Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxytocin‐monomeric red fluorescent protein 1 synthesis in the hypothalamus under osmotic challenge and acute hypovolemia in a transgenic rat line

We generated a transgenic rat line that expresses oxytocin (OXT)‐monomeric red fluorescent protein 1 (mRFP1) fusion gene to visualize the dynamics of OXT. In this transgenic rat line, hypothalamic OXT can be assessed under diverse physiological and pathophysiological conditions by semiquantitative fluorometry of mRFP1 fluorescence intensity as a surrogate marker for endogenous OXT. Using this transgenic rat line, we identified the changes in hypothalamic OXT synthesis under various physiological conditions. However, few reports have directly examined hypothalamic OXT synthesis under hyperosmolality or hypovolemia. In this study, hypothalamic OXT synthesis was investigated using the transgenic rat line after acute osmotic challenge and acute hypovolemia induced by intraperitoneal (i.p.) administration of 3% hypertonic saline (HTN) and polyethylene glycol (PEG), respectively. The mRFP1 fluorescence intensity in the paraventricular (PVN) and supraoptic nuclei (SON) was significantly increased after i.p. administration of HTN and PEG, along with robust Fos‐like immunoreactivity (co‐expression). Fos expression showed neuronal activation in the brain regions that are associated with the hypothalamus and/or are involved in maintaining water and electrolyte homeostasis in HTN‐ and PEG‐treated rats. OXT and mRFP1 gene expressions were dramatically increased after HTN and PEG administration. The plasma OXT level was extremely increased after HTN and PEG administration. Acute osmotic challenge and acute hypovolemia induced upregulation of hypothalamic OXT in the PVN and SON. These results suggest that not only endogenous arginine vasopressin (AVP) but also endogenous OXT has a key role in maintaining body fluid homeostasis to cope with hyperosmolality and hypovolemia.
The deleterious effect of stress‐induced depression on rat liver: Protective role of resveratrol and dimethyl fumarate via inhibiting the MAPK/ERK/JNK pathway

This study aimed to uncover the protective potentiality of resveratrol and dimethyl fumarate (DMF) in the liver of a chronic unpredictable mild stress (CUMS)‐induced depression animal model. Resveratrol and DMF significantly alleviated CUMS‐induced behavioral abnormalities in stressed rats through improving sucrose preference in sucrose preference test and decreasing immobility time in a forced swimming test. They also mitigated serum corticosterone levels and elevated serum serotonin levels, which were formerly disturbed in CUMS rats. The hepatoprotective effect is evidenced by improvement in hepatic histopathological examinations, as well as normalized serum alanine aminotransferase and aspartate aminotransferase activities. Molecular signaling of resveratrol and DMF was estimated by diminishing hepatic expression of phosphorylated p38 mitogen‐activated protein kinase (MAPK), extracellular signal‐regulated kinase1/2 (ERK1/2), and c‐Jun N‐terminal kinase (JNK). Consequently, they improved the hepatic antioxidant and anti‐inflammatory activities as elaborated by the normalization of total antioxidant capacity, glutathione, malondialdehyde, nuclear factor‐κB, tumor necrosis factor‐α, and myeloperoxidase levels. In addition, they inhibited hepatocyte apoptosis as evidenced by the increased expression of B‐cell lymphoma 2, the decreased expression of Bax, as well as the suppressed activity of caspase‐3. In conclusion, resveratrol and DMF purveyed a significant anti‐depressant effect, which may be mediated, at least in part, via inhibiting the MAPK/ERK/JNK pathway in the CUMS rat model.
Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats

Neuropathic pain is more complex and severely affects the quality of patients’ life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.
Siwi levels reversibly regulate secondary piRISC biogenesis by affecting Ago3 body morphology in Bombyx mori

Silkworm ovarian germ cells produce the Siwi‐piRNA‐induced silencing complex (piRISC) through two consecutive mechanisms, the primary pathway and the secondary ping‐pong cycle. Primary Siwi‐piRISC production occurs on the outer mitochondrial membrane in an Ago3‐independent manner, where Tudor domain‐containing Papi binds unloaded Siwi via its symmetrical dimethylarginines (sDMAs). Here, we now show that secondary Siwi‐piRISC production occurs at the Ago3‐positive nuage Ago3 bodies, in an Ago3‐dependent manner, where Vreteno (Vret), another Tudor protein, interconnects unloaded Siwi and Ago3‐piRISC through their sDMAs. Upon Siwi depletion, Ago3 is phosphorylated and insolubilized in its piRISC form with cleaved RNAs and Vret, suggesting that the complex is stalled in the intermediate state. The Ago3 bodies are also enlarged. The aberrant morphology is restored upon Siwi re‐expression without Ago3‐piRISC supply. Thus, Siwi depletion aggregates the Ago3 bodies to protect the piRNA intermediates from degradation until the normal cellular environment returns to re‐initiate the ping‐pong cycle. Overall, these findings reveal a unique regulatory mechanism controlling piRNA biogenesis.
Characterization of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) and Its Potential Involvement in Shell Formation and Metamorphosis of Pacific Abalone, Haliotis discus hannai

