The secret of success

Parts of Antarctica have experienced warming almost an order of magnitude greater than the global average over the past 50 years, with the Antarctic Peninsula ranking among the three fastest-warming regions on Earth. Antarctic ecosystems have been affected by the warming that has taken place. Perhaps the most notable impact has been a dramatic expansion of the two species of flowering plant that occur on the continent \u2014 Antarctic pearlwort and Antarctic hair gras

FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni

Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca2+ influx through sarcolemmal voltage operated Ca2+ channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca2+ influx through VOCC currents using a PKC-dependent pathway

Improving Vitamin D Intake in Young Children—Can an Infographic Help Parents and Carers Understand the Recommendations?

Vitamin D deficiency is a serious public health issue in the United Kingdom. Those at increased risk, such as pregnant women, children under 5 years and people from ethnic groups with dark skin, are not all achieving their recommended vitamin D. Effective vitamin D education is warranted. A qualitative study was undertaken to evaluate the acceptability and understanding of a vitamin D infographic, developed using recommendations from previous research. Fifteen parents/carers, recruited through local playgroups and adverts on popular parent websites, participated in focus groups and telephone interviews. The majority were female, White British and educated to degree level. A thematic analysis methodology was applied. The findings indicated that understanding and acceptability of the infographic were satisfactory, but improvements were recommended to aid interpretation and create more accessible information. These included additional content (what vitamin D is; other sources; its health benefits; methods/doses for administration and scientific symbols used) and improved presentation (eye-catching, less text, simpler language, more images and a logo). Once finalized, the infographic could be a useful tool to educate families around vitamin D supplementation guidelines, support the UK Healthy Start vitamins scheme and help improve vitamin D status for pregnant and lactating women and young children

Computational modelling of solvent effects in a prolific solvatomorphic porous organic cage

Crystal structure prediction methods can enable the in silico design of functional molecular crystals, but solvent effects can have a major influence on relative lattice energies sometimes thwarting predictions. This is particularly true for porous solids, where solvent included in the pores can have an important energetic contribution. Here we present a Monte Carlo solvent insertion procedure for predicting the solvent filling of porous structures from crystal structure prediction landscapes, tested using a highly solvatomorphic porous organic cage molecule, CC1. We use this method to rationalise the fact that the predicted global energy minimum structure for CC1 is never observed from solvent crystallisation. We also explain the formation of three different solvatomorphs of CC1 from three structurally-similar chlorinated solvents. Calculated solvent stabilisation energies are found to correlate with experimental results from thermogravimetric analysis, suggesting a future computational framework for a priori materials design that includes solvation effects

Glucanase Inhibitor Protein (GIP)

Several key cellular events, such as adhesion to the host surface, penetration, and colonization of host tissue, take place during plant infection by oomycetes that can also manipulate biochemical and physiological processes in their host plants through a diverse array of virulence or avirulence molecules, known as effectors (Birch et al. 2006; Ellis et al. 2006; Kamoun 2007; Schornack et al. 2009). In susceptible plants, these effectors promote infection by suppressing defense responses, enhancing susceptibility, or inducing disease symptoms. In resistant plants, the products of the resistance genes are able to recognize the effectors, promoting an efective defense response known as hypersensitive response (HR) which restricts the pathogen to an area of scorched earth besides host cell death (Kamoun 2003; Kamoun 2007; Schornack et al. 2009). Phytophthora effectors that suppress host defense responses have be ...info:eu-repo/semantics/publishedVersio

Organizational Stress in High-Level Field Hockey: Examining Transactional Pathways Between Stressors, Appraisals, Coping, and Performance Satisfaction

This study investigated transactional pathways between organizational stressors and their 28 underpinning situational properties, appraisals, coping, perceived coping effectiveness (PCE) 29 and performance satisfaction in athletes. Ten high-level field hockey players were 30 interviewed. Data relating to stressors, situational properties, appraisals and coping were 31 analysed using directed content analysis. Mean PCE scores were calculated and subjective 32 performance satisfaction data were categorised as satisfied, neutral, or dissatisfied. A variety 33 of organizational stressors was reported, which were underpinned by five situational 34 properties. Challenge, threat and harm/loss appraisals were experienced and problem solving 35 was the most commonly reported family of coping. High PCE was not always associated with 36 performance satisfaction. Performance satisfaction was, however, linked to the appraisal 37 experienced. A battery of stress management techniques and ways of coping is useful for 38 optimising appraisals and alleviating negative outcomes of stress

Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences

YesThere are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification