Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Cardiometabolic Disease Markers by Type I Interferon Inhibition in Systemic Lupus Erythematosus

Neutrophil dysregulation and the type I interferon (IFN) axis have been proposed to contribute to premature cardiovascular disease, a leading cause of mortality in patients with systemic lupus erythematosus (SLE). In the present study, we evaluated the ability of anifrolumab, a type I IFN receptor–blocking antibody, to reduce neutrophil extracellular trap (NET) formation and modulate cardiometabolic disease markers in comparison to placebo.
Gallic acid is a dual α/β-secretase modulator that reverses cognitive impairment and remediates pathology in Alzheimer mice

Several plant-derived compounds have demonstrated efficacy in pre-clinical Alzheimer's disease (AD) rodent models. Each of these compounds share a gallic acid (GA) moiety, and initial assays on this isolated molecule indicated that it might be responsible for the therapeutic benefits observed. To test this hypothesis in a more physiologically relevant setting, we investigated the effect of GA in the mutant human amyloid β-protein precursor/presenilin 1 (APP/PS1) transgenic AD mouse model. Beginning at 12 months, we orally administered GA (20 mg/kg) or vehicle once daily for 6 months to APP/PS1 mice that have accelerated Alzheimer-like pathology. At 18 months of age, GA therapy reversed impaired learning and memory as compared with vehicle, and did not alter behavior in nontransgenic littermates. GA-treated APP/PS1 mice had mitigated cerebral amyloidosis, including brain parenchymal and cerebral vascular β-amyloid deposits, and decreased cerebral amyloid β-proteins. Beneficial effects co-occurred with reduced amyloidogenic and elevated nonamyloidogenic APP processing. Furthermore, brain inflammation, gliosis, and oxidative stress were alleviated. We show that GA simultaneously elevates α- and reduces β-secretase activity, inhibits neuroinflammation, and stabilizes brain oxidative stress in a pre-clinical mouse model of AD. We further demonstrate that GA increases abundance of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10, Adam10) proprotein convertase furin and activates ADAM10, directly inhibits β-site APP cleaving enzyme 1 (BACE1, Bace1) activity but does not alter Adam10 or Bace1 transcription. Thus, our data reveal novel post-translational mechanisms for GA. We suggest further examination of GA supplementation in humans will shed light on the exciting therapeutic potential of this molecule.
Applied tele-audiology research in clinical practice during the past decade: a scoping review

Abstract Objective The purpose of this scoping review was two-fold, (1) to provide information about the characteristics, type of service delivery, participant information and outcomes related to tele-audiology in clinical popluations, and (2) to describe documented facilitators and barriers to tele-audiology delivery from the perspectives of practitioners and service recipients. Knowledge of these findings can assist audiologists in considering remote service delivery options for their practices. Design A scoping review was conducted in November 2019 to identify English-language peer-reviewed journal articles published from 1 January 2010 to 30 October 2019 related to remote clinical service delivery in audiology. Results Thirty-six published research articles were included. Research studies were classified into four broad areas with some articles including more than one area within the scope of their article: Screening (n = 5), Diagnostic (n = 5), Intervention (n = 18), and Perspectives (n = 22). Conclusion Hearing healthcare service delivery is expanding with the changing technological landscape, providing greater opportunities and flexibility for audiologists and patients. There are clear opportunities for interdisciplinary collaboration and for collaboration with on-site local facilitators. Local facilitators, with training, can assist in connecting individuals to follow-up care, provide educational support, and needed hands-on assistance for specialised testing.
Impact of COVID-19 lockdown on A&E performances in an NHS Foundation Trust

County Durham and Darlington Foundation Trust (CDDFT) is a National Health Service (NHS) Trust and is one of the largest integrated care providers in England. It serves a population of around 650 000 people.1 The two major acute hospitals in this Trust are the University Hospital of North Durham (UHND) and Darlington Memorial Hospital (DMH). Both of those hospitals have type 1 Accident and Emergency (A&E) departments,2 3 which means that they are a consultant lead 24-hour service with full resuscitation facilities and designated accommodation for the reception of accident and emergency patients. During the COVID-19 pandemic, strategies were put in place to deal with spread of the virus. In the UK, there was an attempt to flatten the curve so that the NHS would be able to deal with sicker patients and provide all the support needed. To enable this, lockdown was introduced with social distancing, stay at home message and advice to wash hands regularly in order to break the cycle of spread of the virus. The NHS also restructured all the hospitals in order to prepare for the crisis. All the wards in UHND and DMH were sectioned into red and blue zones to aid with the patient flow. The AE red area was for patients with respiratory or COVID-19 symptoms, and blue area was for patients with non-respiratory symptoms. Doctors were redeployed from the community placements and other non-essential rotations to A&E and other essential wards. All the elective and non-emergency operations were halted during the lockdown. Outpatient departments were also closed …
Long non coding RNA NRON inhibited breast cancer development through regulating miR-302b/SRSF2 axis.