Insulin-like growth factor binding proteins (IGFBPs) are secreted proteins that play an important role in IGF regulation of growth and development of vertebrate and invertebrates. In this study, the IGFBP7 gene was cloned and characterized from mantle tissues of H. discus hannai, and designated as Hdh IGFBP7. The full-length cDNA sequence transcribed from the Hdh IGFBP7 gene was 1519-bp long with an open reading frame of 720-bp corresponding to a putative polypeptide of 239 amino acids. The molecular mass of its mature protein was approximately 23.44 KDa with an estimated isoelectric point (pI) of 5.35, and it shared significant homology with IGFBP7 gene of H. madaka. Hdh IGFBP7 has a characteristic IGFBP N-terminal domain (22–89 aa), a kazal-type serine proteinase inhibitor domain (77–128), and an immunoglobulin-like C2 domain (144–223). Furthermore, twelve cysteine residues and a signature motif of IGFBPs (XCGCCXXC) were found in its N-terminal domain. Phylogenetic analysis revealed that Hdh IGFBP7 was aligned with IGFBP7 of H. madaka. Tissue distribution analysis showed that the mRNA of Hdh IGFBP7 was expressed in all examined tissues, with the highest expression level observed in the mantle and gill tissues. The expression level of Hdh IGFBP7 mRNA was relatively higher at the juvenile stage during its metamorphosis period. In situ hybridization showed that Hdh IGFBP7 transcript was expressed in epithelial cells of the dorsal mantle pallial and mucus cells of the branchial epithelium in gill. These results provide basic information for future studies on the role of IGFBP7 in IGF regulation of shell growth, development and metamorphosis of abalone.
A high burden of adverse life events and poor coping mechanisms experienced by urban-dwelling black South Africans

Aim In view of the current context of poverty and socio-economic inequalities and the high and rising burdens of HIV infection and non-communicable diseases in South Africa, this study aims to describe the distribution of adverse life events (ALEs) by age and gender, and examine the socio-demographic characteristics, psychosocial coping mechanisms, risky lifestyle behaviours and family burden of HIV-related ill-health associated with ALEs in 25-74-year-old black residents of Cape Town. Materials and methods In a random cross-sectional sample, 12 ALEs, tobacco and alcohol use, sense of coherence (SOC), locus of control (LOC) and impact of HIV in the family were determined by administered questionnaires. Data analyses included descriptive statistics adjusted for the realised sample. Multivariable linear regression models assessed the independent associations of increasing number of ALEs. Results Among 1099 participants, mean lifetime score of ALE categories examined was 6.1 ±2.1 (range 0–12) with men reporting significantly higher number of events compared with women (p<0.001). The most frequent ALE was the death of a loved one (88.5%) followed by a major financial crisis (81.2%) with no trend across gender or age group. In the multivariable linear regression model, increasing ALEs were significantly associated with male gender, unemployment, having spent >50% of life in urban areas, >7 years of education, problematic alcohol use and poorer psychosocial coping mechanisms defined by low SOC and LOC. All four variables pertaining to HIV-related burden of ill-health in the family were significantly associated with increasing ALEs. Conclusions Considering that lower SOC and LOC and problem drinking were significantly linked to ALEs, policymakers need to formulate strategies that improve coping mechanisms and promote problem-solving behaviours, target the high burden of alcohol misuse and address unemployment.
Identification and Characterization of a Novel Thermostable and Salt-Tolerant β-1,3 Xylanase from Flammeovirga pacifica Strain WPAGA1

