The proteomic response in the crustacean molting gland of land crab Gecarcinus lateralis in response to artificially induced molting throughout its molting cycle.

Molting in crustaceans is a highly complex physiological process involving negative regulation by two paired endocrine glands, the X-organ/sinus gland complex (XO/SG) and the Y-organ (YO). The XO/SG complex is responsible for making molt-inhibiting hormone (MIH) which negatively regulates synthesis of molting hormones (ecdysteroids) by the YO. Eyestalk ablation (ESA) removes the source of MIH and provides an experimental means to manipulate and induce molting, although the physiological effects of ESA on the YO have not been fully characterized. Analysis of gene expression in the XOs and YOs has lead to the development of a proposed molecular signaling pathway which regulates ecdysteroidogenesis and subsequent molting (ecdysis) in crustaceans. Results presented depict the changes in significantly different protein abundances in the YO over the course of the molting cycle (early, mid and late premolt) in crabs where 5 or more walking legs were lost, termed multiple leg autotomy (MLA). Proteins were characterized using two-dimensional gel electrophoresis and Delta2D software for statistical analysis. Future analysis will determine whether ESA can effectively mimic premolt conditions in the YO compared to the natural molting progression through protein identification by MALDI-TOF mass spectrometry. This will further resolve the metabolic and physiological changes associated with the transitions experienced by the YO throughout the molting stages. Determining the efficacy of ESA as a means to induce molting and determining molecular regulation of crustacean molting has broad economic impacts for crustacean fisheries as industry demands increase

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Influence of cannibalism on Arizona tiger salamander (Ambystoma mavortium nebulosum) stress physiology

Cannibalism (intraspecific predation) is common in many species because it provides nutritional advantages and reduces within-population competition. Cannibalism is favored in populations with fast growth rates, which leads to opportunistic larger individuals preying on smaller animals of their own species. In the presence of cannibals, small amphibian larvae that are not eaten experience reduced growth rates and activity levels. Such sublethal effects can impact population dynamics and have subsequent cascading effects on surrounding communities. Cannibalism may cause variation in stress responses of individuals; smaller animals may have elevated or chronic stress, as they have a higher risk of becoming consumed by their own species. Chronic stress has adverse effects on long-term individual health that can result in increased mortality. Corticosterone is the primary hormone produced by amphibians in response to stress, and stress can be quantified through measurement of this hormone. Thus, the objective of my study is to assess how the interaction of body size, body condition, and cannibalism causes corticosterone variation in the well-studied population of Arizona tiger salamanders (Ambystoma mavortium nebulosum) at the Mexican Cut Nature Preserve, Colorado. Within 3 minutes of capturing the animal, I will use a non-invasive skin swabbing method to collect corticosterone samples from at least 20 larvae of variable sizes from each pond. Samples will be stored in ethanol at 4°C until they can be processed within the laboratory at Murray State University. Samples will be processed using Arbor Assays corticosterone ELISA kits. A general linear mixed effects model will be used to determine variation in corticosterone samples relative to predation (no cannibalism vs. cannibalism) and predator density. My study will provide a better understanding of the ecological importance of cannibalism among top predators in aquatic ecosystems, as well as the influence of cannibalism and subsequent risk of predation on stress levels in larval salamanders

Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial

Background Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. Methods In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39. Findings Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0.97, 95% CI 0 42-2 26, p=0.47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0.87), and most adverse events were mild. Interpretation Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks