76 research outputs found
Rare single gene disorders:estimating baseline prevalence and outcomes worldwide
As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families. When considered collectively, they account for an important public health burden, which is frequently under-recognised. To document the collective frequency and health burden of rare single gene disorders, it is necessary to aggregate them into large manageable groupings and take account of their family implications, effective interventions and service needs. Here, we present an approach to estimate the burden of these conditions up to 5 years of age in settings without empirical data. This approaches uses population-level demographic data, combined with assumptions based on empirical data from settings with data available, to provide population-level estimates which programmes and policy-makers when planning services can use
A review of elliptical and disc galaxy structure, and modern scaling laws
A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their
models to describe the radial distribution of stars in `nebulae'. This article
reviews the progress since then, providing both an historical perspective and a
contemporary review of the stellar structure of bulges, discs and elliptical
galaxies. The quantification of galaxy nuclei, such as central mass deficits
and excess nuclear light, plus the structure of dark matter halos and cD galaxy
envelopes, are discussed. Issues pertaining to spiral galaxies including dust,
bulge-to-disc ratios, bulgeless galaxies, bars and the identification of
pseudobulges are also reviewed. An array of modern scaling relations involving
sizes, luminosities, surface brightnesses and stellar concentrations are
presented, many of which are shown to be curved. These 'redshift zero'
relations not only quantify the behavior and nature of galaxies in the Universe
today, but are the modern benchmark for evolutionary studies of galaxies,
whether based on observations, N-body-simulations or semi-analytical modelling.
For example, it is shown that some of the recently discovered compact
elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to
appear in "Planets, Stars and Stellar
Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references
incl. many somewhat forgotten, pioneer papers. Original submission to
Springer: 07-June-201
Engineering Yarrowia lipolytica to Produce Glycoproteins Homogeneously Modified with the Universal Man3GlcNAc2 N-Glycan Core
Yarrowia lipolytica is a dimorphic yeast that efficiently secretes various heterologous proteins and is classified as “generally recognized as safe.” Therefore, it is an attractive protein production host. However, yeasts modify glycoproteins with non-human high mannose-type N-glycans. These structures reduce the protein half-life in vivo and can be immunogenic in man. Here, we describe how we genetically engineered N-glycan biosynthesis in Yarrowia lipolytica so that it produces Man3GlcNAc2 structures on its glycoproteins. We obtained unprecedented levels of homogeneity of this glycanstructure. This is the ideal starting point for building human-like sugars. Disruption of the ALG3 gene resulted in modification of proteins mainly with Man5GlcNAc2 and GlcMan5GlcNAc2 glycans, and to a lesser extent with Glc2Man5GlcNAc2 glycans. To avoid underoccupancy of glycosylation sites, we concomitantly overexpressed ALG6. We also explored several approaches to remove the terminal glucose residues, which hamper further humanization of N-glycosylation; overexpression of the heterodimeric Apergillus niger glucosidase II proved to be the most effective approach. Finally, we overexpressed an α-1,2-mannosidase to obtain Man3GlcNAc2 structures, which are substrates for the synthesis of complex-type glycans. The final Yarrowia lipolytica strain produces proteins glycosylated with the trimannosyl core N-glycan (Man3GlcNAc2), which is the common core of all complex-type N-glycans. All these glycans can be constructed on the obtained trimannosyl N-glycan using either in vivo or in vitro modification with the appropriate glycosyltransferases. The results demonstrate the high potential of Yarrowia lipolytica to be developed as an efficient expression system for the production of glycoproteins with humanized glycans
Production in Pichia pastoris of complementary protein-based polymers with heterodimer-forming WW and PPxY domains
Religious Factors and Hippocampal Atrophy in Late Life
Despite a growing interest in the ways spiritual beliefs and practices are reflected in brain activity, there have been relatively few studies using neuroimaging data to assess potential relationships between religious factors and structural neuroanatomy. This study examined prospective relationships between religious factors and hippocampal volume change using high-resolution MRI data of a sample of 268 older adults. Religious factors assessed included life-changing religious experiences, spiritual practices, and religious group membership. Hippocampal volumes were analyzed using the GRID program, which is based on a manual point-counting method and allows for semi-automated determination of region of interest volumes. Significantly greater hippocampal atrophy was observed for participants reporting a life-changing religious experience. Significantly greater hippocampal atrophy was also observed from baseline to final assessment among born-again Protestants, Catholics, and those with no religious affiliation, compared with Protestants not identifying as born-again. These associations were not explained by psychosocial or demographic factors, or baseline cerebral volume. Hippocampal volume has been linked to clinical outcomes, such as depression, dementia, and Alzheimer's Disease. The findings of this study indicate that hippocampal atrophy in late life may be uniquely influenced by certain types of religious factors
Gravitational-wave research as an emerging field in the Max Planck Society. The long roots of GEO600 and of the Albert Einstein Institute
On the occasion of the 50th anniversary since the beginning of the search for
gravitational waves at the Max Planck Society, and in coincidence with the 25th
anniversary of the foundation of the Albert Einstein Institute, we explore the
interplay between the renaissance of general relativity and the advent of
relativistic astrophysics following the German early involvement in
gravitational-wave research, to the point when gravitational-wave detection
became established by the appearance of full-scale detectors and international
collaborations. On the background of the spectacular astrophysical discoveries
of the 1960s and the growing role of relativistic astrophysics, Ludwig Biermann
and his collaborators at the Max Planck Institute for Astrophysics in Munich
became deeply involved in research related to such new horizons. At the end of
the 1960s, Joseph Weber's announcements claiming detection of gravitational
waves sparked the decisive entry of this group into the field, in parallel with
the appointment of the renowned relativist Juergen Ehlers. The Munich area
group of Max Planck institutes provided the fertile ground for acquiring a
leading position in the 1970s, facilitating the experimental transition from
resonant bars towards laser interferometry and its innovation at increasingly
large scales, eventually moving to a dedicated site in Hannover in the early
1990s. The Hannover group emphasized perfecting experimental systems at pilot
scales, and never developed a full-sized detector, rather joining the LIGO
Scientific Collaboration at the end of the century. In parallel, the Max Planck
Institute for Gravitational Physics (Albert Einstein Institute) had been
founded in Potsdam, and both sites, in Hannover and Potsdam, became a unified
entity in the early 2000s and were central contributors to the first detection
of gravitational waves in 2015.Comment: 94 pages. Enlarged version including new results from further
archival research. A previous version appears as a chapter in the volume The
Renaissance of General Relativity in Context, edited by A. Blum, R. Lalli and
J. Renn (Boston: Birkhauser, 2020
An overview of concepts and approaches used in estimating the burden of congenital disorders globally.
Congenital disorders are an important cause of pregnancy loss, premature death and life-long disability. A range of interventions can greatly reduce their burden, but the absence of local epidemiological data on their prevalence and the impact of interventions impede policy and service development in many countries. In an attempt to overcome these deficiencies, we have developed a tool-The Modell Global Database of Congenital Disorders (MGDb) that combines general biological principles and available observational data with demographic data, to generate estimates of the birth prevalence and effects of interventions on mortality and disability due to congenital disorders. MGDb aims to support policy development by generating country, regional and global epidemiological estimates. Here we provide an overview of the concepts and methodological approach used to develop MGDb
Biofilm formation assessment in Sinorhizobium meliloti reveals interlinked control with surface motility
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