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Mesenchymal stem cells and biomaterials systems - perspectives for skeletal muscle tissue repair and regeneration
No full textSkeletal muscle is essential in voluntary movement and other major vital functions. Muscle injuries are important in clinical practice and, despite skeletal muscle’s good regenerative ability, severe tissue loss impairs complete myofibre regeneration, limiting structural and functional recovery of the affected muscle, eventually leading to the development of non-contractile fibrous scar. The intrinsic healing mechanisms rely in great extent on the residing progenitor population but significant drawbacks to their practical application in regenerative strategies boosted the search for alternative cell sources, such as extra-fetal mesenchymal stem cells (MSCs). MSCs have demonstrated to positively influence the regeneration of different disease models. When severe volumetric muscle tissue loss occurs, the body is seldom capable of replacing the lost portions with fully functional tissue. A rational strategy to aid the healing of such situations is the application of biomaterial implants that provide a structural matrix for the ingrowth of regenerating muscle fibres. Both synthetic and natural biomaterials have been hypothesized for this purpose and some have reached as far clinical cases applications. Obvious improvements are observed in most cases, but reaction to some biomaterials and functional recovery are still a challenge. The addition of MSCs to the biomaterials seems to improve the systems’ performance in the overall regenerative milieu. This strategies promote scaffold’s vascularization and integration, as well as accelerated tissue ingrowth and reduces scar formation, resulting in improved recovery rates at both structural and functional levels
From Doktor Kurowski's Schneegrenze to our modern equilibrium line altitude (ELA)
No full textTranslated into modern terminology, Kurowski suggested in 1891 that the equilibrium line altitude (ELA) of a glacier is equal to the mean altitude of the glacier when the whole glacier is in balance between accumulation and ablation.Kurowski’s method has been widely misunderstood, partly due to inappropriate use of statistical terminology by later workers, and has only been tested by Braithwaite and Müller in a 1980 paper (for 32 glaciers). I now compareKurowski’s mean altitude with balanced-budget ELA calculated for 103 present-day glaciers with measured surface mass-balance data. Kurowski’s mean altitude is significantlyhigher (at 95% level) than balanced-budget ELA for 19 outlet and 42 valley glaciers, but not significantly higher for 34 mountain glaciers. The error in Kurowski mean altitude as a predictor of balanced-budget ELA might be due to generally lower balance gradients in accumulation areas compared with ablation areas for many glaciers, as suggested by several workers, but some glaciers have higher gradients, presumably due to precipitation increase with altitude. The relatively close agreement between balanced-budget ELA and mean altitude for mountain glaciers (mean error – 8m with standard deviation 59 m) may reflect smaller altitude ranges for these glaciers such that there is less room for effects of different balance gradients to manifest themselves
ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider
No full textCoupling of vesicle tethering and Rab binding is required for in vivo functionality of the golgin GMAP-210.
No full textGolgins are extended coiled-coil proteins believed to participate in membrane-tethering events at the Golgi apparatus. However, the importance of golgin-mediated tethering remains poorly defined, and alternative functions for golgins have been proposed. Moreover, although golgins bind to Rab GTPases, the functional significance of Rab binding has yet to be determined. In this study, we show that depletion of the golgin GMAP-210 causes a loss of Golgi cisternae and accumulation of numerous vesicles. GMAP-210 function in vivo is dependent upon its ability to tether membranes, which is mediated exclusively by the amino-terminal ALPS motif. Binding to Rab2 is also important for GMAP-210 function, although it is dispensable for tethering per se. GMAP-210 length is also functionally important in vivo. Together our results indicate a key role for GMAP-210-mediated membrane tethering in maintaining Golgi structure and support a role for Rab2 binding in linking tethering with downstream docking and fusion events at the Golgi apparatus
Cloud chamber laboratory investigations into scattering properties of hollow ice particles
