Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Changes in Neuronal Excitability During Osmotic Edema in Juvenile and Adult Hippocampus Through NMDA Receptor Activation - eScholarship

Cerebral edema affects millions of people worldwide and is associated with a plethora of diseases, disorders, and conditions such as traumatic brain injury, stroke, cardiac arrest, autism and epilepsy. Cellular edema has been known to increase epileptiform activity and seizure susceptibility in vitro and in vivo. However, the identity of the cell types undergoing volume increases and the types of excitability changes that occur in neurons remain unclear. Electrophysiological whole-cell patch clamp techniques were used to record currents and potentials from CA1 pyramidal neurons during the application of hypoosmolar ACSF (hACSF) in acutely isolated hippocampal slices from mice. Hypoosmolar ACSF evoked slow inward currents (SICs) in neurons, which initiated after ~1 minute of hACSF application. Neuronal excitability increased as osmolarity decreased in a dose-dependent manner. Even 5% reductions in osmolarity were sufficient to significantly increase neuronal excitability. In addition, hACSF induced neuronal firing of action potentials (APs), independent of AMPA receptor activation. Neuronal excitability was also increased during application of hACSF while blocking both APs and AMPA receptors. Increased sub-threshold EPSPs, neuronal APs, and bursting activity were also evoked in the presence of Mg2+, suggesting that hypoosmolar insults increase neuronal excitability under more physiological conditions. Hypoosmolar insults increased neuronal excitability in both juvenile (P15-P21) and adult 2- to 5-month-old) mice. Bursting activity in adult mice during osmotic insult was elevated compared to juvenile mice. During hypoosmolar insults the frequency of SICs recorded at physiological temperature were significantly elevated from SICs recorded at room temperature. SICs were potentiated by D-serine, and blocked by both DL-AP5 and the NR2B specific compound Ro25-6981. Together, these results indicate that osmotic insults produce cellular edema in both neurons and astrocytes, and increase neuronal excitability within minutes through a combination of synaptic and non-synaptic activation of glutamate receptors.
Organ Restoration With Normothermic Machine Perfusion and Immune Reaction

Liver transplantation is the only recognized effective treatment for end-stage liver disease. However, organ shortages have become the main challenge for patients and physicians within the transplant community. Waiting list mortality remains an issue with around 10% of patients dying whilst waiting for an available organ. The post-transplantation period is also associated with an adverse complication rate for these specific cohorts of high-risk patients, particularly regarding patient and graft survival. Ischaemia reperfusion injury (IRI) has been highlighted as the mechanism of injury that increases parenchymal damage, which eventually lead to significant graft dysfunction and other poor outcome indicators. The consequences of IRI in clinical practice such as reperfusion syndrome, primary non-function of graft, allograft dysfunction, ischaemic biliary damage and early biliary complications can be life-threatening. IRI dictates the development of a significant inflammatory response that drives the pathway to eventual cell death. The main mechanisms of IRI are mitochondrial damage due to low oxygen tension within the hepatic micro-environment and severe adenosine triphosphate (ATP) depletion during the ischaemic period. After the restoration of normal blood flow, this damage is further enhanced by reoxygenation as the mitochondria respond to reperfusion by releasing reactive oxygen species (ROS), which in turn activate Kupffer cells within the hepatic micro-environment, leading to a pro-inflammatory response and eventual parenchymal cell apoptosis and associated tissue degradation. Machine perfusion (MP) is one emergent strategy considered to be one of the most important advances in organ preservation, restoration and transplantation. Indeed, MP has the potential to rescue frequently discarded organs and has been shown to limit the extent of IRI, leading to suppression of the deleterious pro-inflammatory response. This immunomodulation reduces the prevalence of allograft rejection, the use of immunosuppression therapy and minimizes post-transplant complications. This review aims to update the current knowledge of MP with a focus on normothermic machine liver perfusion (NMLP) and its potential role in immune response pathways.
Feedback theory to the well-posedness of evolution equations

