Miracle-dz/UniFAR-FTUs huggingface dataset:
Left ventricular hypertrophy is associated with overexpression of HSP60, TLR2, and TLR4 in the myocardium

Abstract Left ventricular hypertrophy is a common adaptive response to increased cardiac workload. Cardiomyocytes growth and increase in contractile force are conditioned by sufficient energy production, which implies appropriate mitochondrial function. The 60 kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis, but when translocates from mitochondria, it can also act as a potent inflammatory mediator binding to toll-like receptors (TLRs). In this study, we aimed to compare the expression pattern of HSP60, TLR2, and TLR4 in hypertrophic vs non-hypertrophic, normal human myocardium. We further examined whether HSP60 in situ binds to TLRs in hypertrophic myocardial tissue. In addition, expression of activated downstream targets of TLR 2/4 pathways was also evaluated. For this purpose, immunohistochemical expression analyses were performed on myocardial tissue samples obtained during the autopsy of human subjects in which left ventricular hypertrophy was the only cardiopathological finding and had died from sudden cardiac death, as well as from the subjects without any cardiac pathology, that died by unnatural death (accident or suicide). Double immunofluorescence was used to examine HSP60 translocation, while proximity ligation assay (PLA) was performed to assess HSP60 and TLRs interactions. Hypertrophic myocardium showed significantly higher expression of HSP60, TLR2, and TLR4 compared to normal myocardium. Furthermore, in hypertrophic cardiomyocytes, we found membrane translocation of HSP60 and signs of HSP60/TLR interactions. Conclusion: The obtained data point to an important supportive role of HSP60 in adaptive cardiomyocytes growth, while concomitant induction of TLR2 and TLR4 candidates HSP60-TLRs interactions as an early events during pathogenesis of secondary complications consequently to the left ventricular hypertrophy.
Draft Genome Sequence of Staphylococcus pseudintermedius Strain 13-13613, Isolated from a Case of Canine Pyoderma

Here, we report the draft genome sequence of Staphylococcus pseudintermedius strain 13-13613, isolated from a case of canine pyoderma. The draft genome contains 2,533,486 bp in 570 contigs. ABSTRACT Here, we report the draft genome sequence of Staphylococcus pseudintermedius strain 13-13613, isolated from a case of canine pyoderma. The draft genome contains 2,533,486 bp in 570 contigs.
Nutritional value and in situ degradability of oak wood roughage and its feeding effects on growth performance and behavior of Hanwoo steers during the early fattening period

Objective This study was conducted to evaluate changes in nutritional value and in situ dry matter (DM) degradability of oak and pine wood before and after steam-digestion process (60 min/160°C/6 atm) and feeding effect of the oak roughage on performance and behavior of Hanwoo steers. Methods Chemical composition and tannin concentration were analyzed for oak and pine trees before and after the pretreatment. In situ DM and effective degradability of these samples were assessed using a nylon bag method. In vivo trial was performed to estimate animal performance and behavior, using steers fed total mixed ration (TMR) diets containing 0% (control), 25% (OR-25), and 50% (OR-50) of the oak roughage. Eighteen steers were allocated into nine pens (2 steers/pen, 3 pens/treatment) for 52 days according to body weight (BW) and age. Results By the steam-digestion treatment, the neutral detergent-insoluble fiber was decreased from 86.5% to 71.5% for oak and from 92.4% to 80.5% for pine, thereby increasing non-fiber carbohydrate. In situ DM degradability of treated oak reached 38% at 72 h, whereas that of untreated oak was only 11.9%. The 0 h degradability of the treated pine increased from 5.9% to 12.1%, but the degradability was unchanged thereafter. Animal performance including BW, average daily gain, DM intake, and feed conversion ratio was not different among control and oak treatments. No differences were detected in animal behavior such as lying, standing, rumination, drinking, and eating, except walking. Walking was higher in control than oak treatments with numerically higher eating and lower lying times, probably due to bulkier characteristics of rice straw in the diet. Conclusion This study demonstrates that the oak roughage can be substituted for 50% of total forage or 100% of rice straw in TMR diets at early fattening stage of Hanwoo steers.
Prevalent pH Controls the Capacity of Galdieria maxima to Use Ammonia and Nitrate as a Nitrogen Source

Galdieria maxima is a polyextremophilic alga capable of diverse metabolic processes. Ammonia is widely used in culture media typical of laboratory growth. Recent reports that this species can grow on wastes promote the concept that G. maxima might have biotechnological utility. Accordingly, there is a need to know the range of pH levels that can support G. maxima growth in a given nitrogen source. Here, we examined the combined effect of pH and nitrate/ammonium source on the growth and long-term response of the photochemical process to a pH gradient in different G. maxima strains. All were able to use differing nitrogen sources, despite both the growth rate and photochemical activity were significantly affected by the combination with the pH. All strains acidified the NH4+-medium (pH<3); only G. maxima IPPAS P507 showed reduced capacity in lowering the pH from 6.5. pH was a limiting factor in nitrate uptake at pH≥6.5; noteworthy, at pH 5 on nitrate G. maxima ACUF551 showed a good growth performance, despite the alkalization of the medium.
In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan

Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalized medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. Each molecular mechanism generated could be associated to particular individuals, here defined as prototype-patients, hence the generation of models using TPMS technology may be used for detecting adverse effects to specific patients. TPMS operates by (1) modelling the responses in humans with an accurate description of a protein network and (2) applying a Multilayer Perceptron-like and sampling strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a wide range of models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their association with macular degeneration (a potential adverse effect). Among the models generated, we identify a set of mechanisms of action associated to a better response in terms of heart failure treatment, which could also be associated to macular degeneration development. Finally, a set of 30 potential biomarkers are proposed to identify mechanisms (or prototype-patients) more prone of suffering macular degeneration when presenting good heart failure response. All prototype-patients models generated are completely theoretical and therefore they do not necessarily involve clinical effects in real patients. Data and accession to software are available at http://sbi.upf. edu/data/tpms/
Microhabitat contributes to microgeographic divergence in threespine stickleback

Since the New Synthesis, most migration‐selection balance theory has predicted that there should be negligible differentiation over small spatial scales (relative to dispersal), because gene flow should erode any effect of divergent selection. Nevertheless, there are classic examples of microgeographic divergence, which theory suggests can arise under specific conditions: exceptionally strong selection, phenotypic plasticity in philopatric individuals, or nonrandom dispersal. Here, we present evidence of microgeographic morphological variation within lake and stream populations of threespine stickleback (Gasterosteus aculeatus). It seems reasonable to assume that a given lake or stream population of fish is well‐mixed. However, we found this assumption to be untenable. We examined trap‐to‐trap variation in 34 morphological traits measured on stickleback from 16 lakes and 16 streams. Most traits varied appreciably among traps within populations. Both between‐trap distance and microhabitat characteristics such as depth and substrate explained some of the within‐population morphological variance. Microhabitat was also associated with genotype at particular loci but there was no genetic isolation by distance, implying that heritable habitat preferences may contribute to microgeographic variation. Our study adds to growing evidence that microgeographic divergence can occur across small spatial scales within individuals’ daily dispersal neighborhood where gene flow is expected to be strong.
Future Therapeutic Directions for Smac-Mimetics

It is well accepted that the ability of cancer cells to circumvent the cell death program that untransformed cells are subject to helps promote tumor growth. Strategies designed to reinstate the cell death program in cancer cells have therefore been investigated for decades. Overexpression of members of the Inhibitor of APoptosis (IAP) protein family is one possible mechanism hindering the death of cancer cells. To promote cell death, drugs that mimic natural IAP antagonists, such as second mitochondria-derived activator of caspases (Smac/DIABLO) were developed. Smac-Mimetics (SMs) have entered clinical trials for hematological and solid cancers, unfortunately with variable and limited results so far. This review explores the use of SMs for the treatment of cancer, their potential to synergize with up-coming treatments and, finally, discusses the challenges and optimism facing this strategy.
Differential Gene Expression between Fungal Mating Types Is Associated with Sequence Degeneration

