Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life:the Medical Research Council (MRC) National Survey of Health and Development

BACKGROUND: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2-26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5-20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) bone health outcomes at 60-64 years. METHODS: NSHD data were analysed using Super-Imposition by Translation And Rotation (SITAR) growth curve analysis, either alone or jointly with ALSPAC data. Improved estimation of pubertal growth parameters of size, tempo and velocity was assessed by changes in model fit and correlations with contemporary measures of pubertal timing. Bone outcomes of radius [trabecular volumetric bone mineral density (vBMD) and diaphysis cross-sectional area (CSA)] were regressed on the SITAR parameters, adjusted for current body size. RESULTS: The NSHD SITAR parameters were better estimated in conjunction with ALSPAC, i.e. more strongly correlated with pubertal timing. Trabecular vBMD was associated with early height tempo, whereas diaphysis CSA was related to weight size, early tempo and slow velocity, the bone outcomes being around 15% higher for the better vs worse growth pattern. CONCLUSIONS: By pooling NSHD and ALSPAC data, SITAR more accurately summarized pubertal growth and weight gain in NSHD, and in turn demonstrated notable associations between pubertal timing and later bone outcomes. These associations give insight into the importance of the pubertal period for future skeletal health and osteoporosis risk

Headspace analysis of mesothelioma cell lines differentiates biphasic and epithelioid sub-types.

Malignant mesothelioma (MM) is an incurable cancer. MM is often misdiagnosed, with a poor 5-year survival and limited treatment options. The discovery of endogenous volatile organic compounds (VOCs) is required in order to accelerate the development of a breath test as an alternative to conventional MM diagnosis. For the first time, this study used solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) to identify VOCs released directly from the biphasic MM cell line MSTO-211H and the epithelioid MM cell line NCI-H28 as well as the non-malignant mesothelial cell line MET-5A. Multivariate statistical analysis showed separation between MSTO-211H, NCI-H28 and MET-5A results. 2-ethyl-1-hexanol was significantly increased in both MSTO-211H and NCI-H28 cells compared to MET-5A controls. In addition, ethyl propionate and cyclohexanol were significantly increased in MSTO-211H cells and dodecane was significantly increased in NCI-H28 cells. This is the first study reporting headspace analysis of these MM cell lines and the first to consider the effects of mesothelioma sub-type on VOC profile. Current results further highlight the potential for a diagnostic mesothelioma breath test as well as providing proof of concept for the differentiation between biphasic and epithelioid mesothelioma based on VOC profiles

Discrimination of papillary thyroid cancer from non-cancerous thyroid tissue based on lipid profiling by mass spectrometry imaging

Introduction: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical management. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies. In this study we used mass spectrometry imaging to detect lipids discriminating papillary cancer from not cancerous thyroid directly in formalin-fixed tissue sections. Material and methods: For this purpose imaging and profiling of lipids present in non-malignant and cancerous thyroid tissue specimens were conducted. High resolution MALDI-Q-Ion Mobility-TOF-MS technique was used for lipidomic analysis of formalin fixed thyroid tissue samples. Lipids were identified by the comparison of the exact molecular masses and fragmentation pathways of the protonated molecule ions, recorded during the MS/MS experiments, with LIPID MAPS database. Results: Several phosphatidylcholines (32:0, 32:1, 34:1 and 36:3), sphingomyelins (34:1 and 36:1) and phosphatidic acids (36:2 and 36:3) were detected and their abundances were significantly higher in cancerous tissue compared to non-cancerous tissue. The same lipid species were detected in formalin-fixed as in fresh-frozen tissue, but [M + Na]+ions were the most abundant in formalin fixed whereas [M + K]+ions were predominant in fresh tissue. Conclusions: Our results prove the viability of MALDI-MSI for analysis of lipid distribution directly in formalin-fixed tissue, and the potential for their use in the classification of thyroid diseases

Behavior During Tethered Kicking in Infants with Periventricular Brain Injury

Purpose: To describe behavior of children with periventricular brain injury (PBI) in a tethered-kicking intervention. Methods: Sixteen infants with PBI were randomly assigned to exercise or no-training in a longitudinal pilot study. Frequencies of leg movements and interlimb coordination were described from videos at 2 and 4 months\u27 corrected age (CA). Results: Eight of the 13 children (62%) with longitudinal data increased the frequency of leg movements while tethered to a mobile between 2 and 4 months\u27 CA. Movement frequency was correlated with scores on the Test of Infant Motor Performance, but no differences between experimental groups were found. Children with typical development at 12 months\u27 CA increased the proportion of leg movements that were synchronous between 2 and 4 months, as did a child with cerebral palsy in the experimental group. Conclusions: The tethered-kicking intervention facilitates movement in infants with PBI, but effects on development remain to be demonstrated

Classtalk: A Classroom Communication System for Active Learning

This pdf file is an article describing the advantages of using Classtalk technology in the classroom to enhance classroom communication. Classtalk technology cab facilitate the presentation of questions for small group work, collec the student answers and then display histograms showing how the class answered. This new communication technology can help instructors create a more interactive, student centered classroom, especially when teaching large courses. The article describes Classtalk as a very useful tool not only for engaging students in active learning, but also for enhancing the overall communication within the classroom. This article is a selection from the electronic Journal for Computing in Higher Education. Educational levels: Graduate or professional

The Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirements

Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. haemophilum exhibits a unique requirement for iron supplementation to support its growth in culture, but the basis for this property and how it may shape pathogenesis is unclear. Using a combination of Illumina, PacBio, and Sanger sequencing, the complete genome sequence of M. haemophilum was determined. Guided by this sequence, experiments were performed to define the basis for the unique growth requirements of M. haemophilum. We found that M. haemophilum, unlike many other mycobacteria, is unable to synthesize iron-binding siderophores known as mycobactins or to utilize ferri-mycobactins to support growth. These differences correlate with the absence of genes associated with mycobactin synthesis, secretion, and uptake. In agreement with the ability of heme to promote growth, we identified genes encoding heme uptake machinery. Consistent with its propensity to infect the skin, we show at the whole-genome level the genetic closeness of M. haemophilumwith Mycobacterium leprae, an organism which cannot be cultivated in vitro, and we identify genes uniquely shared by these organisms. Finally, we identify means to express foreign genes in M. haemophilum. These data explain the unique culture requirements for this important pathogen, provide a foundation upon which the genome sequence can be exploited to improve diagnostics and therapeutics, and suggest use of M. haemophilum as a tool to elucidate functions of genes shared with M. leprae. IMPORTANCE Mycobacterium haemophilum is an emerging pathogen with an unknown natural reservoir that exhibits unique requirements for iron supplementation to grow in vitro. Understanding the basis for this iron requirement is important because it is fundamental to isolation of the organism from clinical samples and environmental sources. Defining the molecular basis for M. haemophilium\u27s growth requirements will also shed new light on mycobacterial strategies to acquire iron and can be exploited to define how differences in such strategies influence pathogenesis. Here, through a combination of sequencing and experimental approaches, we explain the basis for the iron requirement. We further demonstrate the genetic closeness of M. haemophilum and Mycobacterium leprae, the causative agent of leprosy which cannot be cultured in vitro, and we demonstrate methods to genetically manipulate M. haemophilum. These findings pave the way for the use of M. haemophilum as a model to elucidate functions of genes shared with M. leprae

Novel Associations of Nonstructural Loci with Paraoxonase Activity

The high-density-lipoprotein-(HDL-) associated esterase paraoxonase 1 (PON1) is a likely contributor to the antioxidant and antiatherosclerotic capabilities of HDL. Two nonsynonymous mutations in the structural gene, PON1, have been associated with variation in activity levels, but substantial interindividual differences remain unexplained and are greatest for substrates other than the eponymous paraoxon. PON1 activity levels were measured for three substrates—organophosphate paraoxon, arylester phenyl acetate, and lactone dihydrocoumarin—in 767 Mexican American individuals from San Antonio, Texas. Genetic influences on activity levels for each substrate were evaluated by association with approximately one million single nucleotide polymorphism (SNPs) while conditioning on PON1 genotypes. Significant associations were detected at five loci including regions on chromosomes 4 and 17 known to be associated with atherosclerosis and lipoprotein regulation and loci on chromosome 3 that regulate ubiquitous transcription factors. These loci explain 7.8% of variation in PON1 activity with lactone as a substrate, 5.6% with the arylester, and 3.0% with paraoxon. In light of the potential importance of PON1 in preventing cardiovascular disease/events, these novel loci merit further investigation

High dimensional endophenotype ranking in the search for major depression risk genes.

BACKGROUND: Despite overwhelming evidence that major depression is highly heritable, recent studies have localized only a single depression-related locus reaching genome-wide significance and have yet to identify a causal gene. Focusing on family-based studies of quantitative intermediate phenotypes or endophenotypes, in tandem with studies of unrelated individuals using categorical diagnoses, should improve the likelihood of identifying major depression genes. However, there is currently no empirically derived statistically rigorous method for selecting optimal endophentypes for mental illnesses. Here, we describe the endophenotype ranking value, a new objective index of the genetic utility of endophenotypes for any heritable illness. METHODS: Applying endophenotype ranking value analysis to a high-dimensional set of over 11,000 traits drawn from behavioral/neurocognitive, neuroanatomic, and transcriptomic phenotypic domains, we identified a set of objective endophenotypes for recurrent major depression in a sample of Mexican American individuals (n = 1122) from large randomly selected extended pedigrees. RESULTS: Top-ranked endophenotypes included the Beck Depression Inventory, bilateral ventral diencephalon volume, and expression levels of the RNF123 transcript. To illustrate the utility of endophentypes in this context, each of these traits were utlized along with disease status in bivariate linkage analysis. A genome-wide significant quantitative trait locus was localized on chromsome 4p15 (logarithm of odds = 3.5) exhibiting pleiotropic effects on both the endophenotype (lymphocyte-derived expression levels of the RNF123 gene) and disease risk. CONCLUSIONS: The wider use of quantitative endophenotypes, combined with unbiased methods for selecting among these measures, should spur new insights into the biological mechanisms that influence mental illnesses like major depression

“I don’t want to live too long!”: Successful ageing and the failure of longevity in Japan

This chapter examines ‘successful aging’ through its impacts on formal care workers in Japan. It is based on one year of fieldwork conducted in urban Japan and examines the affective, ethical, and cultural forces that result at times in resilience, compassion, and intimacy between carers and elderly clients, and at other times, in violence, abuse, and abandonment. I argue that locating the source of this divergence in individuals (i.e., adverse coping strategy) reproduces the same neoliberal model of success for care workers as it does for the elderly. Instead, care and abuse in formal care settings can be seen as symptoms of broader political and economic transformations that have been occurring in Japan since the 1990s

EIFiso4G augments the synthesis of specific plant proteins involved in normal chloroplast function

Copyright © 2019 American Society of Plant Biologists. All rights reserved. The plant-specific translation initiation complex eIFiso4F is encoded by three genes in Arabidopsis (Arabidopsis thaliana)-genes encoding the cap binding protein eIFiso4E (eifiso4e) and two isoforms of the large subunit scaffolding protein eIFiso4G (i4g1 and i4g2). To quantitate phenotypic changes, a phenomics platform was used to grow wild-type and mutant plants (i4g1, i4g2, i4e, i4g1 × i4g2, and i4g1 × i4g2 × i4e [i4f]) under various light conditions. Mutants lacking both eIFiso4G isoforms showed the most obvious phenotypic differences from the wild type. Two-dimensional differential gel electrophoresis and mass spectrometry were used to identify changes in protein levels in plants lacking eIFiso4G. Four of the proteins identified as measurably decreased and validated by immunoblot analysis were two light harvesting complex binding proteins 1 and 3, Rubisco activase, and carbonic anhydrase. The observed decreased levels for these proteins were not the direct result of decreased transcription or protein instability. Chlorophyll fluorescence induction experiments indicated altered quinone reduction kinetics for the double and triple mutant plants with significant differences observed for absorbance, trapping, and electron transport. Transmission electron microscopy analysis of the chloroplasts in mutant plants showed impaired grana stacking and increased accumulation of starch granules consistent with some chloroplast proteins being decreased. Rescue of the i4g1 × i4g2 plant growth phenotype and increased expression of the validated proteins to wild-type levels was obtained by overexpression of eIFiso4G1. These data suggest a direct and specialized role for eIFiso4G in the synthesis of a subset of plant proteins