Analysis of Mono-, Di- and Oligosaccharides by CE Using a Two-Stage Derivatization Method and LIF Detection.

A sensitive CE with LIF method has been developed for quantitative analysis of small carbohydrates. In this work, 17 carbohydrates including mono-, di- and oligosaccharides were simultaneously derivatized with 4-fluoro 7-nitrobenzo furazane (NBD-F) via a twostep reaction involving reductive amination with ammonia followed by condensation with NBD-F. Under the optimized derivatization conditions all carbo-hydrates were successfully derivatized within 2.5 h and separated within 15 min using borate buffer (90 mmol/L, pH 9.2). For sugar standards LODs were in the range of 49.7 to 243.6 nmol/L. Migration time and peak area reproducibility were better than RSD 0.1 and 3%, respectively. The method was applied to measure sugars in nanoliter volume samples of phloem sap obtained by stylectomy from wheat and to honeydew samples obtained from aphids feeding from wheat and willow

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

Low levels of cathepsin D are associated with a poor prognosis in endometrial cancer

Total cytosolic cathepsin D (Cat D) levels were estimated by an immunoradiometric assay in a series of 156 consecutive patients with surgical stages I–III primary endometrial adenocarcinoma. Simultaneously, the tissue content of both oestrogen (ER) and progesterone (PR) receptors, and p185HER-2/neu, DNA content (ploidy), and the fraction of S-phase cells (S-phase) were also estimated. Tumoral Cat D content ranged from 0 to 243 pmol mg−1 protein (median 44 pmol mg−1 protein) and was not associated with any of the established clinicopathological and biological prognostic variables, with the exception of a weak positive correlation with the tumoral p185HER-2/neu levels. Univariable analysis performed on a subset of 97 patients, followed for a minimum of 2 years or until death, showed that patient age at diagnosis, high histological grade, advanced surgical stage, vascular invasion, positive peritoneal cytology, low levels of Cat D, negative ER and PR status, aneuploidy, and high S-phase were predictive of the presence of persistent or recurrent disease. However, multivariable analysis revealed that only histological grade, surgical stage, Cat D and PR were significantly associated with the patient's outcome. From these findings, we conclude that Cat D is an independent prognostic factor in endometrial adenocarcinoma, its low levels being associated with a worse clinical outcome. © 1999 Cancer Research Campaig

An examination of the language construct in NIMH's research domain criteria:Time for reconceptualization!

The National Institute of Mental Health’s Research Domain Criteria (RDoC) Initiative “calls for the development of new ways of classifying psychopathology based on dimensions of observable behavior.” As aresult of this ambitious initiative, language has been identifi d as an independent construct in the RDoC matrix. In this article, we frame language within an evolutionary and neuro- psychological context and discuss some of the limitations to the current measurements of language. Findings from genomics and the neuroimaging of performance during language tasks are dis- cussed in relation to serious mental illness and within the context of caveats regarding measuring language. Indeed, the data collec- tion and analysis methods employed to assay language have been both aided and constrained by the available technologies, methodologies, and conceptual defi Consequently, differ- ent fields of language research show inconsistent defi s of language that have become increasingly broad over time. Individ- ually, they have also shown significant improvements in conceptual resolution, aswell as inexperimental and analytic techniques. More recently, language research has embraced collaborations across disciplines, notably neuroscience, cognitive science, and computa- tional linguistics and has ultimately re-defi classical ideas of language. As we move forward, the new models of language with their remarkably multifaceted constructs force a re-examination of the NIMH RDoC conceptualization of language and thus the neuroscience and genetics underlying this concept

Etiological distinction of working memory components in relation to mathematics.

Working memory has been consistently associated with mathematics achievement, although the etiology of these relations remains poorly understood. The present study examined the genetic and environmental underpinnings of math story problem solving, timed calculation, and untimed calculation alongside working memory components in 12-year-old monozygotic (n = 105) and same-sex dizygotic (n = 143) twin pairs. Results indicated significant phenotypic correlation between each working memory component and all mathematics outcomes (r = 0.18 - 0.33). Additive genetic influences shared between the visuo-spatial sketchpad and mathematics achievement was significant, accounting for roughly 89% of the observed correlation. In addition, genetic covariance was found between the phonological loop and math story problem solving. In contrast, despite there being a significant observed relationship between phonological loop and timed and untimed calculation, there was no significant genetic or environmental covariance between the phonological loop and timed or untimed calculation skills. Further analyses indicated that genetic overlap between the visuo-spatial sketchpad and math story problem solving and math fluency was distinct from general genetic factors, whereas g, phonological loop, and mathematics shared generalist genes. Thus, although each working memory component was related to mathematics, the etiology of their relationships may be distinct

COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research

Functional analysis of CHX21: a putative sodium transporter in Arabidopsis

The functional role of CHX21, a member of the Arabi-dopsis thaliana CHX cation transporter family, has been investigated in plants growing under ‘ideal’ conditions and in the presence of elevated NaCl levels. In public databases, AtCHX21 (At2g31910) is annotated as a putative Na1/H1 antiporter. In this study, Southern analysis was used to identify a genotype that con-tained a single transposon insertion within its genome; using PCR, this insertion was shown to be within the CHX21 locus. No CHX21 transcript was detectable in Atchx21 (mutant) plants using RT-PCR. In the absence of salt stress, Atchx21 showed significant quantitative differences from the wild type (AtCHX21) in develop-ment with respect to characters such as rosette width and flowering time. In the presence of 50 mM NaCl, (i) roots of Atchx21 elongated more slowly than the wild type, (ii) the leaf sap Na1 concentration was signifi-cantly lower in Atchx21 compared with the wild type, and (iii) the concentration of Na1 in the xylem was lower compared with the wild type. The concentration of Na1 exported from the leaf in the phloem was unchanged. Thus, loading of Na1 into the root xylem could explain changes in leaf concentration of Na1. This hypothesis was supported by immunolocalization which demonstrated that the AtCHX21 transporter could only be detected in root endodermal cells. Immunogold labelling of ultra-thin sections, followed by transmission electron microscopy, demonstrated the localization of the protein in the plasma membrane. The data demonstrate that the CHX21 transporter may play a role in regulation of xylem Na1 concentration and, consequently, Na1 accumulation in the leaf