β-1,3 xylanase is an important enzyme in the biorefinery process for some algae. The discovery and characterization of new β-1,3 xylanase is a hot research topic. In this paper, a novel β-1,3 xylanase (Xyl88) is revealed from the annotated genome of Flammeovirga pacifica strain WPAGA1. Bioinformatic analysis shows that Xyl88 belongs to the glycoside hydrolase 26 (GH26) with a suspected CBM (carbohydrate-binding module) sequence. The activity of rXyl88 is 75% of the highest enzyme activity (1.5 mol/L NaCl) in 3 mol/L NaCl buffer, which suggests good salt tolerance of rXy188. The optimum reaction temperature in the buffer without NaCl and with 1.5 mol/L NaCl is 45 °C and 55 °C, respectively. Notably, the catalytic efficiency of rXyl88 (kcat/Km) is approximately 20 higher than that of the thermophilic β-1,3 xylanase that has the highest catalytic efficiency. Xyl88 in this study becomes the most efficient enzyme ever found, and it is also the first reported moderately thermophilic and salt-tolerant β-1,3 xylanase. Results of molecular dynamics simulation further prove the excellent thermal stability of Xyl88. Moreover, according to the predicted 3D structure of the Xyl88, the surface of the enzyme is distributed with more negative charges, which is related to its salt tolerance, and significantly more hydrogen bonds and Van der Waals force between the intramolecular residues, which is related to its thermal stability.
“Outcomes of arteriovenous fistulae cannulation in the first 6 weeks of use: A retrospective multicenter observational study”

Background: Arteriovenous fistula (AVF) management for haemodialysis (HD) is one of the most challenging aspects of clinical care. A successful cannulation outcome when an AVF or arteriovenous graft (AVG) is used for the first time can be influenced by many factors, including access maturity, staff skill, and patient factors. This study examined AVF/AVG outcomes at initiation of HD across two major metropolitan public hospitals. Methods: Electronic medical records were reviewed to collect data retrospectively for a cohort of all newly commencing ESRD HD starts during 2018 to identify cannulation outcomes in the first 6 weeks. Results: Of the 117 patients included, AVG use was low (5%). Twenty-four percent of patients required a surgical intervention to salvage a poorly functioning AVF prior to commencing HD. About 32.5% of the cohort had an uneventful start with all successful cannulations. For the remainder of the cohort the number of treatments with unsuccessful cannulation ranged from 1 to 4 or more. About 36% required a surgical intervention for a poorly functioning AVF after commencing HD. Commencing HD with a CVC is associated with a lower likelihood of subsequent successful cannulation (p < 0.001). Conclusion: Even in experienced centres, a subset of patients experienced complicated cannulation in the first 6 weeks of HD. Several areas of improvement could be considered for these patients; timely referral for access creation, post-operative surveillance to ensure AVF maturation inclusive of duplex ultrasonography, gentle induction using small gauge needles and low blood flows, and consideration of a single needle HD initiation pathway.
The influence of social, psychological, and cognitive factors on the clinical course in older patients with bipolar disorder

Research on factors that contribute to recurrence in older adults with bipolar disorder (OABD) is sparse. Previous research showed that clinical factors (e.g., age of onset, lifetime psychotic features, and suicide risk) were not associated with the recurrence in OABD. In younger adults, worse social functioning, coping style, and worse cognitive functioning are found to be associated with an unfavorable course of bipolar disorder. Therefore, this study is focusing on social, psychological, and cognitive factors in OABD. More insight in these factors is essential in order to develop and further specify preventive and treatment interventions.
The host exosome pathway underpins biogenesis of the human cytomegalovirus virion

Human Cytomegalovirus (HCMV) infects over half the world's population, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion maturation, we analysed HCMV virions using proteomics, and identified a significant proportion of host exosome constituents. To validate this acquisition, we characterized exosomes released from uninfected cells, and demonstrated that over 99% of the protein cargo was subsequently incorporated into HCMV virions during infection. This suggested a common membrane origin, and utilization of host exosome machinery for virion assembly and egress. Thus, we selected a panel of exosome proteins for knock down, and confirmed that loss of 7/9 caused significantly less HCMV production. Saliently, we report that VAMP3 is essential for viral trafficking and release of infectious progeny, in various HCMV strains and cell types. Therefore, we establish that the host exosome pathway is intrinsic for HCMV maturation, and reveal new host regulators involved in viral trafficking, virion envelopment, and release. Our findings underpin future investigation of host exosome proteins as important modulators of HCMV replication with antiviral potential.
Characterization of Peach TFL1 and Comparison with FT/TFL1 Gene Families of the Rosaceae

