Biofilm-forming capability of highly virulent, multidrug-resistant Candida auris

The emerging multidrug-resistant yeast pathogen Candida auris has attracted considerable attention as a source of healthcare–associated infections. We report that this highly virulent yeast has the capacity to form antifungal resistant biofilms sensitive to the disinfectant chlorhexidine in vitro

A comparison of the binding sites of antibodies and single-domain antibodies

Antibodies are the largest class of biotherapeutics. However, in recent years, single-domain antibodies have gained traction due to their smaller size and comparable binding affinity. Antibodies (Abs) and single-domain antibodies (sdAbs) differ in the structures of their binding sites: most significantly, single-domain antibodies lack a light chain and so have just three CDR loops. Given this inherent structural difference, it is important to understand whether Abs and sdAbs are distinguishable in how they engage a binding partner and thus, whether they are suited to different types of epitopes. In this study, we use non-redundant sequence and structural datasets to compare the paratopes, epitopes and antigen interactions of Abs and sdAbs. We demonstrate that even though sdAbs have smaller paratopes, they target epitopes of equal size to those targeted by Abs. To achieve this, the paratopes of sdAbs contribute more interactions per residue than the paratopes of Abs. Additionally, we find that conserved framework residues are of increased importance in the paratopes of sdAbs, suggesting that they include non-specific interactions to achieve comparable affinity. Furthermore, the epitopes of sdAbs are only marginally less accessible than those of Abs: we posit that this may be explained by differences in the orientation and compaction of sdAb and Ab CDR-H3 loops. Overall, our results have important implications for the engineering and humanization of sdAbs, as well as the selection of the best modality for targeting a particular epitope

Spectral Analysis of the September 2017 Solar Energetic Particle Events

An interval of exceptional solar activity was registered in early September 2017, late in the decay phase of solar cycle 24, involving the complex Active Region 12673 as it rotated across the western hemisphere with respect to Earth. A large number of eruptions occurred between 4 and 10 September, including four associated with Xclass flares. The X9.3 flare on 6 September and the X8.2 flare on 10 September are currently the two largest during cycle 24. Both were accompanied by fast coronal mass ejections and gave rise to solar energetic particle (SEP) events measured by nearEarth spacecraft. In particular, the partially occulted solar event on 10 September triggered a groundlevel enhancement (GLE), the second GLE of cycle 24. A further, much less energetic SEP event was recorded on 4 September. In this work we analyze observations by the Advanced Composition Explorer (ACE) and the Geostationary Operational Environmental Satellites (GOES), estimating the SEP eventintegrated spectra above 300 keV and carrying out a detailed study of the spectral shape temporal evolution. Derived spectra are characterized by a lowenergy break at few/tens of MeV; the 10 September event spectrum, extending up to 1 GeV, exhibits an additional rollover at several hundred MeV. We discuss the spectral interpretation in the scenario of shock acceleration and in terms of other important external influences related to interplanetary transport and magnetic connectivity, taking advantage of multipoint observations from the Solar Terrestrial Relations Observatory. Spectral results are also compared with those obtained for the 17 May 2012 GLE event

HvALMT1 from barley is involved in the transport of organic anions

Members of the ALMT gene family contribute to the Al3+ resistance of several plant species by facilitating malate efflux from root cells. The first member of this family to be cloned and characterized, TaALMT1, is responsible for most of the natural variation of Al3+ resistance in wheat. The current study describes the isolation and characterization of HvALMT1, the barley gene with the greatest sequence similarity to TaALMT1. HvALMT1 is located on chromosome 2H which has not been associated with Al3+ resistance in barley. The relatively low levels of HvALMT1 expression detected in root and shoot tissues were independent of external aluminium or phosphorus supply. Transgenic barley plants transformed with the HvALMT1 promoter fused to the green fluorescent protein (GFP) indicated that expression of HvALMT1 was relatively high in stomatal guard cells and in root tissues containing expanding cells. GFP fused to the C-terminus of the full HvALMT1 protein localized to the plasma membrane and motile vesicles within the cytoplasm. HvALMT1 conferred both inward and outward currents when expressed in Xenopus laevis oocytes that were bathed in a range of anions including malate. Both malate uptake and efflux were confirmed in oocyte assays using [14C]malate as a radiotracer. It is suggested that HvALMT1 functions as an anion channel to facilitate organic anion transport in stomatal function and expanding cells

Salt restriction lowers blood pressure at rest and during exercise without altering peripheral hemodynamics in hypertensive individuals

Dietary salt restriction is a well-established approach to lower blood pressure and reduce cardiovascular disease risk in hypertensive individuals. However, little is currently known regarding the effects of salt restriction on central and peripheral hemodynamic responses to exercise in those with hypertension. Therefore, this study sought to determine the impact of salt restriction on the central and peripheral hemodynamic responses to static-intermittent handgrip (HG) and dynamic single-leg knee extension (KE) exercise in individuals with hypertension. Twenty-two subjects (14 men and 8 women, 51 ± 10 yr, 173 ± 11 cm, 99 ± 23 kg) forewent their antihypertensive medication use for at least 2 wk before embarking on a 5-day liberal salt (LS: 200 mmol/day) diet followed by a 5-day restricted salt (RS: 10 mmol/day) diet. Subjects were studied at rest and during static intermittent HG exercise at 15, 30, and 45% of maximal voluntary contraction and KE exercise at 40, 60, and 80% of maximum KE work rate. Salt restriction lowered resting systolic blood pressure (supine: −12 ± 12 mmHg, seated: −17 ± 12 mmHg) and diastolic blood pressure (supine: −3 ± 9 mmHg, seated: −5 ± 7 mmHg, P \u3c 0.05). Despite an ~8 mmHg lower mean arterial blood pressure during both HG and KE exercise following salt restriction, neither central nor peripheral hemodynamics were altered. Therefore, salt restriction can lower blood pressure during exercise in subjects with hypertension, reducing the risk of cardiovascular events, without impacting central and peripheral hemodynamics during either arm or leg exercise

FiberGLAST: a scintillating fiber approach to the GLAST mission

FiberGLAST is a scintillating fiber gamma-ray detector designed for the GLAST mission. The system described below provides superior effective area and field of view for modest cost and risk. An overview of the FiberGLAST instrument is presented, as well as a more detailed description of the principle elements of the primary detector volume. The triggering and readout electronics are described, and Monte Carlo Simulations of the instrument performance are presented

Automatic memory processes in normal ageing and Alzheimer’s disease

This study examined the contribution of automatic and controlled uses of memory to stem completion in young, middle-aged and older adults, and compared these data with a study involving patients with Alzheimer’s disease (AD) who performed the same task (Hudson and Robertson, 2007). In an inclusion task participants aimed to complete three-letter word stems with a previously studied word, in an exclusion task the aim was to avoid using studied words to complete stems. Performances under inclusion and exclusion conditions were contrasted to obtain estimates of controlled and automatic memory processes using process-dissociation calculations (Jacoby, 1991). An age-related decline, evident from middle age was observed for the estimate of controlled processing, whereas the estimate of automatic processing remained invariant across the age groups. This pattern stands in contrast to what is observed in AD, where both controlled and automatic processes have been shown to be impaired. Therefore, the impairment in memory processing on stem completion that is found in AD is qualitatively different from that observed in normal ageing

Association of treatment satisfaction and psychopathological sub-syndromes among involuntary patients with psychotic disorders

Publisher's version: http://www.springerlink.com/content/rx24036274667t10