Taurine regulation of short term synaptic plasticity in fragile X mice

Background Fragile X Syndrome is the most common known genetic cause of autism. The Fmr1-KO mouse, lacks the fragile X mental retardation protein (FMRP), and is used as a model of the syndrome. The core behavioral deficits of autism may be conceptualized either as excessive adherence to patterns as seen in repetitive actions and aberrant language, or as insensitivity to subtle but socially important changes in patterns. The hippocampus receives information from the entorhinal cortex and plays a crucial role in the processing of patterned information. To gain more insight into the physiological function of FMRP and the neuronal mechanisms underlying fragile X syndrome, we examined the electrophysiological response of the hippocampus to pair pulse stimulation as a measure of patterned information processing and how it is affected in the Fmr1-KO mouse. Methods In this study, we used paired-pulse stimulation of the afferent perforant path and recorded from the CA1 region of the hippocampus. Two-month-old FVB/NJ male mice and age-matched Fmr1-KO mice were used in this study. Hippocampal slices were prepared, equilibrated in artificial cerebrospinal fluid (aCSF), and excitatory post synaptic potentials (EPSPs) measured by stimulating the perforant path of the dentate gyrus (DG) while recording from the molecular layer of CA1. Stimulation occurred by setting current and pulse width to evoke a fixed percentage of maximal EPSP amplitude. This stimulation paradigm allowed us to examine the processing capabilities of the hippocampus as a function of increasing interstimulus intervals (ISI) and how taurine, a GABAA receptor agonist, affects such information processing. Results We found that hippocampal slices from wild type (WT) showed pair-pulse facilitation at ISI of 100-300 ms whereas slices from Fmr1-KO brains showed a consistent pair-pulse depression at a comparable ISI. Addition of 10 μM taurine to WT slices resulted in a drastic decrease of the peak response to the second stimulus, resulting in an initial depression at 100 ms ISI followed by potentiation at higher ISI (150 ms and above). In the presence of taurine, the amplitude of the second response remained significantly lower than in its absence. Fmr1-KO mice however, were completely insensitive to taurine application and pair-pulse stimulation always resulted in a depression of the response to the second stimulus. Conclusions Previously we reported that Fmr1-KO mice have reduced beta subunits of the GABAA receptors. We also showed as well as others that taurine acts as an agonist or a modulator for GABAA receptors. Therefore, the insensitivity of Fmr1-KO slices to taurine application could be due to the reduced binding sites on the GABAA receptors in the Fmr1-KO mice

A 3D-printed nasopharyngeal swab for COVID-19 diagnostic testing.

The nasopharyngeal swab is a critical component of the COVID-19 testing kit. Supply chain remains greatly impacted by the pandemic. Teams from USF Health Radiology and Northwell Health System developed a 3D-printed stopgap alternative. This descriptive study details the workflow and provides guidance for hospital-based 3D printing labs to leverage the design to make a positive impact on the pandemic. Swab use is also outlined, and the early information regarding clinical use is described, including an ongoing multicenter trial methodology

The maximum modulus of a trigonometric trinomial

Let Lambda be a set of three integers and let C_Lambda be the space of 2pi-periodic functions with spectrum in Lambda endowed with the maximum modulus norm. We isolate the maximum modulus points x of trigonometric trinomials T in C_Lambda and prove that x is unique unless |T| has an axis of symmetry. This permits to compute the exposed and the extreme points of the unit ball of C_Lambda, to describe how the maximum modulus of T varies with respect to the arguments of its Fourier coefficients and to compute the norm of unimodular relative Fourier multipliers on C_Lambda. We obtain in particular the Sidon constant of Lambda

Multivariate Hensel Lemma for ultrametric fields

The Multivariate Hensel Lemma for local rings is usually proved as a consequence of the Grothendieck version of Zariski's Main Theorem. This version deals with a more general situation that is a priori much more difficult. In this paper, we give a direct proof of the Multivariate Hensel Lemma for ultrametric fields, in the framework of constructive mathematics and without using~ZMT. In the framework of classical mathematics, our result entails the Lemma for rank-one valued fields.Comment: In this file you find the English version, 15 pages, starting on the page numbered E1. Then the French version (Lemme de Hensel multivari\'e pour les corps ultram\'etriques), 15 pages, begins on the page numbered F

Assessment of intradimensional/extradimensional attentional set-shifting in rats

The initial development of the attentional set-shifting task was supported by The Wellcome Trust (Project Grant 051945/Z/97/Z) and a Biotechnology and Biological Sciences Research Council (UK) Studentship to Jennifer M. Birrell.The rat intradimensional/extradimensional (ID/ED) task, first described by Birrell and Brown 18 years ago, has become the predominant means by which attentional set-shifting is investigated in rodents: the use of rats in the task has been described in over 135 publications by researchers from nearly 90 universities and pharmaceutical companies. There is variation in the protocols used by different groups, including differences in apparatus, stimuli (both stimulus dimensions and exemplars within), and also the methodology. Nevertheless, most of these variations seem to be of little consequence: there is remarkable similarity in the profile of published data, with consistency of learning rates and in the size and reliability of the set-shifting and reversal ‘costs’. However, we suspect that there may be inconsistent data that is unpublished or perhaps ‘failed experiments’ that may have been caused by unintended deviations from effective protocols. The purpose of this review is to describe our approach and the rationale behind certain aspects of the protocol, including common pitfalls that are encountered when establishing an effective local protocol.PostprintPeer reviewe

Noncommutative Figa-Talamanca-Herz algebras for Schur multipliers

We introduce a noncommutative analogue of the Fig\'a-Talamanca-Herz algebra $A_p(G)$ on the natural predual of the operator space $\frak{M}_{p,cb}$ of completely bounded Schur multipliers on Schatten space $S_p$. We determine the isometric Schur multipliers and prove that the space $\frak{M}_{p}$ of bounded Schur multipliers on Schatten space $S_p$ is the closure in the weak operator topology of the span of isometric multipliers.Comment: 24 pages; corrected typo

Improving detection of familial hypercholesterolaemia in primary care using electronic audit and nurse-led clinics

RATIONALE, AIMS AND OBJECTIVES: In the UK fewer than 15% of familial hypercholesterolemia (FH) cases are diagnosed, representing a major gap in coronary heart disease prevention. We wished to support primary care doctors within the Medway Clinical Commissioning Group (CCG) to implement NICE guidance (CG71) and consider the possibility of FH in adults who have raised total cholesterol concentrations, thereby improving the detection of people with FH. METHODS: Utilizing clinical decision support software (Audit+) we developed an FH Audit Tool and implemented a systematic audit of electronic medical records within GP practices, first identifying all patients diagnosed with FH or possible FH and next electronically flagging patients with a recorded total cholesterol of >7.5 mmol L(-1) or LDL-C > 4.9 mmol L(-1) (in adults), for further assessment. After a 2-year period, a nurse-led clinic was introduced to screen more intensely for new FH index cases. We evaluated if these interventions increased the prevalence of FH closer to the expected prevalence from epidemiological studies. RESULTS: The baseline prevalence of FH within Medway CCG was 0.13% (1 in 750 persons). After 2 years, the recorded prevalence of diagnosed FH increased by 0.09% to 0.22% (1 in 450 persons). The nurse advisor programme ran for 9 months (October 2013-July 2014) and during this time, the recorded prevalence of patients diagnosed with FH increased to 0.28% (1 in 357 persons) and the prevalence of patients 'at risk and unscreened' reduced from 0.58% to 0.14%. CONCLUSIONS: Our study shows that two simple interventions increased the detection of FH. This systematic yet simple electronic case-finding programme with nurse-led review allowed the identification of new index cases, more than doubling the recorded prevalence of detected disease to 1 in 357 (0.28%). This study shows that primary care has an important role in identifying patients with this condition