Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation in seasonal ultrastructure of sexual granules in the renal sexual segment of the Northern Water Snake, Nerodia sipedon sipedon

The renal sexual segment of the kidney (RSS) can be found in many male squamate reptiles, encompassing the distal region of the nephron and, in some cases, collecting ducts. This sexually dimorphic structure exhibits varying degrees of hypertrophy and regression throughout the year. Although researchers have been aware of and have investigated this unique structure for over a century, its ultimate function remains under discussion. In many studies hypertrophy and regression of the RSS have been correlated with testicular activity and androgen secretion. As in most of the snakes studied to date, the male Northern Water Snake (Nerodia s. sipedon) does not exhibit a dramatic cycle of hypertrophy and regression, as reported in lizards. Following the initial hypertrophy at maturity, the male Northern Water Snake maintains a level of RSS hypertrophy throughout the year. Variations in the appearance and makeup of the sexual granules provide an identifiable and quantifiable seasonal pattern that can be correlated with the concentration of plasma androgens. In the Northern Water Snake, plasma androgens are elevated upon emergence and the RSS epithelial cells are filled with solid granules. As androgen levels decline during spring, sexual granule content appears to be breaking down (utilized? ), becoming diffuse in appearance. By mid‐ to late summer androgen synthesis is at a maximum, increasing circulating androgens and stimulating the development and return of the solid granules. This study utilized electron microscopy and steroid radioimmunoassay to examine seasonal cycles of sex granules, in terms of development, maintenance, and regression, correlated with plasma androgen concentration. In addition, this investigation provides evidence of a possible secondary source of androgen secretion. J. Morphol. 261:70–80, 2004. © 2004 Wiley‐Liss, Inc.
Neural Responses to Physical Characteristics of a High-velocity, Low-amplitude Spinal Manipulation: Effect of Thrust Direction

Study Design. Electrophysiological recordings were obtained from proprioceptors in deep lumbar paraspinal muscles of anesthetized cats during high-velocity low-amplitude spinal manipulation (HVLA-SM). Objective. To determine how thrust direction of an HVLA-SM affects neural input from back musculature. Summary of Background Data. A clinician's ability to apply the thrust of an HVLA-SM in a specified direction is considered an important component of its optimal delivery. However, previous biomechanical studies indicate that the shear force component of the thrust vector is not actually transmitted to paraspinal tissues deep to the thoracolumbar fascia because the skin–fascia interface is frictionless. Methods. Neural activity from muscle spindles in the multifidus and longissimus muscles was recorded from L6 dorsal rootlets in 18 anesthetized cats. After preload to the spinal tissues, HVLA-SMs (100-ms thrust duration) were applied through the intact skin overlying the L6 lamina. Thrusts were applied at angles oriented perpendicularly to the back and obliquely at 15° and 30° medialward or cranialward using a 6 × 6 Latin square design with three replicates. The normal force component was kept constant at 21.3 N. HVLA-SMs were preceded and followed by simulated spinal movement applied to the L6 vertebra. Changes in mean instantaneous discharge frequency (&Dgr;MIF) of muscle spindles were determined both during the thrust and spinal movement. Results. &Dgr;MIFs during the HVLA-SM thrust were significantly greater in response to all thrust directions compared with the preload alone, but there was no difference in &Dgr;MIF for any of the thrust directions during the HVLA-SM. HVLA-SM decreased some of the responses to simulated spinal movement but thrust direction had no effect on these changes. Conclusion. The shear force component of an HVLA-SM's thrust vector is not transmitted to the underlying vertebra sufficient to activate muscle spindles of the attached muscles. Implications for clinical practice and clinical research are discussed. Level of Evidence: N/A
Causes of childhood blindness in the People’s Republic of China: results from 1131 blind school students in 18 provinces