In this paper, we cross the boundary between semigroup theory and general infinite-dimensional systems to bridge the isolated research activities in the two areas. Indeed, we first give a chronological history of the development of the semigroup approach for control theory. Second, we use the feedback theory to prove the well-posedness of a class of dynamic boundary problems. Third, the obtained results are applied to the well-posedness of neutral equations with non-autonomous past. We will also see that the strong connection between semigroup and control theories lies in feedback theory, where different kinds of perturbations appear. This article is part of the theme issue ‘Semigroup applications everywhere’.
Genome-Wide DNA Methylation Analysis of Mammary Gland Tissues From Chinese Holstein Cows With Staphylococcus aureus Induced Mastitis

Staphylococcus aureus intramammary infection is one of the most common causes of chronic mastitis in dairy cows, whose development may be associated with epigenetic changes in the expression of important host defense genes. This study aimed to construct a genome-wide DNA methylation profile of the mammary gland of Chinese Holstein cows (n = 3) following experimentally induced S. aureus mastitis, and to explore the potential gene regulatory mechanisms affected by DNA methylation during S. aureus mastitis. DNA was extracted from S. aureus-positive (n = 3) and S. aureus-negative (n = 3) mammary gland quarters and subjected to methylation-dependent restriction-site associated DNA sequencing (Methyl-RAD Seq). Results showed that CmCGG/CmCWGG DNA methylation sites were unevenly distributed and concentrated on chromosomes 5, 11, and 19, and within intergenic regions and intron regions of genes. Compared with healthy control quarters, 9,181 significantly differentially methylated (DM) CmCGG sites and 1,790 DM CmCWGG sites were found in the S. aureus-positive quarters (P < 0.05, |log2FC| > 1). Furthermore, 363 CmCGG differently methylated genes (DMGs) and 301 CmCWGG DMGs (adjusted P < 0.05, |log2FC| > 1) were identified. Gene ontology and KEGG enrichment analysis indicated that CmCGG DMGs are involved in immune response pathways, while the CmCWGG DMGs were mainly enriched in gene ontology terms related to metabolism. The mRNAs of 526 differentially methylated CmCGG genes and 124 differentially methylated CmCWGG genes were also significantly differentially expressed (RNA-Seq data) in the same samples, herein denoted differentially methylated and expressed genes (DMEGs) (P < 0.05). Functional enrichment analysis of DMEGs revealed roles related to biological processes, especially the regulation of immune response to diseases. CmCGG DMEGs like IL6R, TNF, BTK, IL1R2, and TNFSF8 enriched in several immune-related GO terms and pathways indicated their important roles in host immune response and their potential as candidate genes for S. aureus mastitis. These results suggest potential regulatory roles for DNA methylation in bovine mammary gland processes during S. aureus mastitis and serves as a reference for future epigenetic regulation and mechanistic studies.
Spatially uniform establishment of chromatin accessibility in the early Drosophila embryo

As the Drosophila embryo transitions from the use of maternal RNAs to zygotic transcription, domains of open chromatin, with relatively low nucleosome density and specific histone marks, are established at promoters and enhancers involved in patterned embryonic transcription. However, it remains unclear whether open chromatin is a product of activity - transcription at promoters and patterning transcription factor binding at enhancers - or whether it is established by independent mechanisms. Recent work has implicated the ubiquitously expressed, maternal factor Zelda in this process. To assess the relative contribution of activity in the establishment of chromatin accessibility, we have probed chromatin accessibility across the anterior-posterior axis of early Drosophila melanogaster embryos by applying a transposon based assay for chromatin accessibility (ATAC-seq) to anterior and posterior halves of hand-dissected, cellular blastoderm embryos. We find that genome-wide chromatin accessibility is remarkably similar between the two halves. Promoters and enhancers that are active in exclusively one half of the embryo have open chromatin in the other half, demonstrating that chromatin accessibility is not a direct result of activity. However, there is a small skew at enhancers that drive transcription exclusively in either the anterior or posterior half of the embryo, with greater accessibility in the region of activity. Taken together these data support a model in which regions of chromatin accessibility are defined and established by ubiquitous factors, and fine-tuned subsequently by activity.
Field-Testing Pheromone Traps for Predicting Masked Chafer (Coleoptera: Scarabaeidae) Grub Density in Golf Course Turf and Home Lawns

