Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis

Androgens are essential for sexual development and reproduction. However, androgen regulation in health and disease is poorly understood. We showed that human adrenocortical H295R cells grown under starvation conditions acquire a hyperandrogenic steroid profile with changes in steroid metabolizing enzymes HSD3B2 and CYP17A1 essential for androgen production. Here we studied the regulatory mechanisms underlying androgen production in starved H295R cells. Microarray expression profiling of normal versus starved H295R cells revealed fourteen differentially expressed genes; HSD3B2, HSD3B1, CYP21A2, RARB, ASS1, CFI, ASCL1 and ENC1 play a role in steroid and energy metabolism and ANGPTL1, PLK2, DUSP6, DUSP10 and FREM2 are involved in signal transduction. We discovered two new gene networks around RARB and ANGPTL1, and show how they regulate androgen biosynthesis. Transcription factor RARB stimulated the promoters of genes involved in androgen production (StAR, CYP17A1 and HSD3B2) and enhanced androstenedione production. For HSD3B2 regulation RARB worked in cooperation with Nur77. Secretory protein ANGPTL1 modulated CYP17A1 and DUSP6 expression by inducing ERK1/2 phosphorylation. By contrast, our studies revealed no evidence for hormones or cell cycle involvement in regulating androgen biosynthesis. In summary, these studies establish a firm role for RARB and ANGPTL1 in the regulation of androgen production in H295R cells.

In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements: We thank Ms Margaret Fraser, Ms Samantha Flannigan, and Dr Wing Yee Kwong for their expert assistance. The staff at Grampian NHS Pregnancy Counselling Service were essential for collecting fetuses. We thank Professor Geoffrey Hammond and Dr Marc Simard, University of British Colombia for helpful comments on the manuscript. Supported by grants as follows: Scottish Senior Clinical Fellowship (AJD); Chief Scientist Office (Scottish Executive, CZG/1/109 to PAF, & CZG/4/742 (PAF & PJOS); NHS Grampian Endowments 08/02 (PAF, SB & PJOS); the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no 212885 (PAF & SMR); the Medical Research Council grants MR/L010011/1 (PAF & PJOS) and MR/K018310/1 (AJD). None of the funding bodies played any role in the design, collection, analysis, and interpretation of data, in the writing of the manuscript, nor in the decision to submit the manuscript for publication

Maternal smoking dysregulates protein expression in second trimester human fetal livers in a sex-specific manner

Acknowledgments The staff at Grampian National Health Service Pregnancy Counseling Service were essential for collecting fetuses. We thank the Aberdeen Proteomics Core Facility (University of Aberdeen) for their expert assistance. Support for the study was provided by the Chief Scientist Office (Scottish Executive, CZG/1/109, & CZG/4/742), National Health Service Grampian Endowments (08/02), the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no 212885, and the Medical Research Council, UK (MR/L010011/1).

Neuronal human BACE1 knock-in induces systemic diabetes in mice

Funding We would like to thank R. Simcox, Romex Oilfield Chemicals, for financial support for KP, and acknowledge additional contributions from the Scottish Alzheimer’s Research UK network for the lipidomics work. The College of Life Science and Medicine, University of Aberdeen, sponsored the imaging study. MD was funded by British Heart Foundation and Diabetes UK; NM was funded by a British Heart Foundation Intermediate Fellowship; KS was funded by a European Foundation for the Study of Diabetes/Lilly programme grant; and RD was funded by an Institute of Medical Sciences PhD studentship.

Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment

IA, JNP, and MP were partly supported by the NIH, grants R01-AI-100947 to MP, and R21-GM-107683 to Matthias Chung, subcontract to MP. JNP was partly supported by an NSF graduate fellowship number DGE750616. IA, JNP, BRL, OCS and MP were supported in part by the Bill and Melinda Gates Foundation, award number 42917 to OCS. JP and AWW received core funding support from The Wellcome Trust (grant number 098051). AWW, and the Rowett Institute of Nutrition and Health, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS).

Generation of Functional Beta-Like Cells from Human Exocrine Pancreas

Funding: This work was supported by a grant from the Medical Research Council MR/J015277/1. The Scottish National Islet Transplant Programme is funded by the National Services Division of NHS Scotland. KRM was funded by a Fellowship from the Wellcome Trust / Scottish Translational Medicine and Therapeutics Initiative 85664. Acknowledgments This work was supported by a grant from the Medical Research Council MR/J015277/1. The Scottish National Islet Transplant Programme is funded by the National Services Division of NHS Scotland. KRM was funded by a Fellowship from the Wellcome Trust/ Scottish Translational Medicine and Therapeutics Initiative 85664. We thank Joanna Sweetman for assistance in optimisation of the immunogold staining.

Molecular markers reveal that population structure of the human pathogen Candida albicans exhibits both clonality and recombination.

The life history of Candida albicans presents an enigma: this species is thought to be exclusively asexual, yet strains show extensive phenotypic variation. To address the population genetics of C. albicans, we developed a genetic typing method for codominant single-locus markers by screening randomly amplified DNA for single-strand conformation polymorphisms. DNA fragments amplified by arbitrary primers were initially screened for single-strand conformation polymorphisms and later sequenced using locus-specific primers. A total of 12 single base mutations and insertions were detected from six out of eight PCR fragments. Patterns of sequence-level polymorphism observed for individual strains detected considerable heterozygosity at the DNA sequence level, supporting the view that most C. albicans strains are diploid. Population genetic analyses of 52 natural isolates from Duke University Medical Center provide evidence for both clonality and recombination in C. albicans. Evidence for clonality is supported by the presence of several overrepresented genotypes, as well as by deviation of genotypic frequencies from random (Hardy-Weinberg) expectations. However, tests for nonrandom association of alleles across loci reveal less evidence for linkage disequilibrium than expected for strictly clonal populations. Although C. albicans populations are primarily clonal, evidence for recombination suggests that sexual reproduction or some other form of genetic exchange occurs in this species.

Stability and sensitivity analysis of Be-CoDiS, an epidemiological model to predict the spread of human diseases between countries. Validation with data from the 2014-16 West African Ebola Virus Disease epidemic.

Ebola virus disease is a lethal human and primate disease that requires a particular attention from the international health authorities due to important recent outbreaks in some Western African countries and isolated cases in European and North-America continents. Regarding the emergency of this situation, various decision tools, such as mathematical models, were developed to assist the authorities to focus their efforts in important factors to eradicate Ebola. In a previous work, we have proposed an original deterministic spatial-temporal model, called Be-CoDiS (Between-Countries Disease Spread), to study the evolution of human diseases within and between countries by taking into consideration the movement of people between geographical areas. This model was validated by considering numerical experiments regarding the 2014-16 West African Ebola Virus Disease epidemic. In this article, we propose to perform a stability analysis of Be-CoDiS. Our first objective is to study the equilibrium states of simplified versions of this model, limited to the cases of one an two countries, and to determine their basic reproduction ratios. Then, in order to give some recommendations for the allocation of resources used to control the disease, we perform a sensitivity analysis of those basic reproduction ratios regarding the model parameters. Finally, we validate the obtained results by considering numerical experiments based on data from the 2014-16 West African Ebola Virus Disease epidemic.

Transcription of liver X receptor is down-regulated by 15-deoxy-Δ12,14-prostaglandin J2 through oxidative stress in human neutrophils

Liver X receptors (LXRs) are ligand-activated transcription factors of the nuclear receptor superfamily. They play important roles in controlling cholesterol homeostasis and as regulators of inflammatory gene expression and innate immunity, by blunting the induction of classical pro-inflammatory genes. However, opposite data have also been reported on the consequences of LXR activation by oxysterols, resulting in the specific production of potent pro-inflammatory cytokines and reactive oxygen species (ROS). The effect of the inflammatory state on the expression of LXRs has not been studied in human cells, and constitutes the main aim of the present work. Our data show that when human neutrophils are triggered with synthetic ligands, the synthesis of LXRα mRNA became activated together with transcription of the LXR target genes ABCA1, ABCG1 and SREBP1c. An inflammatory mediator, 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), hindered T0901317-promoted induction of LXRα mRNA expression together with transcription of its target genes in both neutrophils and human macrophages. This down-regulatory effect was dependent on the release of reactive oxygen species elicited by 15dPGJ2, since it was enhanced by pro-oxidant treatment and reversed by antioxidants, and was also mediated by ERK1/2 activation. Present data also support that the 15dPGJ2-induced serine phosphorylation of the LXRα molecule is mediated by ERK1/2. These results allow to postulate that down-regulation of LXR cellular levels by pro-inflammatory stimuli might be involved in the development of different vascular diseases, such as atherosclerosis.

The relationship between plants used to sustain finches (Fringillidae) and uses for human medicine in southeast Spain

We analyzed plants that are traditionally used by wild bird hunters and breeders to capture and promote captive breeding of Fringillidae (finches or songbirds) in the province of Alicante, Spain. The majority of plants used in songbird breeding have medicinal properties in traditional human medicine (48 different uses); thus, another main goal was to show their relationships with human medical uses. We compiled a list of 97 plant species from 31 botanical families that are used to attract finches and identified 11 different use categories for these plants in finch keeping. The most common uses were for trapping birds and as a source of food for birds in captivity. Cannabis sativa has the greatest cultural importance index (CI = 1.158), and Phalaris canariensis (annual canary grass or alpist) was the most common species used to attract Fringillidae and was used by all informants (n = 158). Most of the 97 species are wild plants and mainly belong to the families Compositae, Gramineae, Cruciferae, and Rosaceae and also have medicinal properties for humans. In the study area, the intensification of agriculture and abandonment of traditional management practices have caused the population of many songbirds to decline, as well as the loss of popular ethnographic knowledge.

3D visual sensing of human hand for remote operation of a robotic hand

New low cost sensors and open free libraries for 3D image processing are making important advances in robot vision applications possible, such as three-dimensional object recognition, semantic mapping, navigation and localization of robots, human detection and/or gesture recognition for human-machine interaction. In this paper, a novel method for recognizing and tracking the fingers of a human hand is presented. This method is based on point clouds from range images captured by a RGBD sensor. It works in real time and it does not require visual marks, camera calibration or previous knowledge of the environment. Moreover, it works successfully even when multiple objects appear in the scene or when the ambient light is changed. Furthermore, this method was designed to develop a human interface to control domestic or industrial devices, remotely. In this paper, the method was tested by operating a robotic hand. Firstly, the human hand was recognized and the fingers were detected. Secondly, the movement of the fingers was analysed and mapped to be imitated by a robotic hand.

Knowledge and attitudes of Spanish adolescent girls towards human papillomavirus infection: where to intervene to improve vaccination coverage

Background: HPV vaccine coverage is far from ideal in Valencia, Spain, and this could be partially related to the low knowledge about the disease and the vaccine, therefore we assessed these, as well as the attitude towards vaccination in adolescent girls, and tried to identify independently associated factors that could potentially be modified by an intervention in order to increase vaccine coverage. Methods: A cross sectional study was conducted in a random selection of schools of the Spanish region of Valencia. We asked mothers of 1278 girls, who should have been vaccinated in the 2011 campaign, for informed consent. Those that accepted their daughters’ participation, a questionnaire regarding the Knowledge of HPV infection and vaccine was passed to the girls in the school. Results: 833 mothers (65.1%) accepted participation. All their daughters’ responded the questionnaire. Of those, 89.9% had heard about HPV and they associated it to cervical cancer. Only 14% related it to other problems like genital warts. The knowledge score of the girls who had heard about HPV was 6.1/10. Knowledge was unrelated to the number of contacts with the health system (Pediatrician or nurse), and positively correlated with the discussions with classmates about the vaccine. Adolescents Spanish in origin or with an older sister vaccinated, had higher punctuation. 67% of the girls thought that the vaccine prevented cancer, and 22.6% felt that although prevented cancer the vaccine had important safety problems. 6.4% of the girls rejected the vaccine for safety problems or for not considering themselves at risk of infection. 71.5% of the girls had received at least one vaccine dose. Vaccinated girls scored higher knowledge (p = 0.05). Conclusion: Knowledge about HPV infection and vaccine was fair in adolescents of Valencia, and is independent to the number of contacts with the health system, it is however correlated to the conversations about the vaccine with their peers and the vaccination status. An action to improve HPV knowledge through health providers might increase vaccine coverage in the adolescents.

Human physiology /

v. 1-2 edited by Dr. M. Camis; v. 3-4, by Gordon M. Holmes; v.5, by M.S. Pembrey.

Desperately seeking donors: The 'saviour siblings' decision in quintaville v human fertilisation embryology authority (UK)

The recent House of Lords decision in Quintavalle v Human Fertilisation and Embryology Authority has raised difficult and complex issues regarding the extent to which embryo selection and reproductive technology can be used as a means of rectifying genetic disorders and treating critically ill children. This comment outlines the facts of Quintavalle and explores how the House of Lords approached the legal, ethical and policy issues that arose out of the Human Fertilisation and Embryology Authority's (UK) decision to allow reproductive and embryo technology to be used to produce a 'saviour sibling' whose tissue could be used to save the life of a critically ill child. Particular attention will be given to the implications of the decision in Quintavalle for Australian family and medical law and policy. As part of this focus, the comment explores the current Australian legislative and policy framework regarding the use of genetic and reproductive technology as a mechanism through which to assist critically ill siblings. It is argued that the present Australian framework would appear to impose significant limits on the medical uses of genetic technology and, in this context, would seem to reflect many of the principles that were articulated by the House of Lords in Quintavalle.

Representation of Maximally Regular Textures in Human Visual Cortex

Copyright © 2016 the authors 0270-6474/16/360714-16$15.00/0. This research was supported by National Science Foundation INSPIRE Grant 1248076, which was awarded to Y.L. and A.M.N.