Miracle-dz/UniFAR-FTUs huggingface dataset:
Disease-age Correlated Study of Some Patients with Solitary Hypertension Attending Central Hospital, Benin City, Nigeria

The study was aimed at verifying how oxidative status varies with age of diabetes mellitus (DM) in sufferers with adequate blood sugar control. Forty-one diabetic otherwise healthy (DOH) volunteers and 57 apparently healthy controls were used and plasma levels of two endogenous antioxidant enzymes (Superoxide dismutase, SOD, and catalase, CAT) as well as two markers of oxidative damage (Malondialdehyde, MDA and erythrocyte osmotic fragility, EOF) were determined. Results obtained showed significant decreases in plasma SOD and CAT activities, and significant increases in plasma levels of MDA and EOF as age of disease increases. In addition, there were clear significant differences between the oxidative status of DOH and apparently healthy control subjects of similar chronological (birth) age group. Plasma MDA and EOF as markers of oxidative damage were significantly higher in DOH subjects compared with healthy control subjects of similar age. However, plasma SOD and CAT activities were observed to be significantly lower in DOH subjects compared with healthy control subject of comparable age. It could thus be concluded that diabetes is associated with progressive increase in tissue oxidative damage.
Cadherin‐6B undergoes macropinocytosis and clathrin‐mediated endocytosis during cranial neural crest cell EMT

The epithelial‐to‐mesenchymal transition (EMT) is important for the formation of migratory neural crest cells during development and is co‐opted in human diseases such as cancer metastasis. Chick premigratory cranial neural crest cells lose intercellular contacts, mediated in part by Cadherin‐6B (Cad6B), migrate extensively, and later form a variety of adult derivatives. Importantly, modulation of Cad6B is crucial for proper neural crest cell EMT. Although Cad6B possesses a long half‐life, it is rapidly lost from premigratory neural crest cell membranes, suggesting the existence of post‐translational mechanisms during EMT. We have identified a motif in the Cad6B cytoplasmic tail that enhances Cad6B internalization and reduces the stability of Cad6B upon its mutation. Furthermore, we demonstrate for the first time that Cad6B is removed from premigratory neural crest cells through cell surface internalization events that include clathrin‐mediated endocytosis and macropinocytosis. Both of these processes are dependent upon the function of dynamin, and inhibition of Cad6B internalization abrogates neural crest cell EMT and migration. Collectively, our findings reveal the significance of post‐translational events in controlling cadherins during neural crest cell EMT and migration.
Assessment of Barriers of Contraceptive Use in Rural Burundi: A Mixed Methods Study

Background: In Burundi, there is very high maternal and child mortality. One of the contributing factors is the high fertility rate, prompted by low rate of contraceptive use. Available sources report a contraceptive use of 18%, among married women in Burundi but this excludes a larger number of women of reproductive age who are sexually active. Methods: A combination of quantitative and qualitative methods was employed to investigate the availability and use of contraceptives among women of reproductive age at health centers in two rural districts of Burundi. First, we administered a survey in 39 clinics to assess the availability and utilization of modern contraceptives and the association between uptake of family planning and availability of contraceptives, and other health facility factors. We then selected sites with different utilization rates and conducted 10 in depth individual interviews and 7 focus groups discussions to understand the issues affecting uptake of modern contraceptives. A total of 56 individuals participated including women, men, facility managers and community leaders. Results: Uptake of family planning averaged 2.96%. Greater uptake was positively associated with the number of health professionals engaged and trained in family planning service provision as well as the number of different types of contraceptives available. Uptake was inversely associated with duration of stockouts and number of contraceptives stocked out. Qualitative data pointed to scarce resources, sociocultural factors, fear of disclosure and side effects, partner‟s disapproval, and lack of information on modern contraceptives as explanations of low uptake. Conclusions: We found a low rate of uptake for contraceptive services in rural Burundi among a broad sample of women of reproductive age accessing care. By focusing on only married women, previously available data overestimates contraceptive use and underestimates need in these communities. There were many social and structural barriers to contraceptive uptake. These factors relate to the underlying extreme poverty in rural Burundi both at the state and individual level. Interventions would need to take into account one or more of these factors in order to improve uptake of family planning.
Reactive oxygen species exert opposite effects on Tyr23 phosphorylation of the nuclear and cortical pools of annexin A2

