Endothelial cell provenance: an unclear role in transplant medicine

An understanding of the interplay between both donor endothelial progenitors and the recipient endothelium (in the case of hematopoietic cell transplant) and recipient endothelial provenance upon the established donor endothelium (in the case of solid organ transplant) is unknown. It is postulated that this interplay and consequences of purported dual endothelial populations may be a component of the post-transplant disease process and contribute to complications of engraftment or rejection. To address this potential confounding and often overlooked arena of vascular biology, a directed brief overview primarily focused on literature presented over the last decade is presented herein

Precision Measurement of the Neutron Spin Asymmetry A1nA_1^n and Spin-Flavor Decomposition in the Valence Quark Region

We have measured the neutron spin asymmetry $A_1^n$ with high precision at three kinematics in the deep inelastic region at $x=0.33$, 0.47 and 0.60, and $Q^2=2.7$, 3.5 and 4.8 (GeV/c)$^2$, respectively. Our results unambiguously show, for the first time, that $A_1^n$ crosses zero around $x=0.47$ and becomes significantly positive at $x=0.60$. Combined with the world proton data, polarized quark distributions were extracted. Our results, in general, agree with relativistic constituent quark models and with perturbative quantum chromodynamics (pQCD) analyses based on the earlier data. However they deviate from pQCD predictions based on hadron helicity conservation.Comment: 5 pages, 2 figures, this is the final version appeared in Phys. Rev. Let

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

This article is made available for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing.BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease

Precision Measurement of the Neutron Spin Asymmetries and Spin-dependent Structure Functions in the Valence Quark Region

We report on measurements of the neutron spin asymmetries $A_{1,2}^n$ and polarized structure functions $g_{1,2}^n$ at three kinematics in the deep inelastic region, with $x=0.33$, 0.47 and 0.60 and $Q^2=2.7$, 3.5 and 4.8 (GeV/c)$^2$, respectively. These measurements were performed using a 5.7 GeV longitudinally-polarized electron beam and a polarized $^3$He target. The results for $A_1^n$ and $g_1^n$ at $x=0.33$ are consistent with previous world data and, at the two higher $x$ points, have improved the precision of the world data by about an order of magnitude. The new $A_1^n$ data show a zero crossing around $x=0.47$ and the value at $x=0.60$ is significantly positive. These results agree with a next-to-leading order QCD analysis of previous world data. The trend of data at high $x$ agrees with constituent quark model predictions but disagrees with that from leading-order perturbative QCD (pQCD) assuming hadron helicity conservation. Results for $A_2^n$ and $g_2^n$ have a precision comparable to the best world data in this kinematic region. Combined with previous world data, the moment $d_2^n$ was evaluated and the new result has improved the precision of this quantity by about a factor of two. When combined with the world proton data, polarized quark distribution functions were extracted from the new $g_1^n/F_1^n$ values based on the quark parton model. While results for $\Delta u/u$ agree well with predictions from various models, results for $\Delta d/d$ disagree with the leading-order pQCD prediction when hadron helicity conservation is imposed.Comment: A typing error in A_\parallel(3He) at x=0.47 in Table VII of Phys. Rev. C has been noticed and correcte

Risk Factors for Noninvasive Ventilation Failure in Children Post-Hematopoietic Cell Transplant

Rationale: Little is known on the use of noninvasive ventilation (NIPPV) in pediatric hematopoietic cell transplant (HCT) patients. Objective: We sought to describe the landscape of NIPPV use and to identify risk factors for failure to inform future investigation or quality improvement. Methods: This is a multicenter, retrospective observational cohort of 153 consecutive children post-HCT requiring NIPPV from 2010-2016. Results: 97 (63%) failed NIPPV. Factors associated with failure on univariate analysis included: longer oxygen use prior to NIPPV (p=0.04), vasoactive agent use (p40 at 4 hours [aOR=6.3 9(95% CI: 2.4, 16.4), p<0.001] and vasoactive use [aOR=4.9 (95% CI: 1.9, 13.1), p=0.001]. Of note, 11 patients had a cardiac arrest during intubation (11%) and 3 others arrested prior to intubation. These 14 patients were closer to HCT [14 days (IQR:4, 73) vs 54 (IQR:21,117), p<0.01] and there was a trend toward beginning NIPPV outside of the PICU and arrest during/prior to intubation (p=0.056). Conclusions: In this cohort respiratory rate at 4 hours and vasoactive use are independent risk factors of NIPPV failure. An objective model to predict which children may benefit from a trial of NIPPV, may also inform the timing of both NIPPV initiation and uncomplicated intubation

