Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth Hormone and Bile Acid Synthesis Key Role for the Activity of Hepatic Microsomal Cholesterol 7 (cid:97) -hydroxylase in the Rat

Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to charac-terize the effects of GH on hepatic cholesterol and bile acid metabolism in the rat. In hypophysectomized (Hx) rats, the activities of the rate-limiting enzymes in cholesterol and bile acid biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and cholesterol 7 (cid:97) -hydroxylase (C7 (cid:97) OH), were reduced by 71 and 64%, respectively. HMG CoA reductase mRNA levels were reduced by 37%, whereas C7 (cid:97) OH mRNA was increased by 81%. LDL receptor expression was reduced by 18% in Hx rats, without any change in the LDL receptor mRNA levels. Although the normal diurnal variation of C7 (cid:97) OH activity was preserved in Hx rats, the activity of C7 (cid:97) OH was much reduced both at midday and midnight. Total hepatic cholesterol was increased by 14% in Hx animals whereas microsomal cholesterol was unchanged. The rate of cholesterol esterification was enhanced (by 38%) in liver microsomes from Hx rats. Stepwise hormonal substitution of Hx rats showed that GH, but not thyroid hormone or cortisone, was essential to normalize the enzymatic activity of C7 (cid:97) OH. GH also normalized the altered plasma lipoprotein pattern in Hx rats, and increased the fecal output of bile acids. The latter effect was particularly evident when GH was combined with cortisone and thyroid hormone. Also in normal rats, GH stimulated C7 (cid:97) OH activity. 1997.
Prostaglandins and Other Lipid Mediators (POLM), Special Issue of the 6th European Workshop on Lipid Mediators

Polyunsaturated fatty acids (PUFA) and their cytochrome P450 (CYP450) metabolites have been linked to angiogenesis and vessel homeostasis. However, the role of individual CYP isoforms and their endogenous metabolites in those processes are not clear. Here, we focused on the role of Cyp2c44 in postnatal retinal angiogenesis and report that Cyp2c44 is highly expressed in Müller glial cells in the retina. The constitutive as well as inducible postnatal genetic deletion of Cyp2c44 resulted in an increased vessel network density without affecting vessel radial expansion during the first postnatal week. This phenotype was associated with an increased endothelial cell proliferation and attenuated Notch signaling. LC-MS/MS analyses revealed that levels of hydroxydocosahexaenoic acids (HDHA), i.e., 10-, 17and 20-HDHA were significantly elevated in retinas from 5 day old Cyp2c44−/− mice compared to their wild-type littermates. Enzymatic activity assays revealed that HDHAs were potential substrates for Cyp2c44 which could account for the increased levels of HDHAs in retinas from Cyp2c44−/− mice. These data indicate that Cyp2c44 is expressed in the murine retina and, like the soluble epoxide hydrolase, is expressed in Corresponding author. Ingrid Fleming PhD, Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. Tel: (+49) 69 6301 6972; Fax: (+49) 69 6301 86880; fleming@em.unifrankfurt. de. *Authors contributed equally Contributors J.H. performed experiments, interpreted the data and drafted the manuscript, A.G. performed experiments and interpreted the data, S.D. performed experiments, K.A. performed LC-MS/MS analyses, D.Z. generated the Cyp2c44 specific antibody, W. -H.S. helped characterize the metabolic properties of Cyp2c44, R.P. generated the confocal images. T.F. designed the generation of the Cyp2c44flox/flox mice, I.F. designed the study and wrote the manuscript. Conflict of interest None Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript Prostaglandins Other Lipid Mediat. Author manuscript; available in PMC 2020 January 14. Published in final edited form as: Prostaglandins Other Lipid Mediat. 2017 November ; 133: 93–102. doi:10.1016/j.prostaglandins. 2017.04. 002. A uhor M anscript
HIV-1 transmission among persons with acute HIV-1 infection in Malawi: demographic, behavioral and phylogenetic relationships.