Sticky traps baited with crude female extract of the southern masked chafer, Cyclocephala lurida Bland, were tested at 28 sites on a golf course and on 27 individual home lawns to determine if the numbers of males captured in short-term trapping could be used to predict subsequent grub densities. Hexane rinses of female beetles were effective in luring males to traps. There was no correlation between male captures and local densities of grubs on the golf course, where movement of beetles between adjacent areas may have confounded our ability to discriminate among high- and low-density sites. In contrast, there was significant, albeit weak correlation (r2 = 0.25) between male captures and subsequent larval populations in home lawns, even though trapping was restricted to only two nights due to limited availability of crude female extract. Identification and synthesis of the C. lurida sex attractant would allow season-long trapping, which could provide a more accurate assessment of beetle populations and pr.
Improvement of Integral Membrane Protein Expression via Optimization of Simulated Integration Efficiency

Integral membrane protein characterization is limited by the low levels of protein obtainable from heterologous overexpression in hosts such as Escherichia coli. Differences in the efficiencies of subdomains of the co-translational integration processes of membrane proteins into the membrane could explain the observed variation in the experimental expression of closely related homologs in E. coli. We have developed a method to predict and increase the expression of individual membrane proteins by optimizing the efficiency of their translocon-mediated integration into the membrane. The integration efficiency of each component of a membrane protein is calculated using a coarse-grained co-translational simulated integration model. The results of model simulations, experimental expression levels quantified by integral membrane protein-GFP fusion fluorescence, and a novel antibiotic survival test that reports on misintegration in vivo are applied to test the relationship between the integration efficiency of specific domains and experimental expression. Changes in simulated integration efficiencies due to sequence modifications agree with the effects on experimental expression in vivo. In the case of the TatC protein family, misintegration of the C-tail is found to be a major contributor to expression failure in E. coli. Beneficial sequence modifications that improve both simulated integration efficiency and experimental expression levels can be identified using the model. Preliminary evidence shows that simulated integration efficiency could potentially predict the effects of mutations on Haemophilus influenzae GlpG experimental expression in E. coli. The process described herein allows for the rational overexpression of integral membrane proteins through the identification and mitigation of inefficiencies in the underlying co-translational membrane integration process.
A Simplified Method For Isolation and Culture of Neural Stem Cells From Adult Mice Brain: in Vitro

The present study aimed to develop an uncomplicated method for isolation and culture of mice brain derived-neural stem cells (NSCs) - neurospheres, using a simplified method. In order to obtain single cells suspension, the brain tissue was dissociated using mechanical methods (trituration) instead of enzymatic method. These single cells suspension were in vitro cultured in DMEM)/Ham's F12 (1:1) mixture (high glucose) plus 20 ng/ml Epidermal growth factor (rHuEGF) and 20 ng/ml Fibroblast growth factor-basic (FGF-2). The results showed the combined actions of rHuEGF and bFGF-2 was in inducing proliferation of brain derived-NSCs. So, after 3 days culture numerous number of NSCs were observed floated in culture medium. Then within the time of culture the numbers of NSCs were increased. After 7 days culture some of these cells began to aggregate and form small sized neurosphere of undifferentiated cells (early stage) and within 3 weeks culture, large sized mature neurospheres were formed. When these neurospheres were aspirated and re-cultured on the gelatin pre- coated Petri dish, these neurospheres were attached and several nerve cells began to migrate from these neurospheres and occupy the surrounding area. This result confirms the incidence of NSCs derived neurospheres and it is ability to differentiate to nerve cell. In conclusion this method is simple and less expensive, less effort, but take longer time to get NSCs derived-neurosphere, as well as it is possible to use mechanical dissociation of cells (trituration) instead of enzymatic method to obtain single cell suspension.
Distribution of Hepatitis C Virus Genotype in Elazığ and the Relantionship Between HCV RNA and Serum Alanine Aminotransferase Levels With Genotype

