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111.
Hélène De Naeyer Veerle Bogaert Annelies De Spaey Greet Roef Sara Vandewalle Wim Derave Youri Taes Jean-Marc Kaufman 《PloS one》2014,9(1)
Objective
The relationship between serum testosterone (T) levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR) gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings.Design
677 men (25–45 years) were recruited in a cross-sectional, population-based sibling pair study.Methods
Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs), sex steroid levels (by LC-MS/MS), body composition (by DXA), muscle cross-sectional area (CSA) (by pQCT), muscle force (isokinetic peak torque, grip strength) and anthropometrics were studied using linear mixed-effect modelling.Results
Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT) and free T (FT) levels were positively related to muscle CSA, whereas estradiol (E2) and free E2 (FE2) concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats.Conclusions
Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR gene also affect muscle mass or function. 相似文献112.
The past two decades of research into Xeroderma pigmentosum (XP), an autosomal recessive disease, has been marked by significant progress in understanding the molecular basis of this rare disease. More importantly, especially from the perspective of the affected families, is that this knowledge has been applied to diagnose the condition both in utero as well as in the very early days of life. The eight known XP genes and their different phenotypes present a number of challenges that the XP Workshop sponsored by the NIH in 2010 has highlighted. There is little current treatment specifically designed for any of the XP types other than standard dermatological and neurological evaluations and care. The Xeroderma Pigmentosum Family Support Group (XPFSG) is dedicated to serving families with children and adults with all forms of XP and to help them better understand the condition, to identify practical measures which can be taken by the XP patients and their families to mitigate the effects of the disease, and to serve as patient advocates to help families discuss issues with their physicians. We summarize our efforts in terms of outreach within the US and abroad to affected families and discuss XPFSG-sponsored clinical initiatives that include molecular diagnoses, treatment, and initial proof-of-concept studies that can, if successful, improve the lives of XP patients in the near term. 相似文献
113.
Nicola Trotta Serge Goldman Benjamin Legros Kristof Baete Koen Van Laere Patrick Van Bogaert Xavier De Tiège 《PloS one》2013,8(6)
Purpose
To investigate epilepsy-induced changes in effective connectivity between the non-epileptic amygdalo-hippocampal complex (AHC) and the rest of the brain in patients with unilateral mesiotemporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS).Methods
Thirty-three patients with unilateral MTLE associated with HS (20 females, mean age: 36 years, 19 left HS) and 33 adult controls matched for age and gender underwent 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Right-HS patients'' FDG-PET data were flipped to obtain a left–epileptic–focus–lateralized group of patients. Voxels of interest (VOI) were selected within the cytoarchitectonic probabilistic maps of the non-epileptic AHC (probability level = 100%, SPM8 Anatomy toolbox v1.7). Patients and controls were compared using VOI metabolic activity as covariate of interest to search for epilepsy-induced changes in the contribution of the non-epileptic AHC to the level of metabolic activity in other brain areas. Age, gender, duration of epilepsy, seizure type and frequency were used as covariates of no-interest for connectivity analyses.Key findings
Significant decrease in effective connectivity was found between the non-epileptic AHC and ventral prefrontal cortical areas bilaterally, as well as with the temporal pole and the posterior cingulate cortex contralateral to HS. Significant increase in connectivity was found between the non-epileptic AHC and midline structures, such as the anterior cingulate and dorsal medial prefrontal cortices, as well as the temporo-parietal junction bilaterally. Connectivity analyses also revealed a preserved positive connectivity between the non-epileptic and the epileptic AHC in the patients'' group.Significance
This study evidences epilepsy-induced changes in connectivity between the non-epileptic AHC and some limbic and default mode network areas. These changes in connectivity probably account for emotional, cognitive and decision-making impairments frequently observed in MTLE patients. The preserved neurometabolic connectivity between the non-epileptic and the epileptic AHC in MTLE patients is pivotal to explain the epilepsy-induced changes found in this study. 相似文献114.
De Maeseneire SL Van Bogaert IN Dauvrin T Soetaert WK Vandamme EJ 《Biotechnology letters》2007,29(12):1845-1855
A quick and reliable method for screening fungal transformants for specific genetic modifications is essential for many molecular
applications. We have compared the applicability of a few rapid DNA extraction methods for Myrothecium and Aspergillus and tested the resulting DNA as to its suitability for PCR. For Myrothecium gramineum, the highest DNA concentration was obtained with the procedure described by N. Vanittanakom et al. (J Clin Microbiol 2002,
40: 1739–1742). For A. nidulans, concentrations higher than 100 ng/μl were reached with the glass bead, the LiCl, the boiling, the liquid N2 and the protoplast-based method. Samples of M. gramineum resulting from the boiling and the liquid N2 procedure were suitable for the amplification of fragments up to 2.3 kb. The direct use of mycelium from M. gramineum in the PCR tube can be employed for the reproducible amplification of fragments up to 1 kb. Amplification of fragments up
to 4.3 kb requires the use of the Elongase Mix on samples extracted with the liquid N2 procedure. 相似文献
115.
