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171 result(s) for "Concepcion, Michael"
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Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a
Background Although highly active antiretroviral therapy (HAART) has significantly reduced the morbidity and mortality in HIV patients, virus continues to reside in the central nervous system (CNS) reservoir. Hence, a complete eradication of virus remains a challenge. HIV productively infects microglia/macrophages, but astrocytes are generally restricted to HIV infection. The relative importance of the possible replication blocks in astrocytes, however, is yet to be delineated. A recently identified restriction factor, sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), restricts HIV infection in resting CD4 + T cells and in monocyte-derived dendritic cells. However, SAMHD1 expression and HIV-1 restriction activity regulation in the CNS cells are unknown. Though, certain miRNAs have been implicated in HIV restriction in resting CD4 + T cells, their role in the CNS HIV restriction and their mode of action are not established. We hypothesized that varying SAMHD1 expression would lead to restricted HIV infection and host miRNAs would regulate SAMHD1 expression in astrocytes. Results We found increased SAMHD1 expression and decreased miRNA expression (miR-181a and miR-155) in the astrocytes compared to microglia. We report for the first time that miR-155 and miR-181a regulated the SAMHD1 expression. Overexpression of these cellular miRNAs increased viral replication in the astrocytes, through SAMHD1 modulation. Reactivation of HIV replication was accompanied by decrease in SAMHD1 expression. Conclusions Here, we provide a proof of concept that increased SAMHD1 in human astrocytes is in part responsible for the HIV restriction, silencing of which relieves this restriction. At this time, this concept is of theoretical nature. Further experiments are needed to confirm if HIV replication can be reactivated in the CNS reservoir.
The effects of extracellular volume and intradialytic peripheral resistance changes on ambulatory blood pressure in hemodialysis patients with and without recurrent intradialytic hypertension
Hypertension and extracellular volume (ECV) overload are interrelated mortality risk factors in hemodialysis (HD) patients, but confounding related to changes in ECV and vasoconstriction during and between treatments obfuscate their relationship. We sought to clarify independent contributions of post-HD ECV and intradialytic changes in vasoconstriction on ambulatory blood pressure (BP) in patients with and without recurrent intradialytic hypertension (IH). In this prospective observational study, we obtained measurements of pre- and post-HD ECV with bioimpedance spectroscopy (BIS), pre- and post-HD total peripheral resistance index and 44-h ambulatory BP. Linear regression determined associations between post-HD ECV/weight and intradialytic change in total peripheral resistance index (TPRI) with interdialytic BP and slope. In fully-adjusted models for participants with complete data, post-HD ECV/weight associated with mean ambulatory BP (  = 133, P = 0.01;  = 52) and ambulatory BP slope (  = -4.28, P = 0.03;  = 42). ECV/weight was associated with mean ambulatory BP in those with recurrent IH (  = 314, P = 0.0005;  = 16) and with ambulatory BP slope in those without recurrent IH (  = -4.56, P = 0.04;  = 28). Interdialytic weight gain percentage and intradialytic TPRI change were not associated with ambulatory BP or slope in any analyses. Ambulatory BP in HD patients is more strongly associated with post-HD ECV assessed with BIS than with intradialytic TPRI changes or interdialytic ECV increases. These findings highlight the essential role of recognizing and managing chronic ECV overload to improve ambulatory BP in HD patients, particularly so for those with IH.
Chile president calls in the army to stop quake looters
\"It fell at the moment the earthquake began,\" said Juan Schulmeyer of Concepcion's Firefighter Company. A full 24 hours later, only 16 people had been pulled out alive, and six bodies had been recovered. \"It's very difficult working in the dark with aftershocks, and inside it's complicated. The apartments are totally destroyed. You have to work with great caution,\" said Paulo Klein, who was leading a group of rescue specialists at the site of the building collapse. FRACTURED LAND: A bridge 200 miles south of Santiago, above, shows the effects of the massive quake; (clockwise from right) police in Concepcion continue their search for survivors; looters raid a supermarket in the city; a woman stands next to what is left of her home in the town of Pelluhue; and rescuers pull a survivor to safety. Picture: Press Association
Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome
The DNA sequencing technologies in use today produce either highly accurate short reads or less-accurate long reads. We report the optimization of circular consensus sequencing (CCS) to improve the accuracy of single-molecule real-time (SMRT) sequencing (PacBio) and generate highly accurate (99.8%) long high-fidelity (HiFi) reads with an average length of 13.5 kilobases (kb). We applied our approach to sequence the well-characterized human HG002/NA24385 genome and obtained precision and recall rates of at least 99.91% for single-nucleotide variants (SNVs), 95.98% for insertions and deletions <50 bp (indels) and 95.99% for structural variants. Our CCS method matches or exceeds the ability of short-read sequencing to detect small variants and structural variants. We estimate that 2,434 discordances are correctable mistakes in the ‘genome in a bottle’ (GIAB) benchmark set. Nearly all (99.64%) variants can be phased into haplotypes, further improving variant detection. De novo genome assembly using CCS reads alone produced a contiguous and accurate genome with a contig N50 of >15 megabases (Mb) and concordance of 99.997%, substantially outperforming assembly with less-accurate long reads.
Phased diploid genome assembly with single-molecule real-time sequencing
The open-source FALCON and FALCON-Unzip software utilize long-read sequencing data to generate contiguous, accurate and phased diploid assemblies, even from genomes that are highly heterozygous. While genome assembly projects have been successful in many haploid and inbred species, the assembly of noninbred or rearranged heterozygous genomes remains a major challenge. To address this challenge, we introduce the open-source FALCON and FALCON-Unzip algorithms ( https://github.com/PacificBiosciences/FALCON/ ) to assemble long-read sequencing data into highly accurate, contiguous, and correctly phased diploid genomes. We generate new reference sequences for heterozygous samples including an F1 hybrid of Arabidopsis thaliana , the widely cultivated Vitis vinifera cv. Cabernet Sauvignon, and the coral fungus Clavicorona pyxidata , samples that have challenged short-read assembly approaches. The FALCON-based assemblies are substantially more contiguous and complete than alternate short- or long-read approaches. The phased diploid assembly enabled the study of haplotype structure and heterozygosities between homologous chromosomes, including the identification of widespread heterozygous structural variation within coding sequences.
Impacts of urbanisation on biodiversity: the role of species mobility, degree of specialisation and spatial scale
Urbanisation has an important impact on biodiversity, mostly driving changes in species assemblages, through the replacement of specialist with generalist species, thus leading to biotic homogenisation. Mobility is also assumed to greatly affect species’ ability to cope in urban environments. Moreover, specialisation, mobility and their interaction are expected to greatly influence ecological processes such as metacommunity dynamics and assembly processes, and consequently the way and the spatial scale at which organisms respond to urbanisation. Here we investigate urbanisation impacts on distinct characteristics of species assemblages – namely specialisation degree in resource use, mobility and number of species, classified according to both characteristics and their combination – for vascular plants, butterflies and birds, across a range of spatial scales (from 1 × 1 km plots to 5 km‐radius buffers around them). We found that the degree of specialisation, mobility and their interaction, greatly influenced species’ responses to urbanisation, with highly mobile specialist species of all taxonomic groups being affected most. Two different patterns were found: for plants, urbanisation induced trait divergence by favouring highly mobile species with narrow habitat ranges. For birds and butterflies, however, it reduced the number of highly mobile specialist species, thus driving trait convergence. Mobile organisms, across and within taxonomic groups, tended to respond at larger spatial scales than those that are poorly mobile. These findings emphasize the need to take into consideration species’ ecological aspects, as well as a wide range of spatial scales when evaluating the impact of urbanisation on biodiversity. Our results also highlight the harmful impact of widespread urban expansion on organisms such as butterflies, especially highly mobile specialists, which were negatively affected by urban areas even at great distances.