Background Understanding of sexual networks involving acute HIV-1 infections (AHI) may lead to prevention opportunities to mitigate high rates of onward transmission. We evaluated HIV-1 phylogenetic and behavioral characteristics among persons with AHI and their referred partners. Methods Between 2012 and 2014, 46 persons with AHI in Malawi participated in a combined behavioral and biomedical intervention. Participants referred sexual partners for HIV-1 testing by passive referral. Demographics and sexual behaviors were collected through interviews. We used maximum-likelihood phylogenetic analyses of HIV-1 pol sequences to assess genetic relationships. Results Among 45 AHI participants with HIV-1 sequences, none was phylogenetically-linked with another AHI index. Nineteen (42%) AHI participants referred a single partner who returned for testing. Most referred partners (n=17) were or became HIV-infected with 15 (88%) presenting with established infection. Fourteen index-partner pairs had sequences available; 13 (93%) pairs were phylogenetically-linked dyads. The AHI index was female in 7/13 (54%) dyads. Age-disparate relationships among dyads were common (≥5-year age difference in 67% of dyads), including 3/6 dyads involving a male AHI index and a younger woman. Index participants with a referred partner were more likely to report no casual partners and to be living with their current partner than participants not in observed dyads. Conclusions Passive partner referral successfully identified partners with genetically similar HIV-infection - the likely source of infection - but only 40% of index cases referred partners who presented for HIV-1 testing. Future work evaluating assisted partner notification may help reach susceptible partners or more people with untreated HIV-1 infection connected to acute transmission.
Making sense of a seemingly odd connection mitochondrial

protein 2 (TRAK2) might alter ATP-binding cassette transporter 1 (ABCA1) expression, cholesterol efflux, and HDL biogenesis. TRAK2 participates in determining the shape, size, and cellular distribution of mitochondria. The mitochondria produce 27-hydroxycholesterol (27-OHC), which is an agonist for liver X receptor (LXR), which increases levels of ABCA1. The mitochondria also produce reactive oxygen species (ROS), which can decrease mRNA and protein levels of ABCA1. ABCA1 regulates the efflux of cholesterol from the cell. Cholesterol transported out of the cell by ABCA1 binds extracellularly to apolipoprotein A-I (apoA-I) and matures into HDL.
Invited Review Therapeutic applications of trans -splicing

Background: RNA trans -splicing joins exons from different pre-mRNA transcripts to generate a chimeric product. Trans- splicing can also occur at the protein level, with split inteins mediating the ligation of separate gene products to generate a mature protein. Sources of data: Comprehensive literature search of published research papers and reviews using Pubmed. Areas of agreement: Trans -splicing techniques have been used to target a wide range of diseases in both in vitro and in vivo models, resulting in RNA, protein and functional correction. Areas of controversy: Off-target effects can lead to therapeutically undesir-able consequences. In vivo efﬁcacy is typically low, and delivery issues remain a challenge. Growing points: research: Increasing trans -splicing efﬁcacy and speciﬁcity by rational design, screening and competitive inhibition of endogenous cis -splicing.
Early-Onset Subicular Microvascular Amyloid and Neuroinflammation Correlate With Behavioral Deficits in Vasculotropic Mutant APP Transgenic Mice

Cerebral microvascular amyloid β protein (Aβ) deposition and associated neuroinflammation are increasingly recognized as an important component leading to cognitive impairment in Alzheimer’s disease and related cerebral amyloid angiopathy (CAA) disorders. Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human Aβ precursor protein in brain (Tg-SwDI) accumulate abundant cerebral microvascular fibrillar amyloid deposits exhibiting robust neuroinflammation. In the present study, we sought to determine if the unique amyloid pathology of Tg-SwDI mice was associated with deficits in behavioral performance. Behavioral performance tests that assessed a variety of psychological functions, including overall activity, motor ability, balance and strength, anxiety, impulsivity, and learning were conducted on homozygous Tg-SwDI mice and similarly aged wild-type C57Bl/6 mice. Our results indicate that Tg-SwDI mice were impaired in the performance of the Barnes maze learning and memory task at 3, 9, and 12 months of age. While more widespread cerebral microvascular Aβ pathology was evident in older animals, the evaluation of the Aβ pathology in the 3 months old transgenic animals revealed specific accumulation of microvascular amyloid and markedly elevated numbers of reactive astrocytes and activated microglia restricted to the subiculum. These findings indicate that early-onset accumulation of subicular microvascular amyloid and accompanying neuroinflammation correlates with impaired performance in the learning and memory task in Tg-SwDI mice.
Global transcriptional silencing and developmental competence in the oocyte mediated by the mRNA decay activator ZFP36L2

Global transcriptional silencing is a highly conserved mechanism central to the oocyte-to-embryo transition. We report the unexpected discovery that global transcriptional silencing in oocytes depends on an mRNA decay activator. Oocyte-specific loss of ZFP36L2—an RNA-binding protein critical for AU-rich element-dependent mRNA decay—prevents global transcriptional silencing and causes oocyte maturation and fertilization defects, as well as complete female infertility in the mouse. Single-cell RNAseq revealed that ZFP36L2 downregulates mRNAs encoding transcription and chromatin modification regulators, including a large group of mRNAs for histone demethylases targeting H3K4 and H3K9, which we show are bound and degraded by ZFP36L2. Oocytes lacking Zfp36l2 fail to accumulate histone methylation at H3K4 and H3K9—marks associated with the transcriptionally silent, developmentally competent oocyte state. Our results uncover a ZFP36L2-dependent mRNA decay mechanism that acts as a developmental switch * during oocyte growth, triggering wide-spread shifts in chromatin modification and global transcription. eTOC Global transcriptional silencing is a highly conserved developmental event central to oocyte developmental competence. Dumdie et al. report that, unexpectedly, this germline-specific global event is driven by an mRNA decay activator. ZFP36L2 downregulates master transcriptional regulators, leading to the chromatin modification and transcriptional silencing events important for oocyte competence. histone methylation at H3K4 and H3K9, global transcriptional silencing and the acquisition of full developmental competence.
Initial Trial of Alpha7-Nicotinic Receptor Stimulation in Two Adult Patients with Autism Spectrum Disorder