Jurre Y. Siegers Kirsty R. Short Lonneke M. E. Leijten Miranda de Graaf Monique I. J. Spronken Eefje J. A. Schrauwen Nicolle Marshall Anice C. Lowen Gülsah Gabriel Albert D. M. E. Osterhaus Thijs Kuiken Debby van Riel 《Journal of virology》2014,88(8):4595-4599
We determined the pattern of attachment of the avian-origin H7N9 influenza viruses A/Anhui/1/2013 and A/Shanghai/1/2013 to the respiratory tract in ferrets, macaques, mice, pigs, and guinea pigs and compared it to that in humans. The H7N9 attachment pattern in macaques, mice, and to a lesser extent pigs and guinea pigs resembled that in humans more closely than the attachment pattern in ferrets. This information contributes to our knowledge of the different animal models for influenza. 相似文献
116.
117.
Jon D. Gabbard Daniel Dlugolenski Debby Van Riel Nicolle Marshall Summer E. Galloway Elizabeth W. Howerth Patricia J. Campbell Cheryl Jones Scott Johnson Lauren Byrd-Leotis David A. Steinhauer Thijs Kuiken S. Mark Tompkins Ralph Tripp Anice C. Lowen John Steel 《Journal of virology》2014,88(3):1502-1512
The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation. 相似文献
118.
Anita C. Schürch Debby Schipper Maarten A. Bijl Jim Dau Kimberlee B. Beckmen Claudia M. E. Schapendonk V. Stalin Raj Albert D. M. E. Osterhaus Bart L. Haagmans Morten Tryland Saskia L. Smits 《PloS one》2014,9(8)
Pathogen surveillance in animals does not provide a sufficient level of vigilance because it is generally confined to surveillance of pathogens with known economic impact in domestic animals and practically nonexistent in wildlife species. As most (re-)emerging viral infections originate from animal sources, it is important to obtain insight into viral pathogens present in the wildlife reservoir from a public health perspective. When monitoring living, free-ranging wildlife for viruses, sample collection can be challenging and availability of nucleic acids isolated from samples is often limited. The development of viral metagenomics platforms allows a more comprehensive inventory of viruses present in wildlife. We report a metagenomic viral survey of the Western Arctic herd of barren ground caribou (Rangifer tarandus granti) in Alaska, USA. The presence of mammalian viruses in eye and nose swabs of 39 free-ranging caribou was investigated by random amplification combined with a metagenomic analysis approach that applied exhaustive iterative assembly of sequencing results to define taxonomic units of each metagenome. Through homology search methods we identified the presence of several mammalian viruses, including different papillomaviruses, a novel parvovirus, polyomavirus, and a virus that potentially represents a member of a novel genus in the family Coronaviridae. 相似文献
119.
Gerwin D. Rodenburg Floris Fransen Debby Bogaert Kim Schipper Rolf H. H. Groenwold Hendrik Jan Hamstra Brenda M. Westerhuis Diederik van de Beek Peter van der Ley Elisabeth A. M. Sanders Arie van der Ende 《PloS one》2012,7(11)
Background
Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.Methods
A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The lpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records.Results
Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95%CI 0.09–0.58) and were less often admitted to intensive care (OR 0.21; 95%CI 0.07–0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics.Conclusions
In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course. 相似文献120.
Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival
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Van Damme P Van Hoecke A Lambrechts D Vanacker P Bogaert E van Swieten J Carmeliet P Van Den Bosch L Robberecht W 《The Journal of cell biology》2008,181(1):37-41
Recently, mutations in the progranulin (PGRN) gene were found to cause familial and apparently sporadic frontotemporal lobe dementia (FTLD). Moreover, missense changes in PGRN were identified in patients with motor neuron degeneration, a condition that is related to FTLD. Most mutations identified in patients with FTLD until now have been null mutations. However, it remains unknown whether PGRN protein levels are reduced in the central nervous system from such patients. The effects of PGRN on neurons also remain to be established. We report that PGRN levels are reduced in the cerebrospinal fluid from FTLD patients carrying a PGRN mutation. We observe that PGRN and GRN E (one of the proteolytic fragments of PGRN) promote neuronal survival and enhance neurite outgrowth in cultured neurons. These results demonstrate that PGRN/GRN is a neurotrophic factor with activities that may be involved in the development of the nervous system and in neurodegeneration. 相似文献