Assessment of Spray Polyurethane Foam Worker Exposure to Organophosphate Flame Retardants Through Measures in Air, Hand Wipes, and Urine

Tris(1-chloro-2-propyl) phosphate (TCPP, also referenced as TCIPP), a flame retardant used in spray polyurethane foam insulation, increases cell toxicity and affects fetal development. Spray polyurethane foam workers have the potential to be exposed to TCPP during application. In this study, we determined exposure to TCPP and concentrations of the urinary biomarker bis(1-chloro-2-propyl) phosphate (BCPP) among 29 spray polyurethane foam workers over 2 work days. Work was conducted at residential or commercial facilities using both open-cell (low density) and closed-cell (high density) foam. Study participants provided two personal air samples (Day 1 and Day 2), two hand wipe samples (Pre-shift Day 2 and Post-shift Day 2), and two spot urine samples (Pre-shift Day 1 and Post-shift Day 2). Bulk samples of cured spray foam were also analyzed. Sprayers were found to have significantly higher TCPP geometric mean (GM) concentration in personal air samples (87.1 μg/m3), compared to helpers (30.2 μg/m3; p = 0.025). A statistically significant difference was observed between TCPP pre- and post-shift hand wipe GM concentrations (p = 0.004). Specifically, TCPP GM concentration in post-shift hand wipe samples of helpers (106,000 ng/sample) was significantly greater than pre-shift (27,300 ng/sample; p \u3c 0.001). The GM concentration of the urinary biomarker BCPP (23.8 μg/g creatinine) was notably higher than the adult male general population (0.159 μg/g creatinine, p \u3c 0.001). Urinary BCPP GM concentration increased significantly from Pre-shift Day 1 to Post-shift Day 2 for sprayers (p = 0.013) and helpers (p = 0.009). Among bulk samples, cured open-cell foam had a TCPP GM concentration of 9.23% by weight while closed-cell foam was 1.68%. Overall, post-shift BCPP urine concentrations were observed to be associated with TCPP air and hand wipe concentrations, as well as job position (sprayer vs. helper). Spray polyurethane foam workers should wear personal protective equipment including air-supplied respirators, coveralls, and gloves during application

Platelet-Induced Clumping of Plasmodium falciparum–Infected Erythrocytes from Malawian Patients with Cerebral Malaria—Possible Modulation In Vivo by Thrombocytopenia

Platelets may play a role in the pathogenesis of human cerebral malaria (CM), and they have been shown to induce clumping of Plasmodium falciparum–parasitized red blood cells (PRBCs) in vitro. Both thrombocytopenia and platelet-inducedPRBCclumping are associated with severe malaria and, especially, withCM.In the present study, we investigated the occurrence of the clumping phenomenon in patients with CM by isolating and coincubating their plasma and PRBCs ex vivo. Malawian children with CM all had low platelet counts, with the degree of thrombocytopenia directly proportional to the density of parasitemia. Plasma samples obtained from these patients subsequently induced weak PRBC clumping. When the assays were repeated, with the plasma platelet concentrations adjusted to within the physiological range considered to be normal, massive clumping occurred. The results of this study suggest that thrombocytopenia may, through reduction of platelet-mediated clumping of PRBCs, provide a protective mechanism for the host during CM

Using gene expression profiles from peripheral blood to identify asymptomatic responses to acute respiratory viral infections

<p>Abstract</p> <p>Background</p> <p>A recent study reported that gene expression profiles from peripheral blood samples of healthy subjects prior to viral inoculation were indistinguishable from profiles of subjects who received viral challenge but remained asymptomatic and uninfected. If true, this implies that the host immune response does not have a molecular signature. Given the high sensitivity of microarray technology, we were intrigued by this result and hypothesize that it was an artifact of data analysis.</p> <p>Findings</p> <p>Using acute respiratory viral challenge microarray data, we developed a molecular signature that for the first time allowed for an accurate differentiation between uninfected subjects prior to viral inoculation and subjects who remained asymptomatic after the viral challenge.</p> <p>Conclusions</p> <p>Our findings suggest that molecular signatures can be used to characterize immune responses to viruses and may improve our understanding of susceptibility to viral infection with possible implications for vaccine development.</p

Down-regulation of hippocampal genes regulating dopaminergic, GABAergic and glutamatergic function following combined neonatal phencyclidine and post-weaning social isolation of rats as a neurodevelopmental model for schizophrenia

Background: Dysfunction of dopaminergic, GABAergic and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP) and post-weaning social isolation of rats produces a behavioral syndrome with translational relevance to several core symptoms of schizophrenia. This study uses DNA microarray to characterise alterations in hippocampal neurotransmitter-related gene expression and examines the ability of the sodium channel blocker, lamotrigine, to reverse behavioral changes in this model. Methods: Fifty-four male Lister-hooded rat pups either received phencyclidine (PCP, 10 mg/kg, s.c.), on post-natal day (PND) 7, 9 and 11 before being weaned on PND 23 into separate cages (isolation, PCP-SI, n=31), or vehicle injection and group-housing (2-4 per cage, V-GH, n=23) from weaning. The effect of lamotrigine on locomotor activity, novel object recognition, and prepulse inhibition of acoustic startle was examined (PND60-75) and drug-free hippocampal gene expression on PND70. Results: Acute lamotrigine (10-15mg/kg i.p.) reversed the hyperactivity and novel object recognition impairment induced by PCP-SI but had no effect on the prepulse inhibition deficit. Microarray revealed small but significant down-regulation of hippocampal genes involved in glutamate metabolism, dopamine neurotransmission and GABA receptor signalling, and in specific schizophrenia-linked genes, including PVALB and GAD67, in PCP-SI rats which resemble changes reported in schizophrenia. Conclusions: Findings indicate that alterations in dopamine neurotransmission, glutamate metabolism and GABA signalling may contribute to some of the behavioral deficits observed following PCP-SI, and that lamotrigine may have some utility as an adjunctive therapy to improve certain cognitive deficits symptoms in schizophrenia

sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data

Class-switch recombination (CSR) is an integral part of B cell maturation. Here we present sciCSR (pronounced 'scissor', single-cell inference of class-switch recombination), a computational pipeline that analyzes CSR events and dynamics of B cells from single-cell RNA sequencing (scRNA-seq) experiments. Validated on both simulated and real data, sciCSR re-analyzes scRNA-seq alignments to differentiate productive heavy-chain immunoglobulin transcripts from germline 'sterile' transcripts. From a snapshot of B cell scRNA-seq data, a Markov state model is built to infer the dynamics and direction of CSR. Applying sciCSR on severe acute respiratory syndrome coronavirus 2 vaccination time-course scRNA-seq data, we observe that sciCSR predicts, using data from an earlier time point in the collected time-course, the isotype distribution of B cell receptor repertoires of subsequent time points with high accuracy (cosine similarity ~0.9). Using processes specific to B cells, sciCSR identifies transitions that are often missed by conventional RNA velocity analyses and can reveal insights into the dynamics of B cell CSR during immune response

Analysis and Computational Dissection of Molecular Signature Multiplicity

Molecular signatures are computational or mathematical models created to diagnose disease and other phenotypes and to predict clinical outcomes and response to treatment. It is widely recognized that molecular signatures constitute one of the most important translational and basic science developments enabled by recent high-throughput molecular assays. A perplexing phenomenon that characterizes high-throughput data analysis is the ubiquitous multiplicity of molecular signatures. Multiplicity is a special form of data analysis instability in which different analysis methods used on the same data, or different samples from the same population lead to different but apparently maximally predictive signatures. This phenomenon has far-reaching implications for biological discovery and development of next generation patient diagnostics and personalized treatments. Currently the causes and interpretation of signature multiplicity are unknown, and several, often contradictory, conjectures have been made to explain it. We present a formal characterization of signature multiplicity and a new efficient algorithm that offers theoretical guarantees for extracting the set of maximally predictive and non-redundant signatures independent of distribution. The new algorithm identifies exactly the set of optimal signatures in controlled experiments and yields signatures with significantly better predictivity and reproducibility than previous algorithms in human microarray gene expression datasets. Our results shed light on the causes of signature multiplicity, provide computational tools for studying it empirically and introduce a framework for in silico bioequivalence of this important new class of diagnostic and personalized medicine modalities

Inside-Out Evacuation of Transitional Protoplanetary Disks by the Magneto-Rotational Instability

How do T Tauri disks accrete? The magneto-rotational instability (MRI) supplies one means, but protoplanetary disk gas is typically too poorly ionized to be magnetically active. Here we show that the MRI can, in fact, explain observed accretion rates for the sub-class of T Tauri disks known as transitional systems. Transitional disks are swept clean of dust inside rim radii of ~10 AU. Stellar coronal X-rays ionize material in the disk rim, activating the MRI there. Gas flows from the rim to the star, at a rate limited by the depth to which X-rays ionize the rim wall. The wider the rim, the larger the surface area that the rim wall exposes to X-rays, and the greater the accretion rate. Interior to the rim, the MRI continues to transport gas; the MRI is sustained even at the disk midplane by super-keV X-rays that Compton scatter down from the disk surface. Accretion is therefore steady inside the rim. Blown out by radiation pressure, dust largely fails to accrete with gas. Contrary to what is usually assumed, ambipolar diffusion, not Ohmic dissipation, limits how much gas is MRI-active. We infer values for the transport parameter alpha on the order of 0.01 for GM Aur, TW Hyd, and DM Tau. Because the MRI can only afflict a finite radial column of gas at the rim, disk properties inside the rim are insensitive to those outside. Thus our picture provides one robust setting for planet-disk interaction: a protoplanet interior to the rim will interact with gas whose density, temperature, and transport properties are definite and decoupled from uncertain initial conditions. Our study also supplies half the answer to how disks dissipate: the inner disk drains from the inside out by the MRI, while the outer disk photoevaporates by stellar ultraviolet radiation.Comment: Accepted to Nature Physics June 7, 2007. The manuscript for publication is embargoed per Nature policy. This arxiv.org version contains more technical details and discussion, and is distributed with permission from the editors. 10 pages, 4 figure

The role of magnetic anisotropy in the Kondo effect

In the Kondo effect, a localized magnetic moment is screened by forming a correlated electron system with the surrounding conduction electrons of a non-magnetic host. Spin S=1/2 Kondo systems have been investigated extensively in theory and experiments, but magnetic atoms often have a larger spin. Larger spins are subject to the influence of magnetocrystalline anisotropy, which describes the dependence of the magnetic moment's energy on the orientation of the spin relative to its surrounding atomic environment. Here we demonstrate the decisive role of magnetic anisotropy in the physics of Kondo screening. A scanning tunnelling microscope is used to simultaneously determine the magnitude of the spin, the magnetic anisotropy and the Kondo properties of individual magnetic atoms on a surface. We find that a Kondo resonance emerges for large-spin atoms only when the magnetic anisotropy creates degenerate ground-state levels that are connected by the spin flip of a screening electron. The magnetic anisotropy also determines how the Kondo resonance evolves in a magnetic field: the resonance peak splits at rates that are strongly direction dependent. These rates are well described by the energies of the underlying unscreened spin states.Comment: 14 pages, 4 figures, published in Nature Physic

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging

Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi-shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD-related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning