Creatine Transporter (CrT; Slc6a8) Knockout Mice as a Model of Human CrT Deficiency

Mutations in the creatine (Cr) transporter (CrT; Slc6a8) gene lead to absence of brain Cr and intellectual disabilities, loss of speech, and behavioral abnormalities. To date, no mouse model of CrT deficiency exists in which to understand and develop treatments for this condition. The purpose of this study was to generate a mouse model of human CrT deficiency. We created mice with exons 2–4 of Slc6a8 flanked by loxP sites and crossed these to Cre:CMV mice to create a line of ubiquitous CrT knockout expressing mice. Mice were tested for learning and memory deficits and assayed for Cr and neurotransmitter levels. Male CrT−/y (affected) mice lack Cr in the brain and muscle with significant reductions of Cr in other tissues including heart and testes. CrT−/y mice showed increased path length during acquisition and reversal learning in the Morris water maze. During probe trials, CrT−/y mice showed increased average distance from the platform site. CrT−/y mice showed reduced novel object recognition and conditioned fear memory compared to CrT+/y. CrT−/y mice had increased serotonin and 5-hydroxyindole acetic acid in the hippocampus and prefrontal cortex. Ubiquitous CrT knockout mice have learning and memory deficits resembling human CrT deficiency and this model should be useful in understanding this disorder

Antibiotic prophylaxis for endocarditis: time to reconsider

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Some cardiac conditions require antibiotic prophylaxis for some types of dental treatment to reduce the risk of infective endocarditis (IE). All medical and dental practitioners are familiar with this practice but tend to use different regimens in apparently similar circumstances. Generally, the trend has been to prescribe antibiotics if in doubt. This review explores the evidence for antibiotic prophylaxis to prevent IE: does it work and is it safe? The changing nature of IE, the role of bacteraemia of oral origin and the safety of antibiotics are also reviewed. Most developed countries have national guidelines and their points of similarity and difference are discussed. One can only agree with the authority who describes antibiotic guidelines for endocarditis as being ‘like the Dead Sea Scrolls, they are fragmentary, imperfect, capable of various interpretations and (mainly) missing!’ Clinical case-controlled studies show that the more widely antibiotics are used, the greater the risk of adverse reactions exceeding the risk of IE. However, the consensus is that antibiotic prophylaxis is mandatory for a small number of high-risk cardiac and high-risk dental procedures. There are a large number of low-risk cardiac and dental procedures in which the risk of adverse reactions to the antibiotics exceeds the risk of IE, where prophylaxis should not be provided. There is an intermediate group of cardiac and dental procedures for which careful individual evaluation should be made to determine whether IE or antibiotics pose the greater risk. These categories are presented. All medical and dental practitioners need to reconsider their approach in light of these current findings.J Singh, I Straznicky, M Avent and AN Gos

A global analysis of terrestrial plant litter dynamics in non-perennial waterways

Perennial rivers and streams make a disproportionate contribution to global carbon (C) cycling. However, the contribution of intermittent rivers and ephemeral streams (IRES), which sometimes cease to flow and can dry completely, is largely ignored although they represent over half the global river network. Substantial amounts of terrestrial plant litter (TPL) accumulate in dry riverbeds and, upon rewetting, this material can undergo rapid microbial processing. We present the results of a global research collaboration that collected and analysed TPL from 212 dry riverbeds across major environmental gradients and climate zones. We assessed litter decomposability by quantifying the litter carbon-to-nitrogen ratio and oxygen (O2) consumption in standardized assays and estimated the potential short-term CO2 emissions during rewetting events. Aridity, cover of riparian vegetation, channel width and dry-phase duration explained most variability in the quantity and decomposability of plant litter in IRES. Our estimates indicate that a single pulse of CO2 emission upon litter rewetting contributes up to 10% of the daily CO2 emission from perennial rivers and stream, particularly in temperate climates. This indicates that the contributions of IRES should be included in global C-cycling assessments