Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPV4 exhibits a functional role in cell-volume regulation

Tight regulation of the cell volume is important for the maintenance of cellular homeostasis. In a hypotonic environment, cells swell owing to osmosis. With many vertebrate cells, swelling is followed by an active reduction of volume, a process called regulatory volume decrease (RVD). A possible participant in RVD is the non-selective cation channel TRPV4, a member of the TRP superfamily that has been shown to react to hypotonic stimuli with a conductance for Ca2+. As a model for cell-volume regulation, we used a human keratinocyte cell line (HaCaT) that produces TRPV4 endogenously. When HaCaT cells were exposed to a hypotonic solution (200 mOsm) maximal swelling was followed by RVD. During swelling and volume regulation, a strong Ca2+ influx was measured. Gd3+, an inhibitor of TRPV4, blocked RVD of HaCaT cells and the accompanying rise of cytosolic Ca2+. To define the role of TRPV4 in volume regulation, a TRPV4-EGFP fusion protein was produced in CHO cells. CHO cells are unable to undergo RVD under hypotonic conditions and do not produce TRPV4 endogenously. Fluorescence imaging revealed that recombinant TRPV4 was localized to the cell membrane. Production of TRPV4 enabled CHO cells to undergo typical RVD after hypo-osmolarity-induced cell swelling. RVD of TRPV4-transfected CHO cells was significantly reduced by Gd3+ treatment or in Ca2+-free solution. Taken together, these results show a direct participation of TRPV4 in RVD.
Using Gene Expression to Improve the Power of Genome-Wide Association Analysis

Background/Aims: Genome-wide association (GWA) studies have reported susceptible regions in the human genome for many common diseases and traits; however, these loci only explain a minority of trait heritability. To boost the power of a GWA study, substantial research endeavors have been focused on integrating other available genomic information in the analysis. Advances in high through-put technologies have generated a wealth of genomic data and made combining SNP and gene expression data become feasible. Results: In this paper, we propose a novel procedure to incorporate gene expression information into GWA analysis. This procedure utilizes weights constructed by gene expression measurements to adjust p values from a GWA analysis. Results from simulation analyses indicate that the proposed procedures may achieve substantial power gains, while controlling family-wise type I error rates at the nominal level. To demonstrate the implementation of our proposed approach, we apply the weight adjustment procedure to a GWA study on serum interferon-regulated chemokine levels in systemic lupus erythematosus patients. The study results can provide valuable insights for the functional interpretation of GWA signals. Availability: The R source code for implementing the proposed weighting procedure is available at http://www.biostat. umn.edu/∼yho/research.html.
PHARMACOKINETIC COMPARISON OF KETOROLAC AFTER INTRACAMERAL, INTRAVITREAL, AND SUPRACHOROIDAL ADMINISTRATION IN RABBITS

Purpose: To investigate the concentrations and pharmacokinetics of ketorolac in the rabbits by three different routes of administrations: a single intracameral, intravitreal, and suprachoroidal injection. Methods: Fifty-four New Zealand white rabbits received ketorolac (250 &mgr;g/0.05 mL) in one eye by a single intracameral injection (group A, n = 18), single intravitreal injection (group B, n = 18), and single suprachoroidal injection (group C, n = 18). Drug concentrations in the vitreous, retina–choroid (RC), and plasma were determined by the methods of high-performance liquid chromatography at 0.5, 1, 2, 4, 8, and 24 hours after injection. The concentrations in the opposite eyes were also investigated. Results: The mean maximum concentrations (Cmax) of ketorolac in the vitreous and RC were 0.378 ± 0.19 &mgr;g/mL and 3.15 ± 0.49 &mgr;g/g (at 0.5 hours), respectively, in group A; 156.2 ± 20.74 &mgr;g/mL (at 0.5 hours) and 208.0 ± 21.67 &mgr;g/g (at 1 hours), respectively, in group B; and 0.873 ± 0.34 &mgr;g/mL and 56.71 ± 22.64 &mgr;g/g (at 0.5 hours), respectively, in group C. In the RC, the area under the curve (AUC0–t) in group B (866.1 ± 52.67 &mgr;g/g·h) was higher (P < 0.01) than that in group C (77.10 ± 25.90 &mgr;g/g·h). The elimination half-life (t1/2) in group B (3.09 hours) was longer (P < 0.01) than that in group C (1.19 hours). In the control eyes, a drug level below 2 &mgr;g/g was detected in the RC in group C. Plasma concentrations were below 0.4 &mgr;g/mL in all 3 groups. Ketorolac was detectable in the RC till 24 hours after the intravitreal injection and 8 hours after the suprachoroidal injection. Conclusion: Intravitreal injection of ketorolac produced higher intraocular drug concentrations for a longer period compared with the other two routes. Suprachoroidal injection of ketorolac could reach an effective drug level in the RC with short half-lives and low drug levels in the vitreous. The plasma drug concentrations were low by all three routes.
Community Health Environment Scan Survey (CHESS): a novel tool that captures the impact of the built environment on lifestyle factors

Background: Novel1 1This study was performed on behalf of the Community Interventions for Health (CIH) collaboration. efforts and accompanying tools are needed to tackle the global burden of chronic disease. This paper presents an approach to describe the environments in which people live, work, and play. Community Health Environment Scan Survey (CHESS) is an empirical assessment tool that measures the availability and accessibility, of healthy lifestyle options lifestyle options. CHESS reveals existing community assets as well as opportunities for change, shaping community intervention planning efforts by focusing on community-relevant opportunities to address the three key risk factors for chronic disease (i.e. unhealthy diet, physical inactivity, and tobacco use). Methods: The CHESS tool was developed following a review of existing auditing tools and in consultation with experts. It is based on the social-ecological model and is adaptable to diverse settings in developed and developing countries throughout the world. Results: For illustrative purposes, baseline results from the Community Interventions for Health (CIH) Mexico site are used, where the CHESS tool assessed 583 food stores and 168 restaurants. Comparisons between individual-level survey data from schools and community-level CHESS data are made to demonstrate the utility of the tool in strategically guiding intervention activities. Conclusion: The environments where people live, work, and play are key factors in determining their diet, levels of physical activity, and tobacco use. CHESS is the first tool of its kind that systematically and simultaneously examines how built environments encourage/discourage healthy eating, physical activity, and tobacco use. CHESS can help to design community interventions to prevent chronic disease and guide healthy urban planning.
Are national guidelines for total hip replacement in the UK reflected in practice?

INTRODUCTION A cross-sectional study was performed to compare the practice of total hip replacement (THR) in the UK against national guidelines. MATERIALS AND METHODS A postal questionnaire was sent to all fellows of the British Orthopaedic Association. RESULTS Of the 1587 questionnaires sent out, 966 (60.9%) were returned. Of these, 706 (73.1%) were available for data collection and analysis. CONCLUSIONS Consensus was observed in several areas including the use of pre-admission clinics and modern cementing techniques. Facilities deemed necessary for THR surgery such as HDU/ITU back-up, ultra-clean air and dedicated orthopaedic wards are almost universally available. However, a lack of consensus is evident in many areas including the process of obtaining written consent, thrombo-embolic prophylaxis, duration of antibiotic prophylaxis, supervision of trainee surgeons and follow-up arrangements. The proliferation in the range of implants, particularly aimed at 'younger' patients, available to surgeons has once again been highlighted.
Diffusion tensor imaging of Parkinson's disease, atypical parkinsonism, and essential tremor

