Miracle-dz/UniFAR-FTUs huggingface dataset:
Slow Muscle Precursors Lay Down a Collagen XV Matrix Fingerprint to Guide Motor Axon Navigation

The extracellular matrix (ECM) provides local positional information to guide motoneuron axons toward their muscle target. Collagen XV is a basement membrane component mainly expressed in skeletal muscle. We have identified two zebrafish paralogs of the human COL15A1 gene, col15a1a and col15a1b, which display distinct expression patterns. Here we show that col15a1b is expressed and deposited in the motor path ECM by slow muscle precursors also called adaxial cells. We further demonstrate that collagen XV-B deposition is both temporally and spatially regulated before motor axon extension from the spinal cord in such a way that it remains in this region after the adaxial cells have migrated toward the periphery of the myotome. Loss- and gain-of-function experiments in zebrafish embryos demonstrate that col15a1b expression and subsequent collagen XV-B deposition and organization in the motor path ECM depend on a previously undescribed two-step mechanism involving Hedgehog/Gli and unplugged/MuSK signaling pathways. In silico analysis predicts a putative Gli binding site in the col15a1b proximal promoter. Using col15a1b promoter-reporter constructs, we demonstrate that col15a1b participates in the slow muscle genetic program as a direct target of Hedgehog/Gli signaling. Loss and gain of col15a1b function provoke pathfinding errors in primary and secondary motoneuron axons both at and beyond the choice point where axon pathway selection takes place. These defects result in muscle atrophy and compromised swimming behavior, a phenotype partially rescued by injection of a smyhc1:col15a1b construct. These reveal an unexpected and novel role for collagen XV in motor axon pathfinding and neuromuscular development. SIGNIFICANCE STATEMENT In addition to the archetypal axon guidance cues, the extracellular matrix provides local information that guides motor axons from the spinal cord to their muscle targets. Many of the proteins involved are unknown. Using the zebrafish model, we identified an unexpected role of the extracellular matrix collagen XV in motor axon pathfinding. We show that the synthesis of collagen XV-B by slow muscle precursors and its deposition in the common motor path are dependent on a novel two-step mechanism that determines axon decisions at a choice point during motor axonogenesis. Zebrafish and humans use common molecular cues and regulatory mechanisms for the neuromuscular system development. And as such, our study reveals COL15A1 as a candidate gene for orphan neuromuscular disorders.
Impact of the Mitogen-activated Protein Kinase Pathway on Parathyroid Hormone-related Protein Actions in Osteoblasts*

Parathyroid hormone-related protein (PTHrP) regulates proliferation and differentiation of osteoblastic cells via binding to the parathyroid hormone receptor (PTH-1R). The cAMP-dependent protein kinase A pathway governs the majority of these effects, but recent evidence also implicates the MAPK pathway. MC3T3-E1 subclone 4 cells (MC4) were treated with the MAPK inhibitor U0126 and PTHrP. In differentiated MC4 cells, osteocalcin and bone sialoprotein gene expression were both down-regulated by PTHrP and also by inhibition of the MAPK pathway. PTHrP-mediated down-regulation of PTH-1R mRNA and up-regulation of c-fos mRNA were MAPK-independent, whereas PTHrP stimulation of fra-2 and interleukin-6 (IL-6) mRNA was MAPK-dependent. Luciferase promoter assays revealed that regulation of IL-6 involved the cAMP-dependent protein kinase A and MAPK pathways with a potential minor role of the protein kinase C pathway, and a promoter region containing an activator protein-1 site was necessary for PTHrP-induced IL-6 gene transcription. An alternative pathway, through cAMP/Epac/Rap1/MAPK, mediated ERK phosphorylation but was not sufficient for IL-6 promoter activation. Phosphorylation of the transcription factor CREB was also necessary but not sufficient for PTHrP-mediated IL-6 promoter activity. Most interesting, a bidirectional effect was found with PTHrP increasing phosphorylated ERK in undifferentiated MC4 cells but decreasing phosphorylated ERK in differentiated cells. These data indicate that inactivation of the MAPK pathway shows differential regulation of PTHrP-stimulated activator protein-1 members, blocks PTHrP-stimulated IL-6, and synergistically down-regulates certain osteoblastic markers associated with differentiation. These novel findings indicate that the MAPK pathway plays a selective but important role in the actions of PTHrP.
Light and Ultrastructural Immunocytochemical Study of Prolactin Cells in Ovine Adenohypophysis

The influence of lactation and weaning on the number, distribution, and structure of mammotroph cells (PRL cells) in ewes was studied using immunocytochemical procedures for light and electron microscopy, as well as morphometric and stereological techniques. The adenohypophyseal gland of 12 ewes of the Segureña breed at different stages of milk production and weaning were analysed, while the same organ of 3 ewes in anestrus served as control. During lactation, PRL cells increased in number and decreased in size. Ultrastructurally, these cells showed a well-developed rough endoplasmic reticulum (RER) and Golgi complex (GC), and large secretory granules. These findings point to increased synthesis and secretion activities during lactation, and a decrease after weaning. One day after weaning ‘storage’ cells increased in number, and crinophagy became evident 7 days after weaning, when the first ‘inactive’ cells were seen (10% of total cells). In anestrus these last cells represented 40% of the total, and showed scarce granules, signs of inactivity, lysosomes and lipid droplets.
TaskPoint: Sampled simulation of task-based programs

Sampled simulation is a mature technique for reducing simulation time of single-threaded programs, but it is not directly applicable to simulation of multi-threaded architectures. Recent multi-threaded sampling techniques assume that the workload assigned to each thread does not change across multiple executions of a program. This assumption does not hold for dynamically scheduled task-based programming models. Task-based programming models allow the programmer to specify program segments as tasks which are instantiated many times and scheduled dynamically to available threads. Due to system noise and variation in scheduling decisions, two consecutive executions on the same machine typically result in different instruction streams processed by each thread. In this paper, we propose TaskPoint, a sampled simulation technique for dynamically scheduled task-based programs. We leverage task instances as sampling units and simulate only a fraction of all task instances in detail. Between detailed simulation intervals we employ a novel fast-forward mechanism for dynamically scheduled programs. We evaluate the proposed technique on a set of 19 task-based parallel benchmarks and two different architectures. Compared to detailed simulation, TaskPoint accelerates architectural simulation with 64 simulated threads by an average factor of 19.1 at an average error of 1.8% and a maximum error of 15.0%.
ME/CFS: A Basic Overview

ME/Chronic Fatigue Syndrome is a chronic, debilitating condition with as yet an unproven cause and unknown mechanism. Whilst there is no diagnostic test, a positive diagnosis can be made clinically, with a reasonable degree of certainty. CFS can affect every system of the body, and consequently, the range of symptoms is broad. People are affected to varying degrees of severity – some experience a mild form of the illness, whilst are so severely affected that they become housebound or bedridden. What symptoms are associated with CFS?
Predictors of change in treatment outcome for parent-delivered guided CBT bibliotherapy for children with anxiety: Effects of age, severity and comorbidity at long term follow-up

This thesis is concerned with an exploration of low-intensity treatments for common mental health problems in childhood and adolescence. Part one is a narrative literature review of trials of low-intensity interventions for children and adolescents with depression or anxiety, including bibliotherapy, computerised CBT and attention-bias modification. Part two is a long term follow-up study examining the effects of age, symptom severity and comorbidity at initial assessment on outcomes for children who had received guided CBT bibliotherapy via their parents four years previously. Part three is a critical appraisal of the thesis, considering the wider methodological and conceptual challenges associated with research across the developmental period.
Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy

Objective:The objective of this study is to determine the incidence rate and risk factors of tuberculosis (TB) among HIV-infected adults accessing antiretroviral therapy (ART) in Tanzania. Design:A prospective observational study among HIV-infected adults attending HIV clinics in Dar es Salaam. Methods:We estimated TB incidence rates among HIV-infected patients prior to and after ART initiation. We used Cox proportional hazard regressions to determine the predictors of incident TB among HIV-infected adults enrolled in the HIV care and treatment programme. Results:We assessed 67 686 patients for a median follow-up period of 24 (interquartile range: 8–49) months; 7602 patients were diagnosed with active TB. The TB incidence rate was 7.9 [95% confidence interval (95% CI), 7.6–8.2] per 100 person-years prior to ART initiation, and 4.4 (95% CI, 4.2–4.4) per 100 person-years for patients receiving ART. In multivariate analyses, patients on ART in the first 3 months had a 57% higher risk of TB (hazard ratio: 1.57, 95% CI, 1.47–1.68) than those not on ART, but the risk significantly decreased with increasing duration of ART. Risk factors for incident TB included being male, having low BMI or middle upper arm circumference, lower CD4+ cell count and advanced WHO disease stage. There was seasonal variation for incident TB, with higher risk observed following the rainy seasons (May, June and November). Conclusion:In TB endemic regions, HIV-infected patients initiating ART, particularly men and those with poor nutritional status, should be closely monitored for active TB at ART initiation. In addition to increasing the access to ART, interventions should be considered to improve nutritional status among HIV-infected patients.
Sex or gender identity? Understanding children's reading choices and motivation

The extent to which children's reading choices could be predicted by their motivation and gender identity was examined. Two hundred and twenty-three children (average age 9 years 11 months) completed questionnaires measuring book reading choices, reading motivation, gender identity (identification with masculine and feminine traits) and a standardised reading assessment. Sex differences were found in children's reading motivation and reading choices. In addition, feminine traits were more closely associated with reading motivation and engagement with neutral books compared to masculine traits. Whilst children's sex predicted their choice of reading male- or female-orientated books, the extent to which they identified with feminine traits was a better predictor in choice of neutral books. Results are discussed in relation to previous research examining sex differences in children's reading choices. In addition, implications for reading activities and choice of books available at school are discussed.
A 36-hospital time and motion study: how do medical-surgical nurses spend their time?

CONTEXT Nurses are the primary hospital caregivers. Increasing the efficiency and effectiveness of nursing care is essential to hospital function and the delivery of safe patient care. OBJECTIVE We undertook a time and motion study to document how nurses spend their time. The goal was to identify drivers of inefficiency in nursing work processes and nursing unit design. DESIGN Nurses from 36 medical-surgical units were invited to participate in research protocols designed to assess how nurses spend their time, nurse location and movement, and nurse physiologic response. MAIN OUTCOME MEASURES Nurses' time was divided into categories of activities (nursing practice, unit-related functions, nonclinical activities, and waste) and locations (patient room, nurse station, on-unit, off-unit). Total distance traveled and energy expenditure were assessed. Distance traveled was evaluated across types of unit design. RESULTS A total of 767 nurses participated. More than three-quarters of all reported time was devoted to nursing practice. Three subcategories accounted for most of nursing practice time: documentation (35.3%; 147.5 minutes), medication administration (17.2%; 72 minutes), and care coordination (20.6%; 86 minutes). Patient care activities accounted for 19.3% (81 minutes) of nursing practice time, and only 7.2% (31 minutes) of nursing practice time was considered to be used for patient assessment and reading of vital signs. CONCLUSION The time and motion study identified three main targets for improving the efficiency of nursing care: documentation, medication administration, and care coordination. Changes in technology, work processes, and unit organization and design may allow for substantial improvements in the use of nurses' time and the safe delivery of care.
Elucidation of the Antibacterial Mechanism of the Curvularia Haloperoxidase System by DNA Microarray Profiling

