Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

The prenatal environment can alter an individual's developmental trajectory with long-lasting effects on health. Animal models demonstrate that the impact of the early life environment extends to subsequent generations, but there is a paucity of data from human populations on intergenerational transmission of environmentally induced phenotypes. Here we investigated the association of parental exposure to energy and nutrient restriction in utero on their children's growth in rural Gambia. In a Gambian cohort with infants born between 1972 and 2011, we used multiple regression to test whether parental season of birth predicted offspring birth weight (n = 2097) or length (n = 1172), height-for-age z score (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ) at 2 yr of age (n = 923). We found that maternal exposure to seasonal energy restriction in utero was associated with reduced offspring birth length (crude:-4.2 mm, P = 0.005; adjusted: -4.0 mm, P = 0.02). In contrast, paternal birth season predicted offspring HAZ at 24 mo (crude: -0.21, P = 0.005; adjusted: -0.22, P = 0.004) but had no discernible impact at birth. Our results indicate that periods of nutritional restriction in a parent's fetal life can have intergenerational consequences in human populations. Fetal growth appears to be under matriline influence, and postnatal growth appears to be under patriline intergenerational influences.-Eriksen, K. G., Radford, E. J., Silver, M. J., Fulford, A. J. C., Wegmüller, R., Prentice, A. M. Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia

Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects

BACKGROUND: Betacellulin is a member of the epidermal growth factor family, expressed at the highest levels predominantly in the pancreas and thought to be involved in islet neogenesis and regeneration. Nonsynonymous coding variants were reported to be associated with type 2 diabetes in African American subjects. We tested the hypotheses that these previously identified variants were associated with type 2 diabetes in African Americans ascertained in Arkansas and that they altered insulin secretion in glucose tolerant African American subjects. METHODS: We typed three variants, exon1 Cys7Gly (C7G), exon 2 Leu44Phe (L44F), and exon 4 Leu124Met (L124M), in 188 control subjects and 364 subjects with type 2 diabetes. We tested for altered insulin secretion in 107 subjects who had undergone intravenous glucose tolerance tests to assess insulin sensitivity and insulin secretion. RESULTS: No variant was associated with type 2 diabetes, and no variant altered insulin secretion or insulin sensitivity. However, an effect on lipids was observed for all 3 variants, and variant L124M was associated with obesity measures. CONCLUSION: We were unable to confirm a role for nonsynonymous variants of betacellulin in the propensity to type 2 diabetes or to impaired insulin secretion

A search for heavy Kaluza-Klein electroweak gauge bosons at the LHC

The feasibility for the observation of a certain leptonic Kaluza-Klein (KK) hard process in {\em pp} interactions at the LHC is presented. Within the $S^1/Z_2$ TeV$^{-1}$ extra dimensional theoretical framework with the focus on the KK excitations of the Standard Model $\gamma$ and $Z^0$ gauge bosons, the hard-process, $f\bar f \to \sum_n\left(\gamma^*/Z^*\right)_n \to F \bar F$, has been used where $f$ is the initial state parton, $F$ the final state lepton and $\left(\gamma^*/Z^*\right)_{n}$ is the $n^{\rm th}$ KK excitation of the $\gamma/Z^0$ boson. For this study the analytic form for the hard process cross section has been independently calculated by the authors and has been implemented using the {\sc Moses} framework. The Moses framework itself, that has been written by the authors, was used as an external process within the {\sc Pythia} Monte Carlo generator which provides the phase space generation for the final state leptons and partons from the initial state hadrons, and the simulation of initial and final state radiation and hadronization. A brief discussion of the possibility for observing and identifying the unique signature of the KK signal given the current LHC program is also presented.Comment: 16 pages 10 figures, MCnet number: MCnet/10/06, Accepted by JHE

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

ProofWatch: Watchlist Guidance for Large Theories in E

Watchlist (also hint list) is a mechanism that allows related proofs to guide a proof search for a new conjecture. This mechanism has been used with the Otter and Prover9 theorem provers, both for interactive formalizations and for human-assisted proving of open conjectures in small theories. In this work we explore the use of watchlists in large theories coming from first-order translations of large ITP libraries, aiming at improving hammer-style automation by smarter internal guidance of the ATP systems. In particular, we (i) design watchlist-based clause evaluation heuristics inside the E ATP system, and (ii) develop new proof guiding algorithms that load many previous proofs inside the ATP and focus the proof search using a dynamically updated notion of proof matching. The methods are evaluated on a large set of problems coming from the Mizar library, showing significant improvement of E's standard portfolio of strategies, and also of the previous best set of strategies invented for Mizar by evolutionary methods.Comment: 19 pages, 10 tables, submitted to ITP 2018 at FLO

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Vicarious Group Trauma among British Jews

This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11133-016-9337-4Given that literature on the intra- and inter-generational transmission of traumas is mainly based on secondary literature and focuses on the transmission of trauma memory in terms of the historical knowledge of group trauma, this article develops the theory of vicarious group trauma and tests this theory by exploring vicarious traumatization in the everyday lives of Jews in Britain through the methods of observation and in-depth interviewing. Vicarious group trauma is defined as a life or safety-threatening event or abuse that happened to some members of a social group but is felt by other members as their own experience because of their personal affiliation with the group. The article finds that the vicarious sensation of traumatic group experiences can create anxiety, elicit perceptions of threat and, by extension, hypervigilance among Jews. The findings demonstrate that group traumas of the past interpenetrate and interweave with members’ current lives and in this way can also become constitutive of their group identity. An institutional focus on threats to Jews can inform the construction and reinforcement of traumatization symptoms and accordingly vicarious group trauma. This article suggests an association between the level of involvement of group members in the collective’s social structure and the prominence of vicarious group trauma among them

Nasal Chemosensory-Stimulation Evoked Activity Patterns in the Rat Trigeminal Ganglion Visualized by In Vivo Voltage-Sensitive Dye Imaging

Mammalian nasal chemosensation is predominantly mediated by two independent neuronal pathways, the olfactory and the trigeminal system. Within the early olfactory system, spatiotemporal responses of the olfactory bulb to various odorants have been mapped in great detail. In contrast, far less is known about the representation of volatile chemical stimuli at an early stage in the trigeminal system, the trigeminal ganglion (TG), which contains neurons directly projecting to the nasal cavity. We have established an in vivo preparation that allows high-resolution imaging of neuronal population activity from a large region of the rat TG using voltage-sensitive dyes (VSDs). Application of different chemical stimuli to the nasal cavity elicited distinct, stimulus-category specific, spatiotemporal activation patterns that comprised activated as well as suppressed areas. Thus, our results provide the first direct insights into the spatial representation of nasal chemosensory information within the trigeminal ganglion imaged at high temporal resolution

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Central synapses release a resource-efficient amount of glutamate.

Why synapses release a certain amount of neurotransmitter is poorly understood. We combined patch-clamp electrophysiology with computer simulations to estimate how much glutamate is discharged at two distinct central synapses of the rat. We found that, regardless of some uncertainty over synaptic microenvironment, synapses generate the maximal current per released glutamate molecule while maximizing signal information content. Our result suggests that synapses operate on a principle of resource optimization