No full textMeasurements are presented of the phase function, P11, and asymmetry parameter, g, of five ice clouds created in a laboratory cloud chamber. At -7 C, two clouds were created: one comprised entirely of solid columns, and one comprised entirely of hollow columns. Similarly at -15 C, two clouds were created: one consisting of solid plates and one consisting of hollow plates. At -30 C, only hollow particles could be created within the constraints of the experiment. The resulting cloud at -30 C contained short hollow columns and thick hollow plates. During the course of each experiment, the cloud properties were monitored using a Cloud Particle Imager (CPI). In addition to this, ice crystal replicas were created using formvar resin. By examining the replicas under an optical microscope, two different internal structures were identified. The internal and external facets were measured and used to create geometric particle models with realistic internal structures. Theoretical results were calculated using both Ray Tracing (RT) and Ray Tracing with Diffraction on Facets (RTDF). Experimental and theoretical results are compared to assess the impact of internal structure on P11 and g and the applicability of RT and RTDF for hollow columns
Automated Quantification of Neuropad Improves Its Diagnostic Ability in Patients with Diabetic Neuropathy
No full textNeuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics)) outputs to diagnose diabetic peripheral neuropathy (DPN). 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS), peroneal motor nerve conduction velocity (PMNCV), sural nerve action potential (SNAP), Deep Breathing-Heart Rate Variability (DB-HRV), intraepidermal nerve fibre density (IENFD), and corneal confocal microscopy (CCM). 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%), CNFD (88%, 78%), and SNAP (88%, 83%), whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV) and 80% for small fibre neuropathy (CNFD). The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%, P = 0.0003) and CNFD (AUC: 82%, P = 0.01) was better than for PMNCV (AUC: 60%). The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics) improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.</p
GDGT distributions in the East Siberian Sea: implications for organic carbon export, burial and degradation
No full textSiberian permafrost contains a globally-significant pool of organic carbon (OC) that is vulnerable to enhanced warming and subsequent release into the contemporary carbon cycle. OC release by both fluvial and coastal erosion has been reported in the region, but the behaviour of this material in the Arctic Ocean is insufficiently understood. The balance between OC deposition and degradation on the East Siberian Arctic Shelf (ESAS) influences the climate-carbon cycle feedback in this area. In this study we couple measurements of glycerol dialkyl glycerol tetraethers (GDGTs) with bulk geochemical observations to improve knowledge of the sources of OC to the ESAS, the behaviour of specific biomarkers on the shelf and the balance between delivery and removal of different carbon pools. Branched GDGT (brGDGT) concentrations were highest close to river mouths, yet low in "Yedoma" permafrost deposits, supporting recent observations that brGDGTs are mostly delivered by fluvial erosion, and may be a tracer for this in complex sedimentary environments. BrGDGT concentrations and the Branched and Isoprenoidal Tetraether (BIT) index reduced quickly offshore, demonstrating a rapid reduction in river influence. Stable carbon isotope ratios changed at a different rate to the BIT index, suggesting that OC on the shelf is not only sourced from fluvial erosion, but that erosion of coastal sediments delivers substantial quantities of OC to the Arctic Ocean. A model of OC export from fluvial, coastal and marine sources is able to recreate the biomarker and bulk observations and provide estimates for the influence of fluvial and coastal OC across the whole shelf. The model shows that coastal erosion delivers 43% of the OC and 87% of the mineral sediment to the ESAS, but that rivers deliver 72% of brGDGTs, indicating that brGDGTs can be used as a proxy for river-derived sediment
People with dementia and carers’ experiences of dementia care and services: Outcomes of a focus group study.
No full textAn ageing population and an associated increase in the prevalence of dementia are of increasing concern in the United Kingdom and worldwide. Recently, the United Kingdom and other European countries implemented national dementia strategies to address this. This paper reports on the outcomes of a focus group study involving people with dementia and carers on their experiences of dementia care and support services in relation to government and third sector agencies’ objectives and recommendations. Three focus groups comprising carers and people with dementia (n = 27) were undertaken covering topics related to experiences, service receipt, information sharing and service development. Some participants experienced difficulties or delays in receiving a dementia diagnosis and in accessing appropriate care. The provision of training, timeliness of information, access to appropriate advice, and consistent and flexible services were deemed important. The findings suggest that some issues raised by participants were highlighted in earlier policy objectives and recommendations but remain of central concern. The projected growth in the number of people with dementia coupled with reduced availability of informal care and increased demand for services emphasises the need to transform dementia care in the United Kingdom