Miracle-dz/UniFAR-FTUs huggingface dataset:
SPOTONE: Hot Spots on Protein Complexes with Extremely Randomized Trees via Sequence-Only Features

Protein Hot-Spots (HS) are experimentally determined amino acids, key to small ligand binding and tend to be structural landmarks on protein–protein interactions. As such, they were extensively approached by structure-based Machine Learning (ML) prediction methods. However, the availability of a much larger array of protein sequences in comparison to determined tree-dimensional structures indicates that a sequence-based HS predictor has the potential to be more useful for the scientific community. Herein, we present SPOTONE, a new ML predictor able to accurately classify protein HS via sequence-only features. This algorithm shows accuracy, AUROC, precision, recall and F1-score of 0.82, 0.83, 0.91, 0.82 and 0.85, respectively, on an independent testing set. The algorithm is deployed within a free-to-use webserver, only requiring the user to submit a FASTA file with one or more protein sequences.
Use of Integrative Interactomics for Improvement of Farm Animal Health and Welfare: An Example with Fescue Toxicosis

Rapid scientific advances are increasing our understanding of the way complex biological interactions integrate to maintain homeostatic balance and how seemingly small, localized perturbations can lead to systemic effects. The ‘omics movement, alongside increased throughput resulting from statistical and computational advances, has transformed our understanding of disease mechanisms and the multi-dimensional interaction between environmental stressors and host physiology through data integration into multi-dimensional analyses, i.e., integrative interactomics. This review focuses on the use of high-throughput technologies in farm animal research, including health- and toxicology-related papers. Although limited, we highlight recent animal agriculture-centered reports from the integrative multi-‘omics movement. We provide an example with fescue toxicosis, an economically costly disease affecting grazing livestock, and describe how integrative interactomics can be applied to a disease with a complex pathophysiology in the pursuit of novel treatment and management approaches. We outline how ‘omics techniques have been used thus far to understand fescue toxicosis pathophysiology, lay out a framework for the fescue toxicosis integrome, identify some challenges we foresee, and offer possible means for addressing these challenges. Finally, we briefly discuss how the example with fescue toxicosis could be used for other agriculturally important animal health and welfare problems.
Role of JAK2/STAT3 pathway in angiotensin II-induced enhanced expression of Giα proteins and hyperproliferation of aortic vascular smooth muscle cells.

We earlier showed that Ang II- induced overexpression of Giα proteins contributes to the hyperproliferation of vascular smooth muscle cells (VSMC). In addition, the implication of JAK2/STAT3 pathway in Ang II-induced hyperproliferation of VSMC has also been reported. However, the role of JAK2/STAT3 pathway in Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC remains unexplored. In the present study, we show that inhibition or knockdown of JAK2/STAT3 pathway by a specific inhibitor 'Cucurbitacin I' (CuI) or siRNAs attenuated Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC. In addition, the enhanced expression of cell cycle proteins induced by Ang II was also attenuated by CuI. Furthermore, Ang II-induced enhanced production of superoxide anion (O2-), H2O2, NADPH oxidase activity, as well as the enhanced expression of NADPH oxidase subunits implicated in enhanced expression of Giα proteins and hyperproliferation were also attenuated by inhibition of JAK2/STAT3 pathway. On the other hand, Ang II-induced inhibition/augmentation of the levels of nitric oxide/ peroxynitrite in VSMC were restored to control levels by CuI. In summary, our results demonstrate that Ang II through JAK2/STAT3 pathway increases nitroxidative stress which contributes to the overexpression of Giα proteins, cell cycle proteins and hyperproliferation of VSMC.
Prevalence of antibiotic-resistant, toxic metal-tolerant and biofilm-forming bacteria in hospital surroundings

The emergence and rapid spread of antibiotic-resistant bacteria due to unethical and non-scientific disposal of hospital wastes and clinical by-products caused an alarming environmental concern and associated public health risks. The present study aims to assess the co-selection of antibiotic resistance and heavy metal tolerance by bacteria isolated from hospital effluents. These isolates were also tested for hemolytic activity, pH-tolerance, thermal inactivation, auto-aggregation, cell-surface hydrophobicity and interaction with other bacteria. The study reports the prevalence of antibiotic-resistant and heavy metal tolerant bacteria in clinical effluents and water samples. Most of these isolates were resistant to vancomycin, clindamycin, ampicillin, rifampicin, penicillin-G, methicillin and cefdinir, and evidenced the production of extended-spectrum β-lactamase enzyme. Toxic metals such as cadmium, copper, iron, lead and zinc also exert a selection pressure towards antibiotic resistance. Pseudomonas aeruginosa strain GCC_19W3, Bacillus sp. strain GCC_19S2 and Achromobacter spanius strain GCC_SB1 showed β-hemolysis, evidenced by the complete breakdown of the red blood cells. Highest auto-aggregation was exhibited by Bacillus sp. strain GCC_19S2; whereas, maximum cell-surface hydrophobicity was displayed by P. aeruginosa strain GCC_19W1. Antagonistic activity by Stenotrophomonas maltophilia strain GCC_19W2, P. aeruginosa strain GCC_19W3 and strains of Achromobacter restricts the growth of other microorganisms by producing some bactericidal substances. The study emphasises undertaking safety measures for the disposal of clinical effluents directly into the environment. The study suggests adopting necessary measures and regulations to restrict the spread of emerging pathogens within the hospital biome and community, which if unnoticed, might pose a significant clinical challenge.
Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus

Abstract Background International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors’ associations and effect modifications with IPT and pregnancy outcomes were examined. Methods Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. Results This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15–2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14–2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22–2.49). Conclusions We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.
EPIBIONTS ON CARAPACES OF SOME MALACOSTRACANS FROM THE GULF OF THAILAND

The prevalence and abundance of sessile, external epibionts on 47 malacostracan species (Amphipoda, Hoplocarida, Decapoda) from the Gulf of Thailand were studied. Densities of microepibionts (bacteria, diatoms, protozoa, fungi) and macroepibionts (macrofauna, macroalgae) on carapaces were estimated. Bacteria were detected on every malacostracan species. Between 0.70 X 103 and 28.72 x 103 cells per mm2 were found. The densities on most species were below 1 x 104 mm-2. Diatoms were recorded on 18 species. Diatom densities ranged from 0.02-7.38 x 103 cm-2. Protozoa occurred in very low numbers (maximum = 0.5 x 103 cm-2) on the carapaces. Protozoa were found on 8 species. Fungal spores were detected on 18 species. Their number ranged from 0.1-2.2 cm-2. Macroorganisms were recorded on 9 species. They covered usually less than 10% of the carapace surface. Hyasthenus diacanthus (Majidae) was the most heavily fouled host. An average of 63% of the carapace surface was covered by metazoans (sponges, hydrozoa, actinians, polychaetes, barnacles, ascidians). However, most crabs appeared to be little fouled, indicating that they possess efficient antifouling mechanisms. An investigation of densities of epibionts on 3 species of crabs (Sphaerozius nitidus, Etisus c.f. laevimanus, Metapograpsus quadridentatus), shells of living oysters, and artificial and natural hard substrata collected at the same location showed that crabs were less heavily fouled than the other substrates. Molting, grooming, chemical defense mechanisms, and environmental factors may account for some of the patterns observed in the prevalence and abundance of colonizers on their hosts.
Programmed DNA Elimination in Vertebrates.

Over the last few decades, an increasing number of vertebrate taxa have been identified that undergo programmed genome rearrangement, or programmed DNA loss, during development. In these organisms, the genome of germ cells is often reproducibly different from the genome of all other cells within the body. Although we clearly have not identified all vertebrate taxa that undergo programmed genome loss, the list of species known to undergo loss now represents ∼10% of vertebrate species, including several basally diverging lineages. Recent studies have shed new light on the targets and mechanisms of DNA loss and their association with canonical modes of DNA silencing. Ultimately, expansion of these studies into a larger collection of taxa will aid in reconstructing patterns of shared/independent ancestry of programmed DNA loss in the vertebrate lineage, as well as more recent evolutionary events that have shaped the structure and content of eliminated DNA. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Functional Recovery of a GCDH Variant Associated to Severe Deflavinylation—Molecular Insights into Potential Beneficial Effects of Riboflavin Supplementation in Glutaric Aciduria-Type I Patients

Riboflavin is the biological precursor of two important flavin cofactors—flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)—that are critical prosthetic groups in several redox enzymes. While dietary supplementation with riboflavin is a recognized support therapy in several inborn errors of metabolism, it has yet unproven benefits in several other pathologies affecting flavoproteins. This is the case for glutaric aciduria type I (GA-I), a rare neurometabolic disorder associated with mutations in the GCDH gene, which encodes for glutaryl-coenzyme A (CoA) dehydrogenase (GCDH). Although there are a few reported clinical cases that have responded to riboflavin intake, there is still not enough molecular evidence supporting therapeutic recommendation. Hence, it is necessary to elucidate the molecular basis in favor of riboflavin supplementation in GA-I patients. Here, using a combination of biochemical and biophysical methodologies, we investigate the clinical variant GCDH-p.Val400Met as a model for a phenotype associated with severe deflavinylation. Through a systematic analysis, we establish that recombinant human GCDH-p.Val400Met is expressed in a nonfunctional apo form, which is mainly monomeric rather than tetrameric. However, we show that exogenous FAD is a driver for structural reorganization of the mutant enzyme with concomitant functional recovery, improved thermolability, and resistance to trypsin digestion. Overall, these results establish proof of principle for the beneficial effects of riboflavin supplementation in GA-I patients.
The Use of Less Conventional Meats or Meat with High pH Can Lead to the Growth of Undesirable Microorganisms during Natural Meat Fermentation

The bacterial communities that are established during natural meat fermentation depend on the processing conditions and the type of meat substrate used. Six pork samples of variable quality (reflected in pH values) and six less conventional meats (beef, horse, hare, wild deer, wild duck, and wild boar) were naturally fermented under controlled conditions in model systems. The development of lactic acid bacteria (LAB), coagulase-negative staphylococci (CNS), and enterobacteria was followed using culture-dependent techniques and (GTG)5-PCR fingerprinting of genomic DNA from the isolates obtained. Taken together, Latilactobacillus sakei was the most abundant LAB species, although Latilactobacillus curvatus was more manifest in high-pH pork. Within staphylococci, common species were encountered (i.e., Staphylococcus equorum, Staphylococcus saprophyticus, and Staphylococcus xylosus), although some atypical ones (i.e., Staphylococcus succinus) were also recovered. Within enterobacteria, Serratia spp. prevailed in more acidic pork batches and in beef, whereas Hafnia spp. prevailed in game meat fermentations. Enterobacterial counts were particularly high in fermentations with low acidity, namely for some pork batches, hare, wild duck, and wild boar. These findings should be considered when naturally fermented meat products are manufactured, as the use of game meat or meat with high pH can give rise to safety concerns.
Genome-Wide Analysis of OPR Family Genes in Cotton Identified a Role for GhOPR9 in Verticillium dahliae Resistance

The 12-oxo-phytodienoic acid reductases (OPRs) have been proven to play a major role in plant development and growth. Although the classification and functions of OPRs have been well understood in Arabidopsis, tomato, rice, maize, and wheat, the information of OPR genes in cotton genome and their responses to biotic and abiotic stresses have not been reported. In this study, we found 10 and 9 OPR genes in Gossypium hirsutum and Gossypium barbadense, respectively. They were classified into three groups, based on the similar gene structure and conserved protein motifs. These OPR genes just located on chromosome 01, chromosome 05, and chromosome 06. In addition, the whole genome duplication (WGD) or segmental duplication events contributed to the evolution of the OPR gene family. The analyses of cis-acting regulatory elements of GhOPRs showed that the functions of OPR genes in cotton might be related to growth, development, hormone, and stresses. Expression patterns showed that GhOPRs were upregulated under salt treatment and repressed by polyethylene glycol 6000 (PEG6000). The expression patterns of GhOPRs were different in leaf, root, and stem under V. dahliae infection. GhOPR9 showed a higher expression level than other OPR genes in cotton root. The virus-induced gene silencing (VIGS) analysis suggested that knockdown of GhOPR9 could increase the susceptibility of cotton to V. dahliae infection. Furthermore, GhOPR9 also modulated the expressions of jasmonic acid (JA) pathway-regulated genes under the V. dahliae infection. Overall, our results provided the evolution and potential functions of the OPR genes in cotton. These findings suggested that GhOPR9 might play an important role in cotton resistance to V. dahliae.
Exploring the Expression of Cardiac Regulators in a Vertebrate Extremophile: The Cichlid Fish Oreochromis (Alcolapia) alcalica

Although it is widely accepted that the cellular and molecular mechanisms of vertebrate cardiac development are evolutionarily conserved, this is on the basis of data from only a few model organisms suited to laboratory studies. Here, we investigate gene expression during cardiac development in the extremophile, non-model fish species, Oreochromis (Alcolapia) alcalica. We first characterise the early development of O. alcalica and observe extensive vascularisation across the yolk prior to hatching. We further investigate heart development by identifying and cloning O. alcalica orthologues of conserved cardiac transcription factors gata4, tbx5, and mef2c for analysis by in situ hybridisation. Expression of these three key cardiac developmental regulators also reveals other aspects of O. alcalica development, as these genes are expressed in developing blood, limb, eyes, and muscle, as well as the heart. Our data support the notion that O. alcalica is a direct-developing vertebrate that shares the highly conserved molecular regulation of the vertebrate body plan. However, the expression of gata4 in O. alcalica reveals interesting differences in the development of the circulatory system distinct from that of the well-studied zebrafish. Understanding the development of O. alcalica embryos is an important step towards providing a model for future research into the adaptation to extreme conditions; this is particularly relevant given that anthropogenic-driven climate change will likely result in more freshwater organisms being exposed to less favourable conditions.
Intravitreous delivery of melatonin affects the retinal neuron survival and visual signal transmission: in vivo and ex vivo study