ABSTRACT A novel antimicrobial enzyme system, the Curvularia haloperoxidase system, was examined with the aim of elucidating its mechanism of antibacterial action. Escherichia coli strain MG1655 was stressed with sublethal concentrations of the enzyme system, causing a temporary arrest of growth. The expression of genes altered upon exposure to the Curvularia haloperoxidase system was analyzed by using DNA microarrays. Only a limited number of genes were involved in the response to the Curvularia haloperoxidase system. Among the induced genes were the ibpA and ibpB genes encoding small heat shock proteins, a gene cluster of six genes (b0301-b0306) of unknown function, and finally, cpxP, a member of the Cpx pathway. Knockout mutants were constructed with deletions in b0301-b0306, cpxP, and cpxARP, respectively. Only the mutant lacking cpxARP was significantly more sensitive to the enzyme system than was the wild type. Our results demonstrate that DNA microarray technology cannot be used as the only technique to investigate the mechanisms of action of new antimicrobial compounds. However, by combining DNA microarray analysis with the subsequent creation of knockout mutants, we were able to pinpoint one of the specific responses of E. coli—namely, the Cpx pathway, which is important for managing the stress response from the Curvularia haloperoxidase system.
Advantages of Gardening as a Form of Physical Activity in an After-School Program.

Children who normally abstain from physical activity may view gardening as a viable non-competitive alternative. The study reported here evaluated the effect of an Oklahoma Cooperative Extension Service after-school gardening program on self-reported physical activity level of children in 3rd through 5th grade using the ACTIVITY self-report instrument. The ACTIVITY instrument described and demonstrated three physical activity levels; non-moving, moving, and fast-moving. A significant difference between preand post-test scores of children's self-reported physical activity level was observed. The results of the study indicate gardening was an effective non-competitive way to increase children's self-reported physical activity level in an after-school setting. Overweight among children is a leading health concern in the United States, with 33.3% of children 6-11 years of age being classified as overweight or obese in 2003-2006 (Ogden, Carroll, & Flegal, 2008). Advantages of Gardening as a Form of Physical Activity in an After-School Program 12/16/10 06:36:26
Upregulation of the Drosophila Friend of GATA Gene u-shaped by JAK/STAT Signaling Maintains Lymph Gland Prohemocyte Potency

ABSTRACT Studies using Drosophilamelanogaster have contributed significantly to our understanding of the interaction between stem cells and their protective microenvironments or stem cell niches. During lymph gland hematopoiesis, the Drosophila posterior signaling center functions as a stem cell niche to maintain prohemocyte multipotency through Hedgehog and JAK/STAT signaling. In this study, we provide evidence that the Friend of GATA protein U-shaped is an important regulator of lymph gland prohemocyte potency and differentiation. U-shaped expression was determined to be upregulated in third-instar lymph gland prohemocytes and downregulated in a subpopulation of differentiating blood cells. Genetic analyses indicated that U-shaped maintains the prohemocyte population by blocking differentiation. In addition, activated STAT directly regulated ush expression as evidenced by results from loss- and gain-of-function studies and from analyses of the u-shaped hematopoietic cis-regulatory module. Collectively, these findings identify U-shaped as a downstream effector of the posterior signaling center, establishing a novel link between the stem cell niche and the intrinsic regulation of potency and differentiation. Given the functional conservation of Friend of GATA proteins and the role that GATA factors play during cell fate choice, these factors may regulate essential functions of vertebrate hematopoietic stem cells, including processing signals from the stem cell niche.
Optimal electrode placement and frequency range selection for the detection of lung water using Bioimpedance Spectroscopy

Bioimpedance spectroscopy (BIS) is a noninvasive technique for the determination of human body composition such as water or fat content. Next to absolute body water determination, it enables also the detection of body water shifts. Therefore, it seems to be a good candidate to detect cardiac lung edema at an early stage and to monitor its medical treatment. However, stable long term BIS measurements are very difficult to make. The measurement conditions and hardware specifications of BIS devices must be well chosen in order to get correct and reproducible results. Thus, a finite element simulation of the human thorax is implemented to find the most sensitive electrode position for a BIS measurement as well as a MatLab simulation of the optimal frequency range. Both simulations and results are presented in this article and shall contribute to increase the accuracy and significance of BIS thoracic measurements.
Sentimantics: Conceptual Spaces for Lexical Sentiment Polarity Representation with Contextuality

Current sentiment analysis systems rely on static (context independent) sentiment lexica with proximity based fixed-point prior polarities. However, sentiment-orientation changes with context and these lexical resources give no indication of which value to pick at what context. The general trend is to pick the highest one, but which that is may vary at context. To overcome the problems of the present proximity-based static sentiment lexicon techniques, the paper proposes a new way to represent sentiment knowledge in a Vector Space Model. This model can store dynamic prior polarity with varying contextual information. The representation of the sentiment knowledge in the Conceptual Spaces of distributional Semantics is termed Sentimantics.
Hormone therapy and the medical encounter: a qualitative analysis of women's experiences

Objective: The aim of this article was to explore women's experiences in biomedical consultations for menopause symptoms, with a particular focus on how hormone therapy (HT) featured during the encounter. Methods: Semistructured interviews were conducted with 39 women, and data were analyzed using a qualitative strategy referred to as Thematic Networks. Results: Several participants whose menopause started before the period of the HT "scares" described being "put on" HT as a matter of course, even when their symptoms were mild. By contrast, some of those presenting in the more recent time period with what they deemed to be severe symptoms were more likely to describe scenarios whereby they pressured their physicians for an HT prescription. Once on HT, participants were found to be far from passive recipients of a biomedical "treatment" but rather embarked on an active dialogue with themselves about how to manage the distressing aspects of menopause. Conclusions: Using HT did not tend to spell a transition to biomedical advocacy, despite its reported effectiveness in moderating bodily distresses. Rather, HT tended to retain a tentative status as a temporary relief and not a long-term panacea.
Maternity blues as predictor of postpartum depression: A prospective cohort study among Japanese women

Background. Maternity blues and postpartum depression are common complications of childbearing. However, few studies have shown the relationship between the severity of maternity blues and the risk of postnatal depression. We carried out a longitudinal study among Japanese women to show that maternity blues is a useful factor for predicting postpartum depression. Methods. Two hundred and thirty-five women completed questionnaires before delivery, and five days, one month, and three months after delivery. They were required to answer the Stein's Blues Scale and Edinburgh Postnatal Depression Scale and other variables. A sequential logistic regression analysis was performed to estimate the association of maternity blues with postpartum depression. The stratum-specific likelihood ratio was then calculated. Results. The prevalence of postpartum depression was 12.8%. A Stein's Blues Scale of eight or above was significantly associated with postnatal depression. Likelihood ratios (95% CI ) for the Stein's Blues Scale of 0 to 3, 4 to 7, 8 to 11 and 12 or more were 0.33 (0.16–0.65), 1.06 (0.60–1.88), 3.42 (1.64–7.12) and 9.57 (3.41–26.86), respectively. Conclusions. These findings suggest that maternity blues is a strong predictor of postpartum depression. The higher the blues score, the higher the risk of postpartum depression.
Expression of GABAB Receptors in Magnocellular Neurosecretory Cells of Male, Virgin Female and Lactating Rats

GABA is one of the key neurotransmitters that regulate the firing activity of neurones in the supraoptic (SON) and paraventricular (PVN) nuclei. In the present study, we used immunohistochemical techniques to study the distribution and subcellular localisation of metabotropic GABAB receptors in magnocellular neurones in the SON and PVN. Robust GABAB receptor immunoreactivity (GABABR; both subunit 1 and subunit 2 of the heterodimer), was observed in the SON and PVN. At the light microcope level, GABABR immonoreactivity displayed a clustered pattern localised both intracytoplasmically and at the plasma membrane. Densitometry analysis indicated that GABABR immunoreactivity was significantly more intense in vasopressin cells than in oxytocin cells, both in male, virgin female and lactating rats, and was denser in males than in virgin females. Light and electron microscope studies indicated that cytoplasmic GABABR was localised in various organelles, including the Golgi, early endosomes and lysosomes, suggesting the cycling of the receptor within the endocytic and trafficking pathways. Some smaller clusters at the level of the cell plasma membrane were apposed to glutamic acid decarboxylase 67 immunoreactive boutons, and appeared to be colocalised with gephyrin, a constituent protein of the postsynaptic density at inhibitory synapses. The presence of GABABR immunoreactivity at synaptic and extrasynaptic sites was supported by electron microscopy. These results provide anatomical evidence for the expression of postsynaptic GABAB receptors in magnocellular neurosecretory cells.