Cytogenetic and Reproductive studies of Bulls Born Co-Twin to Freemartins

International audienc

Modelling the global spread of diseases: A review of current practice and capability

Mathematical models can aid in the understanding of the risks associated with the global spread of infectious diseases. To assess the current state of mathematical models for the global spread of infectious diseases, we reviewed the literature highlighting common approaches and good practice, and identifying research gaps. We followed a scoping study method and extracted information from 78 records on: modelling approaches; input data (epidemiological, population, and travel) for model parameterization; model validation data. We found that most epidemiological data come from published journal articles, population data come from a wide range of sources, and travel data mainly come from statistics or surveys, or commercial datasets. The use of commercial datasets may benefit the modeller, however makes critical appraisal of their model by other researchers more difficult. We found a minority of records (26) validated their model. We posit that this may be a result of pandemics, or far-reaching epidemics, being relatively rare events compared with other modelled physical phenomena (e.g. climate change). The sparsity of such events, and changes in outbreak recording, may make identifying suitable validation data difficult. We appreciate the challenge of modelling emerging infections given the lack of data for both model parameterisation and validation, and inherent complexity of the approaches used. However, we believe that open access datasets should be used wherever possible to aid model reproducibility and transparency. Further, modellers should validate their models where possible, or explicitly state why validation was not possible

Using VCP mutant hiPSC-derived motor neurons and glia to capture early molecular pathogenic events in MND

Motor neuron disease (MND) is rapidly progressive and invariably fatal, and with no significantly impactful therapies available to date there is desperate and unmet clinical need. Recent discoveries in the underlying pathology and genetics of MND suggest that altered proteostasis, RNA regulation and glial contribution play key roles in molecular pathogenesis. I have used a combination of human induced pluripotent stem cell (hiPSC) models and functional genomic technologies to characterize early pathogenic events in VCP-related MND. I hypothesize that the early pathogenic events in MND differ during the differentiation of motor neurons and astrocytes; therefore I first generated enriched populations of both motor neurons (MNs) and astrocytes (ACs) from control and VCP mutant patient iPSCs. Next to understand if changes in RNA regulation contribute to pathogenic events in VCP-related MND, I carried out a temporal analysis using RNA sequencing (RNAseq) of control and VCP mutant iPSCs neural derivatives. Additionally, I examined the results of this transcriptional study in light of collaborative live cell imaging experiments, performed across a matched time-course, that have uncovered cell-type specific organellar dysfunction in VCP mutant MNs. This paradigm importantly enabled us to discriminate primary from secondary pathogenic events in VCP-related MND. Further, after the onset of pathogenesis I also used individual nucleotide resolution UV cross linking with immunoprecipitation (iCLIP) to study RNA interactions of the candidate RNA-binding protein TDP43, which forms the pathological hallmark of MND. Together, this provides new insights into the earliest molecular pathogenic events in MND and has highlighted the contribution of both motor neurons and astrocytes. By identifying key disease mechanisms this study aims to guide future therapeutic strategy

HTR4 gene structure and altered expression in the developing lung

Background: Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT4R) gene (HTR4) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach

Linking water quality to living resources in a mid-Atlantic lagoon system, USA

The mid-Atlantic coastal bays are shallow coastal lagoons, separated from the Atlantic Ocean by barrier sand islands with oceanic exchanges restricted to narrow inlets. The relatively poor flushing of these lagoon systems makes them susceptible to eutrophication resulting from anthropogenic nutrient loadings. An intensive water quality and seagrass monitoring program was initiated to track ecological changes in the Maryland and Virginia coastal bays. The purpose of this study was to analyze existing monitoring data to determine status and trends in eutrophication and to determine any associations between water quality and living resources. Analysis of monitoring program data revealed several trends: (1) decadal decreases in nutrient and chlorophyll concentrations, followed by recently increasing trends; (2) decadal increases in seagrass coverage, followed by a recent period of no change; (3) blooms of macroalgae and brown tide microalgae; and (4) exceedance of water quality thresholds: chlorophyll a (15 mu g/L), total nitrogen (0.65 mg/L or 46 mu mol/L), total phosphorus (0.037 mg/L or 1.2 mu mol/L), and dissolved oxygen (5 mg/L) in many areas within the Maryland coastal bays. The water quality thresholds were based on habitat requirements for living resources (seagrass and fish) and used to calculate a water quality index, which was used to compare the bay segments. Strong gradients in water quality were correlated to changes in seagrass coverage between segments. These factors indicate that these coastal bays are in a state of transition, with a suite of metrics indicating degrading conditions. Continued monitoring and intensified management will be required to avert exacerbation of the observed eutrophication trends. Coastal lagoons worldwide are experiencing similar degrading trends due to increasing human pressures, and assessing status and trends relative to biologically relevant thresholds can assist in determining monitoring and management priorities and goals

The indentation response of Nickel nano double gyroid lattices

The indentation response of Nickel nano double gyroid films has been measured using a Berkovich nanoindenter and the effective mechanical properties of the Ni double gyroid lattices inferred via a multi-scale finite element analysis. The 1μm thick double gyroid films were manufactured by block copolymer self-assembly followed by electrodeposition of the Ni resulting in two interpenetrating single gyroids of opposite chirality, an overall relative density of 38% and a cell size of about 45 nm. The measured hardness was ∼0.6 GPa with no discernable indentation size effect. A multi-scale finite element (FE) analysis revealed that the uniaxial compressive strength is approximately equal to the hardness for this compressible lattice. Thus, the 38% relative density Ni double gyroid has a strength equal to or greater than the strongest fully dense bulk Ni alloys. The FE calculations revealed that this was a consequence of that fact that the Ni in the 13 nm gyroid struts was essentially dislocation free and had a strength of about 5.7 GPa, i.e. approaching the theoretical strength value of Ni. The measurements and calculations reported here suggest that in spite of the nano gyroids having a bending-dominated topology they attain strengths higher than those reported for stretching-dominated micron scale lattice materials made via 3D printing. We thus argue that relatively fast and easy self-assembly processes are a competitive alternative to 3D printing manufacture methods for making high strength lattice materials

Seventy years of sex education in Health Education Journal: a critical review

This paper examines key debates and perspectives on sex education in Health Education Journal (HEJ), from the date of the journal’s first publication in March 1943 to the present day. Matters relating to sexuality and sexual health are revealed to be integral to HEJ’s history. First published as Health and Empire (1921 – 1942), a key purpose of the journal since its inception has been to share information on venereal disease and its prevention within the UK and across the former British Empire. From 1943 to the present day, discussions on sex education in the newly-christened HEJ both reflect and respond to evolving socio-cultural attitudes towards sexuality in the UK. Changing definitions of sex education across the decades are examined, from the prevention of venereal disease and moral decline in war-time Britain in the 1940s, to a range of responses to sexual liberation in the 1960s and 1970s; from a focus on preventing sexually-transmitted infections, teenage pregnancy and HIV in the 1980s, to the provision of sexual health services alongside sex education in the 2000s. Over the past 70 years, a shift from prevention of pre-marital sexual activity to the management of its outcomes is apparent; however, while these changes over time are notable, perhaps the most striking findings of this review are the continuities in arguments for and against the discussion of sexual issues. After more than 70 years of debate, it would seem that there is little consensus concerning motivations for and the content of sex education

The singlet scalar as FIMP dark matter

The singlet scalar model is a minimal extension of the Standard Model that can explain the dark matter. We point out that in this model the dark matter constraint can be satisfied not only in the already considered WIMP regime but also, for much smaller couplings, in the Feebly Interacting Massive Particle (FIMP) regime. In it, dark matter particles are slowly produced in the early Universe but are never abundant enough to reach thermal equilibrium or annihilate among themselves. This alternative framework is as simple and predictive as the WIMP scenario but it gives rise to a completely different dark matter phenomenology. After reviewing the calculation of the dark matter relic density in the FIMP regime, we study in detail the evolution of the dark matter abundance in the early Universe and the predicted relic density as a function of the parameters of the model. A new dark matter compatible region of the singlet model is identified, featuring couplings of order 10^-11 to 10^-12 for singlet masses in the GeV to TeV range. As a consequence, no signals at direct or indirect detection experiments are expected. The relevance of this new viable region for the correct interpretation of recent experimental bounds is emphasized.Comment: 12 pages, 6 figure