogenase; cancer metabolism; hydroxyglutarate; gliomas; oncometabolites
Online: 20 April 2023 (02:28:47 CEST)
Altered metabolism is a common feature of many cancers and in some cases is a consequence of mutation in metabolic genes, such as the ones involved in Krebs cycle. Isocitrate dehydrogenase (IDH) gene is mutated in many gliomas and other cancers. Physiologically IDH converts isocitrate to αketoglutarate (αKG), but when mutated, IDH reduces αKG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at high levels in IDH mutant cancers, and in the last decade, a massive effort has been done to develop small inhibitors targeting mutant IDH. In this review, we summarize current knowledge about the cellular and molecular consequences of IDH mutations, and the therapeutic approached developed to target IDH mutant tumours, with a focus on gliomas.
Wed, 19 April 2023
REVIEW | doi:10.20944/preprints202304.0538.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Ral-interacting protein 76; vascular endothelial growth factor; small GTPase; hypoxia-inducible factor-1; corpus luteum; tumor
Online: 19 April 2023 (04:10:47 CEST)
Ral-interacting protein 76 (RLIP76) is a potential factor with vascular endothelial growth factor (VEGF) in the corpus luteum and tumor angiogenesis. RLIP76, VEGF, and hypoxia-inducible factor-1 (HIF-1) are proteins that activate angiogenic functions in tumor and endothelial cells. RLIP76 is a main factor in tumor growth, and VEGF is a major endothelial cell protein for angiogenesis. Also, RLIP76 regulates a small GTPase (R-Ras, oncogene) in cell survival, spreading, and migration. HIF-1 is important in the corpus luteum, tumor angiogenesis, and tumor growth. VEGF and HIF-1 regulate the angiogenic function of RLIP76, and RLIP76 controls vascular growth in endothelial and tumor cells. RLIP76, R-Ras, VEGF, and HIF-1 may be useful in the research of corpus luteum and cancer therapy and the study of mechanisms of tumor angiogenesis. This review will help to elucidate the roles of RLIP76/R-Ras and VEGF via HIF-1 in corpus luteum and tumor angiogenesis, tumorigenesis, and the specific regulation of RLIP76 in luteal, tumor, and endothelial cells. Thus, we reviewed the angiogenesis of the corpus luteum and tumor in the ovarian and tumor microenvironment.
Tue, 18 April 2023
REVIEW | doi:10.20944/preprints202304.0478.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: isocitrate dehydrogenase, cancer metabolism, hydroxyglutarate, gliomas, oncometabolites
Online: 18 April 2023 (04:12:06 CEST)
Altered metabolism is a common feature of many cancers and in some cases is a consequence of mutation in metabolic genes, such as the ones involved in Krebs cycle. Isocitrate dehydrogenase (IDH) gene is mutated in many gliomas and other cancers. Physiologically IDH converts isocitrate to αketoglutarate (αKG), but when mutated, IDH reduces αKG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at high levels in IDH mutant cancers, and in the last decade, a massive effort has been done to develop small inhibitors targeting mutant IDH. In this review, we summarize current knowledge about the cellular and molecular consequences of IDH mutations, and the therapeutic approached developed to target IDH mutant tumours, with a focus on gliomas.
Mon, 17 April 2023
ARTICLE | doi:10.20944/preprints202304.0433.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: glaucoma; intraocular pressure; ocular hemodynamics; ocular vasculature; super- 19 resolution ultrasound; ultrasound localization microscopy
Online: 17 April 2023 (09:40:21 CEST)
Imaging of the ocular vasculature can provide new insights into the pathophysiology of ocular diseases. This study proposes a novel high-frequency super-resolution ultrasound localization microscopy (SRULM) technique and evaluates its ability to measure in vivo perfusion changes in the rat eye at elevated intraocular pressure (IOP). A 38.4 MHz center frequency linear array transducer on a VisualSonics Vevo F2 imaging platform was used to collect high frame rate (1 kHz) radiofrequency data of the posterior rat eye following systemic microbubble contrast injection. Following clutter and spatiotemporal non-local means filtering, individual microbubbles were localized and tracked. The microbubble tracks were accumulated over 10,000 frames to generate vascular images quantifying perfusion velocity and direction. Experiments were performed using physiologic relevant controlled flow states for algorithm validation and subsequently performed in vivo on the rat eye at 10 mm Hg IOP increments from 10 to 60 mm Hg. The posterior vasculature of the rat eye, including the ophthalmic artery, long posterior ciliary arteries and their branches, central retinal artery and retinal arterioles and venules were successfully visualized, and velocities quantified at each IOP level. Significant reductions in arterial flow were measured as IOP was elevated. High-frequency SRULM can be used to visualize and quantify perfusion velocity of the rat eye in both the retrobulbar and intraocular vasculature simultaneously. The ability to detect ocular perfusion changes throughout the depth of the eye may help elucidate the role ischemia has in the pathophysiology of ocular diseases such as glaucoma.
REVIEW | doi:10.20944/preprints202304.0414.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: N3PUFA; EPA; DHA; omega-3; cardiovascular; coagulation; thrombosis; COVID-19; inflammation; oxidative stress.
Online: 17 April 2023 (07:01:59 CEST)
Accumulating literature demonstrates that omega-3 polyunsaturated fatty acid (N3PUFA) can be incorporated into the phospholipid bilayer of cell membrane in the human body to positively affect the cardiovascular system, including improving epithelial function, decreasing coagulopathy, and attenuating uncontrolled inflammatory responses and oxidative stress. Moreover, it has been proven that the N3PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of some potent endogenous bioactive lipid mediators that mediate some favorable effects attributed to their parent substances. A linear dose-response relationship between increased EPA and DHA intake and reduced thrombotic outcomes have been reported. The excellent safety profile of dietary N3PUFA makes them a prospective adjuvant treatment for people exposed to a higher risk of cardiovascular problems associated with COVID-19. This review presented the potential mechanisms that might contribute to the beneficial effect of N3PUFA and the optimal form and dose applied.
ARTICLE | doi:10.20944/preprints202304.0388.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: prostate cancer; SNP; TP53; Pro47Ser; Arg72Pro; African American
Online: 17 April 2023 (03:41:25 CEST)
Growing evidence indicates the involvement of a genetic component for CaP susceptibility and clinical severity. Somatic mutations of TP53 have been associated with 50% of diverse human cancers. Studies have also reported the role of germ line mutations and single nucleotide poly-morphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single De-partment of Defense institutional retrospective study, we identified common SNPs in the TP53 gene in AA and CA men and performed association analyses for functional TP53 SNPs with clinico-pathological features of CaP. The CPDR Oncoarray database on blood derived genomic DNA from 321 men treated by radical prostatectomy at WRNMMC were used to examine clini-co-pathological associations with TP53 SNPs. The SNP genotyping analysis on the final cohort of 308 patients (212 AA; 95 CA) identified 74 SNPs in the TP53 gene region with a minor allele fre-quency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region of TP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant, had a minor allele frequency of 0.01 in AA, however, was not detected in CA. Arg72Pro was the most common SNP with a minor allele frequency of 0.50 (0.41 in AA; 0.68 in CA). Additionally, Arg72Pro was associated with time to biochemical recurrence (BCR) after statistical adjustment for patient age at diagnosis, self-reported race, and Gleason score (p= 0.046; HR = 1.52). The present study demonstrated ancestral differences in allele frequencies of TP53 Arg72Pro and Pro47Ser SNPs in AA and CA CaP, providing a valuable framework for the interrogating CaP disparity among AA and CA men.
Fri, 14 April 2023
ARTICLE | doi:10.20944/preprints202304.0335.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: light therapy; sleep disorder; daytime sleepiness; circadian rhythm; clock gene
Online: 14 April 2023 (03:14:34 CEST)
Background and Objectives: Light therapy (LT) is used as an adjunctive treatment for sleep problems. This study evaluates the impact of LT on sleep quality and sleep-related parameters in patients with sleep disorders. Materials and Methods: We performed a pilot randomized, open-label clinical trial. Fourteen patients aged 20–60 years with sleep disorders for more than three months were randomized into the control and LT groups (1:1 ratio). The LT group was instructed to use a device that provides bright LT (6000 K, 380 lux, wavelength 480 nm) for at least 25 minutes before 09:00 am for two weeks. A self-reported questionnaire was used to evaluate circadian preference, mood, and sleep-related parameters. We analyzed serum cortisol levels and clock genes expression. Results: The Epworth Sleepiness Scale (ESS), insomnia severity index, and Pittsburgh Sleep Quality index were significantly improved within the LT group only after the two-week period. When comparing the two groups, only the change in ESS significant was significant (mean difference; control: -0.14 vs LT: -1.43, p=0.021) after adjusting for baseline characteristics. There were no significant differences in serum cortisol or clock genes expression. Conclusions: LT can improve daytime sleepiness in patients with sleep disorders; however, further well-designed studies are warranted to confirm its efficacy.
Wed, 12 April 2023
ARTICLE | doi:10.20944/preprints202304.0231.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: reptilian; reptoid; ufology; Life Sequence Conjecture; extraterrestrials; convergent evolution; homologous evolution; parallel evolution; divergent evolution; chaos evolution
Online: 12 April 2023 (03:09:29 CEST)
Reptilians or reptoids are staple characters of Hollywood cinema, science fiction literature, ufology and conspiracy theories. Despite its popularity, the reptoid has been dismissed by the scientific community as a figment of the imagination; born out of a speculation, paranoia and wanton anthropocentricism. In this paper, however, the Life Sequence Conjecture is advanced as a supportive framework for the notion of reptilian extraterrestrials. This paper is not an argument in support of the existence of extraterrestrials. Rather, it proposes that if extraterrestrials do exist, then a reptilian morphology is not untenable.
Tue, 11 April 2023
ARTICLE | doi:10.20944/preprints202304.0221.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: shallow-water vent; Tyrrhenian Sea; Tor Caldara; chemolithotroph; Alphaproteobacteria; Thalasso-spiraceae; genome; geothermal; sulfur oxidation; DNA uptake; nitrogen fixation; carbon fixation
Online: 11 April 2023 (10:31:58 CEST)
Varunaivibrio sulfuroxidans type strain TC8T is a mesophilic, facultatively anaerobic, facultatively chemolithoautotrophic alphaproteobacterium, isolated from a sulfidic shallow-water marine gas vent located at Tor Caldara, Tyrrhenian Sea, Italy. V. sulfuroxidans belongs to the family Thalassospiraceae within the Alphaproteobacteria, with Magnetovibrio blakemorei as its closest relative. The genome of V. sulfuroxidans encodes the genes involved in sulfur, thiosulfate and sulfide oxidation, as well as nitrate and oxygen respiration. The genome encodes the genes involved in carbon fixation via Calvin-Benson-Bassham cycle, in addition to genes involved in glycolysis and TCA cycle, indicating a mixotrophic lifestyle. Genes involved in the detoxification of mercury and arsenate are also present. The genome also encodes a complete flagellar complex, one intact prophage and one CRISPR, as well as a putative DNA uptake mechanism mediated by the type IVc (aka Tad pilus) secretion system. Overall, the genome of Varunaivibrio sulfuroxidans indicates that the bacterium is metabolically versatile and well-adapted to the dynamic environmental conditions of sulfidic gas vents.
Mon, 10 April 2023
ARTICLE | doi:10.20944/preprints202304.0160.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: origin of life; genetic code; biophysical interactions; hydrophobicity; anticodon; molecular dynamics; NMR
Online: 10 April 2023 (09:07:19 CEST)
The genetic code conceals a ‘code within the codons’, which hints at biophysical interactions between amino acids and their cognate nucleotides. But research over decades has failed to corroborate systematic biophysical interactions across the code. Using molecular dynamics simulations and NMR, we have analysed interactions between the 20 standard proteinogenic amino acids and four RNA mononucleotides in three charge states. Our simulations show that 50% of amino acids bind best with their anticodonic middle base in the -1 charge state common to the backbone of RNA, while 95% of amino acids interact most strongly with at least one of their codonic or anticodonic bases. Preference for the cognate anticodonic middle base was greater than 99% of randomized assignments. We verify a selection of our results using NMR, and highlight challenges with both techniques for interrogating large numbers of weak interactions. Finally, we extend our simulations to a range of amino acids and dinucleotides, and corroborate similar preferences for cognate nucleotides. Despite some discrepancies between the predicted patterns and those observed in biology, the existence of weak stereochemical interactions means that random RNA sequences could template non-random peptides. This offers a compelling explanation for the emergence of genetic information in biology.
Fri, 7 April 2023
ARTICLE | doi:10.20944/preprints202304.0125.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: kistomin; rhodostoxin; rhodostomin; rhodocytin; rhodocetin; ancrod
Online: 7 April 2023 (11:36:15 CEST)
In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study assembled and analyzed the de novo venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI>PII>PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensinogen-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%) and others (1.78%). The expressions of SVMP, CTL and SVSP correlate with hemorrhagic, anti-platelet and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) is platelet-inhibitory. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitor), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.
ARTICLE | doi:10.20944/preprints202304.0110.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Information; matter-related information; micro/macro structuration/destructuration; non-living/living structures; Informational Model of the Human Body and Living Structures; Infor-mational Model of Consciousness
Online: 7 April 2023 (03:56:25 CEST)
This paper is referred to a top frontline research in life science, showing that in spite of the large variation of the physiological architecture and behavioral forms of the living systems, the fundamental structure of their informational system is basically the same, allowing the body growth/development by micro to macro-structuration processes, maintaining the same informational configuration and functions like the basic unit of life – the eukaryotic cell. Starting and based on the determination of the special/specific info-operability in living structures and the role of information in structuration and their functionality, there are discussed the informational functions of the eukaryotic/prokaryotic cells, the simplest units of life and is elaborated and presented the Informational Model of the Living Structures, showing that these structures operate on the basis of two main informational systems: one of them defined as the Programmed Informational System, composed by three components, assuring respectively the info-generation, maintenance and the proliferation/reproduction, and another one defined as the Operative Informational System, necessary for the continuous communication with the environment for adaptation, consisting in four main components referred to memory, decision, sentience and info-connection/info-selection. The revealed properties are compared with the Informational System of the Human Body, as a prototype of a living system on the top of the evolutionary scale, showing/demonstrating the compatibility of structuration and functions on the entire scale, from prokaryotic/eukaryotic unit cells to multicellular organisms – plants, animals and human, by means of a continuous adaptation process, which always follows the same line of micro to macro-structuration process based on the same Info-organization and functionality. These models are new and revolutionary in the information and life sciences
Wed, 5 April 2023
COMMUNICATION | doi:10.20944/preprints202304.0068.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: cancer; amino acids; colon; nitrogen; diet; mice
Online: 5 April 2023 (15:45:18 CEST)
Abstract: Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood although there is a vast literature suggesting that huge amounts of both energy and substrates are require for synthesis of components of new neoplastic cells so that any macronutrient may be efficiently utilized. Recently, in vitro data show that EAA supplementation promoted colon cancer cells apoptosis by enhanced autophagy. Therefore, in this study we tested in vivo the effects of matched macronutrients standard laboratory diet (control) versus EAA rich modified diet (EAArmd) in mice injected with colon cancer cells. Results of the first set of 12 animals, 6 controls and 6 EAArmd-fed, showed that controls mice develop cancer volume cancers 5 times larger and heavier than EAArmd-fed. If confirmed, these results would open new scenarios for the cancer integrate therapies.
Tue, 4 April 2023
HYPOTHESIS | doi:10.20944/preprints202304.0041.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Hepatology; Oncology; Biomarkers; Hepatocellular Carcinoma
Online: 4 April 2023 (09:28:52 CEST)
In this study, novel biomarkers in Blood Mononuclear Cells (PBMCs) of Hepatocellular Carcinoma (HCC) patients were identified through microarray data analysis. The problem that prompted the study was the lack of reliable biomarkers for early diagnosis and monitoring of HCC. The purpose of this study was to discover potential biomarkers in PBMCs of HCC patients that can be used for early diagnosis and monitoring of the disease. The main hypothesis was that there are genes that are overexpressed in PBMC of HCC patients compared to healthy individuals. The results showed that genes HBB, WBP2, HBA2, and HBA1 were overexpressed in PBMCs of HCC patients. Additionally, nine genes were found to be upregulated in HCC patients and had a relation between KEGG pathways of RA, suggesting a link between the two diseases. These genes are TLR4, IL1B, CXCL5, IL11, HLA-DQA1, HLA-DRA, LBT, ATP6V1B2 and ATP6V1C1. The Gene ontology analysis revealed biological processes used in the process of how these genes play a role in development of HCC. In conclusion, this study identified potential biomarkers in PBMC of HCC patients that can aid in early diagnosis and monitoring of the disease. The findings of this study have important implications for improving the clinical management of HCC patients.
CASE REPORT | doi:10.20944/preprints202304.0037.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: acute hepatic porphyria; cholangiocarcinoma; delta aminolevulinic acid; porphobilinogen; hydroxymethylbilane synthase
Online: 4 April 2023 (04:53:33 CEST)
Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.
Mon, 27 March 2023
REVIEW | doi:10.20944/preprints202303.0448.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: LLPS; liquid-liquid phase separation; non-coding RNA; intrinsically disordered proteins; membrane-less organelles; stress-response; biomolecular condensates
Online: 27 March 2023 (05:43:50 CEST)
At the beginning of the 21st century, it became obvious that radical changes had taken place in the concept of living matter and, in particular, in the concept of the organization of intracellular space. The accumulated data testify to the essential importance of phase transitions of biopolymers (first of all, intrinsically disordered proteins and RNA) in the spatiotemporal organization of the intracellular space. Of particular interest is the stress-induced reorganization of the intracellular space. Examples of organelles formed in response to stress are nuclear A-bodies and nuclear stress granules. The formation of these organelles is based on LLPS of intrinsically disordered proteins and non-coding RNA. Despite the overlapping composition and similar mechanism of formation, these organelles have different functional activities and physical properties. In this review, we will focus our attention on these MLOs and describe their functions, structure, and mechanism of formation.
Tue, 28 June 2022
REVIEW | doi:10.20944/preprints202206.0370.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: GADV hypothesis; origin of life; protein 0th-order structure; origin of protein; [GADV]-microsphere; origin of gene: the core life system
Online: 28 June 2022 (03:41:15 CEST)
One of the problems, which make it difficult to solve the mystery of the origin of life, would be how life emerged in chemically complex messy environments on the primitive Earth. It is considered that three main points contributed to open the way to the emergence of life. (1) A characteristic inherent in [GADV]-amino acids, which are easily produced with prebiotic means. (2) Protein 0th-order structure or [GADV]-amino acid composition generating water-soluble globular protein with some flexibility, which can be produced even by random joining of [GADV]-amino acids. (3) Formation of versatile [GADV]-microspheres, which can grow, divide, proliferate even without genetic system, was the emergence of proto-life. (4) [GADV]-microspheres with a higher proliferation ability than others could be selected. The proto-Dawin evolution made it possible to proceed forward to creation of the core life system composed of (GNC)n gene, anticodon stem-loop tRNA or AntiC-SL tRNA (GNC genetic code) and [GADV]-protein. (5) Eventually, the first genuine life with the core life system emerged. Thus, the formation processes of [GADV]-protein and (GNC)n gene in chemically complex messy environments were the steps to the emergence of genuine life.
Tue, 21 June 2022
ARTICLE | doi:10.20944/preprints202206.0287.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: origin of life; disspative structuring; non-equilibrium thermodynamics; prebiotic chemistry; abiogenisis; adenine; guanine; hypoxanthine; xanthine; purines
Online: 21 June 2022 (05:14:12 CEST)
We have suggested that the abiogenisis of life around the beginning of the Archean may have been an example of microscopic dissipative structuring of UVC pigments (the fundamental molecules of life) under the prevailing surface UV solar spectrum. In a previous article in this series, we have describe the non-equilibrium thermodynamics and the photochemical mechanisms which may have been involved in the dissipative structuring of the purines adenine and hypoxanthine from the common precursor molecules of HCN and water under UVC light. In this article we extend our analysis to include the production of the other two important purines, guanine and xanthine, from these same precursors. The photochemical reactions are presumed to occur within a fatty acid vesicle floating on a hot ocean surface exposed to the prevailing UV light. Reaction-diffusion equations are resolved under different environmental conditions. Significant amounts of adenine (∼10−5 M) and guanine (∼10−6 M) are obtained within only a few months at 80 °C under plausible initial concentrations of HCN and cyanogen (a photochemical product of HCN).
Wed, 2 February 2022
REVIEW | doi:10.20944/preprints202202.0031.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: photosynthesis; photosystem; water oxidation; oxygenic; evolution; origin of life
Online: 2 February 2022 (12:17:37 CET)
What if oxygenic photosynthesis is a primordial process with roots at the origin of life? What would the impact of this change in perspective be on our understanding of the early Earth and of the emergence and diversification of life? In here, I will examine some of the historical context of the study of the evolution of photosynthesis, which led to the consolidation of the current notion that the origin of anoxygenic photosynthesis occurred before the origin of oxygenic photosynthesis. I will show with a few examples how the mainstream view on the evolution of photosynthesis traces back to Oparin’s ‘primordial soup’ scenario for the origin of life, fuelled by the century-old perception that oxygenic photosynthesis is a plant rather than a bacterial trait. However, it has become more evident than ever before that the mainstream view is not supported by the evolution of the photosystems. In other words, the origin of biological water oxidation appears to be the seed from where photosynthesis sprout. Somewhat troubling and contrary to all predictions that derive from the mainstream view, photosystem II—the water-splitting and oxygen-evolving enzyme—shows features that are better explained if photochemical reaction centres originated during the establishment of oxygenic photosynthesis. An urgent revision of the evolution of photosynthesis procured to be free from biases of interpretations and presuppositions is strongly encouraged from all angles of the Life and Earth Sciences.
Mon, 25 January 2021
ARTICLE | doi:10.20944/preprints202101.0500.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: origin of life; disspative structuring; prebiotic chemistry; abiogenisis; adenine
Online: 25 January 2021 (13:57:05 CET)
I describe the non-equilibrium thermodynamics and the photochemical mechanisms which may have been involved in the dissipative synthesis, proliferation, and evolution of the fundamental molecules at the origin of life from simpler and more common precursor molecules such as HCN, H2O and CO2 under the impressed UVC photon flux of the Archean. The fundamental molecules absorb strongly in this UVC region and exhibit strong coupling between their electronic excited and ground states which endows them with efficient photon disipative capacity (broad wavelength absorption and rapid radiationless dexcitation) suggestive of dissipative structuring. The autocatalytic nature of the synthesized molecules in dissipating the same photochemical potential that directed their synthesis leads to their proliferation. The non-linearity in the photochemical and chemical reaction rates provides numerous stationary states which can be reached by amplification of a molecular concentration fluctuation near a bifurcation, promoting the system into states of generally higher photon disspative efficacy. An example is given of the UV photochemical dissipative structuring, proliferation, and evolution of molecules on route to the nucleobase adenine from the common precursor molecules HCN and H2O occurring within a fatty acid vesicle. The kinetic equations are resolved under different environmental conditions, providing a non-equilibrium thermodynamic analysis of the appearance of an early important molecule for the origin of life.
Thu, 17 September 2020
ARTICLE | doi:10.20944/preprints202009.0409.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: clay; mica; biotite; muscovite; origin of life; origins of life; mechanical energy; work; wet-dry cycles
Online: 17 September 2020 (13:01:15 CEST)
An origin of life between the sheets of micaceous clay is proposed to involve the following steps: 1) evolution of metabolic cycles and nucleic acid replication, in separate niches in biotite mica; 2) evolution of protein synthesis on ribosomes formed by liquid-in-liquid phase separation; 3) repeated encapsulation by membranes of molecules required for the metabolic cycles, replication, and protein synthesis; 4) interactions and fusion of the these membranes containing enclosed molecules; resulting eventually in 5) an occasional living cell, containing everything necessary for life. The spaces between mica sheets have many strengths as a site for life’s origins: mechanochemistry and wet-dry cycles as energy sources, an 0.5-nm anionic crystal lattice with potassium counterions (K+), hydrogen-bonding, enclosure, and more. Mica pieces in micaceous clay are large enough to support mechanochemistry from moving mica sheets. Biotite mica is an iron-rich mica capable of redox reactions, where the stages of life’s origins could have occurred, in micaceous clay.
Sun, 17 November 2019
COMMUNICATION | doi:10.20944/preprints201911.0193.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: human origins; mitochondrial DNA; Africa; human evolution
Online: 17 November 2019 (00:55:26 CET)
Chan and colleagues in their paper titled “Human origins in a southern African palaeo-wetland and first migrations” (https://www.nature.com/articles/s41586-019-1714-1) report 198 novel whole mitochondrial DNA (mtDNA) sequences and infer that ‘anatomically modern humans’ originated in the Makgadikgadi–Okavango palaeo-wetland of southern Africa around 200 thousand years ago. This claim relies on weakly informative data. In addition to flawed logic and questionable assumptions, the authors surprisingly disregard recent evidence and debate on human origins in Africa. As a result, the emphatic and high profile conclusions of the paper are unjustified.
Tue, 8 October 2019
ARTICLE | doi:10.20944/preprints201910.0086.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: phylogenomics; phylogenetics; codon usage bias; Tree of Life
Online: 8 October 2019 (10:43:24 CEST)
Phylogenies depict shared evolutionary patterns and structures on a tree topology, enabling the identification of hierarchical and historical relationships. Recent analyses indicate that phylogenetic signals extend beyond the primary structure of protein or DNA, and various aspects of codon usage biases are phylogenetically conserved. Several functional biases exist within genes, including the number of codons that are used, the position of the codons, and the overall nucleotide composition of the genome. Codon usage biases can significantly affect transcription and translational efficiencies, leading to differential gene expression. Although systematic codon usage biases originate from the overall GC content of a species, ramp sequences, codon aversion, codon pairing, and tRNA competition also significantly affect gene expression and are phylogenetically conserved. We review recent advances in analyzing codon usage biases and their implications in phylogenomics. We first outline common phylogenomic techniques. Next, we identify several codon usage biases and their effects on secondary structure, gene expression, and implications in phylogenetics. Finally, we suggest how codon usage biases can be included in phylogenomics. By incorporating various codon usage biases in common phylogenomic algorithms, we propose that we can significantly improve tree inference. Since codon usage biases have significant biological implications, they should be considered in conjunction with other phylogenetic algorithms.
Tue, 23 July 2019
ARTICLE | doi:10.20944/preprints201806.0035.v2
Subject: Biology And Life Sciences, Life Sciences Keywords: origin of life; LUCA; FUCA; RNA World; PTC; Archaea; translation system
Online: 23 July 2019 (08:13:32 CEST)
The existence of a common ancestor to all living organisms in Earth is a necessary corollary of Darwin idea of common ancestry. The Last Universal Common Ancestor (LUCA) has been normally considered as the ancestor of cellular organisms that originated the three domains of life: Bacteria, Archaea and Eukarya. Recent studies about the nature of LUCA indicate that this first organism should present hundreds of genes and a complex metabolism. Trying to bring another of Darwin ideas into the origins of life discussion, we went back into the prebiotic chemistry trying to understand how LUCA could be originated under gradualist assumptions. Along this line of reasoning, it became clear to us that the definition of another ancestral should be of particular relevance to the understanding about the emergence of biological systems. Together with the view of biology as a language for chemical translation, on which proteins are encoded into nucleic acids polymers, we glimpse a point in the deep past on which this Translation mechanism could have taken place. Thus, we propose the emergence of this process shared by all biological systems as a point of interest and propose the existence of this pre-cellular entity named FUCA, as the First Universal Common Ancestor. FUCA was born in the very instant on which RNA-world replicators started to be capable to catalyze the bonding of amino acids into oligopeptides. FUCA has been considered mature when the translation system apparatus has been assembled together with the establishment of a primeval, possibly error-prone genetic code. This is FUCA, the earliest ancestor of LUCA’s lineage.
Mon, 29 April 2019
Subject: Biology And Life Sciences, Life Sciences Keywords: origin of life; origins of life; mechanical energy; work; entropic forces; mica; biotite; Muscovite; wet/dry cycles; clay
Online: 29 April 2019 (07:51:38 CEST)
Forces and mechanical energy are prevalent in living cells. This may be because forces and mechanical energy preceded chemical energy at life’s origins. Mechanical energy is more readily available in non-living systems than the various other forms of energy used by living systems. Two possible prebiotic environments that might have provided mechanical energy are hot pools that experience wet/dry cycles and mica sheets as they move, open and shut, as heat pumps or in response to water movements.
Mon, 25 December 2017
REVIEW | doi:10.20944/preprints201712.0170.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: RNA world; [GADV]-protein world; GADV hypothesis; origin of life; protein 0th-order structure; origin of protein; origin of genetic code; origin of gene
Online: 25 December 2017 (08:08:37 CET)
All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.