AIMS To determine the anatomical site and underlying causes of blindness and severe visual impairment in children under 16 years of age in special education in the People’s Republic of China with a view to determining potentially preventable and treatable causes. METHODS A national study of children attending schools for the blind in China was conducted between April and June 1998 using the WHO Prevention of Blindness Programme (WHO/PBL) eye examination record for children with blindness and low vision. Eight Chinese ophthalmologists attended a training workshop before conducting the study. 36 blind schools in 18 provinces of China were included. RESULTS 1245 children aged between 5 and 15 years were examined, of whom 1131 (91%) were blind or severely visually impaired (visual acuity less than 6/60 in the better eye). The commonest anatomical sites of visual loss were whole globe (mainly microphthalmos) 25.5% and retina (mainly dystrophies) 24.9%. Lens was the major site in 18.8%, optic nerve in 13.6%, and glaucoma in 9%. Corneal scarring was not a major cause of visual loss. The aetiology was unknown in 52.9%, hereditary factors were responsible in 30.7%, and childhood causes in 14%. 15% of cases were considered potentially preventable and 22.5% potentially treatable. CONCLUSION The pattern of childhood blindness seen in this study is likely to reflect the improved health and socioeconomic status of China but may partly reflect bias in admission to, and location of, blind schools, with higher socioeconomic groups overrepresented. Nutritional and infective causes of blindness are uncommon, and hereditary and unknown factors are now the predominant causes.
Direct Hepatotoxic Effect of KC Chemokine in the Liver Without Infiltration of Neutrophils

KC is a mouse homolog of human chemokine gro-α (CXCL1), expression of which is increased in liver diseases. We show that activated, but not quiescent, hepatic stellate cells (HSCs) express KC. Hepatic stellate cells constitutively express the KC receptor, CXCR2. Addition of recombinant KC to HSCs undergoing activation in culture Increases secretion and processing of Type I collagen. Overexpression of endogenous KC in the mouse liver could be achieved by an intraperitoneal injection CCl4 followed after 24 hrs by an injection of recombinant KC into circulation. This protocol resulted in about a 14-fold increase in concentration of KC protein in the liver. Overexpression of KC was associated with upregulation of the mRNA for CXCR2 and MIP-2 and with necrosis and increased synthesis of Type I collagen. This suggests that KC has a direct hepatotoxic effect, which led to a massive liver necrosis after 48 hrs. No accumulation of neutrophils was seen in the livers as judged by histology and reverse transcriptase-polymerase chain reaction analysis of myeloperoxidase mRNA. Autostimulation of KC and CXCR2 expression by recombinant KC protein in the mice with preexisting liver injury indicates a positive feedback regulation. Such regulation and direct hepatotoxicity of KC with increased collagen synthesis represent novel findings about the role of KC/gro-α in liver pathology.
HMGB 2 Regulates Satellite Cell-Mediated Skeletal Muscle Regeneration via IGF 2 BP 2

Although the mechanism underlying modulation of transcription factors in myogenesis has been well elucidated, the function of the transcription cofactors involved in this process remains poorly understood. Here, we identified HMGB2 as an essential nuclear transcriptional co-regulator in myogenesis. HMGB2 was highly expressed in undifferentiated myoblasts and regenerating muscle. Knockdown of HMGB2 inhibited myoblast proliferation and stimulated its differentiation. HMGB2 depletion down-regulated Myf5 and Cyclin A2 on the protein but not mRNA level. In contrast, overexpression of HMGB2 promoted Myf5 and Cyclin A2 protein upregulation. Furthermore, we found that the RNA-binding protein IGF2BP2 is a downstream target of HMGB2, as previously shown for HMGA2. IGF2BP2 binds to mRNAs of Myf5 or Cyclin A2, resulting in translation enhancement or mRNA stabilization, respectively. Notably, overexpression of IGF2BP2 could partially rescue protein levels of Myf5 and Cyclin A2, in response to HMGB2 decrease. Moreover, depletion of HMGB2 in vivo severely attenuated muscle repair; this was due to a decrease in satellite cells. Together, these results highlight the previously undiscovered and critical role of HMGB2-IGF2BP2 axis in myogenesis and muscle regeneration. Jo ur na l o f C el l S ci en ce • A dv an ce a rt ic le
Differential Initiation of Innate Immune Responses Induced by Human Cytomegalovirus Entry into Fibroblast Cells1