AIMS Long noncoding RNA NRON has been investigated in various tumors, such as hepatocellular carcinoma. However, the role of lncRNA NRON in breast cancer remains unclear. The aim of this study was to explore the function and mechanism of lncRNA NRON in breast cancer. MATERIALS AND METHODS Overexpression and knockdown vectors were constructed. Proliferation and invasion were measured to evaluate the function of lncRNA NRON. A dual-luciferase reporter assay was utilized to analyze the potential binding target of lncRNA NRON. A rescue experiment was performed to verify the relationship between lncRNA NRON and SRSF2. RESULTS Our results showed that the expression of lncRNA NRON was significantly downregulated in breast cancer tissues. Overexpression of lncRNA NRON significantly inhibited proliferation and invasion in breast cancer cell lines. Knockdown of lncRNA NRON promoted breast cancer development. We also provided evidence that lncRNA NRON negatively regulated miR-302b. Moreover, we identified SRSF2 as a downstream target of miR-302b. CONCLUSION Overall, we performed a comprehensive analysis to indicate that the lncRNA NRON/miR-302b/SRSF2 axis plays an important role in breast cancer. Our study is the first to prove that lncRNA NRON functions as a tumor suppressor in breast cancer.
Nutritional value and biological effects of macrofungi

Macrofungi lacking chlorophyll, belong to the Basidiomycetes and Ascomycetes classes. Naturally grown and cultured macrofungi are consumed as a food source also in our country. Wild macrofungi are a major source of living for forest loggers and it is exported to other countries. Macrofungi contain water (up to 95%), proteins, lipids, and carbohydrates. c. Agaricus species have the highest protein and lipid content of
Characterization of Integrin αIIbβ3-Mediated Outside-in Signaling by Protein Kinase Cδ in Platelets

Engagement of integrin αIIbβ3 promotes platelet–platelet interaction and stimulates outside-in signaling that amplifies activation. Protein kinase Cδ (PKCδ) is known to play an important role in platelet activation, but its role in outside-in signaling has not been established. In the present study, we determined the role of PKCδ and its signaling pathways in integrin αIIbβ3-mediated outside-in signaling in platelets using PKCδ-deficient platelets. Platelet spreading to immobilized fibrinogen resulted in PKCδ phosphorylation, suggesting that αIIbβ3 activation caused PKCδ activation. αIIbβ3-mediated phosphorylation of Akt was significantly inhibited in PKCδ -/- platelets, indicating a role of PKCδ in outside-in signaling. αIIbβ3-mediated PKCδ phosphorylation was inhibited by proline-rich tyrosine kinase 2 (Pyk2) selective inhibitor, suggesting that Pyk2 contributes to the regulation of PKCδ phosphorylation in outside-in signaling. Additionally, Src-family kinase inhibitor PP2 inhibited integrin-mediated Pyk2 and PKCδ phosphorylation. Lastly, platelet spreading was inhibited in PKCδ -/- platelets compared to the wild-type (WT) platelets, and clot retraction from PKCδ -/- platelets was markedly delayed, indicating that PKCδ is involved in the regulation of αIIbβ3-dependent interactivities with cytoskeleton elements. Together, these results provide evidence that PKCδ plays an important role in outside-in signaling, which is regulated by Pyk2 in platelets.
Ponatinib and other CML Tyrosine Kinase Inhibitors in Thrombosis

Abl1 kinase has important biological roles. The Bcr-Abl1 fusion protein creates undesired kinase activity and is pathogenic in 95% of chronic myeloid leukemia (CML) and 30% of acute lymphoblastic leukemia (ALL) patients. Targeted therapies to these diseases are tyrosine kinase inhibitors. The extent of a tyrosine kinase inhibitor’s targets determines the degree of biologic effects of the agent that may influence the well-being of the patient. This fact is especially true with tyrosine kinase inhibitor effects on the cardiovascular system. Thirty-one percent of ponatinib-treated patients, the tyrosine kinase inhibitor with the broadest inhibitory spectrum, have thrombosis associated with its use. Recent experimental investigations have indicated the mechanisms of ponatinib-associated thrombosis. Further, an antidote to ponatinib is in development by re-purposing an FDA-approved medication.
The Effect of Barley and Lysine Supplementation on the longissimus lumborum Meat Quality of Pasture-Raised Fallow Deer (Dama dama)

The chemical characteristics (proximate composition, amino acids, and fatty acids) and sensory quality of the longissimus lumborum (LL) muscle of 45 farmed male fallow deer were investigated. The animals were divided into three separate groups (n = 15 per treatment): pasture-fed (P), pasture-fed and supplemented with barley (B), and pasture-fed and supplemented with barley and lysine (BL). Differences were observed in LL moisture and the intramuscular fat contents, the latter being almost two-fold greater in the meat of B and BL groups compared to P. The concentrations of histidine, leucine, alanine, glutamic acid and glycine in the raw meat were higher in the BL group compared to the P group. Higher contents of n–3 polyunsaturated fatty acids (PUFAs), and consequently lower n–3 ratios, were found in the P group, compared to the BL group. The grilled meat samples from the P group scored higher than the other groups for grassy flavour, and lower for liver flavour.
DNA RELATEDNESS AMONG PHENOTYPICALLY SIMILAR SPECIES OF PICHIA

Comparisons of nuclear DNA complementarity were used to determine the extent of genetic relatedness between phenotypically similar species of Pichia. Pichia xylosa, a presumed synonym of P. toletana, proved to be a distinct but closely related species. P. guilliermondii and Candida guilliermondii were confirmed as a teleomorph/anamorph pair. Hansenula ukrainica was shown to be conspecific with P. (H.) anomala and P. cellobiosa to be conspecific with P. methanolica.
SeqHoundRWeb.py: interface to a comprehensive online bioinformatics resource

In the post-genomic era, getting useful answers to challenging biological questions often demands signiﬁcant expertise and resources not only to acquire the requisite biological data but also to manage it. The storage required to maintain a workable genomic or proteomic database is usually out of reach for most bi-ologists. Some toolsets already exist to facilitate some aspects of data analysis, and others for access to particular data stores (e.g., NCBI Toolkit), but there is a substantial learning curve to these tools and installation is often non-trival. SeqHoundRWeb.py grew out of a common frustration in bioinformatics—the initiate bioinformaticist often has substantial biological knowledge, but little experience in computing; Python is often held up as a good ﬁrst scripting language to learn, and in our experience new users can be productive fairly rapidly.
Gene expression in the genus Deinococcus

A type II restriction endonuclease, Dral, isolated from Deinococcus radiophilu5 ATCC 27603 recognises the palindromic hexanucleotide sequence 5' 3 '-A-A-AT-T-T-5' and cleaves it, as indicated by the arrows, to produce blunt-ended fragments. The yield of enzyme is 100 to 1000 times that of the only other known type II restriction endonuclease that recognises a sequence composed solely of A:T basepairs, the isoschizomer AhaIll (1). Ultraviolet irradiation of the DNA substrate at relatively low doses inhibits the activity of Dral by "protecting' the recognition sequence and this may be exploited to give control of partial digestion of DNA by Dral. INTRODUCTION D. radiophilus belongs to the Family Deinococcaceae, the major characteristic of members of this group being their extreme resistance to the lethal effects of both ionising and ultraviolet radiations (2). The type species of the group D. radiodurans ATCC 13939, has been shown to possess a type II restriction endonuclease (3), MraI, recognising the sequence 5'-C-C-G-C-G-G-3' 3' -G-G-C-G-C-C-5' We report here a description of the isolation and characterisation of the site-specific endonuclease Dral, and a method by which partial digestion of DNA molecules by Dral may be controlled. METHODS Assay for Restriction Enzyme activity was estimated by incubating a sample (usually 1 p1) with either 1 pg A-DNA or ColE1:Tn5 ccc DNA. One unit of enzyme represents that activity which completely digests 1 pg of DNA during 1 hour's incubation at 37 ° C in restriction buffer (10 mM Mg, 10 mM Tris-HC1, pH 8.0). © I R L Press Limited, Oxford, England. 5467 Nucleic Acids Research Protein estimation Protein concentration was measured both by comparative absorption at 260 nm and 280 nm wavelength light and using a Bio-Rad protein assay kit. Isolation of Dral Three one-litre cultures of D. radiophilus in nutrient broth No 2 (Oxoid) were grown to early stationary phase by shaking at 37 °C. It should be noted that protease activity increases greatly in late stationary and decline phase. About 15 g wet weight of cells was harvested by centrifugation at 10,000 g for 10 mm. The bacteria were resuspended in 30 ml 10 MM Tris-HC1, 2 mM 2-mercaptoethanol (MSH), 0.1 mM phenylmethylsulphonylfluoride (PMSF), pH 7.5 and broken open in a French pressure cell at 3,000 psi. Following centrifugation at 10,000 g for 10 minutes to remove undamaged cells and large fragments, the lysate was centrifuged at 100,000 g for 2 hours. Most of the DNA present in the supernate was removed using polyethylene glycol 6,000 (PEG): dextran T500 phase partition (4). This procedure also removed significant amounts of non-specific exonuclease activity. The enzyme preparation was dialysed (10-20 hours) against column buffer 1 (CB1 10 mM Tris-HC1, 2 mM MSH, 0.1 mM PMSF and 0.075M NaCl, pH 8.0) and applied to a 20 x 2.6 cm DEAE-sephacel (Bio-Rad) column-, previously equilibrated with CB1. After washing, the column was developed with a linear NaCI gradieni (M) sorbance 26OnM Fig. 1. Protein Elution profile of D.radiophilus cell extraction DEAE-Sephacel
Activity Metabolism of Painted Turtles (Chrysemys picta)

JACOB, J. S. , AND C. W. PAINTER. 1980. Overwinter thermal ecology of Crotalus viridis in the North-central plains of New Mexico. Copeia 1980:799-805. LOWE, C. H. , P.J. LARDNER AND E. A. HALPERN. 1971. Supercooling in reptiles and other vertebrates. Comp. Biochem. Physiol. 39:125-135. McCoy, C. J. 1974. Communal hibernation of the lizard Cnemidophorus tigris (Teiidae) in Colorado. Southwestern Nat. 19:218.
Carbon isotope ratios of plants of a tropical dry forest in Mexico

Carbon isotope ratios were measured on leaves of the dominant species within a tropical dry forest in Mexico, which was characterized as being strongly drought deciduous. A variety of succulent epiphytes from diverse microsites had carbon isotope ratios indicating obligate crassulacean acid metabolism. All woody species examined had isotope ratios indicative of the C3 photosynthetic pathway, although there was a wide range of isotopic values. Two of the woody species that retained leaves during the dry season showed a large variation in carbon isotope ratios (up to 6 %o) that was dependent on microsite location. Key-words: Epiphytes, isotope ratios, crassulacean acid metabolism, water-use-efficiency, succulents
Simulations of octapeptin–outer membrane interactions reveal conformational flexibility is linked to antimicrobial potency

The octapeptins are lipopeptide antibiotics that are structurally similar to polymyxins yet retain activity against polymyxin-resistant Gram-negative pathogens, suggesting they might be used to treat recalcitrant infections. However, the basis of their unique activity is unclear because of the difficulty in generating high-resolution experimental data of the interaction of antimicrobial peptides with lipid membranes. To elucidate these structure–activity relationships, we employed all-atom molecular dynamics simulations with umbrella sampling to investigate the conformational and energetic landscape of octapeptins interacting with bacterial outer membrane (OM). Specifically, we examined the interaction of octapeptin C4 and FADDI-115, lacking a single hydroxyl group compared with octapeptin C4, with the lipid A–phosphoethanolamine modified OM of Acinetobacter baumannii. Octapeptin C4 and FADDI-115 both penetrated into the OM hydrophobic center but experienced different conformational transitions from an unfolded to a folded state that was highly dependent on the structural flexibility of their respective N-terminal fatty acyl groups. The additional hydroxyl group present in the fatty acyl group of octapeptin C4 resulted in the molecule becoming trapped in a semifolded state, leading to a higher free energy barrier for OM penetration. The free energy barrier for the translocation through the OM hydrophobic layer was ∼72 kcal/mol for octapeptin C4 and 62 kcal/mol for FADDI-115. Our results help to explain the lower antimicrobial activity previously observed for octapeptin C4 compared with FADDI-115 and more broadly improve our understanding of the structure–function relationships of octapeptins. These findings may facilitate the discovery of next-generation octapeptins against polymyxin-resistant Gram-negative 'superbugs. '
Annual Changes in Spermatozoan Production and Associated Organs of White-Tailed Deer

The left testis and epididymis were collected from each of 60 wild adult (>12 months old) male white-tailed deer (Odocoileus virgin'anus) over approximately 1 year in southwest Virginia. Testes and epididymides were weighed separately and numbers of spermatozoa in each organ were determined. All gonadal parameters were at baseline values from February through June. Testis and epididymis weights and testicular spermatozoan numbers rose markedly from June to July. Epididymal spermatozoan numbers increased from July to August as storage of spermatozoa began. Testis and epididymis weights (g) and testicular and epididymal spermatozoan numbers (x 10") increased to maximum values (46.76 ? 8.16 S.E., 7.40 -11.11 S.E., 4.406 ? -t 0.577 S.E., and 6.602 ? 1.600 S.E., respectively) during November when does normally are bred in southwest Virginia. Male deer apparently have breeding capability and sexual libido from the latter part of September through January in the study area. However, the breeding capability of the male had begun to diminish in December as indicated by the regression of all gonadal measurements. J. WILDL. MANAGE. 41(1):92-99 Deer herds are being managed with everincreasing intensity. The primary management plan has been one directed at increasing productivity of white-tailed deer through habitat manipulation and harvest regulation. However, knowledge of the reproductive physiology of both sexes is necessary to produce optimum sustained deer yields. In particular, certain aspects of the male deer's reproductive physiology need to be known in more detail. Measurements of the testicular and epididymal spermatozoan reserves of wild deer can provide valuable data on the breeding potential of individual animals. Reliable physiological data of this type could contribute to maximization of the male deer harvest and hunter satisfaction. This research was undertaken to define more clearly the nature of reproductive changes during the annual reproductive cycle of the male white-tailed deer. We thank the personnel of the Radford Army Ammunition Plant for their cooperation during the study, and the Virginia Cooperative Wildlife Research Unit for the use of its vehicles throughout the study.
“Repair Me if You Can”: Membrane Damage, Response, and Control from the Viral Perspective

Cells are constantly challenged by pathogens (bacteria, virus, and fungi), and protein aggregates or chemicals, which can provoke membrane damage at the plasma membrane or within the endo-lysosomal compartments. Detection of endo-lysosomal rupture depends on a family of sugar-binding lectins, known as galectins, which sense the abnormal exposure of glycans to the cytoplasm upon membrane damage. Galectins in conjunction with other factors orchestrate specific membrane damage responses such as the recruitment of the endosomal sorting complex required for transport (ESCRT) machinery to either repair damaged membranes or the activation of autophagy to remove membrane remnants. If not controlled, membrane damage causes the release of harmful components including protons, reactive oxygen species, or cathepsins that will elicit inflammation. In this review, we provide an overview of current knowledge on membrane damage and cellular responses. In particular, we focus on the endo-lysosomal damage triggered by non-enveloped viruses (such as adenovirus) and discuss viral strategies to control the cellular membrane damage response. Finally, we debate the link between autophagy and inflammation in this context and discuss the possibility that virus induced autophagy upon entry limits inflammation.
Prevalence of Feline Coronavirus Shedding in German Catteries and Associated Risk Factors

The aim of this prospective study was to determine prevalence and potential risk factors of feline coronavirus (FCoV) shedding. Four consecutive fecal samples of 179 cats from 37 German breeding catteries were analyzed for FCoV ribonucleic acid (RNA) by real-time reverse transcriptase polymerase chain reaction (RT-qPCR). Prevalence of shedding was calculated using different numbers of fecal samples per cat (1–4) and different sampling intervals (5–28 days). Information on potential risk factors for FCoV shedding was obtained by a questionnaire. Risk factor analysis was performed using a generalized linear mixed model (GLMM). Most cats (137/179, 76.5%, 95% confidence interval (CI) 69.8–82.2) shed FCoV at least at once. None of the tested 37 catteries was free of FCoV. Prevalence calculated including all four (76.5%, 95% CI 69.8–82.2) or the last three (73.7%, 95% CI 66.8–79.7) samples per cat was significantly higher than the prevalence calculated with only the last sample (61.5%, 95% CI 54.2–68.3; p = 0.0029 and 0.0175, respectively). Young age was significantly associated with FCoV shedding while the other factors were not. For identification of FCoV shedders in multi-cat households, at least three fecal samples per cat should be analyzed. Young age is the most important risk factor for FCoV shedding.