The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an ...atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.
This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific.
In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.
Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial.
To compare the analgesic and cognitive effects ...of opioids with those of TCA and placebo in the treatment of PHN.
Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication.
Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02).
Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.
Introduction
Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most ...deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures.
Methods
Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of “small molecules of new agents.”
Conclusion
Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent’s treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.
Managing mining of the deep seabed Wedding, L M; Reiter, S M; Smith, C R ...
Science (American Association for the Advancement of Science),
07/2015, Letnik:
349, Številka:
6244
Journal Article
Recenzirano
Odprti dostop
Contracts are being granted, but protections are lagging
Interest in mining the deep seabed is not new; however, recent technological advances and increasing global demand for metals and rare-earth ...elements may make it economically viable in the near future (
1
). Since 2001, the International Seabed Authority (ISA) has granted 26 contracts (18 in the last 4 years) to explore for minerals on the deep seabed, encompassing ∼1 million km
2
in the Pacific, Atlantic, and Indian Oceans in areas beyond national jurisdiction (
2
). However, as fragile habitat structures and extremely slow recovery rates leave diverse deep-sea communities vulnerable to physical disturbances such as those caused by mining (
3
), the current regulatory framework could be improved. We offer recommendations to support the application of a precautionary approach when the ISA meets later this July.
This study evaluated the effect of 4 weeks of low‐load resistance exercise with blood flow restriction (BFRE) on increasing strength in comparison with high‐load resistance exercise (HLE), and ...assessed changes in blood, vascular and neural function. Healthy adults performed leg extension BFRE or HLE 3 days/week at 30% and 80% of strength, respectively. During BFRE, a cuff on the upper leg was inflated to 30% above systolic blood pressure. Strength, pulse‐wave velocity (PWV), ankle‐brachial index (ABI), prothrombin time (PT) and nerve conduction (NC) were measured before and after training. Markers of coagulation (fibrinogen and D‐dimer), fibrinolysis tissue plasminogen activator (tPA) and inflammation high sensitivity C‐reactive protein (hsCRP) were measured in response to the first and last exercise bouts. Strength increased 8% with BFRE and 13% with HLE (P<0.01). No changes in PWV, ABI, PT or NC were observed following training for either group (P>0.05). tPA antigen increased 30–40% immediately following acute bouts of BFRE and HLE (P=0.01). No changes were observed in fibrinogen, D‐dimer or hsCRP (P>0.05). These findings indicate that both protocols increase the strength without altering nerve or vascular function, and that a single bout of both protocols increases fibrinolytic activity without altering selected markers of coagulation or inflammation in healthy individuals.
The structure and evolution of a cold front that produced a tornadic narrow cold‐frontal rainband (NCFR) over the UK on 20 November 2013 is explored using reanalysis data, high‐resolution model ...simulations and observations. Physical links are found to exist across a range of spatiotemporal scales, through which the evolving large‐scale flow field exerts an influence on the timing and location of miso‐scale vortex genesis, and therefore the potential for tornado genesis. The synoptic‐scale flow pattern exhibited amplification, consisting of upstream ridge building and downstream trough extension. A prominent jet streak and associated positive potential vorticity (PV) anomaly and tropopause fold moved rapidly southeastward on the rear flank of the extending upper‐level trough, the leading edge of these features eventually overspreading the surface cold front over the UK. Increasing 850 hPa frontogenesis occurred underneath the left exit of the jet streak and associated, intensifying, PV anomaly. A filament of dry, high‐PV air was extruded from the overlying tropopause fold within an intensifying front‐transverse circulation in this region. This dry filament eventually penetrated to low levels immediately behind the front, where it undercut the upper, rearward parts of the wide cold‐frontal precipitation band. Model fields and observations suggest that diabatic cooling, associated with sublimation of solid hydrometeors falling into the dry filament, led to the development of local downdraft and near‐surface divergence maxima and a prominent cold pool immediately behind the surface cold front over central England. Increases in horizontal convergence, updraft speed, and horizontal temperature gradients along the frontal boundary immediately ahead of the cold pool resulted in development of a locally well‐defined cold front and associated NCFR, where the surface front was formerly (and elsewhere continued to be) relatively weak. Tornadoes occurred in association with miso‐scale vortices that developed rapidly along an intensifying vertical vortex sheet at the NCFR.
Multiscale analysis of a tornadic cold front is conducted using reanalysis, model, and observations data. A jet streak at the rear flank of an equatorward‐extending upper‐level trough approaches the surface front, whereupon a filament of dry, high‐PV air is extruded into the lower troposphere underneath part of the frontal precipitation band, promoting post‐frontal diabatic cooling and local intensification of the front. Miso‐scale vortex genesis and associated tornado genesis occur along an intensifying vertical vortex sheet at the surface front in this region.
Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human ...curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.
Experimental results on the
α
decay and fission of high-
K
isomers are reviewed. Despite the sparse available information, it seems that there is hindrance to the
α
decay and fission processes from ...isomeric states relative to the same processes in the ground states. This may have profound consequences, especially for the creation and observation of super-heavy nuclei. To understand the hindrances to
α
decay and fission that arise when high-
K
isomers are involved, theoretical descriptions must reflect the pair-broken character of the states, which alters both the potential and inertial terms used in describing these fundamental processes.
The Canadian Penning Trap mass spectrometer at the Californium Rare Isotope Breeder Upgrade (CARIBU) facility was used to measure the masses of eight neutron-rich isotopes of Nd and Sm. These ...measurements are the first to push into the region of nuclear masses relevant to the formation of the rare-earth abundance peak at A∼165 by the rapid neutron-capture process. We compare our results with theoretical predictions obtained from "reverse engineering" the mass surface that best reproduces the observed solar abundances in this region through a Markov chain Monte Carlo technique. Our measured masses are consistent with the reverse-engineering predictions for a neutron star merger wind scenario.
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