Abstract Degenerative mutations in non-recombining regions, such as in sex chromosomes, may lead to differential expression between alleles if mutations occur stochastically in one or the other allele. Reduced allelic expression due to degeneration has indeed been suggested to occur in various sex-chromosome systems. However, whether an association occurs between specific signatures of degeneration and differential expression between alleles has not been extensively tested, and sexual antagonism can also cause differential expression on sex chromosomes. The anther-smut fungus Microbotryum lychnidis-dioicae is ideal for testing associations between specific degenerative signatures and differential expression because 1) there are multiple evolutionary strata on the mating-type chromosomes, reflecting successive recombination suppression linked to mating-type loci; 2) separate haploid cultures of opposite mating types help identify differential expression between alleles; and 3) there is no sexual antagonism as a confounding factor accounting for differential expression. We found that differentially expressed genes were enriched in the four oldest evolutionary strata compared with other genomic compartments, and that, within compartments, several signatures of sequence degeneration were greater for differentially expressed than non-differentially expressed genes. Two particular degenerative signatures were significantly associated with lower expression levels within differentially expressed allele pairs: upstream insertion of transposable elements and mutations truncating the protein length. Other degenerative mutations associated with differential expression included nonsynonymous substitutions and altered intron or GC content. The association between differential expression and allele degeneration is relevant for a broad range of taxa where mating compatibility or sex is determined by genes located in large regions where recombination is suppressed.
In Steatotic Cells, ATP-Citrate Lyase mRNA Is Efficiently Translated through a Cap-Independent Mechanism, Contributing to the Stimulation of De Novo Lipogenesis

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease in which excessive amount of lipids is accumulated as droplets in hepatocytes. Recently, cumulative evidences suggested that a sustained de novo lipogenesis can play an important role in NAFLD. Dysregulated expression of lipogenic genes, including ATP-citrate lyase (ACLY), has been found in liver diseases associated with lipid accumulation. ACLY is a ubiquitous cytosolic enzyme positioned at the intersection of nutrients catabolism and cholesterol and fatty acid biosyntheses. In the present study, the molecular mechanism of ACLY expression in a cell model of steatosis has been reported. We identified an internal ribosome entry site (IRES) in the 5′ untranslated region of the ACLY mRNA, that can support an efficient mRNA translation through a Cap-independent mechanism. In steatotic HepG2 cells, ACLY expression was up-regulated through IRES-mediated translation. Since it has been demonstrated that lipid accumulation in cells induces endoplasmic reticulum (ER) stress, the involvement of this cellular pathway in the translational regulation of ACLY has been also evaluated. Our results showed that ACLY expression was increased in ER-stressed cells, through IRES-mediated translation of ACLY mRNA. A potential role of the Cap-independent translation of ACLY in NAFLD has been discussed.
Comparative Study of Synthesis Methods to Prepare New Functionalized Adsorbent Materials Based on MNPs–GO Coupling

In this work, the synthesis of new adsorbent nanomaterials based on the coupling of magnetic nanoparticles and graphene oxide (MNPs–GO) was addressed. Separately, MNPs and GO have adsorbent properties of great interest, but their use involves certain difficulties. The coupling seeks compensation for their disadvantages, while maintaining their excellent properties. Three different routes to synthesize coupled MNPs–GO were studied and are compared in this work. The three synthesized materials were functionalized with chelating groups: [1,5-bis (di-2-pyridyl) methylene] thiocarbonohydrazide (DPTH) and [1,5-bis(2-pyridyl)3-sulfophenylmethylene] thiocarbonohydrazide (PSTH). The new adsorbent nanomaterials were characterized adequately. Moreover, their capacities of adsorption toward heavy and noble metals were determined, in order to apply them as extractants in magnetic solid-phase extraction to preconcentrate metals in environmental samples. The results showed that one of the routes provided nanomaterials with better adsorbent characteristics and higher yields of functionalization.
Validation of the Chinese Version of the Somatic Symptom Disorder–B Criteria Scale for Detecting DSM-5 Somatic Symptom Disorders: A Multicenter Study