Infection of permissive fibroblasts with human CMV (HCMV, AD169) is accompanied by a robust activation of innate immune defense. In this study, we show that inflammatory cytokine (IC) secretion and activation of the type I IFN pathway (αβ IFN) are initiated through distinct mechanisms. HCMV is recognized by TLR2 leading to the NF-κB activation and IC secretion. However, the IFN response to HCMV is not a TLR2-dependent process, as a dominant negative TLR2 does not affect the antiviral response to infection. Additionally, bafilomycin, an endosomal acidification inhibitor, has no effect on HCMV-induced IFN responses suggesting that IFN signaling is independent of endosomal resident TLRs. By contrast, disruption of lipid rafts by depletion of cellular cholesterol inhibits both HCMV entry as well as IFN responses. Cholesterol depletion had no effect on the induction of ICs by HCMV, illustrating a biological distinction at the cellular level with the initiation of innate immune pathways. Furthermore, HCMV entry inhibitors block IFN responses but not IC signaling. In particular, blocking the interaction of HCMV with β1 integrin diminished IFN signaling, suggesting that this virus-cell interaction or subsequent downstream steps in the entry pathway are critical for downstream signal transduction events. These data show that HCMV entry and IFN signaling are coordinated processes that require cholesterol-rich microdomains, whereas IC signaling is activated through outright sensing via TLR2. These findings further highlight the complexity and sophistication of innate immune responses at the earliest points in HCMV infection.
Clock and Synchronization Networks for a 3 GHz 64 Bit ARMv8 8-Core SoC

This paper describes the clock distribution and synchronization network for a 64 bit ARMv8 8-core microprocessor. Embedded in a SoC for cloud computing platforms, the processor is fabricated in a 40 nm CMOS technology and operates at 3.0 GHz. The system PLL has a measured rms jitter <;1 ps and features dynamic frequency hopping for DVFS applications. In conjunction with a Star/H/Mesh topology, the clock distribution uses both CML and CMOS circuits to minimize period jitter and nominally achieves <;0.8 ps/mV | rms and <;9 ps of period jitter and skew, respectively. By using local Duty Cycle Adjustment circuits in each core to properly offset the clock duty cycle and ease timing critical paths, the processor performance improves by more than 5%. A simple probing circuit for high speed clock measurements can be used to monitor the high frequency excursions of the internal supply to counteract any timing violation that could occur. Finally an enhanced latch, which improves MTBF by up to 5 orders of magnitude and thus is suited for high speed synchronization operations, is proposed.
CaMKII: do not work too hard in the failing heart

CaMKIIδ, a calcium/calmodulin‐dependent protein kinase, plays pivotal roles in the development of heart disease. In this issue of The Journal of Pathology, Salma Awad and colleagues demonstrate that CaMKIIδ is engaged in both pathological hypertrophy and heart failure. By analysis of mouse and human heart samples, they found that the level of CaMKIIδ is increased in both pathological processes. Further studies demonstrated that CaMKIIδ mediates the phosphorylation of histone H3 at serine 10 (H3S10), which then tethers the chaperone protein 14‐3‐3 to promoter regions of fetal cardiac genes to activate their transcription. Combined with recent highlights on transcription regulation, this study revealed a fuzzy boundary between pathological hypertrophy and subsequent heart failure and indicates that current therapeutic strategies towards heart failure may have potential risks to patients. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Effect of 3 Years of Treatment With Exenatide on Postprandial Glucagon Levels

α-Cell dysfunction contributes to hyperglycemia in type 2 diabetes and is characterized by inappropriately increased basal and postprandial glucagon levels (1). The regulation of glucagon secretion remains poorly understood. Glucagon-like peptide 1 (GLP-1), a gut-derived hormone with glucose-dependent insulinotropic effects, has been shown, albeit mostly in short-term studies, to reduce fasting and postprandial glucagon levels. Thus, the glucagonostatic effect of GLP-1 receptor agonists has been considered as one of the key mechanisms by which they improve glycemia (2). However, in a recent 48-week study with the GLP-1 receptor agonist liraglutide, a paradoxical postprandial increase in glucagon levels was observed (3). This study challenged our understanding of the effects of GLP-1 receptor agonists on glucagon. We assessed the effects of 3-year treatment with the GLP-1 receptor agonist exenatide (EXE) versus insulin glargine (GLAR) on fasting and postprandial glucagon levels. Details of the study design were reported previously (4). In short, 36 …
Clinical significance and pathogenic function of connective tissue growth factor (CTGF/CCN2) in osteolytic mandibular squamous cell carcinoma.

