Miracle-dz/UniFAR-FTUs huggingface dataset:
NOD2/c-Jun NH2-Terminal Kinase Triggers Mycoplasma ovipneumoniae-Induced Macrophage Autophagy

M. ovipneumoniae, which lacks a cell wall, causes infectious pleuropneumonia in goats and sheep. In the present study, we focused on the interaction between NOD and M. ovipneumoniae, as well as its association with autophagy. We showed for the first time that NOD2 was activated by M. ovipneumoniae even when peptidoglycans were not present. We also observed that both NOD2 and JNK pathway activation promoted M. ovipneumoniae-induced autophagy. ABSTRACT Mycoplasma ovipneumoniae belongs to Mycoplasma, a genus containing the smallest self-replicating microorganisms, and causes infectious pleuropneumonia in goats and sheep. Nucleotide-binding oligomerization domain-containing protein (NOD2), an intracellular pattern recognition receptor, interacts with muramyl dipeptide (MDP) to recognize bacterial peptidoglycans and is involved in autophagy induction. However, there have been no reports about NOD recognition of mycoplasmas or M. ovipneumoniae-induced autophagy. In this study, we sought to determine the role of NOD2 in M. ovipneumoniae-induced autophagy using Western blotting, immunofluorescence, real-time PCR (RT-PCR), and color-changing unit (CCU) analysis. M. ovipneumoniae infection markedly increased NOD2 but did not increase NOD1 expression in RAW 264.7 cells. Treating RAW 264.7 cells with MDP significantly increased colocalization of M. ovipneumoniae and LC3, whereas treatment with NOD inhibitor, NOD-IN-1, decreased colocalization of M. ovipneumoniae and LC3. Furthermore, suppressing NOD2 expression with small interfering RNA (siRNA)-NOD2 failed to trigger M. ovipneumoniae-induced autophagy by detecting autophagy markers Atg5, beclin1, and LC3-II. In addition, M. ovipneumoniae infection significantly increased the phosphorylated c-Jun NH2-terminal kinase (p-JNK)/JNK, p-Bcl-2/Bcl-2, beclin1, Atg5, and LC3-II ratios in RAW 264.7 cells. Treatment with JNK inhibitor, SP600126, or siRNA-NOD2 did not increase this reaction. These findings suggested that M. ovipneumoniae infection activated NOD2, and both NOD2 and JNK pathway activation promoted M. ovipneumoniae-induced autophagy. This study provides new insight into the NOD2 reorganization mechanism and the pathogenesis of M. ovipneumoniae infection. IMPORTANCE M. ovipneumoniae, which lacks a cell wall, causes infectious pleuropneumonia in goats and sheep. In the present study, we focused on the interaction between NOD and M. ovipneumoniae, as well as its association with autophagy. We showed for the first time that NOD2 was activated by M. ovipneumoniae even when peptidoglycans were not present. We also observed that both NOD2 and JNK pathway activation promoted M. ovipneumoniae-induced autophagy.
Influence of Self-Expanding Paclitaxel-Eluting Stent Sizing on Neointimal Hyperplasia in Superficial Femoral Artery Lesions.

BACKGROUND Although self-expanding drug-eluting stents (DES) have recently shown superior outcomes for superficial femoral artery (SFA) lesions, optimal sizing of DES diameter in SFA intervention is unclear.Methods and Results:A total of 40 de novo SFA lesions were randomized 1:1 to receive self-expanding DES with either a 1-mm or 2-mm larger diameter than the reference vessel diameter. Follow-up optical coherence tomography (OCT) was scheduled 6 months after DES implantation to evaluate the vascular response to the stents. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was neointimal VI at 6 months. Baseline reference vessel diameter was similar between the 1-mm larger diameter group and the 2-mm larger diameter group (5.0±0.8 mm vs. 4.7±0.9 mm, P=0.35). Stent diameter was 6.3±0.6 mm in the 1-mm larger group and 7.1±0.6 mm in the 2-mm larger group (P<0.0001), and stent to reference vessel diameter ratio (SV ratio) was 1.3±0.2 and 1.5±0.2 (P<0.0001), respectively. At 6-month, neointimal VI was greater in the 2-mm larger diameter group (5.5±1.5 mm2vs. 9.6±3.4 mm2, P<0.001). The correlation analysis revealed that degree of neointimal VI was positively correlated with SV ratio (r=0.43, P<0.01). CONCLUSIONS Implantation of self-expanding DES with a considerably high SV ratio resulted in neointimal hyperplasia in SFA lesions.
Identification of novel implantation-related genes in the ovine uterus

Identification of Novel Implantation-Related Genes in the Ovine Uterus. (May 2007) Gwon Hwa Song, B.S., Dankook University; M.S., Seoul National University Co-Chairs of Advisory Committee: Dr. Fuller W. Bazer Dr. Thomas E. Spencer The peri-implantation period in mammals is critical with respect to survival of the conceptus and establishment of pregnancy. During this period of pregnancy, reciprocal communication between ovary, conceptus, and endometrium is required for successful implantation and placentation. Therefore, studies were conducted to indentify and characterize novel endometrial genes important for implantation and conceptus development in the ovine uterus. The first and second studies defined the uterine expression of seven members of the cathepsin (CTS) family of lysosomal proteases, and a secreted inhibitor of CTSL called cystatin C (CST3) during the peri-implantation period. In addition, regulation of CTS and CST3 by progesterone (P4) and interferon tau (IFNT) was evaluated. CTSL was the most abundant CTS in the ovine ovine uterus and was also coordinately expressed with CST3 in the endometrial epithelia and conceptus trophectoderm. CTSL and CST3 were found to be novel P4-induced and IFNT-stimulated genes in the luminal epithelial cells of the ovine endometrium. The third study identified radical S-adenosyl methionine domain containing 2 (RSAD2) and interferon-induced with helicase C domain 1 (IFIH1) in the ovine uterus. Results of this study indicated that IFNT induces RSAD2 and IFIH1 in a P4-independent manner in the stroma, immune cells, and glands of the ovine endometrium. These two genes are proposed to have biological roles in the establishment of uterine receptivity to the conceptus during implantation. The fourth study characterized endometrial expression of stanniocalcins (STC) during pregnancy. STC1 appeared in the endometrial glands on Day 18 of pregnancy,
Maternal perspectives on infant feeding practices in Soweto, South Africa

Abstract Objective: To (i) describe the infant feeding practices of South African women living in Soweto and (ii) understand from the mothers’ perspective what influences feeding practices. Design: Semi-structured focus group discussions (FGD) and in-depth interviews (IDI) were conducted, and data were analysed using thematic analysis. Setting: Soweto, South Africa. Participants: Nineteen mothers were stratified into three FGD according to their baby’s age as follows: 0–6-month-olds, 7–14-month-olds and 15–24-month-olds. Four mothers from each FGD then attended an IDI. Results: Although mothers understood that breast-feeding was beneficial, they reported short durations of exclusive breast-feeding. The diversity and quality of weaning foods were low, and ‘junk’ food items were commonly given. Infants were fed using bottles or spoons and feeding commonly occurred separately to family meal times. Feeding practices were influenced by mothers’ beliefs that what babies eat is important for their health and that an unwillingness to eat is a sign of ill health. As such, mothers often force-fed their babies. In addition, mothers believed that feeding solid food to babies before 6 months of age was necessary. Family matriarchs were highly influential to mothers’ feeding practices; however, their advice often contradicted that of health professionals. Conclusions: In South Africa, interventions aimed at establishing healthier appetites and eating behaviours in early life should focus on: (i) fostering maternal self-efficacy around exclusive breast-feeding; (ii) challenging mixed feeding practices and encouraging more responsive feeding approaches and (iii) engaging family members to promote supportive household and community structures around infant feeding.
The final step in phage lysis: The role of the Rz-Rz1 spanin complex in the disruption of the outer membrane