ABSTRACT Annexin A2 (AnxA2) is a multi-functional and -compartmental protein whose subcellular localisation and functions are tightly regulated by its post-translational modifications. AnxA2 and its Tyr23-phosphorylated form (pTyr23AnxA2) are involved in malignant cell transformation, metastasis and angiogenesis. Here, we show that H2O2 exerts rapid, simultaneous and opposite effects on the Tyr23 phosphorylation status of AnxA2 in two distinct compartments of rat pheochromocytoma (PC12) cells. Reactive oxygen species induce dephosphorylation of pTyr23AnxA2 located in the PML bodies of the nucleus, whereas AnxA2 associated with F-actin at the cell cortex is Tyr23 phosphorylated. The H2O2-induced responses in both compartments are transient and the pTyr23AnxA2 accumulating at the cell cortex is subsequently incorporated into vesicles and then released to the extracellular space. Blocking nuclear export by leptomycin B does not affect the nuclear pool of pTyr23AnxA2, but increases the amount of total AnxA2 in this compartment, indicating that the protein might have several functions in the nucleus. These results suggest that Tyr23 phosphorylation can regulate the function of AnxA2 at distinct subcellular sites. Summary: Reactive oxygen species cause two opposite and transient Tyr23-based modifications of annexin A2; its dephosphorylation in the nucleus and phosphorylation at the cell cortex, resulting in release of the protein in exosomes.
Multifunctional Abl kinases in health and disease

ABSTRACT The Abelson tyrosine kinases were initially identified as drivers of leukemia in mice and humans. The Abl family kinases Abl1 and Abl2 regulate diverse cellular processes during development and normal homeostasis, and their functions are subverted during inflammation, cancer and other pathologies. Abl kinases can be activated by multiple stimuli leading to cytoskeletal reorganization required for cell morphogenesis, motility, adhesion and polarity. Depending on the cellular context, Abl kinases regulate cell survival and proliferation. Emerging data support important roles for Abl kinases in pathologies linked to inflammation. Among these are neurodegenerative diseases and inflammatory pathologies. Unexpectedly, Abl kinases have also been identified as important players in mammalian host cells during microbial pathogenesis. Thus, the use of Abl kinase inhibitors might prove to be effective in the treatment of pathologies beyond leukemia and solid tumors. In this Cell Science at a Glance article and in the accompanying poster, we highlight the emerging roles of Abl kinases in the regulation of cellular processes in normal cells and diverse pathologies ranging from cancer to microbial pathogenesis. Summary: We highlight the emerging roles of Abl kinases in the regulation of cellular processes in normal cells and diverse pathologies that range from cancer to microbial pathogenesis.
Imaging of tumour-induced osteomalacia using a gallium-68 labelled somatostatin analogue

A 51-year-old man presented with generalised bone pain. Initial evaluation revealed a low serum phosphorus level and elevated urinary phosphorus excretion. Aminoaciduria was normal. Standard imaging showed only minimal changes. The patient was treated with daily oral supplementation with phosphate (1 g/day) and 1,25-dihydroxyvitamin D3 (1 μg/day) to maintain euphosphataemia. In spite of the fact that this treatment was maintained for 3 years, there was no modification of renal phosphate clearance. A diagnosis of hypophosphataemic osteomalacia with renal phosphate wasting was proposed. Therefore, tumour-induced osteomalacia was suspected, triggering a diagnostic workup to find the primary tumour. These tumours are known to express somatostatin receptors, so whole body positron emission tomography (CT) imaging was performed after intravenous administration of 68Ga-DOTA-TOC (68Ga-DOTA-D-Phe1-Tyr3-pentreotide). A solitary intense hot spot was detected in soft tissue near the right femoral internal condyle. Based on this result, curative resection of the tumour was performed.
zole-resistance in Aspergillus: Proposed nomenclature and breakpoints

Reports of itraconazole resistance in Aspergillus fumigatus have been more frequent since the millennium. Identifying azole resistance is critically method dependent; nevertheless reproducible methods, reflective of in vivo outcome, are now in routine use. Some isolates also have elevated MICs to posaconazole and voriconazole. Multiple mechanisms of resistance are now known to be responsible, with differing degrees of azole cross-resistance, including mutations in the Cyp51A gene at G54, L98 + TR, G138, M220, G448. Establishing breakpoints for Aspergillus is probably impossible with clinical data alone for multiple reasons yet there is an urgent need to do so. We propose the following breakpoints for A. fumigatus complex using the proposed EUCAST susceptibility testing methodology: for itraconazole and voriconazole, <2 mg/L (susceptible), 2 mg/L (intermediate) and >2 mg/L (resistant); for posaconazole, <0.25, 0.5 and >0.5 mg/L respectively. We recognize that additional work will be needed to confirm these proposed breakpoints, including in vivo and clinical correlative responses. We also propose nomenclature for genotypic resistance, in the event an isolate is not cultured, typified by ITZgR, VCZgI, POSgR (G54W) indicating W su erme that the isolate has a G54 and posaconazole and int
The Drosophila tricellular junction protein Gliotactin regulates its own mRNA levels through BMP-mediated induction of miR-184

ABSTRACT Epithelial bicellular and tricellular junctions are essential for establishing and maintaining permeability barriers. Tricellular junctions are formed by the convergence of three bicellular junctions at the corners of neighbouring epithelia. Gliotactin, a member of the Neuroligin family, is located at the Drosophila tricellular junction, and is crucial for the formation of tricellular and septate junctions, as well as permeability barrier function. Gliotactin protein levels are tightly controlled by phosphorylation at tyrosine residues and endocytosis. Blocking endocytosis or overexpressing Gliotactin results in the spread of Gliotactin from the tricellular junction, resulting in apoptosis, delamination and migration of epithelial cells. We show that Gliotactin levels are also regulated at the mRNA level by micro (mi)RNA-mediated degradation and that miRNAs are targeted to a short region in the 3′UTR that includes a conserved miR-184 target site. miR-184 also targets a suite of septate junction proteins, including NrxIV, coracle and Mcr. miR-184 expression is triggered when Gliotactin is overexpressed, leading to activation of the BMP signalling pathway. Gliotactin specifically interferes with Dad, an inhibitory SMAD, leading to activation of the Tkv type-I receptor and activation of Mad to elevate the biogenesis and expression of miR-184. Summary: Gliotactin, a key tricellular junction protein, is controlled by miR-184-mediated mRNA degradation. Excess Gliotactin triggers miR-184 expression by activating the BMP type-1 receptor Thickveins.
CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly

ABSTRACT Although it is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity, the pathways leading to the formation and maintenance of centromere chromatin remain unclear. We previously generated human artificial chromosomes (HACs) whose centromeres contain a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator (alphoidtetO). We also obtained cell lines bearing the alphoidtetO array at ectopic integration sites on chromosomal arms. Here, we have examined the regulation of CENP-A assembly at centromeres as well as de novo assembly on the ectopic arrays by tethering tetracycline repressor (tetR) fusions of substantial centromeric factors and chromatin modifiers. This analysis revealed four classes of factors that influence CENP-A assembly. Interestingly, many kinetochore structural components induced de novo CENP-A assembly at the ectopic site. We showed that these components work by recruiting CENP-C and subsequently recruiting M18BP1. Furthermore, we found that CENP-I can also recruit M18BP1 and, as a consequence, enhances M18BP1 assembly on centromeres in the downstream of CENP-C. Thus, we suggest that CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly. Highlighted Article: Tethering analysis using various centromere and kinetochore factors, and chromatin modifiers reveals that CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly.
Effect of lactoferrin on some selective immunological parameters in rats immunosuppressed by cyclophosphamide

Eighty male albino rats (350±10 g) 10 to 12 weeks old were conducted in our study. Rats were randomly divided into four, equal groups. The groups treated as following: 1st control group (Gp. A) was given intraperitoneal normal saline (1 mL). 2nd group (Gp. B) was given a single intraperitoneal dose (250 mg/kg body weight) of Cyclophosphamide (CP) on the first day of the experimental period. 3rd group (Gp. C) CP and lactoferrin (LF) treated group. 4th group (Gp. D) administrated LF only (0.5%) in drinking water. Two separate blood samples were collected from heart puncture at end of 1st and 3rd week post treatment for hematological, biochemical and immunological studies. The leukogram of CP treatment group showed severe leucopenia (lymphopenia, neutropenia as well as eozinopenia) as well as decrease total protein and albumin blood level. Immunosuppressive effect of CP is documented in our work by decrease gamma globulin and elevation tumor necrosis factor Alfa (TNF ά). This study revealed that oral treatment with LF can partially
Actin visualization at a glance

ABSTRACT Actin functions in a multitude of cellular processes owing to its ability to polymerize into filaments, which can be further organized into higher-order structures by an array of actin-binding and regulatory proteins. Therefore, research on actin and actin-related functions relies on the visualization of actin structures without interfering with the cycles of actin polymerization and depolymerization that underlie cellular actin dynamics. In this Cell Science at a Glance and the accompanying poster, we briefly evaluate the different techniques and approaches currently applied to analyze and visualize cellular actin structures, including in the nuclear compartment. Referring to the gold standard F-actin marker phalloidin to stain actin in fixed samples and tissues, we highlight methods for visualization of actin in living cells, which mostly apply the principle of genetically fusing fluorescent proteins to different actin-binding domains, such as LifeAct, utrophin and F-tractin, as well as anti-actin-nanobody technology. In addition, the compound SiR-actin and the expression of GFP–actin are also applicable for various types of live-cell analyses. Overall, the visualization of actin within a physiological context requires a careful choice of method, as well as a tight control of the amount or the expression level of a given detection probe in order to minimize its influence on endogenous actin dynamics. Summary: Here, we present current approaches to visualize actin filaments, emphasizing the advantages and pitfalls of available tools to investigate F-actin not only in the cytoplasm, but also in the somatic cell nucleus.
Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies

BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m2 per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.
Chronic Fatigue Syndrome at Age 16 Years

BACKGROUND: In the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, chronic disabling fatigue lasting ≥6 months affected 1.3% of 13-year-olds, was equally common in boys and girls, and became more prevalent with increasing family adversity. METHODS: ALSPAC data were used to estimate the prevalence of chronic fatigue syndrome (CFS) at age 16 years, defined by parental report of unexplained disabling fatigue lasting ≥6 months. We investigated gender and a composite 14-item family adversity index as risk factors. School absence data were obtained from the National Pupil Database. Multiple imputation was used to address bias caused by missing data. RESULTS: The prevalence of CFS was 1.86% (95% confidence interval [CI]: 1.47 to 2.24). After excluding children with high levels of depressive symptoms, the prevalence was 0.60% (95% CI: 0.37 to 0.84). Authorized school absences were much higher (mean difference: 35.6 [95% CI: 26.4 to 44.9] half-day sessions per academic year) and reported depressive symptoms were much more likely (odds ratio [OR]: 11.0 [95% CI: 5.92 to 20.4]) in children with CFS than in those without CFS. Female gender (OR: 1.95 [95% CI: 1.33 to 2.86]) and family adversity (OR: 1.20 [95% CI: 1.01 to 1.42] per unit family adversity index) were also associated with CFS. CONCLUSIONS: CFS affected 1.9% of 16-year-olds in a UK birth cohort and was positively associated with higher family adversity. Gender was a risk factor at age 16 years but not at age 13 years or in 16-year-olds without high levels of depressive symptoms.
Physical Activity Why and How

Modern physical activity research began in the 1950s with the studies by Morris and colleagues on bus drivers and conductors [3]. Today there is strong scientific evidence that regular physical activity promoting health and preventing many chronic diseases. [4-7]. Physical activity has multifactorial effects, meaning that it affects many systems in the body at the same time and can thereby influence both physical and mental health [4,8-12].
TRPV4 mediates the Ca2+ influx required for the interaction between flightless-1 and non-muscle myosin, and collagen remodeling

ABSTRACT Fibroblasts remodel extracellular matrix collagen, in part, through phagocytosis. This process requires formation of cell extensions, which in turn involves interaction of the actin-binding protein flightless-1 (FliI) with non-muscle myosin IIA (NMMIIA; heavy chain encoded by MYH9) at cell–matrix adhesion sites. As Ca2+ plays a central role in controlling actomyosin-dependent functions, we examined how Ca2+ controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca2+ influx at the extensions of fibroblasts. Western blotting and quantitative (q)PCR showed high expression levels of the Ca2+-permeable transient receptor potential vanilloid-4 (TRPV4) channel, which co-immunoprecipitated with β1 integrin and localized to adhesions. Treatment with α2β1-integrin-blocking antibody or the TRPV4-specific antagonist AB159908, as well as reduction of TRPV4 expression through means of siRNA, blocked Ca2+ influx. These treatments also inhibited the interaction of FliI with NMMIIA, reduced the number and length of cell extensions, and blocked collagen remodeling. Pulldown assays showed that Ca2+ depletion inhibited the interaction of purified FliI with NMMIIA filaments. Fluorescence resonance energy transfer experiments showed that FliI–NMMIIA interactions require Ca2+ influx. We conclude that Ca2+ influx through the TRPV4 channel regulates FliI–NMMIIA interaction, which in turn enables generation of the cell extensions essential for collagen remodeling. Highlighted Article: TRPV4 is a Ca2+-permeable channel in the plasma membrane that regulates FliI–NMMIIA interactions, which in turn affects the cell extension formation necessary for the control of collagen remodeling and matrix biology.
Prevalence of erectile dysfunction in men diagnosed with heart failure: implications for practice

The management of heart failure is often a complex process and therefore best managed via a multidisciplinary approach. Patients with heart failure express anxiety in relation to sexual activity and need guidance and support from their clinical team. One anxiety reported is erectile dysfunction (ED). ED has a prevalence of 8% in 40-year-old men which increases to 40% in 60-year-old men. In a survey of 52 men attending a heart failure clinic, the prevalence was 90%. Quality of life was adversely affected and men erroneously believed that treatment was unavailable or contra-indicated by virtue of their diagnosis of heart failure. Quality of erection was established using the self-reported Sexual Health Inventory for Men (SHIM) which is a 5-item questionnaire examining various aspects of sexual function. The mean SHIM score was 11.1, indicating moderate ED. The aim of this paper is to identify the prevalence of ED in a convenience sample of men attending a heart failure clinic in East London, and to discuss .