Supplemental digital content is available in the text. ABSTRACT Objective This study aimed to validate the Chinese version of the Somatic Symptom Disorder–B Criteria Scale (SSD-12) in an outpatient sample from Chinese general hospitals and to determine the diagnostic performance of the SSD-12 as a screening tool for somatic symptom disorder (SSD). Methods The Chinese version of the SSD-12 was completed by 699 outpatients from nine general hospitals during a 16-month period (2016–2018). The SSD section of the Structured Clinical Interview for DSM Disorders, Fifth Edition, Research Version, was used to determine diagnostic accuracy (criterion validity). The construct validity of the SSD-12 was evaluated by examining correlations with the Whiteley Index-7, Patient Health Questionnaire-15, Patient Health Questionnaire-9, General Anxiety Disorder-7, World Health Organization Disability Assessment Schedule, and Medical Outcome Study 12-item Short Form Health Survey (SF-12). Results The SSD-12 had excellent internal consistency in this sample (Cronbach α = .95). Confirmatory factor analyses replicated a three-factor structure that reflects the cognitive, affective, and behavioral aspects (Comparative Fit Index = 0.963, Tucker-Lewis Index = 0.952, root mean square error of approximation = 0.08, 90% confidence interval = 0.08–0.09), but was also consistent with a general one-factor model of the SSD-12 (Comparative Fit Index = 0.957, Tucker-Lewis Index = 0.948, root mean square error of approximation = 0.09, 90% confidence interval = 0.08–0.10). The optimal cutoff point for the Structured Clinical Interview for DSM Disorders–based diagnosis of SSD was 16 (sensitivity = 0.76, specificity = 0.80). The SSD-12 sum score was significantly associated with somatic symptom burden (Patient Health Questionnaire-15: r = 0.52, p < .001), health anxiety (Whiteley Index-7: r = 0.82, p < .001), depressive symptoms (Patient Health Questionnaire-9: r = 0.63, p < .001), general anxiety (General Anxiety Disorder-7: r = 0.64, p < .001), health-related quality of life (physical component score of SF-12: r = −0.49, p < .001; mental component score of SF-12: r = −0.61, p < .001), and health-related disabilities (World Health Organization Disability Assessment Schedule: r = 0.56, p < .001). Conclusions Initial assessment indicates that the Chinese version of the SSD-12 has sufficient reliability and validity to warrant further testing in both research and clinical settings.
Assessment of the Phenolic Profiles, Hypoglycemic Activity, and Molecular Mechanism of Different Highland Barley (Hordeum vulgare L.) Varieties

The phenolic profiles, hypoglycemic activity, and molecular mechanism of the effect on type 2 diabetes mellitus (T2DM) of four highland barley varieties were investigated in the present study. The fundamental phenolics in highland barley were ferulic acid, naringin, and catechin, which mainly existed in bound form. These varieties showed favorable hypoglycemic activity via inhibition of α-glucosidase and α-amylase activities, enhancement of glucose consumption, glycogen accumulation and glycogen synthase 2 (GYS2) activity, and down-regulation of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities. Specifically, ZQ320 variety exhibited the strongest hypoglycemic activity compared to the other varieties. Highland barley phenolics could inhibit gluconeogenesis and motivate glycogen synthesis via down-regulating the gene expression of G6Pase, PEPCK, and glycogen synthase kinase 3β (GSK3β), while activating the expression of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), serine/threonine kinase (Akt), GYS2, and glucose transporter type 4 (GLUT4). Therefore, phenolics from highland barley could be served as suitable candidates for therapeutic agent in T2DM to improve human health.
Nanopharmaceutics: Part I—Clinical Trials Legislation and Good Manufacturing Practices (GMP) of Nanotherapeutics in the EU

The latest advances in pharmaceutical technology are leading to the development of cutting edged approaches to produce what is now known as the “Holy Grail” of medicine—nanopharmaceutics. Over the latest decade, the pharmaceutical industry has made important contributions to the scale up of these new products. To ensure their quality, efficacy, and safety for human use, clinical trials are mandatory. Yet, regulation regarding nanopharmaceuticals is still limited with a set of guidelines being recently released with respect to compliance with quality and safety. For the coming years, updates on regulatory issues about nanopharmaceuticals and their use in clinical settings are expected. The use of nanopharmaceuticals in clinical trials depends on the approval of the production methods and assurance of the quality of the final product by implementation and verification of the good manufacturing practices (GMP). This review addresses the available legislation on nanopharmaceuticals within the European Union (EU), the GMP that should be followed for their production, and the current challenges encountered in clinical trials of these new formulations. The singular properties of nanopharmaceuticals over their bulk counterparts are associated with their size, matrix composition, and surface properties. To understand their relevance, four main clinical trial guidelines, namely, for intravenous iron-based nanopharmaceuticals, liposomal-based nanopharmaceuticals, block copolymer micelle-based nanopharmaceuticals, and related to surface coating requirements, are described here.
Barriers and enablers of implementing bubble Continuous Positive Airway Pressure (CPAP): Perspectives of health professionals in Malawi

Background Preterm birth complications are the leading cause of neonatal deaths. Malawi has high rates of preterm birth, with 18.1 preterm births per 100 live births. More than 50% of preterm neonates develop respiratory distress which if left untreated, can lead to respiratory failure and death. Term and preterm neonates with respiratory distress can often be effectively managed with Continuous Positive Airway Pressure (CPAP) and this is considered an essential intervention for the management of preterm neonates by the World Health Organization. Bubble CPAP may represent a safe and cost-effective method for delivering CPAP in low-income settings. Objective The study explored the factors that influence the implementation of bubble CPAP among health care professionals in secondary and tertiary hospitals in Malawi. Methods This was a qualitative study conducted in three district hospitals and a tertiary hospital in southern Malawi. We conducted 46 in-depth interviews with nurses, clinicians and clinical supervisors, from June to August 2018. All data were digitally recorded, transcribed verbatim and thematically analyzed. Results Factors that influenced implementation of bubble CPAP occurred in an interconnected manner and included: inadequate healthcare provider training in preparation for use, rigid division of roles and responsibilities among providers, lack of effective communication among providers and between providers and newborn’s caregivers, human resource constraints, and inadequate equipment and infrastructure. Conclusion There are provider, caregiver and health system level factors that influence the implementation of bubble CPAP among neonates in Malawian health facilities. Ensuring adequate staffing in the nurseries, combined with ongoing training for providers, team cohesion, improved communication with caregivers, and improved hospital infrastructure would ensure optimal utilization of bubble CPAP and avoid inadvertent harm from inappropriate use.
The Exacerbation of Aging and Oxidative Stress in the Epididymis of Sod1 Null Mice

There is growing evidence that the quality of spermatozoa decreases with age and that children of older fathers have a higher incidence of birth defects and genetic mutations. The free radical theory of aging proposes that changes with aging are due to the accumulation of damage induced by exposure to excess reactive oxygen species. We showed previously that absence of the superoxide dismutase 1 (Sod1) antioxidant gene results in impaired mechanisms of repairing DNA damage in the testis in young Sod1−/− mice. In this study, we examined the effects of aging and the Sod−/− mutation on mice epididymal histology and the expression of markers of oxidative damage. We found that both oxidative nucleic acid damage (via 8-hydroxyguanosine) and lipid peroxidation (via 4-hydroxynonenal) increased with age and in Sod1−/− mice. These findings indicate that lack of SOD1 results in an exacerbation of the oxidative damage accumulation-related aging phenotype.