TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis

Background: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS. Methodology/Principal Findings: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus

Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62552/1/nature06742.pd

The Baryon Census in a Multiphase Intergalactic Medium: 30% of the Baryons May Still Be Missing

For low-redshift cosmology and galaxy formation rates, it is important to account for all the baryons synthesized in the Big Bang. Although galaxies and clusters contain 10% of the baryons, many more reside in the photoionized Lyman-alpha forest and shocked-heated warm-hot intergalactic medium (WHIM) at T = 10^5 to 10^7 K. Current tracers of WHIM at 10^5 to 10^6 K include the O VI 1032, 1038 absorption lines, together with broad Lyman-alpha absorbers (BLAs) and EUV/X-ray absorption lines from Ne VIII, O VII, and O VIII. We improve the O VI baryon surveys with corrections for oxygen metallicity (Z/Zsun) and O VI ionization fraction (f_OVI) using cosmological simulations of heating, cooling, and metal transport in a density-temperature structured medium. Statistically, their product correlates with column density, (Z/Zsun)(f_OVI) = (0.015)(N_OVI/10^{14} cm^-2)^0.70. The N_OVI-weighted mean is 0.01, which doubles previous estimates of WHIM baryon content. We also reanalyze H I data from the Hubble Space Telescope, applying redshift corrections for absorber density, photoionizing background, and proper length, dl/dz. We find substantial baryon fractions in the photoionized Lya forest (28 +/- 11%), O VI/BLA-traced WHIM (25 +/- 8%), and collapsed phase (18 +/- 4%) in galaxies, groups, clusters, and circumgalactic gas. The baryon shortfall is 29 +/- 13%, which may be detected in X-ray absorbers from hotter WHIM or in weaker Lya and O VI absorbers. Further progress will require higher-precision baryon surveys of weak absorbers at column densities N_HI > 10^{12.0} cm^-2, N_OVI > 10^{12.5} cm^-2, and N_OVII > 10^{14.5} cm^-2, with moderate-resolution UV and X-ray spectrographs.Comment: 14 pages, 9 figures, revised submission to ApJ (new Fig 2, Appendices A,B

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Nuclear and Chloroplast Microsatellites Show Multiple Introductions in the Worldwide Invasion History of Common Ragweed, Ambrosia artemisiifolia

BACKGROUND: Ambrosia artemisiifolia is a North American native that has become one of the most problematic invasive plants in Europe and Asia. We studied its worldwide population genetic structure, using both nuclear and chloroplast microsatellite markers and an unprecedented large population sampling. Our goals were (i) to identify the sources of the invasive populations; (ii) to assess whether all invasive populations were founded by multiple introductions, as previously found in France; (iii) to examine how the introductions have affected the amount and structure of genetic variation in Europe; (iv) to document how the colonization of Europe proceeded; (v) to check whether populations exhibit significant heterozygote deficiencies, as previously observed. PRINCIPAL FINDINGS: We found evidence for multiple introductions of A. artemisiifolia, within regions but also within populations in most parts of its invasive range, leading to high levels of diversity. In Europe, introductions probably stem from two different regions of the native area: populations established in Central Europe appear to have originated from eastern North America, and Eastern European populations from more western North America. This may result from differential commercial exchanges between these geographic regions. Our results indicate that the expansion in Europe mostly occurred through long-distance dispersal, explaining the absence of isolation by distance and the weak influence of geography on the genetic structure in this area in contrast to the native range. Last, we detected significant heterozygote deficiencies in most populations. This may be explained by partial selfing, biparental inbreeding and/or a Wahlund effect and further investigation is warranted. CONCLUSIONS: This insight into the sources and pathways of common ragweed expansion may help to better understand its invasion success and provides baseline data for future studies on the evolutionary processes involved during range expansion in novel environments