Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. ...Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease
and nominating testable therapeutic targets
. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability
. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection
, we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.
The Earth Observing System (EOS) Microwave Limb Sounder (MLS) aboard the Aura satellite has provided essentially daily global measurements of ozone (O3) profiles from the upper troposphere to the ...upper mesosphere since August of 2004. This paper focuses on validation of the MLS stratospheric standard ozone product and its uncertainties, as obtained from the 240 GHz radiometer measurements, with a few results concerning mesospheric ozone. We compare average differences and scatter from matched MLS version 2.2 profiles and coincident ozone profiles from other satellite instruments, as well as from aircraft lidar measurements taken during Aura Validation Experiment (AVE) campaigns. Ozone comparisons are also made between MLS and balloon‐borne remote and in situ sensors. We provide a detailed characterization of random and systematic uncertainties for MLS ozone. We typically find better agreement in the comparisons using MLS version 2.2 ozone than the version 1.5 data. The agreement and the MLS uncertainty estimates in the stratosphere are often of the order of 5%, with values closer to 10% (and occasionally 20%) at the lowest stratospheric altitudes, where small positive MLS biases can be found. There is very good agreement in the latitudinal distributions obtained from MLS and from coincident profiles from other satellite instruments, as well as from aircraft lidar data along the MLS track.
Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24 h after experimental stroke and ...that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24 h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation.
Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24 h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues.
At 24 h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke.
Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24 h after stroke. This may contribute to reported increases in intracranial pressure at 24 h after stroke and thus worsen stroke outcomes.
Summary
This guidance for the management of patients with allergic and non‐allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and ...Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web‐based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co‐morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.
Abstract
Hatching eggs collected from resident broiler breeders at 48 wk of age were used to produce male and female chicks that were assigned sex separately to 96 new litter pens and fed either a 0 ...or 50 g/MT RFC (refined functional carbohydrate feed additive derived from yeast) diet. There were 24 replicate pens of 12 broilers each per diet per sex. Feed intake and BW were determined at 14, 28, and 42 d of age. Litter was sampled by pen using sterile socks at 35 d and tested for Salmonella spp. using an enzyme linked fluorescence assay method. Salmonella spp. was isolated from 7 of 48 control-fed broiler pens but no RFC-fed pens (P ≤ 0.05). Thereafter, 48 males and 48 females were selected based on litter Salmonella presence and RFC treatment. The cecas of these broilers were aseptically excised after feed withdrawal and lairage and tested for presence of Salmonella spp. There were 18 of the 48 control-fed broilers confirmed positive from litter-positive pens but none from litter-negative pens fed RFC. The serovar of litter and cecal Salmonella isolates was Salmonella enterica subsp. enterica serovar Senftenberg (S. Senftenberg). Female broilers that were fed RFC exhibited greater BW at 28 d (P ≤ 0.05) and 42 d (P ≤ 0.05) while RFC-fed males exhibited improved feed efficiency during the 15-28 d period (P = 0.06). These data demonstrated that dietary RFC reduced the prevalence of Salmonella in the litter and ceca of broilers when fed continuously while not being detrimental to broiler live performance.
Broiler breeders hatched from Salmo-nella negative grandparents received either zero or 50 g/MT of refined functional carbohydrates (RFC) in their diets from d of placement to end of lay. There were ...no other treatments used. Pullets and cockerels were reared separately in an enclosed litter-floor house to 21 wk of age when 28 randomly selected pullets from each diet were transferred to individual cages for an additional 14 d before they were killed, and their ceca were excised aseptically and tested for Salmonella spp. The remaining birds were transferred to a two-thirds slat and one-third litter curtain-sided laying house. There were 8 pens of 60 to 65 females and 8 to 18 males, depending upon flock age and housing type, fed each diet, and there was no effort made to isolate pens from typical daily foot traffic between pens. At 51 wk of age, male progeny broiler chicks were hatched and received either zero or 50 g/MT of RFC to complete a 2 × 2 design with 4 replicate pens of 12 males per interaction. All broilers were tested for cecal Salmonella spp. at 34 d of age. Ceca were collected from 30 breeder hens from each treatment at 64 wk of age and tested for Salmonella spp. Of the ceca sampled at 23 wk from the control pullets, 71.4% were found to contain Salmonella spp., while none of the ceca from the RFC pullets tested positive. Of the ceca sampled from the control hens at 64 wk, 40% were found to contain Salmonella spp., while none of the ceca from the RFC hens tested positive. Salmonella spp. was isolated from broilers in one pen of the control broilers that were also progeny of control breeders out of 4 replicates but not from any pens in which the breeders had been fed RFC. These data demonstrated that RFC reduced natural Salmonella spp. colonization of broiler breeder hen and broiler progeny ceca during a complete production cycle.
Abstract
The star formation rate in the Central Molecular Zone (CMZ) is an order of magnitude lower than predicted according to star formation relations that have been calibrated in the disc of our ...own and nearby galaxies. Understanding how and why star formation appears to be different in this region is crucial if we are to understand the environmental dependence of the star formation process. Here, we present the detection of a sample of high-mass cores in the CMZ's ‘dust ridge’ that have been discovered with the Submillimeter Array. These cores range in mass from ∼50–2150 M⊙ within radii of 0.1–0.25 pc. All appear to be young (pre-UCHII), meaning that they are prime candidates for representing the initial conditions of high-mass stars and sub-clusters. We report that at least two of these cores (‘c1’ and ‘e1’) contain young, high-mass protostars. We compare all of the detected cores with high-mass cores and clouds in the Galactic disc and find that they are broadly similar in terms of their masses and sizes, despite being subjected to external pressures that are several orders of magnitude greater, ∼108 K cm−3, as opposed to ∼105 K cm−3. The fact that >80 per cent of these cores do not show any signs of star-forming activity in such a high-pressure environment leads us to conclude that this is further evidence for an increased critical density threshold for star formation in the CMZ due to turbulence.
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