Hepatit C virüsü (HCV) RNA yapısında ve Flaviviridae ailesinin bir üyesi olup, yüksek genetik heterojeniteye sahiptir. HCV’nin birçok genotipi ve çok sayıda subtipi tanımlanmıştır. HCV infeksiyonunun klinik seyri, tedavi süresi ve tedaviye verilen yanıt genetik heterojeniteyle ilişkilidir. Çalışmamızda Elazığ ilindeki kronik Hepatit C hastalarında genotip dağılımları ile kantitatif HCV RNA ve serum alanin aminotransferaz (ALT) düzeyleri arasındaki ilişkinin belirlenmesi amaçlanmıştır. Çalışmamıza Ocak 2014-Mart 2016 tarihleri arasında infeksiyon hastalıkları polikliniğine başvuran anti-HCV ve HCV RNA’sı pozitif 71 hasta dahil edilmiştir. Hastaların cinsiyet, yaş, HCV RNA ve ALT düzeyleri retrospektif olarak değerlendirilmiştir. Yetmiş bir hastanın 28’i kadın (% 39.4), 43’ü erkektir (% 60.5). Hastaların ALT düzeyleri ortalama 52.4±43.7 IU/ml, ortanca HCV RNA değer ise 1654267.00 IU/ml olarak bulunmuştur. Hastaların HCV genotip dağılımları incelendiğinde 62 (% 87.3) hastada genotip-1, yedi hastada (% 9.9) genotip 3 ve iki hastada (% 2.8) genotip 2 olarak tespit edilmiştir. Ülkemiz için kronik hepatit C infeksiyonu önemli bir sağlık sorunudur. Klinik sürecin takibi, tedavi seçimi ve prognozunun ön görüsünde HCV’nin genotip tayini yol göstericidir. Bu çalışmada incelenen hastalarda elde edilen HCV genotip dağılımı ülkemizde yapılmış diğer çalışma sonuçları ile uyumlu bulunmuş olup, elde edilen sonuçların bölgemiz için faydalı olacağı kanaatindeyiz.
Mechanisms underlying the effects of inulin-type fructans on the intestinal calcium absorption

Inulin-type fructans in a diet are selectively fermented by the large intestinal microflora which causes a multitude of effects that are considered as beneficial for human health and well-being. One of these well documented actions is an increased intestinal calcium absorption, similarly observed in experimental animals and in humans. Since the underlying mechanisms are not yet understood, various in vivo and in vitro experiments with rats were conducted to elucidate the molecular actions of these fructans on mineral homeostasis. The ingestion of inulin-type fructans to rats in the presented studies resulted in an increased intestinal apparent absorption, whole body retention (balance), and accumulation of calcium in femur. Similar effects were also observed for magnesium and zinc. Feeding these fructans increased also markedly the caecal absorptive surface, enhanced caecal and colonic mucosal mass, and increased caecal and colonic intraluminal contents. Analysis of the contents revealed huge increases in soluble and ionised calcium pools in rats fed the fructans. Studies on the transepithelial calcium transport in the large intestine conducted in the Ussing chambers revealed that a calcium concentration gradient (mucosal > serosal), the presence of short-chain fatty acids, and the presence of intact inulin-type fructans increased the transepithelial calcium transport. Though, feeding these fructans to rats for three weeks showed no significant alterations of the transepithelial calcium transport in the Ussing chamber experiments. However, when based on the total absorptive caecal surface – which was enlarged by the fructan feeding – net calcium absorption was doubled. Transcriptome analysis performed in large intestinal tissue samples by DNA microarrays, identified mostly regulated genes that are linked to cell cycle control. Selected genes encoding proteins involved in transcellular and paracellular calcium transport routes were analysed by real-time RT-PCR and revealed mostly increased mRNA levels in at least one of the large intestinal segments from fructan-fed animals. The present findings strongly suggest that inulin-type fructans increase the large intestinal calcium absorption primarily by a) an increased calcium availability, b) enlarging the apparent absorptive surface area, c) increasing transepithelial calcium transport directly in the presence of inulin-type fructans and their metabolites (short-chain fatty acids), and d) increased mRNA levels of proteins related to calcium transport pathways. Since some of the effects like the intestinal tissue architecture and mineral availability are not calcium specific, inulin-type fructans can increase intestinal absorption of other minerals, too, as shown here for magnesium and zinc.
Tolerance properties and growth performance assessment of Yarrowia lipolytic lipase in broilers

ABSTRACT Lipases have attracted more interest for several biotechnological applications due to their unique properties, such as security, high stability at low pH values and substrate specificity. Nevertheless, no systematic studies on its effectiveness in corn-soybean when fed to broilers have been published. In this study, in vitro and in vivo assessment of a lipase from the yeast Yarrowia lipolytica for feed purpose was performed. Results showed that Y. lipolytica lipase (YLL) displayed the highest stability at low pH values when compared with other lipases from different sources. YLL stabilized with skimmed milk powder and starch maintained 55% and 48% of its initial activity after 2 h of incubation at pH 6 with bile salt and proteases, respectively. In addition, using broilers fed as substrate, YLL formulations displayed a higher hydrolysis degree after 6 h reaction in the presence of bile salt and digestive enzymes. Moreover, in vivo effect of YLL on growth performance in broilers was studied. From 1 to 42 d, it appears from this study that there is a significant (P <. 05) effect for YLL to improve feed conversion ratio. Consequently, YLL has a great potential for using as a feed supplement in the poultry industry.
Impact of Glyphosate Herbicide and Salicylic Acid on Seed Germination, Cell Structure and Physiological Activities of Faba Bean (Vicia faba L.) Plant

The effects of salicylic acid (SA), glyphosate (Gly) and interaction of SA + Gly on seed germination and seedling growth, leaf morphology, cell ultrastructure and physiological alterations of Vicia faba plants were evaluated. SA (50 and 100 µM) reduced root seedling growth. Exposure to 250 and 500 µM Gly with or without SA caused an inhibition in seed germination and seedling growth of V. faba plants. Chlorosis, necrosis, welting, and growth reduction of V. faba was noticed in response to Gly and SA + Gly treatments. The photosynthetic pigment (Chlorophyll a (Chl a ), Chlorophyll b (Chl b ) and carotenoid (Car) contents of glyphosate and SA + Gly-treated plants were declined compared to the control. Electron microscopic observations of glyphosate-treated plants revealed disorganization in the internal structure of chloroplasts. Formation of vesicles within chloroplasts was observed in glyphosate and interaction of SA + Gly-treated plants. The lamellae and stroma thylakoids of chloroplasts were degenerated. Contents of soluble proteins and total phenolic compounds were decreased in glyphosate and SA + Gly-treated plants compared to the control. Peroxidase (POX) activity significantly increased with application of SA and glyphosate as well as with the interaction of SA + Gly compared to the control. Malondialdehyde (MDA) content in glyphosate and interaction of SA + Gly-treated plants increased compared to untreated one. The obtained results indicate that the root seedling growth of V . faba is sensitive to SA and Gly, while shoot was only sensitive to Gly herbicide treatments. The vegetative growth, cell organelles and physiological functions was negatively affected by Gly. Application doses of SA appear to be did not alleviate the toxicity of Gly herbicide on V. faba .
Prediction and visualization of the carcinogenic potential of chemicals with short-term omics assays

Drug candidates that induce or promote cancer formation must be identified and eliminated during the preclinical phase of drug development to minimize the risk of adverse, carcinogenic effects in patients. Genotoxic carcinogens can be identified with short-term assays. In contrast, the lifetime rodent cancer bioassay that is used to identify nongenotoxic carcinogenic substances, requires a high number of test animals and takes up to five years for completion. In addition, the lifetime rodent cancer bioassay does not provide sufficient data to evaluate the human risk if carcinogenic effects are observed in rodents. This can result in discontinuation of the development of the drug candidate or a black label warning on the drug packaging. The application of high-throughput omics methods such as transcriptomics or proteomics in toxicological studies is a promising approach for the development of short-term alternatives to the lifetime rodent cancer bioassay. However, these omics methods are difficult to use for life sciences researchers and few specialized visualization tools exist for toxicogenomics data. Furthermore, most existing studies used only a single omics platform to determine the molecular effects of carcinogens. This thesis introduces new approaches that integrate multiple omics platforms for the identification of nongenotoxic carcinogens and presents analysis and visualization tools that were specifically developed for toxicogenomics data. We performed a series of experiments to demonstrate that our multi-omics approach improves the prediction performance compared to single-omics approaches. To facilitate the access to our analysis and visualization tools, we implemented two web platforms, the ZBIT Bioinformatics Toolbox and MARCARviz. These web platforms enable toxicologists to gain new insights into the mechanisms of nongenotoxic tumor promotion. Furthermore, we demonstrated that our multi-omics approach can provide the basis of new short-term alternatives to the lifetime rodent cancer bioassay.