Base-enhanced catalytic water oxidation by a carboxylate–bipyridine Ru(II) complex
In aqueous solution above pH 2.4 with 4% (vol/vol) CH₃CN, the complex [RuII(bda)(isoq)₂] (bda is 2,2′-bipyridine-6,6′-dicarboxylate; isoq is isoquinoline) exists as the open-arm chelate, [RuII(CO₂-bpy-CO₂⁻)(isoq)₂(NCCH₃)], as shown by ¹H and13C-NMR, X-ray crystallography, and pH titrations. Rates of water oxidation with the open-arm chelate are remarkably enhanced by added proton acceptor bases, asmeasured by cyclic voltammetry (CV). In 1.0 M PO₄3–, the calculated half-time for water oxidation is ∼7 μs. The key to the rate accelerations with added bases is direct involvement of the buffer base in either atom–proton transfer (APT) or concerted electron–proton transfer (EPT) pathways.
Solar water splitting in a molecular photoelectrochemical cell
Artificial photosynthesis and the production of solar fuels could be a key element in a future renewable energy economy providing a solution to the energy storage problem in solar energy conversion. We describe a hybrid strategy for solar water splitting based on a dye sensitized photoelectrosynthesis cell. It uses a derivatized, core–shell nanostructured photoanode with the core a high surface area conductive metal oxide film––indium tin oxide or antimony tin oxide––coated with a thin outer shell of TiO ₂ formed by atomic layer deposition. A “chromophore–catalyst assembly” 1, [(PO ₃H ₂) ₂bpy) ₂Ru(4-Mebpy-4-bimpy)Rub(tpy)(OH ₂)] ⁴⁺, which combines both light absorber and water oxidation catalyst in a single molecule, was attached to the TiO ₂ shell. Visible photolysis of the resulting core–shell assembly structure with a Pt cathode resulted in water splitting into hydrogen and oxygen with an absorbed photon conversion efficiency of 4.4% at peak photocurrent.
Splitting CO₂ into CO and O₂ by a single catalyst
The metal complex [(tpy)(Mebim-py)Ru ᴵᴵ(S)] ²⁺ (tpy = 2,2 ′ : 6 ′,2 ′′-terpyridine; Mebim-py = 3-methyl-1-pyridylbenzimidazol-2-ylidene; S = solvent) is a robust, reactive electrocatalyst toward both water oxidation to oxygen and carbon dioxide reduction to carbon monoxide. Here we describe its use as a single electrocatalyst for CO ₂ splitting, CO ₂ → CO + 1/2 O ₂, in a two-compartment electrochemical cell.
Possible Loss of the Chloroplast Genome in the Parasitic Flowering Plant Rafflesia lagascae (Rafflesiaceae)
Rafflesia is a genus of holoparasitic plants endemic to Southeast Asia that has lost the ability to undertake photosynthesis. With short-read sequencing technology, we assembled a draft sequence of the mitochondrial genome of Rafflesia lagascae Blanco, a species endemic to the Philippine island of Luzon, with ∼350× sequencing depth coverage. Using multiple approaches, however, we were only able to identify small fragments of plastid sequences at low coverage depth (<2×) and could not recover any substantial portion of a chloroplast genome. The gene fragments we identified included photosynthesis and energy production genes (atp, ndh, pet, psa, psb, rbcL), ribosomal RNA genes (rrn16, rrn23), ribosomal protein genes (rps7, rps11, rps16), transfer RNA genes, as well as matK, accD, ycf2, and multiple nongenic regions from the inverted repeats. None of the identified plastid gene sequences had intact reading frames. Phylogenetic analysis suggests that ∼33% of these remnant plastid genes may have been horizontally transferred from the host plant genus Tetrastigma with the rest having ambiguous phylogenetic positions (<50% bootstrap support), except for psaB that was strongly allied with the plastid homolog in Nicotiana. Our inability to identify substantial plastid genome sequences from R. lagascae using multiple approaches—despite success in identifying and developing a draft assembly of the much larger mitochondrial genome—suggests that the parasitic plant genus Rafflesia may be the first plant group for which there is no recognizable plastid genome, or if present is found in cryptic form at very low levels.