A pilot randomised control trial of the efficacy of stability-based training with visualisation for people with chronic ankle instability

Background: Chronic ankle instability (CAI) is associated with recurring symptoms that inhibit daily activity. Stability-based rehabilitative training is recommended for CAI. Visualisation (VIS) produces real-time feedback using motion capture and virtual reality. This pilot study aimed to determine the feasibility, adherence, safety, and efficacy of incorporating VIS into stability training for people with CAI. Efficacy was examined through effect of VIS training on dynamic stability, perception of stability, and rehabilitative experience. Methods: Individuals with CAI completed a 4-week stability-based training programme with VIS, or without visualisation (NO-VIS). Participants completed the Star Excursion Balance Test (SEBT) and Cumberland Ankle Instability Tool (CAIT) prior to, and after training. Enjoyment of training was recorded using the Physical Activity Enjoyment Scale (PACES-8). Results: Of 17 participants (VIS=10,NO-VIS=7), there were 2 drop outs (VIS=1,NO-VIS=1). No adverse events were reported and participant drop-out was due to injury unrelated to the study. The VIS group showed a significantly greater increase in average SEBT reach distance (d=1.7,p=0.02). No significant differences were reported for the CAIT or PACES-8. Conclusion: This study supports the feasibility and safety of stability-based training with VIS in those with CAI. The enhanced performance outcome on the SEBT suggests VIS may enhance stability-based training

Myiasis in domestic cats: A global review

Myiasis is an infestation caused by larvae of Diptera in humans and other vertebrates. In domestic cats, Felis silvestris catus L. (Carnivora: Felidae), four dipteran families have been reported as agents of obligatory and facultative myiasis: Oestridae, Calliphoridae, Sarcophagidae and Muscidae. Among agents of obligatory myiasis, the most frequent genus is Cuterebra Clark (Oestridae) and the most frequent species is Cochliomyia hominivorax (Coquerel) (Calliphoridae). Among the agents of facultative myiasis, the most frequent species is Lucilia sericata (Meigen) (Calliphoridae). A survey of myiasis in cats reported in literature shows that the cases are distributed worldwide and linked to the geographical range of the dipteran species. Factors favouring the occurrence of myiasis in cats are prowling in infested areas, poor hygiene conditions due to diseases and/or neglect, and wounds inflicted during territorial or reproductive competition. The aim of the review is to provide an extended survey of literature on myiasis in cats, as general information and possible development of guidelines for veterinarians, entomologists and other researchers interested in the field

Gap Opening in Double-Sided Highly Hydrogenated Free-Standing Graphene

Conversion of free-standing graphene into pure graphane-where each C atom is sp3bound to a hydrogen atom-has not been achieved so far, in spite of numerous experimental attempts. Here, we obtain an unprecedented level of hydrogenation (≈90% of sp3bonds) by exposing fully free-standing nanoporous samples-constituted by a single to a few veils of smoothly rippled graphene-to atomic hydrogen in ultrahigh vacuum. Such a controlled hydrogenation of high-quality and high-specific-area samples converts the original conductive graphene into a wide gap semiconductor, with the valence band maximum (VBM) ∼3.5 eV below the Fermi level, as monitored by photoemission spectromicroscopy and confirmed by theoretical predictions. In fact, the calculated band structure unequivocally identifies the achievement of a stable, double-sided fully hydrogenated configuration, with gap opening and no trace of πstates, in excellent agreement with the experimental results

Self-oligomerization Regulates Stability of Survival Motor Neuron Protein Isoforms by Sequestering an SCF\u3csup\u3eSlmb\u3c/sup\u3e Degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substrates in silico. This analysis identified many known substrates and suggested numerous candidates. Unexpectedly, chromatin regulatory proteins are enriched among putative substrates, and we show experimentally that several chromatin proteins bind APC/C, oscillate during the cell cycle, and are degraded following APC/C activation, consistent with being direct APC/C substrates. Additional analysis revealed detailed mechanisms of ubiquitylation for UHRF1, a key chromatin regulator involved in histone ubiquitylation and DNA methylation maintenance. Disrupting UHRF1 degradation at mitotic exit accelerates G1-phase cell cycle progression and perturbs global DNA methylation patterning in the genome. We conclude that APC/C coordinates crosstalk between cell cycle and chromatin regulatory proteins. This has potential consequences in normal cell physiology, where the chromatin environment changes depending on proliferative state, as well as in disease. Copyright

Geological and Hydrogeological Characterization of Springs in a DSGSD Context (Rodoretto Valley – NW Italian Alps)

As continuous groundwater monitoring in the upper sector of Rodoretto Valley (Germanasca Valley, Italian Western Alps) is hampered by logistical problem of data collection during winter and spring months, the only tools currently available to derive hydrogeological information are non-continuous and non-long-term dataset of spring discharge (Q), temperature (T) and electrical conductivity (EC). In order to quantity aquifer groundwater reserve, available Q dataset of a small mountain spring (Spring 1 CB) was investigated by applying the analytical solutions developed by Boussinesq (J Math Pure Appl 10:5–78, 1904) and Maillet (Essais dı’hydraulique souterraine et fluviale, vol 1. Herman et Cie, Paris, 1905); T and EC datasets were also used to provide qualitative information about the nature of the aquifer that supplies the spring. The outcomes of the elaborations highlighted the limits of applicability of these methods in the presence of a non-continuous Q dataset: both Boussinesq (J Math Pure Appl 10:5–78, 1904) and Maillet (Essais dı’hydraulique souterraine et fluviale, vol 1. Herman et Cie, Paris, 1905) estimated that discharge values as a function of recession time were found to be consistently lower than the available discharge ones and the estimated groundwater volumes stored over time above the spring level turned out to be underestimated. Continuous (hourly value) and long-term Q, EC and T values are, therefore, needful to correctly quantify and to make a proper management of groundwater resources in mountain areas

Changing climate both increases and decreases European river floods

Climate change has led to concerns about increasing river floods resulting from the greater water-holding capacity of a warmer atmosphere1. These concerns are reinforced by evidence of increasing economic losses associated with flooding in many parts of the world, including Europe2. Any changes in river floods would have lasting implications for the design of flood protection measures and flood risk zoning. However, existing studies have been unable to identify a consistent continental-scale climatic-change signal in flood discharge observations in Europe3, because of the limited spatial coverage and number of hydrometric stations. Here we demonstrate clear regional patterns of both increases and decreases in observed river flood discharges in the past five decades in Europe, which are manifestations of a changing climate. Our results\u2014arising from the most complete database of European flooding so far\u2014suggest that: increasing autumn and winter rainfall has resulted in increasing floods in northwestern Europe; decreasing precipitation and increasing evaporation have led to decreasing floods in medium and large catchments in southern Europe; and decreasing snow cover and snowmelt, resulting from warmer temperatures, have led to decreasing floods in eastern Europe. Regional flood discharge trends in Europe range from an increase of about 11 per cent per decade to a decrease of 23 per cent. Notwithstanding the spatial and temporal heterogeneity of the observational record, the flood changes identified here are broadly consistent with climate model projections for the next century4,5, suggesting that climate-driven changes are already happening and supporting calls for the consideration of climate change in flood risk management

Olives and olive oil are sources of electrophilic fatty acid nitroalkenes

Extra virgin olive oil (EVOO) and olives, key sources of unsaturated fatty acids in the Mediterranean diet, provide health benefits to humans. Nitric oxide (•NO) and nitrite (NO2-)-dependent reactions of unsaturated fatty acids yield electrophilic nitroalkene derivatives (NO 2-FA) that manifest salutary pleiotropic cell signaling responses in mammals. Herein, the endogenous presence of NO2-FA in both EVOO and fresh olives was demonstrated by mass spectrometry. The electrophilic nature of these species was affirmed by the detection of significant levels of protein cysteine adducts of nitro-oleic acid (NO2-OA-cysteine) in fresh olives, especially in the peel. Further nitration of EVOO by NO2- under acidic gastric digestive conditions revealed that human consumption of olive lipids will produce additional nitro-conjugated linoleic acid (NO2-cLA) and nitro-oleic acid (NO2-OA). The presence of free and protein-adducted NO2-FA in both mammalian and plant lipids further affirm a role for these species as signaling mediators. Since NO2-FA instigate adaptive anti-inflammatory gene expression and metabolic responses, these redox-derived metabolites may contribute to the cardiovascular benefits associated with the Mediterranean diet. © 2014 Fazzari et al

Nanofluidic transport governed by the liquid/vapour interface

Liquid/vapour interfaces govern the behaviour of a wide range of systems but remain poorly understood, leaving ample margin for the exploitation of intriguing functionalities for applications. Here, we systematically investigate the role of liquid/vapour interfaces in the transport of water across apposing liquid menisci in osmosis membranes comprising short hydrophobic nanopores that separate two fluid reservoirs. We show experimentally that mass transport is limited by molecular reflection from the liquid/vapour interface below a certain length scale, which depends on the transmission probability of water molecules across the nanopores and on the condensation probability of a water molecule incident on the liquid surface. This fundamental yet elusive condensation property of water is measured under near-equilibrium conditions and found to decrease from 0.36 ± 0.21 at 30 °C to 0.18 ± 0.09 at 60 °C. These findings define the regime in which liquid/vapour interfaces govern nanofluidic transport and have implications for understanding mass transport in nanofluidic devices, droplets and bubbles, biological components and porous media involving liquid/vapour interfaces.Center for Clean Water and Clean Energy at MIT and KFUPM (Project R10-CW-09

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions