Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites

Duplicated var2csa genes in one strain of Plasmodium falciparum are simultaneously transcribed, challenging the dogma of mutual exclusive var gene transcriptio

The Generation R study: A candidate gene study and genome-wide association study (GWAS) on health-related quality of life (HRQOL) of mothers and young children

Aim: The aim of this paper is to describe the Generation R study as a template that enables candidate gene study and genome-wide association study regarding health-related quality of life (HRQOL) of mothers and their young children. Methods: Generation R is a population-based prospective cohort study from fetal life onwards in Rotterdam, The Netherlands. Children were born in 2002-2006. Blood from mothers and placenta cord blood were sampled. Mothers' HRQOL was measured 5 times during pregnancy and after birth using SF-12 and EQ-5D. Children's HRQOL was measured 5 times between age 1 and 5/6 years using Infant-Toddler Quality Of Life questionnaire (ITQOL), Health Status Classification System PreSchool (HSCS-PS) and Child Health Questionnaire Parent Form 28 items (CHQ-PF28), respectively. Results: DNA is available for 8,055 mothers and 5,908 children. Genotyping of various candidate genes and a genome-wide association (GWA) scan (Illumina 610K) of child DNA were done. A template for gene-HRQOL analyses is provided. We start with candidate gene study on HRQOL of mothers and children. Gene-environment interaction and interaction with medical indicators of health status will be explored. Next, GWA study on HRQOL will be performed. Conclusions: Gaining insight into the determinants of HRQOL is essential to assisting efforts in health policy and clinical application to improve well-being and health. In the future, it might be possible to complement HRQOL assessments by examinations of genetic markers. Strengths and weaknesses of the Generation R study are discussed

Keep it SMPL: Automatic Estimation of 3D Human Pose and Shape from a Single Image

We describe the first method to automatically estimate the 3D pose of the human body as well as its 3D shape from a single unconstrained image. We estimate a full 3D mesh and show that 2D joints alone carry a surprising amount of information about body shape. The problem is challenging because of the complexity of the human body, articulation, occlusion, clothing, lighting, and the inherent ambiguity in inferring 3D from 2D. To solve this, we first use a recently published CNN-based method, DeepCut, to predict (bottom-up) the 2D body joint locations. We then fit (top-down) a recently published statistical body shape model, called SMPL, to the 2D joints. We do so by minimizing an objective function that penalizes the error between the projected 3D model joints and detected 2D joints. Because SMPL captures correlations in human shape across the population, we are able to robustly fit it to very little data. We further leverage the 3D model to prevent solutions that cause interpenetration. We evaluate our method, SMPLify, on the Leeds Sports, HumanEva, and Human3.6M datasets, showing superior pose accuracy with respect to the state of the art.Comment: To appear in ECCV 201

Game theory of mind

This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

Reliability and validity of the Infant and Toddler Quality of Life Questionnaire (ITQOL) in a general population and respiratory disease sample

Objective: To evaluate feasibility, internal consistency, test-retest reliability, and concurrent and discriminative validity of the Infant and Toddler Quality of Life Questionnaire (ITQOL) for parents of pre-school children with 12 scales (103-items) covering physical and psychosocial domains and impact of child health on parents, in comparison with the TNO-AZL Pre-school Children Quality of Life Questionnaire (TAPQOL). Methods: Parents of children from a random general population sample (2 months-4 years old; n = 500) and of an outpatient clinic sample of children with respiratory disease (5 months-51/2 years old; n = 217) were mailed ITQOL and TAPQOL questionnaires; a retest was sent after two weeks. Results: Feasibility: The response was ≥80% with few missing and non-unique ITQOL-answers (25% at maximum score). Internal consistency: All Cronbach's α >0.70. Test-retest Intraclass Correlation Coefficients (ICCs) were moderate or adequate (≥0.50; p < 0.01) for 10 ITQOL-scales. Validity: ITQOL-scales, with a few exceptions, correlated better with predefined parallel TAPQOL scales than with non-parallel scales. Five to eight ITQOL-scales discriminated clearly between children with few and with many parent-reported chronic conditions, between children with and without doctor-diagnosed respiratory disease and with a low and a high parent-reported medical consumption (p < 0.05). Conclusions: This study supported the evidence that the ITQOL is a feasible instrument with adequate psychometric properties. The study provided reference ITQOL scores for gender/age subgroups. We recommend repeated evaluations of the ITQOL in varied populations, especially among very young children, including repeated assessments of test-retest characteristics and evaluations of responsiveness to change. We recommend developing and evaluating a shortened ITQOL version

Cytokeratin expression during mouse embryonic and early postnatal mammary gland development

Cytokeratins are intermediate filament proteins found in most epithelial cells including the mammary epithelium. Specific cytokeratin expression has been found to mark different epithelial cell lineages and also to associate with putative mammary stem/progenitor cells. However, a comparative analysis of the expression of cytokaratins during embryonic and postnatal mammary development is currently lacking. Moreover, it is not clear whether the different classes of putative mammary stem/progenitor cells exist during embryonic development. Here, we use double/triple-label immunofluorescence and immunohistochemistry to systematically compare the expression of cytokeratin 5 (K5), cytokeratin 6 (K6), cytokeratin 8 (K8), cytokeratin 14 (K14) and cytokeratin 19 (K19) in embryonic and early postnatal mouse mammary glands. We show that K6+ and K8+/K14+ putative mammary progenitor cells arise during embryogenesis with distinct temporal and spatial distributions. Moreover, we describe a transient disconnection of the expression of K5 and K14, two cytokeratins that are often co-expressed, during the first postnatal weeks of mammary development. Finally, we report that cytokeratin expression in cultured primary mammary epithelial cells mimics that during the early stages of postnatal mammary development. These studies demonstrate an embryonic origin of putative mammary stem/progenitor cells. Moreover, they provide additional insights into the use of specific cytokeratins as markers of mammary epithelial differentiation, or the use of their promoters to direct gene overexpression or ablation in genetic studies of mouse mammary development

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

A novel human skin chamber model to study wound infection ex vivo

Wound infections with multi-drug resistant bacteria increase morbidity and mortality and have considerable socioeconomic impact. They can lead to impaired wound healing, resulting in rising treatment costs. The aim of this study was to investigate an ex vivo human wound infection model. Human full-thickness skin from the operating room (OR) was placed into the Bo-Drum® and cultivated for 7 days in an air–liquid interphase. On day 8, the skin was inoculated with either (1) Pseudomonas aeruginosa, (2) Staphylococcus aureus (105 CFU, n = 3) or (3) carrier control. 1, 3 and 7 days after inoculation colony forming units in the tissue/media were determined and cytokine expression was quantified. A reliable and reproducible wound infection could be established for 7 days. At this timepoint, 1.8 × 108 CFU/g tissue of P. aeruginosa and 2 × 107 CFU/g tissue of S. aureus were detected. Immunohistochemical analysis demonstrated bacterial infection and epidermolysis in infected skin. RT-PCR analysis exhibited a significant induction of proinflammatory cytokines after infection. The BO-drum® is a robust, easy-to-use, sterilizable and reusable ex vivo full-skin culture system. For investigation of wound infection, treatment and healing, the BO-drum® presents a convenient model and may help to standardize wound research

Improvements to water purification and sanitation infrastructure may reduce the diarrheal burden in a marginalized and flood prone population in remote Nicaragua

<p>Abstract</p> <p>Background</p> <p>The isolated northern region of Nicaragua has one of the highest rates of diarrheal disease in Central America. Political and environmental hardships faced by inhabitants of this region are contributing factors to this health inequity. The aim of this study was to assess the relationship between water and latrine infrastructure and the prevalence of diarrhea in this region.</p> <p>Methods</p> <p>A population-based, cross-sectional survey of women of reproductive age was conducted in the Sahsa region of northern Nicaragua in July, 2009. Households were selected by two stage cluster sampling methodology. A questionnaire was administered in Spanish and Miskito with assessment of household and socioeconomic conditions, sanitation practices, and health care access. Diarrhea prevalence differences at the household level over a two week reporting period were estimated with a standardized instrument which included assessment of water treatment and latrine use and maintenance.</p> <p>Results</p> <p>There were 189 women enrolled in the current study. The use of water purification methods, such as chlorine and filters, and latrine ownership were not associated with reduced prevalence of household diarrhea in the two week reporting period. Latrine overflow, however, was associated with an increased prevalence of diarrhea during the same two week period [adjusted prevalence difference and 95% CI: 0.19 (0.03, 0.36)].</p> <p>Conclusions</p> <p>Simple, low cost interventions that improve water and latrine infrastructure may reduce the prevalence of diarrheal disease in the isolated regions of Nicaragua and Central America.</p

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family