Eph-Dependent Tyrosine Phosphorylation of Ephexin1 Modulates Growth Cone Collapse

SummaryEphs regulate growth cone repulsion, a process controlled by the actin cytoskeleton. The guanine nucleotide exchange factor (GEF) ephexin1 interacts with EphA4 and has been suggested to mediate the effect of EphA on the activity of Rho GTPases, key regulators of the cytoskeleton and axon guidance. Using cultured ephexin1−/− mouse neurons and RNA interference in the chick, we report that ephexin1 is required for normal axon outgrowth and ephrin-dependent axon repulsion. Ephexin1 becomes tyrosine phosphorylated in response to EphA signaling in neurons, and this phosphorylation event is required for growth cone collapse. Tyrosine phosphorylation of ephexin1 enhances ephexin1’s GEF activity toward RhoA while not altering its activity toward Rac1 or Cdc42, thus changing the balance of GTPase activities. These findings reveal that ephexin1 plays a role in axon guidance and is regulated by a switch mechanism that is specifically tailored to control Eph-mediated growth cone collapse

Effects of an Extract of the Brown Seaweed <i>Ascophylum nodosum</i> on Postprandial Glycaemic Control in Healthy Subjects: A Randomized Controlled Study

The effects of the consumption of an extract of the brown seaweed Ascophyllum nodosum (BSW) on postprandial glucose and insulin responses to white bread were investigated in an acute, randomized, double-blind, three-arm, crossover, controlled trial in healthy, normoglycemic subjects. Sixteen subjects were administered either control white bread (50 g total digestible carbohydrates) or white bread with 500 mg or 1000 mg of BSW extract. Biochemical parameters were measured in venous blood over 3 h. Significant inter-individual variation in the glycaemic response to white bread was observed. Analysis of the responses of all subjects to either 500 mg or 1000 mg of BSW extract versus control revealed no significant effects of treatments. The variation in response to the control was used to classify individuals into glycaemic responders and non-responders. In the sub-cohort of 10 subjects with peak glucose levels after white bread above 1 mmol/L, we observed a significant decrease in maximum levels of plasma glucose after the intervention meal with 1000 mg of extract compared with the control. No adverse effects were reported. Further work is warranted to define all factors that determine “responders” to the effects of brown seaweed extracts and identify the cohort that would benefit the most from their consumption

Epidemiology of dermatomycoses and onychomycoses in Ireland (2001–2020): A single-institution review

Background: Fungal skin infections are recognised as one of the most common health disorders globally, and dermatophyte infections of the skin, hair and nails are the most common fungal infections. Dermatophytes can be classified as anthropophilic, zoo-philic or geophilic species based on their primary habitat association, and this classification makes epidemiological analysis useful for the prevention and control of these infections. The Irish contribution to the epidemiology of these infections has been scant, with just two papers (both reporting paediatric tinea capitis only) published in the last 20 years, and none in the last seven. Objectives: To perform a comprehensive retrospective epidemiological analysis of all dermatological mycology tests performed in University Hospital Limerick over a 20-year period. Methods: All mycology laboratory test results were extracted from the Laboratory Information Management System (LIMS, iLab, DXC Technologies) from 2001 to 2020 inclusive for analysis. Specimen types were categorised according to the site of sampling. The data were analysed using Microsoft Excel. Results: About 12,951 specimens of skin, hair and nails were studied. Median patient age was 42 years (IQR 26–57) with a slight female preponderance (57.2%). Two thirds of samples (67%, n = 8633) were nail, 32% were skin scrapings (n = 4118) and 200 hair samples (1.5%) were received. Zoophilic dermatophytes were more commonly present in females (38% F, 23% M, proportion of dermatophytes) and in those under 10 years of age or from 45 to 70 years (36% and 34% zoophiles, respectively, proportion of dermatophytes), although anthropophiles predominated every age and gender category. Anthropophiles had their highest prevalence in the 10–20 years age category (80% anthropophiles, proportion of dermatophytes), and yeast infections were more prevalent in older patients (29% of >60 year olds vs. 17% of Conclusions: This study provides a detailed overview of the epidemiology of the fungal cultures of skin, nail and hair samples in the Mid-West of Ireland over a 20-year period. Monitoring this changing landscape is important in identifying likely sources of infections, to identifying potential outbreaks, and may help guide empiric treatment. To the best of our knowledge, this study provides the first detailed analysis from Ireland of fungal detections from skin, hair and nail samples, and is the first epidemiological fungal report of any kind in over 7 years. </p

