Miracle-dz/UniFAR-FTUs huggingface dataset:
High bone density due to a mutation in LDL-receptor-related protein 5.

BACKGROUND Osteoporosis is a major public health problem of largely unknown cause. Loss-of-function mutations in the gene for low-density lipoprotein receptor-related protein 5 (LRP5), which acts in the Wnt signaling pathway, have been shown to cause osteoporosis-pseudoglioma. METHODS We performed genetic and biochemical analyses of a kindred with an autosomal dominant syndrome characterized by high bone density, a wide and deep mandible, and torus palatinus. RESULTS Genetic analysis revealed linkage of the syndrome to chromosome 11q12-13 (odds of linkage, >1 million to 1), an interval that contains LRP5. Affected members of the kindred had a mutation in this gene, with valine substituted for glycine at codon 171 (LRP5V171). This mutation segregated with the trait in the family and was absent in control subjects. The normal glycine lies in a so-called propeller motif that is highly conserved from fruit flies to humans. Markers of bone resorption were normal in the affected subjects, whereas markers of bone formation such as osteocalcin were markedly elevated. Levels of fibronectin, a known target of signaling by Wnt, a developmental protein, were also elevated. In vitro studies showed that the normal inhibition of Wnt signaling by another protein, Dickkopf-1 (Dkk-1), was defective in the presence of LRP5V171 and that this resulted in increased signaling due to unopposed Wnt activity. CONCLUSIONS The LRP5V171 mutation causes high bone density, with a thickened mandible and torus palatinus, by impairing the action of a normal antagonist of the Wnt pathway and thus increasing Wnt signaling. These findings demonstrate the role of altered LRP5 function in high bone mass and point to Dkk as a potential target for the prevention or treatment of osteoporosis.
Range expansion of a fouling species indirectly impacts local species interactions

We investigated how recent changes in the distribution and abundance of a fouling organism affected the strength of interactions between a commercially important foundation species and a common predator. Increases in the abundance of boring sponges that bioerode the calcified shells of oysters and other shelled organisms have been attributed to increased salinization of estuarine ecosystems. We tested the hypothesis that fouling by boring sponges will change the interaction strength between oysters and a common predator (stone crabs). We generated five oyster density treatments crossed with two sponge treatments (sponge and no sponge). We contrasted the interaction strength between stone crabs and fouled and non-fouled oysters by comparing the parameters of fitted functional response curves based on Rogers random predation model. We found that fouled oysters suffered higher predation from stone crabs, and that the increased predation risk stemmed from a reduction in the handling time needed to consume the fouled oysters. These findings highlight the importance of understanding the effects of abiotic changes on both the composition of ecological communities, and on the strengths of direct and indirect interactions among species. Global climate change is altering local ecosystems in complex ways, and the success of restoration, management, and mitigation strategies for important species requires a better appreciation for how these effects cascade through ecosystems.
Viscerotopic representation of the upper alimentary tract in the rat: Sensory ganglia and nuclei of the solitary and spinal trigeminal tracts

The aim of this study was to map the viscerotopic representation of the upper alimentary tract in the sensory ganglia of the IXth and Xth cranial nerves and in the subnuclei of the solitary and spinal trigeminal tracts. Therefore, in 172 rats 0.5–65 μl of horseradish peroxidase (HRP), wheat germ agglutinin‐HRP, or cholera toxin‐HRP were injected into the trunks and major branches of the IXth and Xth cranial nerves as well as into the musculature and mucosa of different levels of the upper alimentary and respiratory tracts.
Modulation of Immune Responses to Mycobacterium bovis in Cattle Depleted of WC1+ γδ T Cells

ABSTRACT It is accepted that cell-mediated immune responses predominate in mycobacterial infections. Many studies have shown that CD4+ T cells produce Th1 cytokines, such as gamma interferon (IFN-γ), in response to mycobacterial antigens and that the cytolytic activity of CD8+ cells toward infected macrophages is important. However, the extent and manner in which γδ T cells participate in this response remain unclear. In ruminants, γδ T cells comprise a major proportion of the peripheral blood mononuclear cell population. We have previously shown that WC1+ γδ T cells are involved early in Mycobacterium bovis infection of cattle, but their specific functions are not well understood. Here we describe an in vivo model of bovine tuberculosis in which the WC1+ γδ T cells were depleted from the peripheral circulation and respiratory tract, by infusion of WC1+-specific monoclonal antibody, prior to infection. While no effects on disease pathology were observed in this experiment, results indicate that WC1+ γδ T cells, which become significantly activated (CD25+) in the circulation of control calves from 21 days postinfection, may play a role in modulating the developing immune response to M. bovis. WC1+-depleted animals exhibited decreased antigen-specific lymphocyte proliferative response, an increased antigen-specific production of interleukin-4, and a lack of specific immunoglobulin G2 antibody. This suggests that WC1+ γδ TCR+ cells contribute, either directly or indirectly, toward the Th1 bias of the immune response in bovine tuberculosis—a hypothesis supported by the decreased innate production of IFN-γ, which was observed in WC1+-depleted calves.
Injectable Biomaterials for Dental Tissue Regeneration

Injectable biomaterials scaffolds play a pivotal role for dental tissue regeneration, as such materials are highly applicable in the dental field, particularly when compared to pre-formed scaffolds. The defects in the maxilla-oral area are normally small, confined and sometimes hard to access. This narrative review describes different types of biomaterials for dental tissue regeneration, and also discusses the potential use of nanofibers for dental tissues. Various studies suggest that tissue engineering approaches involving the use of injectable biomaterials have the potential of restoring not only dental tissue function but also their biological purposes.
Determination of Adequate Defibrillation of Ventricular Tachycardia Using Computer Simulation of Electroporation Aftershock Effects on Human Cardiomyocytes

Electric defibrillation is a life-saving therapy for clinically dangerous ventricular arrhythmias. Unfortunately, direct-current (DC) shock treatment often induces or worsens other tachyarrhythmias. The adverse effects of electric shock delivered to human ventricular cardiomyocytes are not fully understood. This study thus uses computer simulation to investigate the pathogenesis of the electrophoresis in epicardial and endocardial human tissue. The O'Hara-Rudy dynamic human ventricular cell model incorporated with Ohuchi's mathematical DC shock model is used. The effect of electroporation is described as a transmembrane pore, mimicking the reversible breakdown of the cell membrane. The aftershock effects on epiardial and endocardial ventricular cardiomyocytes are evaluated. The effects of delivering shock from the endocardium and epicardium using a multicellular one-dimensional strand model are also investigated. Ventricular tachycardia can be terminated by a low-strength shock to endocardial cardiomyocytes. However, an excessively strong shock to epicardial cardiomyocytes induces early afterdepolarization and is arrhythmogenic. The aftershock effect of the electroporation is serious for epicardial ventricular myocytes. The optimization of defibrillation energy delivery to the maximum membrane potential and the pathogenesis of the aftershock effect during ventricular tachycardia are also investigated. The aftershock effect of electroporation is more serious in epicardial cells than it is in endocardial cells. It is suggested that the DC shock be delivered to endocardium cells before the maximum membrane potential of the epicardial cell in a multicellular one-dimensional strand model is reached, which is before the electrocardiogram R wave spike.
Association between diabetes mellitus and active tuberculosis: A systematic review and meta-analysis

The burgeoning epidemic of diabetes mellitus (DM) is one of the major global health challenges. We systematically reviewed the published literature to provide a summary estimate of the association between DM and active tuberculosis (TB). We searched Medline and EMBASE databases for studies reporting adjusted estimates on the TB–DM association published before December 22, 2015, with no restrictions on region and language. In the meta-analysis, adjusted estimates were pooled using a DerSimonian-Laird random-effects model, according to study design. Risk of bias assessment and sensitivity analyses were conducted. 44 eligible studies were included, which consisted of 58,468,404 subjects from 16 countries. Compared with non-DM patients, DM patients had 3.59–fold (95% confidence interval (CI) 2.25–5.73), 1.55–fold (95% CI 1.39–1.72), and 2.09–fold (95% CI 1.71–2.55) increased risk of active TB in four prospective, 16 retrospective, and 17 case-control studies, respectively. Country income level (3.16–fold in low/middle–vs. 1.73–fold in high–income countries), background TB incidence (2.05–fold in countries with >50 vs. 1.89–fold in countries with ≤50 TB cases per 100,000 person-year), and geographical region (2.44–fold in Asia vs. 1.71–fold in Europe and 1.73–fold in USA/Canada) affected appreciably the estimated association, but potential risk of bias, type of population (general versus clinical), and potential for duplicate data, did not. Microbiological ascertainment for TB (3.03–fold) and/or blood testing for DM (3.10–fold), as well as uncontrolled DM (3.30–fold), resulted in stronger estimated association. DM is associated with a two- to four-fold increased risk of active TB. The association was stronger when ascertainment was based on biological testing rather than medical records or self-report. The burgeoning DM epidemic could impact upon the achievements of the WHO “End TB Strategy” for reducing TB incidence.
Suppression of chaos by resonant parametric perturbations.

