Role of CrkII in Fc gamma receptor-mediated phagocytosis

Phagocytosis of IgG-opsonized pathogens by Fc gamma receptors requires extensive remodeling of the actin cytoskeleton, a process regulated by the small GTPase Rac. Vav was thought to be the guanine nucleotide exchange factor responsible for the activation of Rac, but recent evidence indicates that Fc gamma receptor-mediated phagocytosis is unaffected in macrophages lacking all three isoforms of Vav. We therefore tested whether another GEF, DOCK180, participates in Fc gamma receptor-initiated phagocytosis. DOCK180 associates with the adaptor protein Crk, which mediates recruitment of the GEF to sites of tyrosine phosphorylation. CrkII and DOCK180 were found to accumulate at the phagocytic cup. Knockdown of Crk or DOCK180 in murine macrophages using small interfering RNA inhibited phagocytosis of IgG-opsonized particles. Moreover, transfection of dominant negative CrkII prevented both recruitment of DOCK180 and the activation of Rac at the phagocytic cup. This is the first report of a role for either Crk or DOCK180 in Fc gamma receptor-mediated phagocytosis. The Crk-DOCK180 complex is involved in the clearance of apoptotic cells, which unlike the ingestion of IgG-opsonized particles, is an anti-inflammatory process. The finding that CrkII-DOCK180 is also responsible, at least in part, for the effects of Fc gamma receptors implies that additional, parallel pathways must account for the associated pro-inflammatory effect

Application of single cell transcriptomics to kinetoplastid research

Kinetoplastid parasites are responsible for both human and animal diseases across the globe where they have a great impact on health and economic well-being. Many species and life cycle stages are difficult to study due to limitations in isolation and culture, as well as to their existence as heterogeneous populations in hosts and vectors. Single-cell transcriptomics (scRNA-seq) has the capacity to overcome many of these difficulties, and can be leveraged to disentangle heterogeneous populations, highlight genes crucial for propagation through the life cycle, and enable detailed analysis of host–parasite interactions. Here, we provide a review of studies that have applied scRNA-seq to protozoan parasites so far. In addition, we provide an overview of sample preparation and technology choice considerations when planning scRNA-seq experiments, as well as challenges faced when analysing the large amounts of data generated. Finally, we highlight areas of kinetoplastid research that could benefit from scRNA-seq technologies

Contextual Factors Associated With County-Level Suicide Rates in the United States, 1999 to 2016

Importance Understanding geographic and community-level factors associated with suicide can inform targeted suicide prevention efforts. Objectives To estimate suicide rates and trajectories, assess associated county-level contextual factors, and explore variation across the rural-urban continuum. Design, Setting, and Participants This cross-sectional study included all individuals aged 25 to 64 years who died by suicide from January 1, 1999, to December 31, 2016, in the United States. Spatial analysis was used to map excess risk of suicide, and longitudinal random-effects models using negative binomial regression tested associations of contextual variables with suicide rates as well as interactions among county-level contextual variables. Data analyses were conducted between January 2019 and July 2019. Exposure County of residence. Main Outcomes and Measures Three-year county suicide rates during an 18-year period stratified by rural-urban location. Results Between 1999 and 2016, 453 577 individuals aged 25 to 64 years died by suicide in the United States. Decedents were primarily male (349 082 [77.0%]) with 101 312 (22.3%) aged 25 to 34 years, 120 157 (26.5%) aged 35 to 44 years, 136 377 (30.1%) aged 45 to 54 years, and 95 771 (21.1%) aged 55 to 64 years. Suicide rates were higher and increased more rapidly in rural than in large metropolitan counties. The highest deprivation quartile was associated with higher suicide rates compared with the lowest deprivation quartile, especially in rural areas, although this association declined during the period studied (rural, 1999-2001: incidence rate ratio [IRR], 1.438; 95% CI, 1.319-1.568; P \u3c .001; large metropolitan, 1999-2001: 1.208; 95% CI, 1.149-1.270; P \u3c .001; rural, 2014-2016: IRR, 1.121; 95% CI, 1.032-1.219; P = .01; large metropolitan, 2014-2016: IRR, 0.942; 95% CI, 0.887-1.001; P = .06). The presence of more gun shops was associated with an increase in county-level suicide rates in all county types except the most rural (rural: IRR, 1.001; 95% CI, 0.999-1.004; P = .40; micropolitan: IRR, 1.005; 95% CI, 1.002-1.007; P \u3c .001; small metropolitan: IRR, 1.010; 95% CI, 1.006-1.014; P \u3c .001; large metropolitan: IRR, 1.012; 95% CI, 1.006-1.018; P \u3c .001). High social capital was associated with lower suicide rates than low social capital (IRR, 0.917; 95% CI, 0.891-0.943; P \u3c .001). High social fragmentation, an increasing percentage of the population without health insurance, and an increasing percentage of veterans in a county were associated with higher suicide rates (high social fragmentation: IRR, 1.077; 95% CI, 1.050-1.103; P \u3c .001; percentage of population without health insurance: IRR, 1.005; 95% CI, 1.004-1.006; P \u3c .001; percentage of veterans: IRR, 1.025; 95% CI, 1.021-1.028; P \u3c .001). Conclusions and Relevance This study found that suicide rates have increased across the nation and most rapidly in rural counties, which may be more sensitive to the impact of social deprivation than more metropolitan counties. Improving social connectedness, civic opportunities, and health insurance coverage as well as limiting access to lethal means have the potential to reduce suicide rates across the rural-urban continuum

The Commensal Real-time ASKAP Fast Transients (CRAFT) survey

We are developing a purely commensal survey experiment for fast (<5s) transient radio sources. Short-timescale transients are associated with the most energetic and brightest single events in the Universe. Our objective is to cover the enormous volume of transients parameter space made available by ASKAP, with an unprecedented combination of sensitivity and field of view. Fast timescale transients open new vistas on the physics of high brightness temperature emission, extreme states of matter and the physics of strong gravitational fields. In addition, the detection of extragalactic objects affords us an entirely new and extremely sensitive probe on the huge reservoir of baryons present in the IGM. We outline here our approach to the considerable challenge involved in detecting fast transients, particularly the development of hardware fast enough to dedisperse and search the ASKAP data stream at or near real-time rates. Through CRAFT, ASKAP will provide the testbed of many of the key technologies and survey modes proposed for high time resolution science with the SKA.Comment: accepted for publication in PAS

Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania

SummaryThis study was part of a larger cross-sectional survey that was evaluating tuberculosis (TB) infection in humans, livestock and wildlife in the Serengeti ecosystem in Tanzania. The study aimed at evaluating the genetic diversity of Mycobacterium tuberculosis isolates from TB patients attending health facilities in the Serengeti ecosystem. DNA was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated TB patients aged ≥18 years. Spacer oligonucleotide typing (spoligotyping) and Mycobacterium Interspersed Repetitive Units and Variable Number Tandem Repeat (MIRU-VNTR) were used to genotype M. tuberculosis to establish the circulating lineages. Of the214 M. tuberculosis isolates genotyped, 55 (25.7%) belonged to the Central Asian (CAS) family, 52 (24.3%) were T family (an ill-defined family), 38 (17.8%) belonged to the Latin American Mediterranean (LAM) family, 25 (11.7%) to the East-African Indian (EAI) family, 25 (11.7%) comprised of different unassigned (‘Serengeti’) strain families, while 8 (3.7%) belonged to the Beijing family. A minority group that included Haarlem, X, U and S altogether accounted for 11 (5.2%) of all genotypes. MIRU-VNTR typing produced diverse patterns within and between families indicative of unlinked transmission chains. We conclude that, in the Serengeti ecosystem only a few successful families predominate namely CAS, T, LAM and EAI families. Other types found in lower prevalence are Beijing, Haarlem, X, S and MANU. The Haarlem, EAI_Somalia, LAM3 and S/convergent and X2 subfamilies found in this study were not reported in previous studies in Tanzania