Abnormalities in CHRNA7, the alpha7-nicotinic receptor gene, have been reported in autism spectrum disorder. These genetic abnormalities potentially decrease the receptor’s expression and diminish its functional role. This double-blind, placebo-controlled crossover study in two adult patients investigated whether an investigational receptor-specific partial agonist drug would increase the inhibitory functions of the gene and thereby increase patients’ attention. An electrophysiological biomarker, P50 inhibition, verified the intended neurobiological effect of the agonist, and neuropsychological testing verified a primary cognitive effect. Both patients perceived increased attention in their self-ratings. Alpha7-nicotinic receptor agonists, currently the target of drug development in schizophrenia and Alzheimer Disease, may also have positive clinical effects in autism spectrum disorder.
Full Reviews Mineralocorticoid-receptor signalling in vascular smooth muscle

Human data suggest that eplerenone and spironolactone lowers blood pressure by mechanisms independent of the distal tubule. Now, a novel inducible conditional knockout model of the mineralocorticoid receptor (MR) in vascular smooth muscle cells (VSMCs) brings out understanding further. The mineralocorticoid receptor (MR) belongs to the nuclear receptor subfamily 3, group C, member 2, (NR3C2) and is a protein that in humans is encoded by the NR3C2 gene on chromosome 4q31.1-31.2. The MR ligand is aldosterone, although the MR also has great af ﬁ nity for cortisol. The MR is ‘ protected ’ from glucocorticoids by co-localization of an enzyme, corticosteroid 11-beta-dehydrogenase iso-enzyme 2 (11ß-HSD2), which converts cortisol to cortisone that does not bind to the MR. The MR also responds to some progestins. Spironolactone and eplerenone are approved MR antagonists. Binding of the MR to its ligand aldosterone results in its trans-location to the cell nucleus, homodimerization and binding to hormone-response elements present in the promoter of certain genes. ABSTRACT Renal transplantation is the best option for patients with end-stage renal disease (ESRD), but its half-life is limited to a decade. Clinical and histological markers measurable within the ﬁ rst year of transplantation can be used to predict its outcome. These markers are important for selecting kidneys for transplantation, for identifying the main causes of late allograft loss, for therapeutic decisions and as surrogate markers in therapeutic trials. ‘ Basal state ’ markers, such as age, glomer-ular ﬁ ltration rate and ﬁ brotic lesions, are highly predictive of allograft loss, showing that early and stable pathological mechanisms contribute considerably to this loss. On the other hand, some more dynamic predictors such as treatment, recur-rence of the initial disease, in ﬂ ammation and epithelial pheno-typic changes offer clinicians and researchers opportunities to in ﬂ uence the fate of allografts.
Improvement of maintenance management through Lean Philosophy and Industry 4.0

For companies to be able not only to survive, but also to differentiate themselves in the current global market scenario, all their functional areas must be in line with short, medium, and long-term management objectives and policies. The performance and competitiveness of companies depend on the behaviour of their production system, so an ambitious and adequate maintenance management is necessary. In this way, companies seek to adopt new methodologies and approaches to maintenance management that allow them to prepare maintenance for the challenges of Lean Philosophy and Industry 4.0. The Lean philosophy aims to do more and more with less and less, that is, using less equipment, less human effort, less space, and time, trying to offer customers exactly what they want, at the right time. On the other hand, Industry 4.0 is based on intelligent factories with production processes with a computer interface between people, machines, and resources, through extensive communication networks that combine the virtual and the real world, to obtain all integrated processes generating thus a real-time information system. Thus, an adequate maintenance management system contributes not only to improve maintenance performance as well as the production system. The maintenance management system, when combined with Lean Philosophy and Industry 4.0 concepts, makes it more efficient and effective. To improve maintenance performance, a system that combines these three concepts is proposed.
NDT_A_361353 1249..1257

