Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Roles of Interferon Alpha and Beta in Controlling Chikungunya Virus Replication and Modulating Neutrophil-Mediated Inflammation

Type I interferons (IFNs) possess a range of biological activity and protect against a number of viruses, including alphaviruses. Despite signaling through a shared receptor, there are established biochemical and functional differences among the IFN subtypes. The significance of our research is in demonstrating that IFN-α and IFN-β both have protective roles during acute chikungunya virus (CHIKV) infection but do so by distinct mechanisms. IFN-α limits CHIKV replication and dissemination, whereas IFN-β protects from CHIKV pathogenesis by limiting inflammation mediated by neutrophils. Our findings support the premise that the IFN subtypes have distinct biological activities in the antiviral response. ABSTRACT Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice treated with a pan-IFN-α-blocking antibody). Mice lacking either IFN-α or IFN-β developed severe clinical disease following infection with CHIKV, with a marked increase in foot swelling compared to wild-type mice. Virological analysis revealed that mice lacking IFN-α sustained elevated infection in the infected ankle and in distant tissues. In contrast, IFN-β-KO mice displayed minimal differences in viral burdens within the ankle or at distal sites and instead had an altered cellular immune response. Mice lacking IFN-β had increased neutrophil infiltration into musculoskeletal tissues, and depletion of neutrophils in IFN-β-KO but not IRF7-KO mice mitigated musculoskeletal disease caused by CHIKV. Our findings suggest disparate roles for the IFN subtypes during CHIKV infection, with IFN-α limiting early viral replication and dissemination and IFN-β modulating neutrophil-mediated inflammation. IMPORTANCE Type I interferons (IFNs) possess a range of biological activity and protect against a number of viruses, including alphaviruses. Despite signaling through a shared receptor, there are established biochemical and functional differences among the IFN subtypes. The significance of our research is in demonstrating that IFN-α and IFN-β both have protective roles during acute chikungunya virus (CHIKV) infection but do so by distinct mechanisms. IFN-α limits CHIKV replication and dissemination, whereas IFN-β protects from CHIKV pathogenesis by limiting inflammation mediated by neutrophils. Our findings support the premise that the IFN subtypes have distinct biological activities in the antiviral response.
n-3 PUFA Sources (Precursor/Products): A Review of Current Knowledge on Rabbit

Simple Summary The nutritional quality of fat for human consumption is usually evaluated in terms of the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio (with optimal values ≤4). Moreover, with respect to animal production, the standard feed is unbalanced in terms of n-6/n-3 polyunsaturated fatty acids (PUFAs) with a lower proportion of the latter. Such discrepancy negatively affects the health status of animals, the productive and reproductive performances, and the general quality of their products. Hence, n-3 PUFA intake should be promoted. The increase in n-3 PUFA proportions in animal products would also be in accordance with the human dietary recommendations that often focus on the need of increasing the intake of long-chain n-3 PUFAs. In this regard, two main strategies could be implemented, namely to furnish precursor (α-linolenic acid) or long-chain derivatives (eicosapentaenoic and docosahexaenoic acids). In the present review, the effects of different n-3 PUFA sources on biological activity, physiological/reproductive endpoints, and health implications are compared focusing on the most recent results obtained in the rabbit. Abstract This review compares the effects of different n-3 polyunsaturated fatty acid (PUFA) sources on biological activity, physiological/reproductive endpoints, and health implications with a special emphasis on a rabbit case study. Linoleic acid (LA) and α-linolenic acid (ALA) are members of two classes of PUFAs, namely the n-6 and n-3 series, which are required for normal human health. Both are considered precursors of a cascade of molecules (eicosanoids), which take part in many biological processes (inflammation, vasoconstriction/vasodilation, thromboregulation, etc.). However, their biological functions are opposite and are mainly related to the form (precursor or long-chain products) in which they were administered and to the enzyme–substrate preference. ALA is widely present in common vegetable oils and foods, marine algae, and natural herbs, whereas its long-chain PUFA derivatives are available mainly in fish and animal product origins. Recent studies have shown that the accumulation of n-3 PUFAs seems mostly to be tissue-dependent and acts in a tissue-selective manner. Furthermore, dietary n-3 PUFAs widely affect the lipid oxidation susceptibility of all tissues. In conclusion, sustainable sources of n-3 PUFAs are limited and exert a different effect about (1) the form in which they are administered, precursor or derivatives; (2) their antioxidant protections; and (3) the purpose to be achieved (health improvement, physiological and reproductive traits, metabolic pathways, etc.).
Identification of an allosteric binding site on the human glycine transporter, GlyT2, for bioactive lipid analgesics

The treatment of chronic pain is poorly managed by current analgesics, and there is a need for new classes of drugs. We recently developed a series of bioactive lipids that inhibit the human glycine transporter GlyT2 (SLC6A5) and provide analgesia in animal models of pain. Here, we have used functional analysis of mutant transporters combined with molecular dynamics simulations of lipid-transporter interactions to understand how these bioactive lipids interact with GlyT2. This study identifies a novel extracellular allosteric modulator site formed by a crevice between transmembrane domains 5, 7, and 8, and extracellular loop 4 of GlyT2. Knowledge of this site could be exploited further in the development of drugs to treat pain, and to identify other allosteric modulators of the SLC6 family of transporters.
Effect of both selenium and biosynthesized nanoselenium particles on cadmium-induced neurotoxicity in albino rats

Because cadmium (Cd) is not naturally degradable by ecosystems, it interferes with many types of food chains. Cd accumulates in the kidney, liver and in the nervous tissues, especially the brain. The neurotoxicity of Cd is very high, as it alters the integrity, and increases the permeability, of the blood–brain barrier. Cd penetrates and accumulates in neurons in the brains of rats. This study reveals that Cd decreases antioxidant enzymes and increases oxidative stress in the brain. In addition, Cd increases lipid peroxidation of brain tissues. Cd increases the expression of the Cu/Zn superoxide dismutase gene. It also affects cholinergic, glutamatergic, gamma-Aminobutyric acid (GABAergic), dopamine, serotonin and acetylcholine neurotransmitters in brain tissue. Consequently, Cd increases the formation of amyloid β, a neurotoxic index, and induces apoptosis by changing the quality and the quantity of Bcl-2, Bax and p53 proteins. In conclusion, both selenium and nanoselenium show potential antioxidant activity and promote recovery from the neurotoxic action of Cd.
Health assessment of Conolophus subcristatus, Conolophus pallidus, and C. subcristatus X Amblyrhynchus cristatus hybrid (Galápagos land iguanas)

The land iguanas, Conolophus pallidus and Conolophus subcristatu are large and charismatic lizards endemic to the Galápagos archipelago, but little information exists on their normal health parameters. The former is restricted to Santa Fe island, while C. subcristatus inhabits the islands of the central and western region of the archipelago. Both species are classified as vulnerable by the IUCN Red List of Threatened Species. As part of a population health assessment authorized by the Galápagos National Park, wild adult iguanas from three islands (North Seymour, South Plazas, and Santa Fe) were captured in July 2018. Data from a single C. subcristatus X Amblyrhynchus cristatus hybrid captured on South Plazas is also included. We analyzed blood samples drawn from 52 healthy wild adult land iguanas captured on three islands. An iSTAT portable blood analyzer was used to obtain values for pH, lactate, pO2, pCO2, HCO3-, sO2%, hematocrit, packed cell volume (PCV), hemoglobin Na, K, iCa, and glucose. Standard laboratory hematology techniques were employed for PCV determination; resulting values were also compared to the hematocrit values generated by the iSTAT. Body temperature, heart rate, respiratory rate, and body measurements were also recorded and compared to previously published data for the marine iguana (Amblyrhynchus cristatus), which shares a common ancestor with the land iguana. The data reported here provide preliminary baseline values that may be useful in comparisons between captive and wild populations, between wild populations, and in detecting changes in health status among Galápagos land iguanas affected by anthropogenic threats, climate change, or natural disturbances.
Steatosis and steatohepatitis found in adults after death due to non-burn trauma

OBJECTIVE: With the increasing prevalence of steatosis, the number of steatotic liver grafts from deceased donors is also increasing. Thus, determining the prevalence and the population risk factors of steatosis may assist in risk stratification. The aim of this study was to evaluate the prevalence and predictors of steatosis and steatohepatitis among livers from adults who died due to non-burn trauma. METHODS: Specimens were collected from 224 adults undergoing autopsy at a regional autopsy referral center from September 2011 to April 2013. Histopathological examination was performed on six samples obtained from different lobes of each liver. The outcomes of interest were the presence of steatosis, steatohepatitis, NASH inflammation and NASH fibrosis. The main predictors were body mass index, abdominal circumference, liver weight and volume, presence of cholelithiasis, and siderosis. Our modeling strategy made use of a series of generalized linear models with a binomial family. RESULTS: Our sample had a mean age of 40 years; steatosis was diagnosed in 48.2% of cases, and steatohepatitis was diagnosed in 2.7%. The presence of a high proportion of fatty changes was more prevalent among males and older individuals, with the most affected age group being 41-60 years. When evaluating the crude odds ratio for steatosis, the factors significantly associated with an increased risk of steatosis were greater abdominal circumference, BMI, and liver weight and the presence of siderosis. CONCLUSION: Our study reinforces the role of older age, obesity and hepatomegaly as predictors of fatty liver disease. These variables should be considered in the assessment of fatty changes in the livers of potential liver donors.
Development of birth weight for gestational age charts and comparison with currently used charts: defining growth in the Polish population

Abstract Objectives This study aimed to obtain the reference curves of birth weight for gestational age percentiles for the Polish population and to compare them to published charts in terms of detected proportions of small for gestational age (SGA) and large for gestational age (LGA). Methods The reference curves of birth weight from 24 to 42 weeks of gestation were computed based on 39,092 singleton deliveries. The nomograms included the 3rd to the 97th percentiles and standard deviations. The percentiles were calculated for female and male newborns. The theoretical and true proportions of percentiles for the studied population were estimated based on six growth charts (Fenton, Intergrowth Project, global reference chart, Yudkin, Dubiel, and the World Health Organization chart). Results The 50th percentile male and female newborns at 40 weeks weighed 3645.8 and 3486.7 g, respectively. The difference was 159.1 g. The ranges between the 3rd and 97th percentile at 40 weeks were 1481.5 g for males and 1423.5 for females. A total of 9.8% SGA and 10.27% LGA were defined, higher than that identified using the Fenton chart and even higher than that identified using the Intergrowth Project. Conclusion Population growth charts identify more newborns with abnormal growth (both LGA and SGA). The similarity between charts in LGA above the 95th percentile is observed. The discrepancies in SGA are significantly greater, specifically in preterm births than in term births. Similar coverage is found in term pregnancies, regardless of birth weight for gestational age or intrauterine charts. The feasibility of a Polish population growth chart needs to be validated for predicting adverse perinatal outcomes.
TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer.