First observation of Bs -> D_{s2}^{*+} X mu nu decays

Using data collected with the LHCb detector in proton-proton collisions at a centre-of-mass energy of 7 TeV, the semileptonic decays Bs -> Ds+ X mu nu and Bs -> D0 K+ X mu nu are detected. Two structures are observed in the D0 K+ mass spectrum at masses consistent with the known D^+_{s1}(2536) and $D^{*+}_{s2}(2573) mesons. The measured branching fractions relative to the total Bs semileptonic rate are B(Bs -> D_{s2}^{*+} X mu nu)/B(Bs -> X mu nu)= (3.3\pm 1.0\pm 0.4)%, and B(Bs -> D_{s1}^+ X munu)/B(Bs -> X mu nu)= (5.4\pm 1.2\pm 0.5)%, where the first uncertainty is statistical and the second is systematic. This is the first observation of the D_{s2}^{*+} state in Bs decays; we also measure its mass and width.Comment: 8 pages 2 figures. Published in Physics Letters

Current water quality guidelines across North America and Europe do not protect lakes from salinization

Human-induced salinization caused by the use of road deicing salts, agricultural practices, mining operations, and climate change is a major threat to the biodiversity and functioning of freshwater ecosystems. Yet, it is unclear if freshwater ecosystems are protected from salinization by current water quality guidelines. Leveraging an experimental network of land-based and in-lake mesocosms across North America and Europe, we tested how salinization-indicated as elevated chloride (C-) concentration-will affect lake food webs and if two of the lowest Cl- thresholds found globally are sufficient to protect these food webs. Our results indicated that salinization will cause substantial zooplankton mortality at the lowest Cl- thresholds established in Canada (120 mg Cl-/L) and the United States (230 mg Cl-/L) and throughout Europe where Cl- thresholds are generally higher. For instance, at 73% of our study sites, Cl- concentrations that caused a >= 50% reduction in cladoceran abundance were at or below Cl thresholds in Canada, in the United States, and throughout Europe. Similar trends occurred for copepod and rotifer zooplankton. The loss of zooplankton triggered a cascading effect causing an increase in phytoplankton biomass at 47% of study sites. Such changes in lake food webs could alter nutrient cycling and water clarity and trigger declines in fish production. Current Cl- thresholds across North America and Europe clearly do not adequately protect lake food webs. Water quality guidelines should be developed where they do not exist, and there is an urgent need to reassess existing guidelines to protect lake ecosystems from human-induced salinization.Peer reviewe

Prostaglandin E2 Synthesizing Enzymes in Rheumatoid Arthritis B Cells and the Effects of B Cell Depleting Therapy on Enzyme Expression

Introduction: B cells may play an important role in promoting immune activation in the rheumatoid synovium and can produce prostaglandin E-2 (PGE(2)) when activated. In its turn, PGE(2) formed by cyclooxygenase (COX) and microsomal prostaglandin E-2 synthase 1 (MPGES1) contributes to the rheumatoid arthritis (RA) pathological process. Therapeutic depletion of B cells results in important improvement in controlling disease activity in rheumatoid patients. Therefore we investigated the expression of PGE(2) pathway enzymes in RA B cells and evaluated the effects of B cell depleting therapy on their expression in RA tissue. Methods: B cells expressing MPGES1 and COX-2 were identified by flow cytometry in in vitro stimulated and control mononuclear cells isolated from synovial fluid and peripheral blood of RA patients. Synovial biopsies were obtained from 24 RA patients before and at two consecutive time points after rituximab therapy. Expression of MPGES1, COX-1 and COX-2, as well as interleukin (IL)-1 beta and IL-6, known inducers of MPGES1, was quantified in immunostained biopsy sections using computerized image analysis. Results: Expression of MPGES1 or COX-2 was significantly upregulated upon stimulation of B cells from blood and synovial fluid while control cells displayed no detectable enzymes. In synovial biopsy sections, the expression of MPGES1, COX-1 or COX-2 was resistant to rituximab therapy at 8 or 16 weeks after start of treatment. Furthermore expression of IL-1 beta in the synovial tissue remained unchanged, while IL-6 tended to decrease after therapy. Conclusions: Therapy with B cell depleting agents, although efficient in achieving good clinical and radiographic response in RA patients, leaves important inflammatory pathways in the rheumatoid synovium essentially unaffecte

Lake salinization drives consistent losses of zooplankton abundance and diversity across coordinated mesocosm experiments

Human-induced salinization increasingly threatens inland waters; yet we know little about the multifaceted response of lake communities to salt contamination. By conducting a coordinated mesocosm experiment of lake salinization across 16 sites in North America and Europe, we quantified the response of zooplankton abundance and (taxonomic and functional) community structure to a broad gradient of environmentally relevant chloride concentrations, ranging from 4 to ca. 1400 mg Cl- L-1. We found that crustaceans were distinctly more sensitive to elevated chloride than rotifers; yet, rotifers did not show compensatory abundance increases in response to crustacean declines. For crustaceans, our among-site comparisons indicate: (1) highly consistent decreases in abundance and taxon richness with salinity; (2) widespread chloride sensitivity across major taxonomic groups (Cladocera, Cyclopoida, and Calanoida); and (3) weaker loss of functional than taxonomic diversity. Overall, our study demonstrates that aggregate properties of zooplankton communities can be adversely affected at chloride concentrations relevant to anthropogenic salinization in lakes.Peer reviewe

Melanism in Peromyscus Is Caused by Independent Mutations in Agouti

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought