Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiotic resistance of Escherichia coli isolated from captive Bengal tigers at Safari parks in Bangladesh

Objectives: The present study was carried out to assess the antibiotic resistance and to identify the resistance genes in Escherichia coli from captive Bengal tigers at two Safari parks in Bangladesh. Materials and Methods: A number of 24 environmental fecal swab samples of Bengal tigers were collected from two different Safari parks in Bangladesh. For the isolation of E. coli, samples were submitted to a number of bacteriological screening and biochemical tests. The antibiotic susceptibility of E. coli isolates was determined by disk diffusion method. Results: Results demonstrated that 18 environmental fecal samples were positive to E. coli in bacteriological screening and biochemical test. The overall prevalence of E. coli in Bengal tiger was 75% (n = 18/24). The antibiogram study unveiled that all the isolates were resistant to ampicillin. Sulfamethoxazole-trimethoprim, nalidixic acid, and tetracycline were 89% (n = 16/18) resistant. On the contrary, 100% (n = 18/18) of the isolates were sensitive to colistin sulfate. blaTEM was detected in 78% (n = 14/18) ampicillin-resistant isolates, whereas sul2 was found in 31% (n = 5/16) of the sulfamethoxazole-trimethoprim-resistant isolates. Conclusion: This study, first time in Bangladesh, highlights a significant proportion of environmental fecal samples from captive Bengal tigers at Safari parks harboring antibiotic resistant E. coli. Transmission of resistant E. coli from Bengal tigers to humans and the environment could pose a public health risk at Safari parks in Bangladesh.
NNT Regulates Mitochondrial Metabolism in NSCLC Through Maintenance of Fe-S Protein Function

Human lung tumors exhibit robust and complex mitochondrial metabolism, likely precipitated by the highly oxygenated nature of pulmonary tissue. As ROS generation is a byproduct of this metabolism, reducing power in the form of nicotinamide adenine dinucleotide phosphate (NADPH) is required to mitigate oxidative stress in response to this heightened mitochondrial activity. Nicotinamide nucleotide transhydrogenase (NNT) is known to sustain mitochondrial antioxidant capacity through the generation of NADPH, however its function in non-small cell lung cancer (NSCLC) has not been established. We found that NNT expression significantly enhances tumor formation and aggressiveness in mouse models of lung tumor initiation and progression. We further show that NNT loss elicits mitochondrial dysfunction independent of substantial increases in oxidative stress, but rather marked by the diminished activities of proteins dependent on resident iron-sulfur clusters. These defects were associated with both NADPH availability and ROS accumulation, suggesting that NNT serves a specific role in mitigating the oxidation of these critical protein cofactors.
Conformation-Dependent Influences of Hydrophobic Amino Acids in Two In-Register Parallel β-Sheet Amyloids, an α-Synuclein Amyloid and a Local Structural Model of PrPSc

Prions are unconventional pathogens that encode the pathogenic information in conformations of the constituent abnormal isoform of prion protein (PrPSc), independently of the nucleotide genome. Therefore, conformational diversity of PrPSc underlies the existence of many prion strains and species barriers of prions, although the conformational information is extremely limited. Interestingly, differences between polymorphic or species-specific residues responsible for the species/strain barriers are often caused by conservative replacements between hydrophobic amino acids. This implies that subtle differences among hydrophobic amino acids are significant for PrPSc structures. Here, we analyzed the influence of different hydrophobic residues on the structures of an in-register parallel β-sheet amyloid of α-synuclein (αSyn) using molecular dynamics (MD) simulation, and applied the knowledge from the αSyn amyloid to modeling a local structure of human PrPSc encompassing residues 107–143. We found that mutations equivalent to polymorphisms that cause transmission barriers substantially affect the stabilities; for example, the G127V mutation, which makes the host resistant to various human prion diseases, greatly destabilized the model amyloid. Our study demonstrates specifically how and in what structures hydrophobic residues can exert unique effects on in-register parallel β-sheet amyloids and provides insights into the molecular mechanism of the strain diversity of prions and other pathogenic amyloids. For Table of Contents Only
Mitochondrial landscape of indigenous pig germplasm of Andaman and Nicobar Islands