Genomic evidence of SARS-CoV-2 reinfection in Ireland

Presentation  A 40-year-old healthcare worker (HCW) presented with cough, headache, sore throat, fatigue and myalgia seven months after primary infection with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms were milder and recovery was faster on the second episode.  Diagnosis  Reinfection with phylogenetically distinct SARS-CoV-2 was confirmed by whole-genome sequencing (WGS).  Treatment  Management involved symptomatic treatment and self-isolation.  Discussion  The incidence of SARS-CoV-2 reinfection is not well characterised. Infection control precautions may still be required in healthcare facilities, even in previously infected and possibly in vaccinated individuals while SARS-CoV-2 remains in circulation. Further research on the nature and duration of immunity is required to inform public health and infection control policy.</p

Engineered Female-Specific Lethality for Control of Pest Lepidoptera

The sterile insect technique (SIT) is a pest control strategy involving the mass release of radiation-sterilized insects, which reduce the target population through nonviable matings. In Lepidoptera, SIT could be more broadly applicable if the deleterious effects of sterilization by irradiation could be avoided. Moreover, male-only release can improve the efficacy of SIT. Adequate methods of male-only production in Lepidoptera are currently lacking, in contrast to some Diptera. We describe a synthetic genetic system that allows male-only moth production for SIT and also replaces radiation sterilization with inherited female-specific lethality. We sequenced and characterized the <i>doublesex</i> (<i>dsx</i>) gene from the pink bollworm (<i>Pectinophora gossypiella</i>). Sex-alternate splicing from <i>dsx</i> was used to develop a conditional lethal genetic sexing system in two pest moths: the diamondback moth (<i>Plutella xylostella</i>) and pink bollworm. This system shows promise for enhancing existing pink bollworm SIT, as well as broadening SIT-type control to diamondback moth and other Lepidoptera

Engineered Repressible Lethality for Controlling the Pink Bollworm, a Lepidopteran Pest of Cotton

<div><p>The sterile insect technique (SIT) is an environmentally friendly method of pest control in which insects are mass-produced, irradiated and released to mate with wild counterparts. SIT has been used to control major pest insects including the pink bollworm (<em>Pectinophora gossypiella</em> Saunders), a global pest of cotton. Transgenic technology has the potential to overcome disadvantages associated with the SIT, such as the damaging effects of radiation on released insects. A method called RIDL (Release of Insects carrying a Dominant Lethal) is designed to circumvent the need to irradiate insects before release. Premature death of insects’ progeny can be engineered to provide an equivalent to sterilisation. Moreover, this trait can be suppressed by the provision of a dietary antidote. In the pink bollworm, we generated transformed strains using different DNA constructs, which showed moderate-to-100% engineered mortality. In permissive conditions, this effect was largely suppressed. Survival data on cotton in field cages indicated that field conditions increase the lethal effect. One strain, called OX3402C, showed highly penetrant and highly repressible lethality, and was tested on host plants where its larvae caused minimal damage before death. These results highlight a potentially valuable insecticide-free tool against pink bollworm, and indicate its potential for development in other lepidopteran pests.</p> </div

Southern blot analysis of OX3402C.

<p>From left to right, lanes are: Dig-labelled DNA molecular weight marker II (M), OX3402C genomic DNA digested with <i>Bgl</i>II (A), <i>Nhe</i>I (B) and <i>Xho</i>I (C).</p