Diffusion tensor imaging could be useful in characterizing movement disorders because it noninvasively examines multiple brain regions simultaneously. We report a multitarget imaging approach focused on the basal ganglia and cerebellum in Parkinson's disease, parkinsonian variant of multiple system atrophy, progressive supranuclear palsy, and essential tremor and in healthy controls. Seventy‐two subjects were studied with a diffusion tensor imaging protocol at 3 Tesla. Receiver operating characteristic analysis was performed to directly compare groups. Sensitivity and specificity values were quantified for control versus movement disorder (92% sensitivity, 88% specificity), control versus parkinsonism (93% sensitivity, 91% specificity), Parkinson's disease versus atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson's disease versus multiple system atrophy (94% sensitivity, 100% specificity), Parkinson's disease versus progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy versus progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson's disease versus essential tremor (92% sensitivity, 87% specificity). The brain targets varied for each comparison, but the substantia nigra, putamen, caudate, and middle cerebellar peduncle were the most frequently selected brain regions across classifications. These results indicate that using diffusion tensor imaging of the basal ganglia and cerebellum accurately classifies subjects diagnosed with Parkinson's disease, atypical parkinsonism, and essential tremor and clearly distinguishes them from control subjects. © 2013 International Parkinson and Movement Disorder Society
Experience-dependent maturation of the glomerular microcircuit

Spontaneous and patterned activity, largely attributed to chemical transmission, shape the development of virtually all neural circuits. However, electrical transmission also has an important role in coordinated activity in the brain. In the olfactory bulb, gap junctions between apical dendrites of mitral cells increase excitability and synchronize firing within each glomerulus. We report here that the development of the glomerular microcircuit requires both sensory experience and connexin (Cx)36-mediated gap junctions. Coupling coefficients, which measure electrical coupling between mitral cell dendrites, were high in young mice, but decreased after postnatal day (P)10 because of a maturational increase in membrane conductance. Sensory deprivation, induced by unilateral naris occlusion at birth, slowed the morphological development of mitral cells and arrested the maturational changes in membrane conductance and coupling coefficients. As the coupling coefficients decreased in normal mice, a glutamate-mediated excitatory postsynaptic current (EPSC) between mitral cells emerged by P30. Although mitral–mitral EPSCs were generally unidirectional, they were not present in young adult Cx36−/− mice, suggesting that gap junctions are required for the development and/or function of the mature circuit. The experience-dependent transition from electrical transmission to combined chemical and electrical transmission provides a previously unappreciated mechanism that may tune the response properties of the glomerular microcircuit.
Sex hormones and lipoprotein(a) concentration

Introduction: Increased level of lipoprotein(a) (Lp(a)) constitutes an emerging, independent risk factor for coronary artery disease. Recently, it has been recommended to lower increased (> 50 mg/dl) Lp(a) concentration. Most lipid lowering agents – except niacin – have little or no effect whereas sex hormones significantly reduce Lp(a) level. The effect of sex hormones on Lp(a) level is related to the setting, the drug, the dose and the way of administration. Androgen esters, oral estrogens, alone or in combination with progestogens, and tibolone constantly decrease Lp(a) level, especially in postmenopausal women. Areas covered: This paper reviews the pathophysiology, structure and metabolism of Lp(a). Clinical studies evaluating, in various settings, the effect of exogenous administration of androgens, estrogens – alone or in combination with progestogens – selective receptor estrogen modulators (SERMs), aromatase inhibitors (AIs) and tibolone on Lp(a) level are analyzed. Expert opinion: The results obtained for SERMs are conflicting whereas AIs do not seem to reduce Lp(a) concentration. The effect of hormonal therapy on lipids is complex, depending on drugs and way of administration. Moreover, both androgens and estrogen could determine, in specific settings, severe adverse effects. These drugs are not currently recommended either for treatment of dyslipidemias with increased Lp(a) level or for the prevention of cardiovascular disease.
Characterization of soluble thrombomodulin levels in patients with stage 3–5 chronic kidney disease

Abstract Objective: This study aims to test the serum levels of soluble thrombomodulin (TM) in patients with chronic kidney disease (CKD)3–5 and to assess their connection with the different stages and severity of disease. Methods: Sixty-seven patients with CKD are included, disease severity was evaluated accordingly to CKD staging and clinical data is collected. Nineteen healthy volunteers served as healthy controls. Serum soluble TM is analyzed by ELISA. Results: The levels of soluble TM in all patients with CKD were significantly higher than those of healthy controls (p < 0.001). CKD5 patients showed higher serum levels of soluble TM, in comparison to CKD4 patients (p = 0.001), CKD3 patients (p < 0.001), and healthy controls (p < 0.001). The correlation analysis revealed significant correlation between serum soluble TM and disease severity (r = 0.714, p < 0.001). Serum soluble TM was found to be correlated with eGFR (r = −0.766; p < 0.001) and serum creatinine (r = 0.778, p < 0.001). Conclusion: Soluble TM concentrations significantly increase in the CKD patients and are associated with the severity of the disease. Soluble TM may play critical roles in the development of CKD, as a biomarker of endothelial cells damage, anticoagulation and anti-inflammation.
Identification of Coli Surface Antigen 23, a Novel Adhesin of Enterotoxigenic Escherichia coli

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea, mainly in developing countries. Although there are 25 different ETEC adhesins described in strains affecting humans, between 15% and 50% of the clinical isolates from different geographical regions are negative for these adhesins, suggesting that additional unidentified adhesion determinants might be present. Here, we report the discovery of Coli Surface Antigen 23 (CS23), a novel adhesin expressed by an ETEC serogroup O4 strain (ETEC 1766a), which was negative for the previously known ETEC adhesins, albeit it has the ability to adhere to Caco-2 cells. CS23 is encoded by an 8.8-kb locus which contains 9 open reading frames (ORFs), 7 of them sharing significant identity with genes required for assembly of K88-related fimbriae. This gene locus, named aal (adhesion-associated locus), is required for the adhesion ability of ETEC 1766a and was able to confer this adhesive phenotype to a nonadherent E. coli HB101 strain. The CS23 major structural subunit, AalE, shares limited identity with known pilin proteins, and it is more closely related to the CS13 pilin protein CshE, carried by human ETEC strains. Our data indicate that CS23 is a new member of the diverse adhesin repertoire used by ETEC strains.
On the syllable structure of English pidgins and creoles

This thesis is an optimality-theoretic investigation of syllable restructuring in the Atlantic and Pacific English-lexicon pidgins and creoles, both in their earlier stages and in the modem varieties. The theoretical framework and the methodology are presented in chapter 2. The next three chapters examine the adjustments that occur in the English pidgins and creoles in two syllabic positions: the onset and the coda. Thus, chapter 3 looks into the strategies used to resolve illicit /s/-initial onset clusters. Chapter 4 investigates the fate of obstruent + sonorant onset clusters, to the exclusion of /s/-initial ones. The clusters at issue are of two types: obstruent + glide, and obstruent + liquid. Particular attention is paid to the treatment of obstruent + liquid onset clusters in the creoles of Surinam, a matter of some dispute in the literature. Syllable restructuring in coda position is discussed in chapter 5, in which reflexes of etyma with both complex and simple codas are analyzed. The last chapter places the findings in the wider context of their implications for phonological theory and for the study of language contacts, as well as of the relevance of optimality theory to the study of syllable restructuring in the English pidgins and creoles. The issues discussed include the role of markedness, the relation between constraints on syllable structure in the English pidgins and creoles and in their respective substrate languages, syllable restructuring in the Atlantic Dutch and French creoles, and a comparison of syllable restructuring in first and second language phonology, in loanword phonology, and in the English pidgins and creoles.
Are cattle surrogate wildlife? Savanna plant community composition explained by total herbivory more than herbivore type.

The widespread replacement of wild ungulate herbivores by domestic livestock in African savannas is composed of two interrelated phenomena: (1) loss or reduction in numbers of individual wildlife species or guilds and (2) addition of livestock to the system. Each can have important implications for plant community dynamics. Yet very few studies have experimentally addressed the individual, combined, and potentially interactive effects of wild vs. domestic herbivore species on herbaceous plant communities within a single system. Additionally, there is little information about whether, and in which contexts, livestock might functionally replace native herbivore wildlife or, alternatively, have fundamentally different effects on plant species composition. The Kenya Long-term Exclosure Experiment, which has been running since 1995, is composed of six treatment combinations of mega-herbivores, meso-herbivore ungulate wildlife, and cattle. We sampled herbaceous vegetation 25 times between 1999 and 2013. We used partial redundancy analysis and linear mixed models to assess effects of herbivore treatments on overall plant community composition and key plant species. Plant communities in the six different herbivore treatments shifted directionally over time and diverged from each other substantially by 2013. Plant community composition was strongly related (R2 = 0.92) to residual plant biomass, a measure of herbivore utilization. Addition of any single herbivore type (cattle, wildlife, or mega-herbivores) caused a shift in plant community composition that was proportional to its removal of plant biomass. These results suggest that overall herbivory pressure, rather than herbivore type or complex interactions among different herbivore types, was the main driver of changes in plant community composition. Individual plant species, however, did respond most strongly to either wild ungulates or cattle. Although these results suggest considerable functional similarity between a suite of native wild herbivores (which included grazers, browsers, and mixed feeders) and cattle (mostly grazers) with respect to understory plant community composition, responses of individual plant species demonstrate that at the plant-population-level impacts of a single livestock species are not functionally identical to those of a diverse group of native herbivores.
Porous scaffold architecture guides tissue formation

Critical‐sized bone defect regeneration is a remaining clinical concern. Numerous scaffold‐based strategies are currently being investigated to enable in vivo bone defect healing. However, a deeper understanding of how a scaffold influences the tissue formation process and how this compares to endogenous bone formation or to regular fracture healing is missing. It is hypothesized that the porous scaffold architecture can serve as a guiding substrate to enable the formation of a structured fibrous network as a prerequirement for later bone formation. An ovine, tibial, 30‐mm critical‐sized defect is used as a model system to better understand the effect of the scaffold architecture on cell organization, fibrous tissue, and mineralized tissue formation mechanisms in vivo. Tissue regeneration patterns within two geometrically distinct macroscopic regions of a specific scaffold design, the scaffold wall and the endosteal cavity, are compared with tissue formation in an empty defect (negative control) and with cortical bone (positive control). Histology, backscattered electron imaging, scanning small‐angle X‐ray scattering, and nanoindentation are used to assess the morphology of fibrous and mineralized tissue, to measure the average mineral particle thickness and the degree of alignment, and to map the local elastic indentation modulus. The scaffold proves to function as a guiding substrate to the tissue formation process. It enables the arrangement of a structured fibrous tissue across the entire defect, which acts as a secondary supporting network for cells. Mineralization can then initiate along the fibrous network, resulting in bone ingrowth into a critical‐sized defect, although not in complete bridging of the defect. The fibrous network morphology, which in turn is guided by the scaffold architecture, influences the microstructure of the newly formed bone. These results allow a deeper understanding of the mode of mineral tissue formation and the way this is influenced by the scaffold architecture. © 2012 American Society for Bone and Mineral Research.
A Novel Role of Hepatocyte Growth Factor as an Immune Regulator through Suppressing Dendritic Cell Function1

Hepatocyte growth factor (HGF) plays an important role in many biological events such as angiogenesis, cell proliferation, anti-fibrosis and antiapoptosis. It is well known that HGF promotes tumor progression and suppresses development of fibrosis after tissue injury. In contrast, its role in immune-mediated disorders has not been fully clarified. In the present study, we examined the role of HGF in Ag-specific immune response using in vitro studies and an experimental model of allergic airway inflammation. We first confirmed that dendritic cells (DCs) expressed the receptor for HGF, c-met, which was not expressed in T cells. Treatment with HGF both in vitro and in vivo potently suppressed DC functions such as Ag-presenting capacity, thus down-regulating Ag-induced Th1- and Th2-type immune responses. Exogenous administration of the HGF expression plasmid into Ag-primed mice markedly suppressed the development of airway eosinophilia and airway hyperresponsiveness, which was induced by Ag inhalation, with suppression of the Ag-presenting capacity of DCs in the lung. HGF exhibited these immunosuppressive effects without up-regulation of IL-10 or TGF-β. We also found that expression of endogenous HGF in the lung significantly increased following Ag sensitization and inhalation challenges. Finally, neutralization of endogenous HGF in vivo significantly increased airway eosinophilia and airway hyperresponsiveness with up-regulation of the Ag-presenting capacity of DCs in the lung. These results demonstrated a novel, significant, and possibly therapeutic role of HGF as a potent regulator in immune-mediated disorders such as asthma.