Abstract Nicobari pig and Andaman Desi pig are indigenous pig germplasm of Andaman and Nicobar islands, India. Over the last two decades, the pig breeds witnessed a rapid decline in population, necessitating immediate characterization and conservation. The present study depicts the complete mitochondrial genome sequence of Nicobari pig and Andaman Desi pig. The mitogenomes of both the breeds encode 37 genes including 13 protein coding genes, 22 tRNAs, and two ribosomal RNA genes. In addition, a control region (D-loop) was also present. Phylogenetic analysis showed that Nicobari is phylogenetically close to Banna mini and Breed I pig, whereas Andaman Desi pig is close to Mong cai and Jinhua pig breeds. The results of the study will be helpful for formulating of conservation strategy of the native swine breeds.
A Physiology-Based Model of Human Bile Acid Metabolism for Predicting Bile Acid Tissue Levels After Drug Administration in Healthy Subjects and BRIC Type 2 Patients

Drug-induced liver injury (DILI) is a matter of concern in the course of drug development and patient safety, often leading to discontinuation of drug-development programs or early withdrawal of drugs from market. Hepatocellular toxicity or impairment of bile acid (BA) metabolism, known as cholestasis, are the two clinical forms of DILI. Whole-body physiology-based modelling allows a mechanistic investigation of the physiological processes leading to cholestasis in man. Objectives of the present study were: (1) the development of a physiology-based model of the human BA metabolism, (2) population-based model validation and characterisation, and (3) the prediction and quantification of altered BA levels in special genotype subgroups and after drug administration. The developed physiology-based bile acid (PBBA) model describes the systemic BA circulation in humans and includes mechanistically relevant active and passive processes such as the hepatic synthesis, gallbladder emptying, transition through the gastrointestinal tract, reabsorption into the liver, distribution within the whole body, and excretion via urine and faeces. The kinetics of active processes were determined for the exemplary BA glycochenodeoxycholic acid (GCDCA) based on blood plasma concentration-time profiles. The robustness of our PBBA model was verified with population simulations of healthy individuals. In addition to plasma levels, the possibility to estimate BA concentrations in relevant tissues like the intracellular space of the liver enhance the mechanistic understanding of cholestasis. We analysed BA levels in various tissues of Benign Recurrent Intrahepatic Cholestasis type 2 (BRIC2) patients and our simulations suggest a higher susceptibility of BRIC2 patients toward cholestatic DILI due to BA accumulation in the liver. The effect of drugs on systemic BA levels were simulated for cyclosporine A (CsA). Our results confirmed the higher risk of DILI after CsA administration in healthy and BRIC2 patients. The presented PBBA model enhances our mechanistic understanding underlying cholestasis and drug-induced alterations of BA levels in blood and organs. The developed PBBA model might be applied in the future to anticipate potential risk of cholestasis in patients.
Generation of Recombinant Mammalian Selenoproteins through Genetic Code Expansion with Photocaged Selenocysteine

Selenoproteins contain the amino acid selenocysteine and are found in all domains of life. The functions of many selenoproteins are poorly understood, partly due to difficulties in producing recombinant selenoproteins for cell-biological evaluation. Endogenous mammalian selenoproteins are produced through a non-canonical translation mechanism requiring suppression of the UGA stop codon, and a selenocysteine insertion sequence (SECIS) element in the 3’ untranslated region of the mRNA. Here, recombinant selenoproteins are generated in mammalian cells through genetic code expansion, circumventing the requirement for the SECIS element, and selenium availability. An engineered orthogonal E. coli leucyl-tRNA synthetase/tRNA pair is used to incorporate a photocaged selenocysteine (DMNB-Sec) at the UAG amber stop codon. Recombinantly expressed selenoproteins can be photoactivated in living cells with spatial and temporal control. Using this approach, the native selenoprotein methionine-R-sulfoxide reductase 1 is generated and activated in mammalian cells. The ability to site-specifically introduce selenocysteine directly in mammalian cells, and temporally modulate selenoprotein activity, will aid in the characterization of mammalian selenoprotein function.
Characterization of the complete mitochondrial genome of Corynespora cassiicola (Pleosporales: Dothideomycetes), with its phylogenetic analysis

Abstract Corynespora cassiicola is a well-known plant pathogen with a broad host range and diverse lifestyles. In this study, we presented the complete mitochondrial genome (mitogenome) of C. cassiicola for the first time. It has a total length of 40,752 bp, which encodes 17 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNA), and 27 transfer RNA (tRNA) genes. The nucleotide composition of the mitogenome is: A (36.24%), T (34.62%), G (15.74%), and C (13.39%). Phylogenetic analysis revealed that C. cassiicola has a close relationship with Didymella pinodes from Didymellaceae.
Phylogenomics Yields New Insight Into Relationships Within Vernonieae (Asteraceae)

Asteraceae, or the sunflower family, is the largest family of flowering plants and is usually considered difficult to work with, not only due to its size, but also because of the abundant cases of polyploidy and ancient whole-genome duplications. Traditional molecular systematics studies were often impaired by the low levels of variation found in chloroplast markers and the high paralogy of traditional nuclear markers like ITS. Next-generation sequencing and novel phylogenomics methods, such as target capture and Hyb-Seq, have provided new ways of studying the phylogeny of the family with great success. While the resolution of the backbone of the family is in progress with some results already published, smaller studies focusing on internal clades of the phylogeny are important to increase sampling and allow morphological, biogeography, and diversification analyses, as well as serving as basis to test the current infrafamilial classification. Vernonieae is one of the largest tribes in the family, accounting for approximately 1,500 species. From the 1970s to the 1990s, the tribe went through several reappraisals, mainly due to the splitting of the mega genus Vernonia into several smaller segregates. Only three phylogenetic studies focusing on the Vernonieae have been published to date, both using a few molecular markers, overall presenting low resolution and support in deepest nodes, and presenting conflicting topologies when compared. In this study, we present the first attempt at studying the phylogeny of Vernonieae using phylogenomics. Even though our sampling includes only around 4% of the diversity of the tribe, we achieved complete resolution of the phylogeny with high support recovering approximately 700 nuclear markers obtained through target capture. We also analyzed the effect of missing data using two different matrices with different number of markers and the difference between concatenated and gene tree analysis.
NLIMED: Natural Language Interface for Model Entity Discovery in Biosimulation Model Repositories

Semantic annotation is a crucial step to assure reusability and reproducibility of biosimulation models in biology and physiology. For this purpose, the COmputational Modeling in BIology NEtwork (COMBINE) community recommends the use of the Resource Description Framework (RDF). This grounding in RDF provides the flexibility to enable searching for entities within models (e.g., variables, equations, or entire models) by utilizing the RDF query language SPARQL. However, the rigidity and complexity of the SPARQL syntax and the nature of the tree-like structure of semantic annotations, are challenging for users. Therefore, we propose NLIMED, an interface that converts natural language queries into SPARQL. We use this interface to query and discover model entities from repositories of biosimulation models. NLIMED works with the Physiome Model Repository (PMR) and the BioModels database and potentially other repositories annotated using RDF. Natural language queries are first “chunked” into phrases and annotated against ontology classes and predicates utilizing different natural language processing tools. Then, the ontology classes and predicates are composed as SPARQL and finally ranked using our SPARQL Composer and our indexing system. We demonstrate that NLIMED's approach for chunking and annotating queries is more effective than the NCBO Annotator for identifying relevant ontology classes in natural language queries.Comparison of NLIMED's behavior against historical query records in the PMR shows that it can adapt appropriately to queries associated with well-annotated models.
Functional Studies on Novel RET Mutations and Their Implications for Genetic Counseling for Hirschsprung Disease

Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of ganglion cells in the gut. RET is considered to be the main susceptibility gene. In our previous screening of 83 HSCR patients, targeted exome sequencing identified nine rare variants of RET, most of which were new discoveries. Here, we performed in vitro arrays with functional studies to investigate their effects. Two variants (p.R77C and p.R67insL) were demonstrated to disrupt the glycosylation of RET and affect its subcellular localization. Three nonsense mutations (p.W85X, p.E252X, and p.Y263X) could not produce detectable RET full-length protein, and the other three mutations (p.R770X, p.Q860X, and p.V778Afs*1) were translated into truncated proteins of predicted sizes. One canonical splice acceptor site mutation (c.2802-2 A > G) was verified to affect gene regulation through aberrant splicing. In addition, we explored the effects of read-through reagents on RET nonsense mutations and showed that G418 significantly increased the full-length RET protein expression of p.Y263X in a dose-dependent manner, together with a mild recovery of p-ERK and p-STAT3. Our data provide a functional analysis of novel RET mutations and suggest that all of the rare variants detected from patients with clinically severe HSCR are indeed pathogenic. Thus, our findings have implications for proper genetic counseling.
Multidisciplinary Biodosimetric Tools for a Large-scale Radiological Emergency : the MULTIBIODOSE Project

Copyright © 2014 by Hirosaki University. All rights reserved. Large scale radiological emergencies pose a particular problem for emergency preparedness because of potentially large numbers of worried well and the necessity to carry out triage in a timely manner. Here, an indispensable tool is biological dosimetry. Although a number of biodosimetric tools exist, not many have been tested and adapted for a large scale emergency scenario. In the framework of an EU-funded project MULTIBIODOSE we tested a variety of biodosimetric tools and adapted them to different mass casualty scenarios. The assays were chosen because they complement each other with respect to sensitivity, specificity to radiation and the exposure scenario, as well as speed of performance. The project was completed in April 2013. Its major conclusions are presented.
Neuronal over-expression of Oxr1 is protective against ALS-associated mutant TDP-43 mislocalisation in motor neurons and neuromuscular defects in vivo

Abstract A common pathological hallmark of amyotrophic lateral sclerosis (ALS) and the related neurodegenerative disorder frontotemporal dementia, is the cellular mislocalization of transactive response DNA-binding protein 43 kDa (TDP-43). Additionally, multiple mutations in the TARDBP gene (encoding TDP-43) are associated with familial forms of ALS. While the exact role for TDP-43 in the onset and progression of ALS remains unclear, the identification of factors that can prevent aberrant TDP-43 localization and function could be clinically beneficial. Previously, we discovered that the oxidation resistance 1 (Oxr1) protein could alleviate cellular mislocalization phenotypes associated with TDP-43 mutations, and that over-expression of Oxr1 was able to delay neuromuscular abnormalities in the hSOD1G93A ALS mouse model. Here, to determine whether Oxr1 can protect against TDP-43-associated phenotypes in vitro and in vivo, we used the same genetic approach in a newly described transgenic mouse expressing the human TDP-43 locus harbouring an ALS disease mutation (TDP-43M337V). We show in primary motor neurons from TDP-43M337V mice that genetically-driven Oxr1 over-expression significantly alleviates cytoplasmic mislocalization of mutant TDP-43. We also further quantified newly-identified, late-onset neuromuscular phenotypes of this mutant line, and demonstrate that neuronal Oxr1 over-expression causes a significant reduction in muscle denervation and neuromuscular junction degeneration in homozygous mutants in parallel with improved motor function and a reduction in neuroinflammation. Together these data support the application of Oxr1 as a viable and safe modifier of TDP-43-associated ALS phenotypes.
Nutrients in the Prevention of Alzheimer's Disease

Alzheimer's disease (AD) is a disease caused by the complex interaction of multiple mechanisms, some of which are still not fully understood. To date, pharmacological treatments and supplementation of individual nutrients have been poorly effective in terms of the prevention and treatment of AD, while alternative strategies based on multimodal approaches (diet, exercise, and cognitive training) seem to be more promising. In this context, the focus on dietary patterns rather than on single food components could be more useful in preventing or counteracting the pathological processes typical of AD, thanks to the potential synergistic effects of various nutrients (neuronutrients). The aim of this narrative review is to summarize the currently existing preclinical and clinical evidence regarding the Mediterranean diet (MeDi), the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which are three dietary patterns with well-known anti-inflammatory and antioxidant properties. Recently, they have been related to brain protection and AD prevention, perhaps thanks to their high content of neuroprotective bioactive compounds. Similarly, intermittent fasting (IF) or calorie restriction (CR) is emerging as interesting approaches that seem to promote hippocampal neurogenesis, activate adaptive stress response systems, and enhance neuronal plasticity, thus leading to motor and cognitive improvements in animal models of AD and hopefully also in human beings.
Evaluation of essential oils and a prebiotic for newborn dairy calves1

Abstract A blend of essential oils (EO) and a prebiotic were combined (EOC) to formulate a colostrum-based liquid birth supplement and a separate feeding supplement (Start Strong and Stay Strong, Ralco Inc., Marshall, MN). These products were designed to promote immunity and stimulate appetite to diminish health challenges and stresses experienced by newborn calves. The hypothesis was that calves supplemented with an oral dose of liquid EOC at birth (10-mL aliquot at birth and 10 mL at 12 h of age) when fed the EOC feeding supplement would result in improved growth performance, health, and immunity. The objective was to determine if an additional feeding of liquid EOC at birth in combination with EOC in the milk replacer (MR) would allow calves to demonstrate improved growth, health, and immunity compare with calves only offered EO in MR. Sixty-one Holstein calves (18 males and 43 females) from a commercial dairy operation were blocked by birth date and randomly assigned to 1 of 3 treatments. Treatments were 1) Control (CON): a 24% crude protein (CP):20% fat (as-fed basis) MR; 2) EP: a 24:20 MR with EOC mixed at 1.25 g/d; or 3) EPC: a 24:20 MR with EOC mixed at 1.25 g/d in addition to calves receiving one 10-mL oral dose of liquid EOC at birth and 10 mL again at 12 h. The 24:20 MR was fed via bucket 2 times per day at a rate of 0.57 kg/calf daily for 14 d, increased to 0.85 kg/calf at 2 times per day until 35 d and was reduced to 0.43 kg at 1 time per day at 36 d to facilitate weaning after 42 d. Decoquinate was added to the MR at 41.6 mg/kg for coccidiosis control. Calves were housed in individual hutches bedded with straw with ad libitum access to a 20% CP-pelleted calf starter and water. All data were analyzed using PROC MIXED as a randomized complete block design. Calves in this study had similar (P > 0.10) average daily gains, body weight, and growth measurements. Calves fed EPC had significantly (P < 0.05) higher IgA titers on day 0 of the trial compared with calves fed EP or CON, which was expected as calves were supplemented with liquid EOC at birth and 12 h later demonstrating an increase in immune response. The use of a liquid EOC product being administrated after birth can improve IgA titers to improve the immune status of the new born calf to fight off potential diseases and pathogens. A formulation error resulted in the EOC being fed at half the rate of the previous experiment of 2.5 g/d, which appears to be below an efficacious dosage.
Accumulation of degree days and their effect on the potential yield of 15 eggplant (Solanum melongena L.) accessions in the Colombian Caribbean

The growing degree-days (GDD) provide an estimate of the accumulated thermal energy available for the development of a crop. The use of GDD allows measuring the heat requirements associated with the phenological stages of the crop, which allows in turn, to predict when a certain plant stage will occur knowing the daily temperatures. The aim of this study was to establish relationships among the effect of degree days (DD) to vegetative growth, first flowering and fructification (VG, Fl and Fr), on total yield per plant (TY/P) of eggplant grown under open-field conditions employing a randomized complete block design with 15 genotypes and four replicates. The results showed that: 1) The genotypes that initiated fruit production in less time required fewer GDD (892.14-1,077.71 °C) for this phenological phase, obtaining higher productivity. 2) The genotypes C035 and C040 had an average yield higher than the national average with values of 83.75 and 84.86 t ha-1, being identified as future varieties to be produced in the Caribbean region. 3) The Caribbean region is suitable for the establishment of the crop as there were no events with limiting temperatures for this species (higher than 35 °C and lower than 15 °C). 4) The principal component analysis showed associations among the variable YT/P with the genotypes C011, C042, and C015; meanwhile, C032, C025, and C028 were associated with the variables DD to VG, Fl, and Fr. These results would be useful in developing a model to estimate yield with DD.