1,643 research outputs found
Election turnout statistics in many countries: similarities, differences, and a diffusive field model for decision-making
We study in details the turnout rate statistics for 77 elections in 11
different countries. We show that the empirical results established in a
previous paper for French elections appear to hold much more generally. We find
in particular that the spatial correlation of turnout rates decay
logarithmically with distance in all cases. This result is quantitatively
reproduced by a decision model that assumes that each voter makes his mind as a
result of three influence terms: one totally idiosyncratic component, one
city-specific term with short-ranged fluctuations in space, and one long-ranged
correlated field which propagates diffusively in space. A detailed analysis
reveals several interesting features: for example, different countries have
different degrees of local heterogeneities and seem to be characterized by a
different propensity for individuals to conform to the cultural norm. We
furthermore find clear signs of herding (i.e. strongly correlated decisions at
the individual level) in some countries, but not in others.Comment: 15 pages, 9 figures, 7 table
Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro.
Oligodendroglial cells are known to de-acetylate the N-acetylaspartate (NAA) synthesized and released by neurons and use it for lipid synthesis. However, the role of NAA regarding their intermediary metabolism remains poorly understood. Two hypotheses were proposed regarding the fate of aspartate after being released by de-acetylation: (1) aspartate is metabolized in the mitochondria of oligodendrocyte lineage cells; (2) aspartate is released to the medium. We report here that aspartoacylase mRNA expression increases when primary rat oligodendrocyte progenitor cells (OPCs) differentiate into mature cells in culture. Moreover, characterising metabolic functions of acetyl coenzyme A and aspartate from NAA catabolism in mature oligodendrocyte cultures after 5 days using isotope-labelled glucose after 5-days of differentiation we found evidence of extensive NAA metabolism. Incubation with [1,6-13C]glucose followed by gas chromatography-mass spectrometry and high performance liquid chromatography analyses of cell extracts and media in the presence and absence of NAA established that the acetate moiety produced by hydrolysis of NAA does not enter mitochondrial metabolism in the form of acetyl coenzyme A. We also resolved the controversy concerning the possible release of aspartate to the medium: aspartate is not released to the medium by oligodendrocytes in amounts detectable by our methods. Therefore we propose that: aspartate released from NAA joins the cytosolic aspartate pool rapidly and takes part in the malate-aspartate shuttle, which transports reducing equivalents from glycolysis into the mitochondria for ATP production and enters the tricarboxylic acid cycle at a slow rate.This work was supported by grants from the
UK Multiple Sclerosis Society and from Qatar Foundation. The
work was further supported by core funding from the Wellcome
Trust and MRC to the Wellcome Trust-Medical Research Council
Cambridge Stem Cell Institute. The authors acknowledge the excellent
technical support in GC-MS and HPLC analysis from Lars Evje
(NTNU, Norway).This is the final version of the article. It first appeared from Springer at http://dx.doi.org/10.1007/s11064-016-1985-y
A method for studying protistan diversity using massively parallel sequencing of V9 hypervariable regions of small-subunit ribosomal RNA genes
© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 4 (2009): e6372, doi:10.1371/journal.pone.0006372.Massively parallel pyrosequencing of amplicons from the V6 hypervariable regions of small-subunit (SSU) ribosomal RNA (rRNA) genes is commonly used to assess diversity and richness in bacterial and archaeal populations. Recent advances in pyrosequencing technology provide read lengths of up to 240 nucleotides. Amplicon pyrosequencing can now be applied to longer variable regions of the SSU rRNA gene including the V9 region in eukaryotes. We present a protocol for the amplicon pyrosequencing of V9 regions for eukaryotic environmental samples for biodiversity inventories and species richness estimation. The International Census of Marine Microbes (ICoMM) and the Microbial Inventory Research Across Diverse Aquatic Long Term Ecological Research Sites (MIRADA-LTERs) projects are already employing this protocol for tag sequencing of eukaryotic samples in a wide diversity of both marine and freshwater environments. Massively parallel pyrosequencing of eukaryotic V9 hypervariable regions of SSU rRNA genes provides a means of estimating species richness from deeply-sampled populations and for discovering novel species from the environment.This work was supported by grants from the W.M. Keck Foundation and the Woods Hole Center for Oceans and Human Health from the National
Institutes of Health and National Science Foundation (NIH/NIEHS 1 P50 ES012742-01 and NSF/OCE 0430724-J) (LAZ and SH)
CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis
BACKGROUND:
Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR.
METHODS:
After conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of NTLA-2001 in six patients with hereditary ATTR amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study.
RESULTS:
Preclinical studies showed durable knockout of TTR after a single dose. Serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. Dose-dependent pharmacodynamic effects were observed. At day 28, the mean reduction from baseline in serum TTR protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram.
CONCLUSIONS:
In a small group of patients with hereditary ATTR amyloidosis with polyneuropathy, administration of NTLA-2001 was associated with only mild adverse events and led to decreases in serum TTR protein concentrations through targeted knockout of TTR. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051. opens in new tab.