ADDITIONAL INDEX WORDS. Prunus persica, gene expression, phylogenetics, ornamental, floral induction ABSTRACT. We investigated theFT/TFL1family of peach (Prunus persica), a gene family that regulatesfloral induction in annual and perennial plants. The peach terminal flower 1 gene (PpTFL1) was expressed in a developmental and tissue-specific pattern that, overall, was similar to that of TFL1 orthologs in other woody Rosaceae species. Consistent with a role as a floral inhibitor, ectopic expression of PpTFL1 in arabidopsis (Arabidopsis thaliana) delayed flowering and prolonged vegetative growth. Other members of the peach FT/TFL1 family were identified from the sequenced genome,includingorthologsoffloweringlocusT,centroradialis,brotherofft,andmotherofftandtfl.Sequenceanalysis found that peach FT/TFL1 family members were more similar to orthologous genes across the Rosaceae than to each other. Together these results suggest that information on genes that regulate flowering in peach could be applied to other Rosaceae species, particularly ornamentals.
Off-pump versus on-pump coronary artery surgery in octogenarians (from the KROK Registry)

Background According to the medical literature, both on-pump and off-pump coronary artery surgery is safe and effective in octogenarians. Objectives The aim of our study was to examine the epidemiology, in-hospital outcomes and long-term follow-up results in octogenarians undergoing off-pump and on-pump coronary artery surgery utilizing nationwide registry data. Methods All octogenarians (≥ 80 years) enrolled in the Polish National Registry of Cardiac Surgical Procedures (KROK Registry), who underwent isolated coronary surgery between January 2006 and September 2017 were identified. Preoperative data, perioperative complications, hospital mortality and long-term mortality were analyzed. Unadjusted and propensity-matched comparisons were performed between octogenarians undergoing off-pump and on-pump coronary artery bypass surgery. Results Octogenarians accounted for 4.1% of the total population undergoing coronary artery surgery in Poland during the analyzed period (n = 152,631) and this percentage is increasing. Among 6,006 analyzed patients, 2,744 (45.7%) were operated on-pump and 3,262 (54.3%) were operated off-pump. Propensity-matched analysis revealed that patients operated on-pump were more often reoperated due to postoperative bleeding and their in-hospital mortality was higher (6.6% vs 4.5%, p = 0.006 and 8.7% vs 5.8%, p = 0.001, respectively). Long-term all-cause mortality was lower among patients operated off-pump (p = 0.013). Conclusion On the basis of our findings we suggest that off pump technique should be considered as perfectly acceptable in octogenarians.
High-dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males.

BACKGROUND Unavoidable periods of disuse lead to muscle atrophy and functional decline. Preventing such declines can reduce the risk of re-injury and improve recovery of normal physiological functioning. OBJECTIVES We aimed to determine the effectiveness of high-dose leucine supplementation on muscle morphology and strength during 7 d of unilateral lower-limb immobilization, and the role of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in disuse atrophy. METHODS Sixteen healthy males (mean ± SEM age: 23 ± 1 y) underwent 7 d of unilateral lower-limb immobilization, with thrice-daily leucine (LEU; n = 8) or placebo (PLA; n = 8) supplementation (15 g/d). Before and after immobilization, muscle strength and compartmental tissue composition were assessed. A primed continuous infusion of l-[ring-13C6]-phenylalanine with serial muscle biopsies was used to determine postabsorptive and postprandial (20 g milk protein) MyoPS and MitoPS, fiber morphology, markers of protein turnover, and mitochondrial function between the control leg (CTL) and the immobilized leg (IMB). RESULTS Leg fat-free mass was reduced in IMB (mean ± SEM: -3.6% ± 0.5%; P = 0.030) but not CTL with no difference between supplementation groups. Isometric knee extensor strength declined to a greater extent in IMB (-27.9% ± 4.4%) than in CTL (-14.3% ± 4.4%; P = 0.043) with no difference between groups. In response to 20 g milk protein, postprandial MyoPS rates were significantly lower in IMB than in CTL (-22% ± 4%; P < 0.01) in both LEU and PLA. Postabsorptive MyoPS rates did not differ between legs or groups. Postabsorptive MitoPS rates were significantly lower in IMB than in CTL (-14% ± 5%; P < 0.01) and postprandial MitoPS rates significantly declined in response to 20 g milk protein ingestion (CTL: -10% ± 8%; IMB: -15% ± 10%; P = 0.039), with no differences between legs or groups. There were no significant differences in measures of mitochondrial respiration between legs, but peroxisome proliferator-activated receptor γ coactivator 1-α and oxidative phosphorylation complex II and III were significantly lower in IMB than in CTL (P < 0.05), with no differences between groups. CONCLUSIONS High-dose leucine supplementation (15 g/d) does not appear to attenuate any functional declines associated with 7 d of limb immobilization in young, healthy males.This trial was registered at clinicaltrials.gov as NCT03762278.
Maternal Cardiovascular Dysfunction is Associated with Hypoxic Cerebral and Umbilical Doppler Changes

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI; the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention.