Abstract Noncoding RNAs (ncRNAs), such as miRNAs and long noncoding RNAs, are key regulators of gene expression at the post-transcriptional level and represent promising therapeutic targets and biomarkers for several human diseases, including Duchenne and Becker muscular dystrophies (DMD/BMD). A role for ncRNAs in the pathogenesis of muscular dystrophies has been suggested, even if it is still incompletely understood. Here, we discuss current progress leading towards the clinical...
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Higher cardiorespiratory fitness is associated with lower pulse wave velocity and arterial stiffness in normal weight individuals, and this has not been examined in obese individuals. It is unclear whether an altered body composition acts as a modifier of the association between cardiorespiratory fitness and arterial stiffness. We examined the association between peak oxygen uptake and brachial-ankle pulse wave velocity and analysed whether body composition attenuates this association in obese middle-aged...
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To identify the availability and unmet need of home adaptations (HAs) among the Swiss population with spinal cord injury (SCI).; Cross-sectional study.; Swiss Spinal Cord Injury Community Survey 2012.; Individuals aged 16 or older with chronic SCI living in Switzerland.; Not applicable.; The availability of ten HAs (self-report) was analyzed by sex, age, living situation, indoor mobility, SCI severity, SCI etiology and time since SCI. The unmet need (self-report of not having a HA but needing it)...
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Cardiopulmonary exercise testing is clinically used to estimate cardiorespiratory fitness (CRF). The relation to total body mass (TBM) leads to an underestimation of CRF in people with obesity and to inappropriate prognostic and therapeutic decisions. This study aimed to determine body composition-derived bias in the estimation of CRF in people with obesity.; Two hundred eleven participants (58.8% women; mean BMI 35.7 kg/m; 2; [± 6.94; 20.7-58.6]) were clinically examined, and body composition (InBody720;...
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To determine the prevalence of shoulder pain and to identify factors associated with shoulder pain in a nationwide survey of individuals living with spinal cord injury (SCI) in Switzerland.; Data was collected through the 2012 community survey of the Swiss SCI Cohort Study (SwiSCI) (N = 1549; age 52.3 ± 14.8; 29% female). Sociodemographic and socioeconomic circumstances, SCI characteristics, health conditions as well as mobility independence and sporting activities were evaluated as predictor variables....
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Organic anion transporting polypeptides (OATPs) and particularly the two members of the OATP1B family are known for their role in pharmacokinetics. Both SLCO1B3 and SLCO1B1 are located on chromosome 12 encompassing the gene locus SLCO1B7. Hitherto, this particular gene has been assumed to be a pseudogene, even though there are published mRNA sequences linked to this chromosomal area. It was aim of this study to further investigate SLCO1B7 and the associated mRNA LST-3TM12. In a first step, we aligned...
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Continuous video-EEG is recommended for patients with altered consciousness; as compared to routine EEG (lasting <30 minutes), it improves seizure detection, but is time- and resource-consuming. Although North American centers increasingly implement continuous video-EEG, most other (including European) hospitals have insufficient resources. Only one study suggested that continuous video-EEG could improve outcome in adults, and recent assessments challenge this view. This article reviews current...
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Here we present a new approach to diffraction imaging of amyloid fibrils, combining a free-standing graphene support and single nanofocused X-ray pulses of femtosecond duration from an X-ray free-electron laser. Due to the very low background scattering from the graphene support and mutual alignment of filaments, diffraction from tobacco mosaic virus (TMV) filaments and amyloid protofibrils is obtained to 2.7 Å and 2.4 Å resolution in single diffraction patterns, respectively. Some TMV diffraction...
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The conjugation of siderophores to antimicrobial molecules is an attractive strategy to overcome the low outer membrane permeability of Gram-negative bacteria. In this Trojan horse approach, the transport of drug conjugates is redirected via TonB-dependent receptors (TBDR), which are involved in the uptake of essential nutrients, including iron. Previous reports have demonstrated the involvement of the TBDRs PiuA and PirA from; Pseudomonas aeruginosa; and their orthologues in; Acinetobacter baumannii;...
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Macrophages release iron into the bloodstream via a membrane-bound iron export protein, ferroportin (FPN). The hepatic iron-regulatory hormone hepcidin controls FPN internalization and degradation in response to bacterial infection. Salmonella typhimurium can invade macrophages and proliferate in the Salmonella-containing vacuole (SCV). Hepcidin is reported to increase the mortality of Salmonella-infected animals by increasing the bacterial load in macrophages. Here we assess the iron levels and...
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Up to 25% of ovulating women suffer from primary dysmenorrhea, a condition associated with pain and transient reduced quality of life, along with greater irritability and impaired sleep. In the present study, we asked whether and if so to what extent melatonin and meloxicam can improve subjective and objective sleep and reduce pain among women with primary dysmenorrhea. To this end we conducted a double-blind cross-over clinical trial lasting for three menstrual cycles. Method: A total of 14 women...
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The phosphatidylinositol 3-kinase related protein kinases (PIKKs) are key to the regulation of a variety of eukaryotic cellular processes including DNA repair and growth regulation. While these massive proteins had long resisted structural analysis, recent advances in electron cryo-microscopy have now facilitated structural analysis of the major examples of PIKKs, including mTOR, DNA-PK, ATM, ATR and TRAPP/Tra1. In these PIKKs, the carboxy-terminal kinase domains and their proximal regions are structurally...
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3' Untranslated regions (3' UTRs) length is regulated in relation to cellular state. To uncover key regulators of poly(A) site use in specific conditions, we have developed PAQR, a method for quantifying poly(A) site use from RNA sequencing data and KAPAC, an approach that infers activities of oligomeric sequence motifs on poly(A) site choice. Application of PAQR and KAPAC to RNA sequencing data from normal and tumor tissue samples uncovers motifs that can explain changes in cleavage and polyadenylation...
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Football (soccer) is very popular among children. Little is known about risk factors for football injuries in children. The aim was to analyze potential injury risk factors in 7- to 12-year-old players. We collected prospective data in Switzerland and the Czech Republic over two seasons. Coaches reported exposure of players (in hours), absence, and injury data via an Internet-based registration system. We analyzed time-to-injury data with extended Cox models accounting for correlations on team- and...
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The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance...
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Pyrin, encoded by the MEFV gene, is an intracellular pattern recognition receptor that assembles inflammasome complexes in response to pathogen infections. Mutations in the MEFV gene have been linked to autoinflammatory diseases such as familial Mediterranean fever (FMF) or pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Recent insights have now revealed how pyrin is activated during infection, providing a molecular basis for the understanding of such disease-causing mutations...
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Genetic innovation may be linked to evolutionary success, and indeed, the invasive round goby mitochondrial genome sequence carries two novel features not previously described in Benthophilinae. First, the round goby mitochondrial genome carries a rearrangement of the tRNA cluster Ile-Glu-Met. Second, the round goby mitochondrial genome features a 1250 bp non-coding sequence insertion downstream of the D-loop region. In this publication, we test where in the goby phylogeny the novel tRNA arrangement...
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The question as to how early life experiences are stored on a molecular level and affect traits later in life is highly topical in ecology, medicine, and epigenetics. In this study, we use a fish model to investigate whether DNA methylation mediates early life experiences and predetermines a territorial male reproductive phenotype. In fish, adult reproductive phenotypes frequently depend on previous life experiences and are often associated with distinct morphological traits. DNA methylation is an...
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Multi-proxy sediment records from Castor Lake and Scanlon Lake, north-central Washington, provide a late Quaternary perspective on lake/catchment hydrologic and ecosystem responses to climate change and the Mazama volcanic ashfall event. Analyses of authigenic carbonate mineral oxygen and carbon isotope values, organic carbon and nitrogen content, and sedimentological facies were conducted on sediment from Castor Lake in order to reconstruct lake/catchment hydrologic balance, the source and abundance...
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Dynamic combinatorial chemistry (DCC) has repeatedly proven to be an effective approach to generate directed ligand libraries for macromolecular targets. In the absence of an external stimulus, a dynamic library forms from reversibly reacting building blocks and reaches a stable thermodynamic equilibrium. However, upon addition of a macromolecular host which can bind and stabilize certain components of the library, the equilibrium composition changes and induces an evolution-like selection and enrichment...
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Background:; Physical activity (PA) is paramount for human health and well-being. However, there is a lack of information regarding the types of PA and the way they can exert an influence on functional and mental health as well as quality of life. Studies have measured and classified PA type in controlled conditions, but only provided limited insight into the validity of classifiers under real-life conditions. The advantage of utilizing the type dimension and the significance of real-life study designs...
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Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell...
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Cyclic nucleotide phosphodiesterases (PDEs) work in conjunction with adenylate/guanylate cyclases to regulate the key second messengers of G protein-coupled receptor signaling. Previous attempts to determine the full-length structure of PDE family members at high-resolution have been hindered by structural flexibility, especially in their linker regions and N- and C-terminal ends. Therefore, most structure-activity relationship studies have so far focused on truncated and conserved catalytic domains...
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Confocal microscopy is used today on a daily basis in life science labs. This "routine" technique contributes to the progress of scientific projects across many fields by revealing structural details and molecular localization, but researchers need to be aware that detection efficiency and emission light path performance is of major influence in the confocal image quality. By design, a large portion of the signal is discarded in confocal imaging, leading to a decreased signal-to-noise ratio (SNR)...
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PglK is a lipid-linked oligosaccharide (LLO) flippase essential for asparagine-linked protein glycosylation in Campylobacter jejuni. Previously we have proposed a non-alternating-access LLO translocation mechanism, where postulated outward-facing states play a primary role. To investigate this unusual mechanistic proposal, we have determined a high-resolution structure of PglK that displays an outward semi-occluded state with the two nucleotide binding domains forming an asymmetric closed dimer with...
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The interactions of nanomedicines with biological environments is heavily influenced by their physicochemical properties. Formulation design and optimization are therefore key steps towards successful nanomedicine development. Unfortunately, detailed assessment of nanomedicine formulations, at a macromolecular level, in rodents is severely limited by the restricted imaging possibilities within these animals. Moreover, rodent in vivo studies are time consuming and expensive, limiting the number of...
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This is the obituary for Francisc Schneider, who introduced clinical physiology in Romania and mentored generations of scientists.
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Indoor air pollution can be a major health risk because urban populations spend up to 90% of their time in closed rooms. Gaseous elemental mercury (GEM) has not been measured as routinely as other indoor air pollutants due to the high costs and limited mobility of active Hg analyzers. However, household GEM concentrations may exceed Hg air quality guidelines as a result of potential indoor GEM sources like broken Hg thermometers. Here we deploy novel low-cost mercury passive air samplers (MerPAS)...
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A novel real-time and non-destructive method for differentiating soft from hard tissue in laser osteotomy has been introduced and tested in a closed-loop fashion. Two laser beams were combined: a low energy frequency-doubled nanosecond Nd:YAG for detecting the type of tissue, and a high energy microsecond Er:YAG for ablating bone. The working principle is based on adjusting the energy of the Nd:YAG laser until it is low enough to create a microplasma in the hard tissue only (different energies are...
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The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients'...
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