BACKGROUND Mandibular bone destruction is a frequent occurrence in oral squamous cell carcinoma. However, the relationship between the bone destruction and associated factors is unclear. Here, the role and diagnostic utility of connective tissue growth factor (CCN2) in bone destruction of the mandible was investigated. PATIENTS AND METHODS The production of CCN2 was explored by using immunohistochemistry on paraffin-embedded tissues from 20 cases of mandibular squamous cell carcinoma. The effect of CCN2 on osteoclastogenesis was examined in vitro by using total bone marrow cell populations from male mice. RESULTS Immunohistochemical analysis showed that CCN2-positive signals were closely associated with destructive invasion of the mandible by oral squamous cell carcinomas. Consistent with these results, recombinant human CCN2 (rCCN2) stimulated tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cell formation in vitro. CONCLUSION CCN2 can be considered a diagnostic marker and target for treatment in oral osteolytic mandibular squamous cell carcinoma.
Raising Awareness of Sleep as a Healthy Behavior

Sleep is an essential component of health, and its timing, duration, and quality are critical determinants of health (1). Sleep may play an important role in metabolic regulation, emotion regulation, performance, memory consolidation, brain recuperation processes, and learning (2). Because of the importance of these functions, sleep should be viewed as being as critical to health as diet and physical activity. However, public health practitioners and other health care providers have not focused major attention on the importance of sleep to health. In this essay, we briefly summarize the scientific literature about hours of sleep needed and why sleep is an important public health issue. We also suggest areas for expanding sleep research and strategies for increasing awareness of the importance of sleep and improving sleep health. Finally, we call for action to bring sleep to the forefront of public health.
Citotoxicity of Fipronil on Hepatocytes Isolated from Rat and Effects of Its Biotransformation

The aim of this study was to characterize the mechanism of toxicity of fipronil on hepatocytes isolated from the rat and the effect of its biotransformation on the toxicological potential. The toxicity of fipronil was assessed by monitoring the oxygen consumption and mitochondrial membrane potential, intracellular ATP concentration, Ca2+ homeostasis and cell viability. The cell viability was evaluated by trypan blue exclusion in hepatocytes that were isolated from the normal rats and by the release of the enzymes alanine transaminase and aspartate transaminase in hepatocytes that were isolated from the normal rats or proadifen-pretreated rats. Fipronil reduced mitochondrial respiration in the cells that were energized with glutamate plus malate in a dose-dependent manner and dissipated the mitochondrial membrane potential that was accompanied by a reduction in ATP concentration and a disruption of intracellular Ca2+ homeostasis. The cell viability was affected by fipronil with higher potency in hepatocytes that were isolated from the normal rats, which indicated that the metabolism of this insecticide increased its toxicological potential. The results of this study indicated that the toxicity of fipronil to the hepatocytes was related to the inhibition of mitochondrial activity, which led to decreased ATP synthesis and a consequent alteration in intracellular Ca2+ homeostasis and ultimately resulted in cell death.
Analysis of Vascular Access in Haemodialysis Patients - Single Center Experience.

BACKGROUND Vascular access is the key in successful management of chronic haemodialysis (HD) patients. Though native arteriovenous fistula (AVF) is considered the access of choice, many patients in our country initiate haemodialysis through central venous catheter (CVC). There is paucity of data on vascular access in haemodialysis patients from southern India. AIM Aim of the present study was to review our experience of vascular access in Haemodialysis patients (both central venous catheters and arteriovenous fistula) and to assess its success rate and common complications. MATERIALS AND METHODS This prospective study was conducted between January 2014 and December 2014 in our institute. A total of 50 patients with Chronic Kidney Disease (CKD) underwent vascular access intervention during the above period. RESULTS A temporary venous catheter (96%) in the right internal jugular vein was the most common mode of initiation of haemodialysis with 34.48% incidence of catheter related sepsis. Fifty percent of catheters were removed electively with mean duration of catheter survival of 77.23 ± 14.8 days. Wrist AVF (60%) was the most common site of AVF creation followed by arm (30%), mid-forearm (7.5%) and leg (2.5%). Complications include distal oedema (17.5%) and venous hypertension (2.5%). Primary failure occurred in 25% of patients and was more common in diabetic, elderly (>60 years) and in distal fistulas. Elderly patients (>60 years) starting dialysis with a CVC were more likely to be CVC dependent at 90 days. CONCLUSION Late presentation and delayed diagnosis of chronic kidney disease (CKD) necessitates dialysis initiation through temporary catheter. Dialysis catheter with its attendant complications further adds to the morbidity, mortality, health care burden and costs. Early nephrology referral and permanent access creation in the pre dialysis stage could avert the unnecessary complications and costs of catheter.
Nemo Solus Satis Sapit: Trends of Research Collaborations in the Vietnamese Social Sciences, Observing 2008-2017 Scopus Data

Nemo solus satis sapit – no one can be wise enough on his own. This is particularly true when it comes to collaborations in scientific research, which are essential for the exchange of knowledge, sharing of workloads, and improvement of output quality. Concerns over this issue in Vietnam, a developing country with limited academic resources, led to an in-depth study on Vietnamese social science research, in which data from 410 Vietnamese authors who had international publications recorded in Google Scholar and Scopus during 2008 2017 were collected for analysis. The results showed that more than 90% of scientists had worked with colleagues to publish, and they had collaborated 13 times on average during the time limit of the data sample. These collaborations, both domestic and international, provided authors with significant advantages, boosting their performance (β au.vn = 0.134, p
Vitamin D Status and Related Factors in Newborns in Shanghai, China

With the increasing recognition of the importance of the non-skeletal effects of vitamin D (VitD), more and more attention has been drawn to VitD status in early life. However, the VitD status of newborns and factors that influence VitD levels in Shanghai, China, remain unclear. A total of 1030 pregnant women were selected from two hospitals in Shanghai, one of the largest cities in China located at 31 degrees north latitude. Umbilical cord serum concentrations of 25-hydroxy vitamin D [25(OH)D] were measured by LC-MS-MS, and questionnaires were used to collect information. The median cord serum 25(OH)D concentration was 22.4 ng/mL; the concentration lower than 20 ng/mL accounted for 36.3% of the participants, and the concentration lower than 30 ng/mL for 84.1%. A multivariable logistic regression model showed that the determinants of low 25(OH)D status were being born during autumn or winter months and a lack of VitD-related multivitamin supplementation. The relative risk was 1.7 for both autumn (95% CI, 1.1–2.6) and winter (95% CI, 1.1–2.5) births (p < 0.05). VitD-related multivitamin supplementation more than once a day during pregnancy reduced the risk of VitD deficiency [adjusted OR (aOR) = 0.6, 95% CI (0.45–1.0) for VitD supplementation] (p < 0.05). VitD deficiency and insufficiency are common in newborns in Shanghai, China, and are independently associated with season and VitD supplementation. Our findings may assist future efforts to correct low levels of 25(OH)D in Shanghai mothers and their newborn children.
TCR-CD3ζ gene polymorphisms and expression profile in rheumatoid arthritis

Abstract Objectives: Recent evidence has demonstrated that CD3ζ (also called CD247) play a vital role in multiple autoimmune diseases. In this study, we explored the association between CD247 gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also evaluated the CD3ζ expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and health controls. Methods: Three CD247 polymorphisms (rs704853, rs1214611 and rs858554) were studied in 612 patients with RA and 848 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array™ Integrated Fluidic Circuit (IFC). For gene expression study, CD3ζ mRNA levels of 36 patients with RA and 39 healthy individuals were assessed by real-time polymerase chain reaction (RT-PCR). Data were analyzed by SPSS 11.5 software. Results: A significant association between rs858554 polymorphism and RA was found under all genetic models (all p < 0.05). Moreover, we found the genotype distribution and allele frequency of rs858554 were significant associated with ACCP+ and RF+ phenotype as compare to health controls (all p < 0.05). Unfortunately, we did not detect any significant associations between rs704853, rs1214611 and RA susceptibility and autoantibody profiles (all p > 0.05). The gene expression assays showed that CD3ζ mRNA levels were downregulated in PBMCs of patients with RA when compared to healthy controls. Conclusions: Our results, the first reported for distinct Chinese populations, support a role of the CD247 gene in the susceptibility to RA. Further studies with more sample size are necessary to clarify the exact role of CD247 gene in the pathogenesis of RA.