The Final Step in Phage Lysis: The Role of the Rz-Rz1 Spanin Complex in the Disruption of the Outer Membrane. (May 2010) Joel Dallas Berry, B.S., Mississippi State University Chair of Advisory Committee: Dr. Ryland F. Young The purpose of the work described in this dissertation is to better understand the role of Rz and Rz1 function with respect to phage lysis. We determined using both a genetic and biochemical approach that the Rz protein is an inner membrane protein containing a single N-terminal transmembrane domain (TMD) with an Nin/Cout topology. Consistent with previous work on Rz1 (Taylor et al., 1996), the Rz1 lipoprotein was found to be localized to the outer membrane (OM). Following localization, both Rz and Rz1 form homodimers in vivo due to intermolecular disulfide formation. Despite being localized to apposing membranes, the two proteins form a complex. A small number of phages encode a potential single protein equivalent of Rz-Rz1. This protein, termed a spanin, is predicted to tether the inner and outer membranes by a single polypeptide chain. Based on complementation, it was concluded that gp11 from the phage T1 is a functional equivalent of Rz-Rz1. Gp11, and by analogy the Rz-Rz1 two-component spanin complex, threads the meshwork of the PG layer. The presence of an Rz-Rz1 complex, which forms in the presence of peptidoglycan (PG), is supported by in vivo results.
Therapeutic effect of AiWalker on balance and walking ability in patients with stroke: A pilot study

ABSTRACT Background AiWalker is a newly developed robot-assisted gait training system, which features over-ground walking paradigm and somatosensory stimulation during training compared to commonly-used robot-assisted gait training devices (e.g. Lokomat). However, no study has examined its true therapeutic effect and possible mechanism or mediating factor(s). Objectives To investigate 1) the therapeutic effect of AiWalker on the balance and walking ability in patients with stroke, and 2) whether the improvement in somatosensory function represents one of the possible mediating factors for such effect. Methods Three patients with impaired balance and walking ability due to stroke were recruited. Two patients received AiWalker training plus conventional training; while the other one only experienced conventional training. Standing balance and walking ability were assessed before and after all the training, which were represented by 6 variables. Lower limb somatosensory function was examined using Fugl-Meyer Assessment Scale. Results Five out of the 6 variables showed greater changes in patients who received AiWalker training compared to the one who only experienced conventional training. Greater improvement in lower limb somatosensory function was observed in one patient who received AiWalker training compared to the one who only experienced conventional training. Conclusion The novel robot-assisted gait training system may elicit greater improvement of balance and walking ability in patients with stroke compared to conventional interventions. Lower limb somatosensory function may be improved by AiWalker, and its improvement might represent one of the possible mediating factors for the therapeutic effect of AiWalker on balance and walking ability.
Timing of diagnosis, depression and self-harm in adolescents with autism spectrum disorder

This exploratory study aimed to explore the association between depression and self-harming behaviour in adolescence and the timing of diagnosis for autism spectrum disorder. We analysed data on 11,320 14 year olds, including 396 children with autism spectrum disorder, from the UK Millennium Cohort Study. Exposures were the timing of diagnosis for autism spectrum disorder confirmed by parental report at ages 5, 7, 11 and 14. Outcomes were depression measured by the Short Mood and Feelings Questionnaire (scores ⩾12) and self-report of self-harming behaviour, both assessed at age 14. Data were analysed using multivariable regression analysis. 91% of the autism spectrum disorder group had within-typical-range cognitive ability. After adjusting for child and family confounders, there was a positive linear trend between diagnostic age and depression, with children diagnosed between ages 7 and 11 and children diagnosed after age 11 showing increased symptoms (odds ratio = 2.21 and 3.58, respectively). A similar trend was observed for self-harming behaviour, with children diagnosed after age 11 showing the strongest association (odds ratio = 3.16). These results suggest the importance of earlier diagnosis in preventing secondary mental health problems in this population, particularly among those without cognitive delays. Further studies replicating across a wider intellectual spectrum and clarifying the underlying mechanism are warranted. Lay Abstract Children with autism spectrum disorder are at increased risk of depression and self-harming behaviours. The question of whether timing of diagnosis of autism spectrum disorder is associated with these consequences in adolescence has not yet been studied. This exploratory study aimed to explore the association between depression and self-harming behaviour in adolescence and the parent-reported timing of diagnosis for autism spectrum disorder using a large population-based cohort in the United Kingdom. Most of the children with autism spectrum disorder in our study had within-typical-range cognitive ability. We found a linear association between timing of autism spectrum disorder diagnosis and depression and self-harming behaviour in adolescence; later diagnosis of autism spectrum disorder, particularly diagnosis in adolescence, was associated with the increased risk of self-reported depressive symptoms and self-harming behaviour in adolescence among children with autism spectrum disorder. Our findings, albeit observational, suggest that interventions targeting the earlier diagnosis of autism spectrum disorder and approaches to improve person–environment fit may help prevent secondary mental health problems in this population, particularly among those without cognitive delays and those diagnosed late. Further studies replicating across a wider intellectual spectrum and clarifying the underlying mechanism are warranted.
Spermatogenesis of Male Patients with Congenital Hypogonadotropic Hypogonadism Receiving Pulsatile Gonadotropin-Releasing Hormone Therapy Versus Gonadotropin Therapy: A Systematic Review and Meta-Analysis

Purpose Pulsatile gonadotropin-releasing hormone (GnRH) therapy and gonadotropin therapy (GT) were widely used for male patients with congenital hypogonadotropic hypogonadism (CHH), but their efficacy was not well compared before. We conducted this meta-analysis to compare the efficacy of restoring fertility using these two therapies. Materials and Methods PubMed, Web of Science, and Scopus were systematically searched for comparative studies evaluating the efficiency of GnRH therapy and GT for male patients with CHH. For continuous outcomes, the weighted mean difference (WMD) was used to measure the difference, whereas the risk ratio with 95% confidence interval was calculated for binary variables. Results Overall, eight articles from seven studies with 420 patients enrolled were included in the analysis. Patients from the two different groups were determined to be comparable in age, proportion with Kallmann syndrome, percentage of cryptorchidism and pretreatment hormones (follicular-stimulating hormone, luteinizing hormone, and testosterone). GnRH therapy was related to a larger testicular volume (standardized mean difference=−1.43; p=0.01) and earlier spermatogenesis (WMD=−5.30 months; p=0.004) compared to GT. However, the difference in the rate of positive sperm detection (p=0.08), sperm concentration (p=0.37), and pregnancy rate (p=0.11) were not significant. Allergic reactions mostly occurred during GnRH therapy, while GT was related to a higher incidence of gynecomastia and acne. Conclusions Compared to GT, GnRH was related to earlier spermatogenesis and less estradiol-related adverse reactions, although there were no significant differences in spermatogenesis rate, sperm concentration, and pregnancy rate. High-quality randomized controlled trials are needed for future research.
SPARC is a key mediator of TGF‐β‐induced renal cancer metastasis

Aberrant expression of transforming growth factor‐β1 (TGF‐β1) is associated with renal cell carcinoma (RCC) progression by inducing cancer metastasis. However, the downstream effector(s) in TGF‐β signaling pathway is not fully characterized. In the present study, the elevation of secreted protein acidic and rich in cysteine (SPARC) as a TGF‐β regulated gene in RCC was identified by applying differentially expressed gene analysis and microarray analysis, we further confirmed this result in several RCC cell lines. Clinically, the expression of these two genes is positively correlated in RCC patient specimens. Furthermore, elevated SPARC expression is found in all the subtypes of RCC and positively correlated with the RCC stage and grade. In contrast, SPARC expression is inversely correlated with overall and disease‐free survival of patients with RCC, suggesting SPARC as a potent prognostic marker of RCC patient survival. Knocking down SPARC significantly inhibits RCC cell invasion and metastasis both in vitro and in vivo. Similarly, in vitro cell invasion can be diminished by using a specific monoclonal antibody. Mechanistically, SPARC activates protein kinase B (AKT) pathway leading to elevated expression of matrix metalloproteinase‐2 that can facilitate RCC invasion. Altogether, our data support that SPARC is a critical role of TGF‐β signaling network underlying RCC progression and a potential therapeutic target as well as a prognostic marker.
Adverse impact of bone metastases on clinical outcomes of patients with advanced non‐small cell lung cancer treated with immune checkpoint inhibitors

Bone metastasis (BoM) is common in patients with advanced non‐small cell lung cancer (NSCLC) and considered as one of the negative prognostic factors. However, the impact of BoM on clinical outcomes of patients with advanced NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear.
A New Hypoglycemic Agent,JTT-608,Evokes Protein Kinase A-Mediated Ca[2+] Signaling in Rat Islet β-cells : Strict Regulation by Glucose,Link to Insulin Release and Cooperation with Glucagon-Like Peptide-1(7-36)amide and Pituitary Adenylate Cyclase-Activating Polypeptide

A new nonsulfonylurea oral hypoglycemic agent, JTT-608, has been reported to stimulate insulin release at elevated, but not low, glucose concentrations and consequently not to induce hypoglycemia in rats. Accordingly, this drug is potentially a safer antidiabetic agent than sulfonylureas. To explore the mechanisms underlying this glucose-dependent insulinotro-pism, the present study investigated the effects of JTT-608 on cytosolic free Ca 2 1 concentration ([Ca 2 1 ] i ) and protein kinase A (PKA) activity in rat islet b -cells by microfluorometry using, respectively, fura-2 and a fluorescence PKA substrate, DR II. In the presence of glucose at normal and elevated concentrations (5.0–16.7 mM) JTT-608 (30–1000 m M) concentration dependently increased [Ca 2 1 ] i in up to 88% of single b -cells, whereas at lower glucose concentrations (2.8 and 4.2 mM) it had little effect. The [Ca 2 1 ] i responses were inhibited under Ca 2 1 -free conditions and by nitrendipine,
Sperm DNA Fragmentation: A New Guideline for Clinicians

Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations. This article provides an overview of SDF types, origin and comparative analysis of various SDF assays while primarily focusing on the clinical indications of SDF testing. Importantly, we report four clinical cases where SDF testing had played a significant role in improving fertility outcome. In light of these clinical case reports and recent scientific evidence, this review provides expert recommendations on SDF testing and examines the advantages and drawbacks of the clinical utility of SDF testing using Strength-Weaknesses-Opportunities-Threats (SWOT) analysis.
Roles for the DNA-PK complex and 53BP1 in protecting ends from resection during DNA double-strand break repair

Abstract p53-binding protein 1 (53BP1) exerts distinct impacts in different situations involving DNA double-strand break (DSB) rejoining. Here we focus on how 53BP1 impacts upon the repair of ionising radiation-induced DSBs (IR-DSBs) and how it interfaces with Ku, the DNA end-binding component of canonical non-homologous end-joining (c-NHEJ), the major DSB repair pathway in mammalian cells. We delineate three forms of IR-DSB repair: resection-independent c-NHEJ, which rejoins most IR-DSBs with fast kinetics in G1 and G2, and Artemis and resection-dependent c-NHEJ and homologous recombination (HR), which repair IR-DSBs with slow kinetics in G1 and G2 phase, respectively. The fast component of DSB repair after X-ray exposure occurs via c-NHEJ with normal kinetics in the absence of 53BP1. Ku is highly abundant and has avid DNA end-binding capacity which restricts DNA end-resection and promotes resection-independent c-NHEJ at most IR-DSBs. Thus, 53BP1 is largely dispensable for resection-independent c-NHEJ. In contrast, 53BP1 is essential for the process of rejoining IR-DSBs with slow kinetics. This role requires 53BP1’s breast cancer susceptibility gene I (BRCA1) C-terminal (BRCT) 2 domain, persistent ataxia telangiectasia mutated (ATM) activation and potentially relaxation of compacted chromatin at heterochromatic-DSBs. In distinction, 53BP1 inhibits resection-dependent IR-DSB repair in G1 and G2, and this resection-inhibitory function can be counteracted by BRCA1. We discuss a model whereby most IR-DSBs are rapidly repaired by 53BP1-independent and resection-independent c-NHEJ due to the ability of Ku to inhibit resection, but, if delayed, then resection in the presence of Ku is triggered, the 53BP1 barrier comes into force and BRCA1 counteraction is required for resection.