Metastasis is the primary cause of treatment failures and mortality in most cancers. Triple-negative breast cancer is refractory to treatment and rapidly progresses to disseminated disease. We utilized an orthotopic mouse model that molecularly and phenotypically resembles human TNBC to study the effects of exogenous, daily TIMP-2 treatment on tumor growth and metastasis. Our results demonstrated that TIMP-2 treatment maximally suppressed primary tumor growth by ~36-50%, and pulmonary metastasis by > 92%. Immuno-staining assays confirmed disruption of the epithelial to mesenchymal transition, and promotion of vascular integrity in primary tumor tissues. Immuno-staining and RNA sequencing analysis of lung tissue lysates from tumor-bearing mice identified significant changes associated with metastatic colony formation. Specifically, TIMP-2 treatment disrupts periostin localization and critical cell signaling pathways, including canonical Wnt-signaling involved in EMT transition, as well as PI3K-signaling which modulates proliferative and metastatic behavior through p27 phosphorylation/localization. In conclusion, our study provides evidence in support of a role for TIMP-2 in suppression of triple negative breast cancer growth and metastasis through modulation of the epithelial to mesenchymal transition, vascular normalization, and signaling pathways associated with metastatic outgrowth. Our findings suggest that TIMP-2, a constituent of the ECM in normal tissues, may have both direct and systemic anti-tumor and metastasis suppressor effects, suggesting potential utility in the clinical management of breast cancer progression.
QTL mapping for protein and sulfur-containing amino acids contents using a high-density bin-map in soybean (Glycine max L. Merr.).

Soybean provides essential protein and amino acids for humans and animals, while sulfur-containing amino acids (SAA), including methionine (Met) and cysteine (Cys), are very limited. In this study, we constructed a high-density bin-map with 3,420 bin markers using 676,857 SNPs of a recombinant-inbred line (RIL) population derived from a cross between Kefeng No. 1 and Nannong 1138-2. Quantitative trait loci (QTL) mapping was performed for Cys, Met, SAA and the protein content (PC) using this high-density bin-map. Twenty-five QTLs linked to these four traits were identified, and four genomic regions located on chromosomes (Chr) 07, 08, 15 and 20 were overlapped by multiple QTLs. Among them, bin 115-124 located on Chr 15 was associated with all four traits and was a novel locus with a high LOD value. These findings will provide a basis for nutritional quality improvement using marker-assisted selection breeding and clarify the genetic mechanisms of SAA and protein in soybean.
Association of prevalence of electronic cigarette use with smoking cessation and cigarette consumption in England: a time–series analysis between 2006 and 2017

Abstract Aims To provide up‐to‐date estimates of how changes in the prevalence of electronic cigarette (e‐cigarette) use in England have been associated with changes in smoking cessation activities and daily cigarette consumption among smokers in England. Design Time–series analysis of population trends. Setting England. Participants Participants came from the Smoking Toolkit Study, which involves repeated, cross‐sectional household surveys of individuals aged 16 years and older in England. Data were aggregated on approximately 1200 past‐year smokers each quarter (total n = 50 498) between 2007 and 2017. Measurements Prevalence of e‐cigarette use in current smokers was used to predict (a) prevalence of quit attempts among last‐year smokers, (b) overall quit rates among last‐year smokers and (c) mean cigarette consumption per day among current smokers. Prevalence of e‐cigarette use during a quit attempt among last‐year smokers was used to predict (a) quit success rate among last‐year smokers and (b) overall quit rates among last‐year smokers. Findings Overall quit rates increased by 0.054% [95% confidence interval (CI) = 0.032–0.076, P < 0.001] and 0.050% (95% CI = 0.031–0.069, P < 0.001) respectively for every 1% increase in the prevalence of e‐cigarette use by smokers and e‐cigarette use during a quit attempt. Quit success rates increased by 0.060% (95% CI = 0.043–0.078, P < 0.001) for every 1% increase in the prevalence of e‐cigarette use during a quit attempt. No clear evidence was found for an association between e‐cigarette use and either prevalence of quit attempt (BAdj = 0.011, 95% CI = −0.046 to 0.069, P = 0.698) or cigarette consumption (BAdj = 0.019, 95% CI = −0.043 to 0.082, P = 0.542). Conclusion Changes in prevalence of e‐cigarette use in England have been positively associated with the overall quit rates and quit success rates but not clearly associated with the prevalence of quit attempts and mean cigarette consumption.
Tumor susceptibility gene 101 ameliorates endotoxin-induced cardiac dysfunction by enhancing Parkin-mediated mitophagy

Cardiac mitochondrial damage and subsequent inflammation are hallmarks of endotoxin-induced myocardial depression. Activation of the Parkin/PTEN-induced kinase 1 (PINK1) pathway has been shown to promote autophagy of damaged mitochondria (mitophagy) and to protect from endotoxin-induced cardiac dysfunction. Tumor susceptibility gene 101 (TSG101) is a key member of the endosomal recycling complexes required for transport, which may affect autophagic flux. In this study, we investigated whether TSG101 regulates mitophagy and influences the outcomes of endotoxin-induced myocardial dysfunction. TSG101 transgenic and knockdown mice underwent endotoxin/lipopolysaccharide treatment (10 μg/g) and were assessed for survival, cardiac function, systemic/local inflammation, and activity of mitophagy mediators in the heart. Upon endotoxin challenge and compared with WT mice, TSG101 transgenic mice exhibited increased survival, preserved cardiac contractile function, reduced inflammation, and enhanced mitophagy activation in the heart. By contrast, TSG101 knockdown mice displayed opposite phenotypes during endotoxemia. Mechanistically, both coimmunoprecipitation assays and coimmunofluorescence staining revealed that TSG101 directly binds to Parkin in the cytosol of myocytes and facilitates translocation of Parkin from the cytosol to the mitochondria. Our results indicate that TSG101 elevation could protect against endotoxin-triggered myocardial injury by promoting Parkin-induced mitophagy.
Location of the Glenoid Defect in Shoulders With Recurrent Posterior Glenohumeral Instability

Background: Posterior glenoid bone deficiency is an increasingly recognized entity in the setting of recurrent posterior shoulder instability; however, little is known about the subject. Due to the paucity of literature on posterior bone loss, historical comparisons with anterior bone loss may not be fully accurate. Purpose: To systematically describe the morphology of posterior bone defects in the setting of recurrent posterior shoulder instability based on several quantitative parameters, including the mean location, orientation, and extent of bone loss on a clockface model, as well as the angle of the defect relative to the long axis of the glenoid. Study Design: Cross-sectional study; Level of evidence, 4. Methods: Three-dimensional reconstructed computed tomography scans of serially collected patients with a history of recurrent posterior shoulder instability were evaluated by 3 separate reviewers. The posterior glenoid bone defect was characterized using the following measures: (1) the mean lesion location and orientation based on a clockface model with 6 o’clock denoted as inferior and 9 o’clock as directly posterior for all patients; (2) the total extent of the posterior bone defect based on the clockface; and (3) the average angle of the bone loss relative to the long axis of the glenoid. Results: A total of 70 male patients and 1 female patient with a mean age of 29.3 years (range, 24.4-35.1 years) were included in the analysis. The mean clockface location of the posterior glenoid defect originated at 6:44 (range, 4:16-8:12) and extended to a mean of 9:28 (range, 7:02-10:38). The mean extent of the posterior glenoid defect was 2:43 (range, 1:08-4:50), which corresponds to a mean total bone loss arc of 81.5° (range, 34.2°-144.9°), nearly 1 quadrant of the glenoid. Posterior bone loss occurred in a posteroinferior direction at a mean angle of 30.7° (range, 8.0°-80.0°) relative to the long axis of the glenoid. Conclusion: Posterior bone defects in the setting of posterior shoulder instability most commonly occur in the posteroinferior quadrant of the glenoid and extend on average from 6:44 to 9:28 (81.5° total degrees of arc) on a clockface model. Posterior bone loss occurs at a mean of 30° off the long axis of the glenoid in a posteroinferior direction, which is historically different from anterior bone loss, which occurs parallel to the long axis of the glenoid. This study serves to highlight the location and orientation of bone loss that one can expect in a patient with recurrent posterior shoulder instability, although additional work is needed to assess why this develops.