Purpose: Depression poses a substantial burden worldwide. Therefore, elucidating the pathophysiological mechanism of depression is important. Sleep disturbance and sleep reactivity are symptoms of depression and are also known to exacerbate depressive symptoms. On the other hand, it is well known that resilience ameliorates depressive symptoms. To our knowledge, there have been no reports to date regarding the interaction effects among sleep disturbance, sleep reactivity, and resilience on depressive symptoms. We hypothesized that resilience buffers the aggravating effects of sleep disturbance and sleep reactivity on depressive symptoms. To test this hypothesis, we conducted hierarchical multiple regression analyses. Subjects and Methods: A total of 584 Japanese adult volunteers were recruited between April 2017 and April 2018 by convenience sampling. Their demographic characteristics, sleep disturbance, sleep reactivity, resilience, and depressive symptoms were investigated using self-administered questionnaires. The data were analyzed using hierarchical multiple regression analyses. Results: Sleep disturbance and sleep reactivity were significantly positively associated with depressive symptoms, whereas resilience was significantly negatively associated with depressive symptoms. Moreover, there was a significant interaction between sleep disturbance or sleep reactivity and resilience on depressive symptoms. Resilience significantly alleviated the aggravating effect of sleep disturbance and sleep reactivity on depressive symptoms. Conclusion: Our results indicate that people with lower resilience have more severe depressive symptoms that are associated with sleep disturbance and sleep reactivity. Therefore, there is a possibility that the enhancement of resilience will buffer the aggravating effects of sleep disturbance and sleep reactivity on depressive symptoms, and that improving sleep quality might alleviate the negative effect of low resilience on depressive symptoms.
Telerehabilitation Interventions in Patients after Stroke: A Systematic Review

Published online: Mar2022 Abstract: Objective: To summarize the best evidence effectiveness of telerehabilitation applications (Telephone, Video Conference, and Virtual Reality Therapy) for improving activities of daily living, upper limb function, balance, and costeffectiveness in stroke patients. Methods: Intensive search was done in electronic databases: PubMed (October 2020), Cochrane Library (November 2020), and PEDro (November 2020), we also checked the reference lists. This search was done to include RCTs that compare telerehabilitation applications with face-to-face therapy for patients after stroke. Then, the methodological quality of each included trial was assessed, and the data was extracted. Finally, the results were analyzed by pooling the data of change scores between pre-and post-intervention through calculation of the overall standardized mean differences with a 95% confidence interval. Results: We included 14 studies with a total of 1353 participants. Telerehabilitation applications may have not a significant effect on activities of daily living, upper limb function, and balance. Only three studies reported the results of the use of the health services provided in the study or the cost of the interventions and found that the number of visits for people who received interventions during the three-month followup evaluation was significantly reduced, but this did not last six months. Conclusion The included randomized controlled trials have no evidence to show the effectiveness of telerehabilitation applications in improving people’s activities of daily living after stroke.
A Simpliﬁed Local Control Model of Calcium-Induced Calcium Release in Cardiac Ventricular Myocytes

Calcium (Ca 2 1 )-induced Ca 2 1 release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca 2 1 release. Existing local control models of Ca 2 1 release in which interactions between L-Type Ca 2 1 channels (LCCs) and ryanodine-sensitive Ca 2 1 release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simpliﬁed models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca 2 1 current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca 2 1 release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.
The Inﬂuence of a Biologically Relevant Substratum Topography on Human Aortic and Umbilical Vein Endothelial Cells

A topographically patterned substrate with stochastic surface order that closely mimics the topographic features of native basement membranes has been fabricated to investigate the inﬂuence of topographic biophysical cueing on human aortic and umbilical vein endothelial cells. The stochastic substrate was fabricated by ﬁrst generating a highly porous polyelectrolyte multilayer ﬁlm of poly(acrylic acid) and poly(allylamine hydrochloride) followed by replicate production of this biomimetic topography via soft lithography. These substrates, which are easy to prepare and replicate, possess a number of prominent features associated with in vivo vascular basement membrane (interwoven ridges and grooves, bumps, and pores), which have typically been studied as singular features that frequently possess anisotropic surface order (e.g., alternating ridges and grooves). When compared to a ﬂat surface of identical chemistry, these biomimetic topographies inﬂuenced a number of important cellular behaviors associated with the homeostasis and degradation of vascular tissues. These include modulating cell migration rate and directional persistence, proliferation rate, and gene expression associated with regulation and remodeling of vascular tissues as well as inﬂammation.
CMAR_A_352334 2055..2064

1Department of Medical Imaging, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Department of Radiology, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China; 3Department of Hepatopathy, Third People Hospital of Taiyuan City, Taiyuan, 030001, People’s Republic of China; 4Department of Radiology, 2nd Hospital, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China