Eukaryotic richness in the abyss: insights from pyrotag sequencing
Background: The deep sea floor is considered one of the most diverse ecosystems on Earth. Recent environmental DNA surveys based on clone libraries of rRNA genes confirm this observation and reveal a high diversity of eukaryotes present in deep-sea sediment samples. However, environmental clone-library surveys yield only a modest number of sequences with which to evaluate the diversity of abyssal eukaryotes. Methodology/Principal Findings: Here, we examined the richness of eukaryotic DNA in deep Arctic and Southern Ocean samples using massively parallel sequencing of the 18S ribosomal RNA (rRNA) V9 hypervariable region. In very small volumes of sediments, ranging from 0.35 to 0.7 g, we recovered up to 7,499 unique sequences per sample. By clustering sequences having up to 3 differences, we observed from 942 to 1756 Operational Taxonomic Units (OTUs) per sample. Taxonomic analyses of these OTUs showed that DNA of all major groups of eukaryotes is represented at the deep-sea floor. The dinoflagellates, cercozoans, ciliates, and euglenozoans predominate, contributing to 17%, 16%, 10%, and 8% of all assigned OTUs, respectively. Interestingly, many sequences represent photosynthetic taxa or are similar to those reported from the environmental surveys of surface waters. Moreover, each sample contained from 31 to 71 different metazoan OTUs despite the small sample volume collected. This indicates that a significant faction of the eukaryotic DNA sequences likely do not belong to living organisms, but represent either free, extracellular DNA or remains and resting stages of planktonic species. Conclusions/Significance: In view of our study, the deep-sea floor appears as a global DNA repository, which preserves genetic information about organisms living in the sediment, as well as in the water column above it. This information can be used for future monitoring of past and present environmental changes.French ANR Aquaparadox; ANR DeepOases; Swiss National Science Foundation [31003A-125372]; WM Keck foundationinfo:eu-repo/semantics/publishedVersio
PCR Primers for Metazoan Mitochondrial 12S Ribosomal DNA Sequences
Background: Assessment of the biodiversity of communities of small organisms is most readily done using PCR-based analysis of environmental samples consisting of mixtures of individuals. Known as metagenetics, this approach has transformed understanding of microbial communities and is beginning to be applied to metazoans as well. Unlike microbial studies, where analysis of the 16S ribosomal DNA sequence is standard, the best gene for metazoan metagenetics is less clear. In this study we designed a set of PCR primers for the mitochondrial 12S ribosomal DNA sequence based on 64 complete mitochondrial genomes and then tested their efficacy. Methodology/Principal Findings: A total of the 64 complete mitochondrial genome sequences representing all metazoan classes available in GenBank were downloaded using the NCBI Taxonomy Browser. Alignment of sequences was performed for the excised mitochondrial 12S ribosomal DNA sequences, and conserved regions were identified for all 64 mitochondrial genomes. These regions were used to design a primer pair that flanks a more variable region in the gene. Then all of the complete metazoan mitochondrial genomes available in NCBI’s Organelle Genome Resources database were used to determine the percentage of taxa that would likely be amplified using these primers. Results suggest that these primers will amplify target sequences for many metazoans. Conclusions/Significance: Newly designed 12S ribosomal DNA primers have considerable potential for metazoa
The prevalence of common skin infections in four districts in Timor-Leste: a cross sectional survey
Background\ud
Skin infections are a common public health problem in developing countries; however, they are rarely managed using a population based approach. Recent data on the burden of skin infections in Timor-Leste are limited. Our survey appears to be the only widespread survey conducted in more than 30 years and was designed to determine the baseline prevalence of some common skin infections in Timor-Leste.\ud
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Methods\ud
We conducted a cross sectional survey in 14 sites including community health clinics, schools and hospitals within four different geographical regions. Participants were examined for five conditions (scabies, pyoderma, fungal infections, leprosy and yaws) by a multidisciplinary team. Analyses were conducted using EpiInfo version 6.04d.\ud
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Results\ud
We examined the skin of 1535 participants aged between four months and 97 years. The majority of participants were male, aged between 11 and 20 years and had at least one condition of interest (56.0%, 56.0%, and 63.1%, respectively). Fungal infections were the most common presentation (39.0%) and males were more commonly affected than females (42.3% vs 34.0%, respectively, pvalue < 0.0001).\ud
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Among those people with more than one condition the two most common co-infections were scabies with either pyoderma or a fungal infection (38.0% and 32.0%, respectively). The survey identified 29 previously undiagnosed cases of leprosy and six cases of yaws.\ud
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Conclusions\ud
Our findings indicate the need for a comprehensive programme to address these conditions. There are successful disease control programmes in place within the country and it is hoped a healthy skin programme could be integrated into an established disease control programme in order to maximise health benefits and resources
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