Starting from a chaotic regime in the dynamics of a Duffing-Holmes oscillator, we show how it is possible, by means of a small parametric perturbation of suitable frequency, to bring the system to a regular regime. This situation is studied from the analytic point of view using the Melnikov method and from the numerical point of view computing Lyapunov exponents. The corresponding bounds for the perturbation are compared. Noting that the time, measured along the original unperturbed separatrix, that elapses between two successive homoclinic intersections grows when we approach the resonance, we propose a possible scenario for this type of regularization of the dynamics.
THE 2007 FRAZIER-ZAUMEYER LECTURE Bean Improvement Cooperative 50 ^ ^ Anniversary Meeting , Madison , WI FROM RALPH CORBETT ' S BEAN FIELD TO MOLECULAR DETAILS OF BROAD SPECTRUM POTYVIRUS RESISTANCE

Genetic resistance to plant viruses has been used for at least eighty years to control agricultural losses to viral diseases. To date, hundreds of naturally occurring genes for resistance to plant viruses have been reported from studies of both monocot and dicot crops, their wild relatives and the plant model, Arabidopsis. While viruses are relatively simple genetic entities and much progress has occurred since the earliest studies, the mechanisms by which the many symptoms of disease are generated, and the mechanisms by which plants resist these effects remain largely unknown. In fact, the study of plant resistance genes raise many fundamental questions regarding the molecular, biochemical, cellular and physiological mechanisms involved in the plant-virus interaction and the evolution of these interactions in natural and agricultural ecosystems.
The Impact of Exacerbations on the Asthmatic Patient's Preference Scores

The purpose of this study was to examine the effect of exacerbations on mild to moderate asthmatic patients' preference-based, health-related, quality of life scores and also to describe the effect of these exacerbations on daily life. In a survey, 100 mild to moderate asthmatic patients in the United Kingdom were asked to rate three different health marker states on a scale between 0 (death) and 100 (perfect health), defined as: your asthma of today, a mild exacerbation, and a severe exacerbation of asthma. They were also asked to describe their symptoms and what they did when experiencing an exacerbation. During exacerbations the vast majority of asthmatic patients have significant symptoms and consume a considerable amount of health care resources, which often overlap. The health marker state “your asthma of today” was given a mean score of 81.0, a mild exacerbation a score of 62.1, and a severe exacerbation a score of 25.6, indicating a large impact on patients' daily life and their health-related quality of life. In conclusion, asthmatic patients are severely affected in their health and daily living by mild and severe exacerbations. Considerable effort should be made to reduce the number and severity of exacerbations.
Firms’ Board Independence and Corporate Social Performance: A Meta-Analysis

This paper investigates the influence of organizations’ board independence on corporate social performance (CSP) using a meta-analytic approach. A sample of 87 published papers is used to identify a set of underlying moderating effects in that relationship. Specifically, differences in the system of corporate governance, CSP measurement models and market conditions have been considered as moderating variables. The results show that the independence of a company’s board positively influences CSP. This is because companies with more independent directors in their boards are more likely to commit to stakeholder engagement, environmental preservation and community well-being. Interestingly, the results also show that the positive connection between board independence and CSP is stronger in civil law countries and when CSP is measured by self-reporting data. Finally, the strength of the influence of the independence of a firm’s board on CSP varies significantly in different market conditions. The paper concludes by presenting the main implications for academics, practitioners and policy makers.
Mutations at embB Codon 306 Are an Important Molecular Indicator of Ethambutol Resistance in Mycobacterium tuberculosis

ABSTRACT Ethambutol resistance in clinical Mycobacterium tuberculosis isolates is associated primarily with missense mutations in the embB gene. However, recent reports have described the presence of embB mutations, especially those at embB codon 306, in isolates susceptible to ethambutol. To clarify the role of embB mutations in ethambutol resistance, we sequenced the ethambutol resistance-determining region in spontaneous ethambutol-resistant mutants. In our study, 66% of spontaneous mutants contained a single point mutation in embB, with 55% of these occurring at embB 306. The MIC of ethambutol for spontaneous mutants was increased two- to eightfold relative to the pansusceptible M. tuberculosis strains from which the mutants were generated. To further characterize the role of embB 306 mutations, we directly introduced mutant alleles, embB(M306V) or embB(M306I), into pansusceptible M. tuberculosis strains and conversely reverted mutant alleles in spontaneous ethambutol-resistant mutants back to those of the wild type via allelic exchange using specialized linkage transduction. We determined that the MIC of ethambutol was reduced fourfold for three of the four spontaneous ethambutol-resistant embB 306 mutants when the mutant allele was replaced with the wild-type embB allele. The MIC for one of the spontaneous mutants genetically reverted to wild-type embB was reduced by only twofold. When the wild-type embB allele was converted to the mutant allele embB(M306V), the ethambutol MIC was increased fourfold, and when the allele was changed to M306I, the ethambutol MIC increased twofold. Our data indicate that embB 306 mutations are sufficient to confer ethambutol resistance, and detection of these mutations should be considered in the development of rapid molecular tests.
Quality of referral of short children to the paediatric endocrinologist and impact of a fax communication system.

BACKGROUND/OBJECTIVES In 2001, a chart review of children referred to the authors' endocrine clinic because of short stature revealed that many were referred with insufficient baseline data, had normal height velocity and were within genetic target height. Therefore, a two-way fax communication system was implemented between referring physicians and the authors' service before the first visit. Aspects that were assessed included whether this system increased the information accompanying the patient at referral, resulted in children with nonpathological shortness not being seen in the clinic, and was used differently by paediatricians and general practitioners. STUDY DESIGN Between January and December 2006, 138 referrals for short stature, diagnosed with familial short stature, constitutional delay or idiopathic short stature, were audited (69 with and 69 without previous fax communication). Data collected included source of referral, clinical information provided, available growth measurements, and results from laboratory and imaging studies. RESULTS Fax communication resulted in growth curves being provided more often (95.6% of cases versus 40.5% of cases without fax communication [P<0.001]) and more investigations being performed by the referring physician (median [range]: six [zero to 13] investigations versus one [zero to 11]; P<0.001), as well as a diagnosis of nonpathological short stature being given to 31 children based on the growth curve, laboratory and imaging results, without the children being seen in the endocrine clinic. Fax communication was also used more frequently by paediatricians (84%) than by general practitioners (15%). CONCLUSION The fax communication system resulted in a more complete evaluation of referred patients by their physicians and reduced the number of unnecessary visits to the authors' specialty clinic while promoting medical education.
Systemic lupus erythematosus. Treatment-related complications superimposed on chronic disease.

SELECTED CASE A 40-YEAR-OLD black woman with systemic lupus erythematosus (SLE) has been followed up in the arthritis clinic at the National Institutes of Health Clinical Center throughout most of the 19 years of her illness. The initial manifestations of her illness developed in the postpartum period of a pregnancy that had been complicated by proteinuria believed to be caused by toxemia. Proteinuria (2.8 g/24 h) accompanied by hematuria and red blood cell casts prompted a renal biopsy that revealed diffuse, proliferative glomerulonephritis (activity index, 6; chronicity index, 0). Other manifestations of her disease included polyarthralgias; erythematous rashes of the face, arms, and legs; and alopecia. Laboratory studies disclosed the following values: serum creatinine, 70 μmol/L; creatinine clearance, 1.75 mL/s; antinuclear antibody, 1:1280 (rim pattern); antibodies to DNA, 98% (Farr assay); and C3, 0.77 g/L. A daily 60-mg dose of prednisone was started, and during the next 2 years the
Design of low-cost portable ultrasound systems: Review

Ultrasound continues to be one of the major imaging modalities used for the diagnosis and treatment of a number of medical conditions. Therefore emphasis on innovation is continually increasing the quality of the ultrasound systems. However focus is just beginning to shift into the low-cost and portable applications of ultrasound. These systems present interesting constraints which must be considered to transform a standalone system into a portable version. This review takes a look at some of the attempts which have been published, as well as some of the issues which have still yet to be resolved. In conclusion, low-cost portable ultrasound has the capability to be developed and commercialized, but until a suitable replacement to piezoelectric crystals has been developed (possibly CMUTs? ) low-cost portable ultrasound system will be held back by the high cost burden associated with the cost of piezoceramics.
Vasopressin activates phospholipase D through pertussis toxin-insensitive GTP-binding protein in aortic smooth muscle cells: function of Ca2+/calmodulin.

In the present study, we examined the effect of vasopressin (AVP) on phosphatidylcholine-hydrolyzing phospholipase D activity in primary cultured rat aortic smooth muscle cells. AVP stimulation of choline formation was dose dependent. The time-course was quite different from those of inositol phosphates. The effect of AVP on the formation of inositol phosphates (EC50 was 3 nM) was more potent than that on the formation of choline (EC50 was 30 nM). 12-O-Tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC), stimulated the formation of choline. However, 4 alpha-phorbol 12,13-didecanoate, which is inactive for PKC, had little effect. Staurosporine, an inhibitor of protein kinases, which inhibited the TPA-induced formation of choline, had little effect on the AVP-induced formation of choline. Neither calphostin C, a highly specific PKC inhibitor, nor PKC down-regulation with TPA affected AVP-induced formation of choline. A combination of AVP and TPA additively stimulated the formation of choline. The depletion of extracellular Ca2+ by (ethylenebis(oxyethylenenitrilo)tetraacetic acid significantly reduced the AVP-induced formation of choline. W-7, an antagonist of calmodulin, inhibited the AVP-induced formation of choline in a dose-dependent manner. NaF, an activator for GTP-binding protein (G-protein), stimulated the formation of choline. However, the formation of choline by a combination of AVP and NaF was not additive. Pertussis toxin had little effect on the AVP-induced formation of choline. (ABSTRACT TRUNCATED AT 250 WORDS)
Cefepime Cerebrospinal Fluid Concentrations in Neonatal Bacterial Meningitis

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