Testing for HFE-related haemochromatosis

HFE-haemochromatosis is a genetic disorder resulting from mutations of the HFE gene. It primarily affects people of Northern European descent. Clinical manifestations result from the progressive deposition of iron into various organs including the liver. An elevated serum ferritin concentration greater than 300 microgram/L and a transferrin saturation of greater than 45% will identify almost all patients with HFE-haemochromatosis. HFE genotyping confirms the diagnosis. In some patients, liver biopsy may still be necessary as the degree of hepatic fibrosis has prognostic implications

Long range transport of ultra cold atoms in a far-detuned 1D optical lattice

We present a novel method to transport ultra cold atoms in a focused optical lattice over macroscopic distances of many Rayleigh ranges. With this method ultra cold atoms were transported over 5 cm in 250 ms without significant atom loss or heating. By translating the interference pattern together with the beam geometry the trap parameters are maintained over the full transport range. Thus, the presented method is well suited for tightly focused optical lattices that have sufficient trap depth only close to the focus. Tight focusing is usually required for far-detuned optical traps or traps that require high laser intensity for other reasons. The transport time is short and thus compatible with the operation of an optical lattice clock in which atoms are probed in a well designed environment spatially separated from the preparation and detection region.Comment: 14 pages, 6 figure

The role of mtDNA in oocyte quality and embryo development

OnlinePublThe mitochondrial genome resides in the mitochondria present in nearly all cell types.The porcine (Sus scrofa) mitochondrial genome is circa 16.7 kb in size and exists in the multimeric format in cells. Individual cell types have different numbers of mitochondrial DNA (mtDNA) copy number based on their requirements for ATP produced byoxidative phosphorylation. The oocyte has the largest number of mtDNA of any celltype. During oogenesis, the oocyte sets mtDNA copy number in order that sufficient copies are available to support subsequent developmental events. It also initiates a program of epigenetic patterning that regulates, for example, DNA methylation levels of the nuclear genome. Once fertilized, the nuclear and mitochondrial genomes establish synchrony to ensure that the embryo and fetus can complete each developmental milestone. However, altering the oocyte's mtDNA copy number by mitochondrial supplementation can affect the programming and gene expression profiles of the developing embryo and, in oocytes deficient of mtDNA, it appears to have a positive impact on the embryo development rates and gene expression profiles. Furthermore,mtDNA haplotypes, which define common maternal origins, appear to affect developmental outcomes and certain reproductive traits. Nevertheless, the manipulation of the mitochondrial content of an oocyte might have a developmental advantage.Justin C. St John, Takashi Okada, Eryk Andreas, Alexander Pen

Construction and Assembly of the Wire Planes for the MicroBooNE Time Projection Chamber

In this paper we describe how the readout planes for the MicroBooNE Time Projection Chamber were constructed, assembled and installed. We present the individual wire preparation using semi-automatic winding machines and the assembly of wire carrier boards. The details of the wire installation on the detector frame and the tensioning of the wires are given. A strict quality assurance plan ensured the integrity of the readout planes. The different tests performed at all stages of construction and installation provided crucial information to achieve the successful realisation of the MicroBooNE wire planes.Comment: 24 pages, 22 figures, accepted for publication as Technical Report in JINS

Longitudinal cohort of HIV-negative transgender women of colour in New York City: protocol for the TURNNT ('Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour') study.

IntroductionIn the USA, transgender women are among the most vulnerable to HIV. In particular, transgender women of colour face high rates of infection and low uptake of important HIV prevention tools, including pre-exposure prophylaxis (PrEP). This paper describes the design, sampling methods, data collection and analyses of the TURNNT ('Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour') study. In collaboration with communities of transgender women of colour, TURNNT aims to explore the complex social and environmental (ie, neighbourhood) structures that affect HIV prevention and other aspects of health in order to identify avenues for intervention.Methods and analysesTURNNT is a prospective cohort study, which will recruit 300 transgender women of colour (150 Black/African American, 100 Latina and 50 Asian/Pacific Islander participants) in New York City. There will be three waves of data collection separated by 6 months. At each wave, participants will provide information on their relationships, social and sexual networks, and neighbourhoods. Global position system technology will be used to generate individual daily path areas in order to estimate neighbourhood-level exposures. Multivariate analyses will be conducted to assess cross-sectional and longitudinal, independent and synergistic associations of personal relationships (notably individual social capital), social and sexual networks, and neighbourhood factors (notably neighbourhood-level social cohesion) with PrEP uptake and discontinuation.Ethics and disseminationThe TURNNT protocol was approved by the Columbia University Institutional Review Board (reference no. AAAS8164). This study will provide novel insights into the relationship, network and neighbourhood factors that influence HIV prevention behaviours among transgender women of colour and facilitate exploration of this population's health and well-being more broadly. Through community-based dissemination events and consultation with policy makers, this foundational work will be used to guide the development and implementation of future interventions with and for transgender women of colour

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Periscope Proteins are variable-length regulators of bacterial cell surface interactions

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this “rule,” suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system