The Consolidation of the White Southern Congressional Vote

This article explores the initial desertion and continued realignment of about one-sixth of the white voters in the South who, until 1994, stood by Democratic congressional candidates even as they voted for Republican presidential nominees. Prior to 1994, a sizable share of the white electorate distinguished between Democratic congressional and presidential candidates; since 1994 that distinction has been swept away. In 1992, a majority of white southern voters was casting their ballot for the Democratic House nominee; by 1994, the situation was reversed and 64 percent cast their ballot for the Republican. Virtually all categories of voters increased their support of Republican congressional candidates in 1994 and the following elections further cement GOP congressional support in the South. Subsequent elections are largely exercises in partisanship, as the congressional votes mirror party preferences. Republicans pull nearly all GOP identifiers, most independents, and a sizeable minority of Democratic identifiers. Democrats running for Congress no longer convince voters that they are different from their party’s presidential standard bearers—a group that has consistently been judged unacceptable to overwhelming proportions of the southern white electorate.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Wading through the swamp: what does tropical peatland restoration mean to national-level stakeholders in Indonesia?

Ecological restoration is considered to play an important role in mitigating climate change, protecting biodiversity and preventing environmental degradation. Yet, there are often multiple perspectives on what outcomes restoration should be aiming to achieve, and how we should get to that point. In this paper we interview a range of policy makers, academics and NGO representatives to explore the range of perspectives on the restoration of Indonesia's tropical peatlands – key global ecosystems that have undergone large‐scale degradation. Thematic analysis suggests that participants agreed about the importance of restoration, but had differing opinions on how effective restoration activities to date have been and what a restored peatland landscape should look like. These results exemplify how ecological restoration can mean different things to different people, but also highlight important areas of consensus for moving forward with peatland restoration strategies

Qatar-2: A K dwarf orbited by a transiting hot Jupiter and a more massive companion in an outer orbit

We report the discovery and initial characterization of Qatar-2b, a hot Jupiter transiting a V = 13.3 mag K dwarf in a circular orbit with a short period, P_ b = 1.34 days. The mass and radius of Qatar-2b are M_p = 2.49 M_j and R_p = 1.14 R_j, respectively. Radial-velocity monitoring of Qatar-2 over a span of 153 days revealed the presence of a second companion in an outer orbit. The Systemic Console yielded plausible orbits for the outer companion, with periods on the order of a year and a companion mass of at least several M_j. Thus Qatar-2 joins the short but growing list of systems with a transiting hot Jupiter and an outer companion with a much longer period. This system architecture is in sharp contrast to that found by Kepler for multi-transiting systems, which are dominated by objects smaller than Neptune, usually with tightly spaced orbits that must be nearly coplanar

Probing Quark-Gluon Interactions with Transverse Polarized Scattering

We have extracted QCD matrix elements from our data on double polarized inelastic scattering of electrons on nuclei. We find the higher twist matrix element \tilde{d_2}, which arises strictly from quark- gluon interactions, to be unambiguously non zero. The data also reveal an isospin dependence of higher twist effects if we assume that the Burkhardt-Cottingham Sum rule is valid. The fundamental Bjorken sum rule obtained from the a0 matrix element is satisfied at our low momentum transfer.Comment: formerly "Nachtmann Moments of the Proton and Deuteron Spin Structure Functions

Proton Spin Structure in the Resonance Region

We have examined the spin structure of the proton in the region of the nucleon resonances (1.085 GeV < W < 1.910 GeV) at an average four momentum transfer of Q^2 = 1.3 GeV^2. Using the Jefferson Lab polarized electron beam, a spectrometer, and a polarized solid target, we measured the asymmetries A_parallel and A_perp to high precision, and extracted the asymmetries A_1 and A_2, and the spin structure functions g_1 and g_2. We found a notably non-zero A_perp, significant contributions from higher-twist effects, and only weak support for polarized quark--hadron duality.Comment: 6 pages, 4 figures, REVTeX4, similar to PRL submission, plots colorized and appenix added, v3: minor edit, matches PR