Abstract Intravitreal delivery can maximize the intensity of therapeutic agents and extend their residence time within ocular tissue. Melatonin is a lipophilic molecule that crosses freely biological barriers and cell membranes. This study intends to investigate the effects of intravitreally delivered melatonin on mouse retina. The visual function of administered mice is assessed by electrophysiological and behavior examinations three weeks after intravitreal delivery. Moreover, multi-electrode array (MEA) was used to assess the electrical activities of retinal ganglion cells (RGCs). We found that intravitreal delivery of high dosage melatonin (400–500 µg/kg) destroyed the retinal architecture and impaired the visual function of mice. Conversely, the melatonin administration at low dose (100–300 µg/kg) did not have any significant effects on the photoreceptor survival or visual function. As shown in the MEA recording, the photoreceptors activity of the central region was more severely disturbed by the high dose melatonin. A pronounced augment of the spontaneous firing frequency was recorded in these mice received high dosage melatonin, indicating that intravitreal delivery of high dosage melatonin would affect the electrical activity of RGCs. Immunostaining assay showed that the vitality of cone photoreceptor was impaired by high dose melatonin. These findings suggest that intravitreal melatonin is not always beneficial for ocular tissues, especially when it is administered at high dosage. These data add new perspectives to current knowledge about melatonin delivery at the ocular level. Further therapeutic strategies should take into consideration of these risks that caused by delivery approach.
Predicting Survival in Glioblastoma Patients Using Diffusion MR Imaging Metrics—A Systematic Review

Simple Summary An accurate survival analysis is crucial for disease management in glioblastoma (GBM) patients. Due to the ability of the diffusion MRI techniques of providing a quantitative assessment of GBM tumours, an ever-growing number of studies aimed at investigating the role of diffusion MRI metrics in survival prediction of GBM patients. Since the role of diffusion MRI in prediction and evaluation of survival outcomes has not been fully addressed and results are often controversial or unsatisfactory, we performed this systematic review in order to collect, summarize and evaluate all studies evaluating the role of diffusion MRI metrics in predicting survival in GBM patients. We found that quantitative diffusion MRI metrics provide useful information for predicting survival outcomes in GBM patients, mainly in combination with other clinical and multimodality imaging parameters. Abstract Despite advances in surgical and medical treatment of glioblastoma (GBM), the medium survival is about 15 months and varies significantly, with occasional longer survivors and individuals whose tumours show a significant response to therapy with respect to others. Diffusion MRI can provide a quantitative assessment of the intratumoral heterogeneity of GBM infiltration, which is of clinical significance for targeted surgery and therapy, and aimed at improving GBM patient survival. So, the aim of this systematic review is to assess the role of diffusion MRI metrics in predicting survival of patients with GBM. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic literature search was performed to identify original articles since 2010 that evaluated the association of diffusion MRI metrics with overall survival (OS) and progression-free survival (PFS). The quality of the included studies was evaluated using the QUIPS tool. A total of 52 articles were selected. The most examined metrics were associated with the standard Diffusion Weighted Imaging (DWI) (34 studies) and Diffusion Tensor Imaging (DTI) models (17 studies). Our findings showed that quantitative diffusion MRI metrics provide useful information for predicting survival outcomes in GBM patients, mainly in combination with other clinical and multimodality imaging parameters.
BEM-ESTAR, AMBIÊNCIA E SAÚDE ANIMAL

A medicina veterinaria tem fundamentado o entendimento da qualidade de vida na saude animal (SAMBRAUS, 1990). Com esta visao os Cursos de Medicina Veterinaria estruturam a formacao do profissional que se envolvera diretamente com o animal de producao para prevenir ou identificar e tratar doencas oferecendo em sua grade curricular conteudos aplicados a Sanidade: epidemiologia e doencas infecciosas; Saude Animal: Clinica e Cirurgia e paralelamente a Zootecnia, em que oferece-se o aprendizado das tecnicas de criacao e as disciplinas que envolvem a nutricao, com uma visao voltada para a produtividade. Nasceu ai um paradigma para a ciencia veterinaria que tinha por tradicao o entendimento de que um animal tem uma otima qualidade de bem-estar se estiver saudavel (livre de doenca) e bem alimentado. Com estas necessidades satisfeitas o animal nao teria razao para sofrer. Este conceito esquece fatores fundamentais que fazem parte do bem-estar de um animal e que consiste na satisfacao das suas necessidades etologicas, que podem resultar em sofrimento psicologico para os quais nos medicos veterinarios fomos menos preparados para compreender, diagnosticar e muito menos para solucionar ou tratar (ALGER, 2008).