T Cells Use Rafts for Survival

T cell homeostasis must be tightly controlled. In this issue of Immunity, Cho et al. (2010) describe results that begin to define the roles of the T cell receptor, self-peptide-MHC ligands, cytokines, and membrane rafts in this dynamic process

The Grade Experience of Online Nurse Practitioner Students

The rapid growth and demand for nurse practitioners (NPs) is expected to increase through 2020. The growing national shortage of physicians in primary care has fueled the demand for NPs. The expansion of health insurance coverage means that more people will be insured and will need health care. Online NP programs are of interest to working students. NP students often want to expedite degree completion by taking more than one clinical course per quarter (OCCPQ). This study examined grade experience differences for online NP students who took more than OCCPQ, compared to those who did not take more than OCCPQ. The study found that students who took more than OCCPQ had increased odds of failing a course.https://scholarworks.waldenu.edu/current/1027/thumbnail.jp

Spin Excitations in BaFe1.84Co0.16As2 Superconductor Observed by Inelastic Neutron Scattering

Superconductivity appears to compete against the spin-density-wave in Fe pnictides. However, optimally cobalt doped samples show a quasi-two-dimensional spin excitation centered at the (0.5, 0.5, L) wavevector, "the spin resonance peak", that is strongly tied to the onset of superconductivity. By inelastic neutron scattering on single crystals we show the similarities and differences of the spin excitations in BaFe1.84Co0.16As2, with respect to the spin excitations in the high-temperature superconducting cuprates. As in the cuprates the resonance occurs as an enhancement to a part of the spin excitation spectrum which extends to higher energy transfer and higher temperature. However, unlike in the cuprates, the resonance peak in this compound is asymmetric in energy.Comment: 12 pages, 6 figures; PACS # 74.70.-b, 74.20.Mn, 78.70.Nx, 74.25.Ha; corrected discussion of figures in tex

Crow Deaths Caused by West Nile Virus during Winter

In New York, an epizootic of American crow (Corvus brachyrhynchos) deaths from West Nile virus (WNV) infection occurred during winter 2004–2005, a cold season when mosquitoes are not active. Detection of WNV in feces collected at the roost suggests lateral transmission through contact or fecal contamination

The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion

Abalance between fission and fusion events determines the morphology of mitochondria. In yeast, mitochondrial fission is regulated by the outer membrane–associated dynamin-related GTPase, Dnm1p. Mitochondrial fusion requires two integral outer membrane components, Fzo1p and Ugo1p. Interestingly, mutations in a second mitochondrial-associated dynamin-related GTPase, Mgm1p, produce similar phenotypes to fzo1 and ugo cells. Specifically, mutations in MGM1 cause mitochondrial fragmentation and a loss of mitochondrial DNA that are suppressed by abolishing DNM1-dependent fission. In contrast to fzo1ts mutants, blocking DNM1-dependent fission restores mitochondrial fusion in mgm1ts cells during mating. Here we show that blocking DNM1-dependent fission in Δmgm1 cells fails to restore mitochondrial fusion during mating. To examine the role of Mgm1p in mitochondrial fusion, we looked for molecular interactions with known fusion components. Immunoprecipitation experiments revealed that Mgm1p is associated with both Ugo1p and Fzo1p in mitochondria, and that Ugo1p and Fzo1p also are associated with each other. In addition, genetic analysis of specific mgm1 alleles indicates that Mgm1p's GTPase and GTPase effector domains are required for its ability to promote mitochondrial fusion and that Mgm1p self-interacts, suggesting that it functions in fusion as a self-assembling GTPase. Mgm1p's localization within mitochondria has been controversial. Using protease protection and immuno-EM, we have shown previously that Mgm1p localizes to the intermembrane space, associated with the inner membrane. To further test our conclusions, we have used a novel method using the tobacco etch virus protease and confirm that Mgm1p is present in the intermembrane space compartment in vivo. Taken together, these data suggest a model where Mgm1p functions in fusion to remodel the inner membrane and to connect the inner membrane to the outer membrane via its interactions with Ugo1p and Fzo1p, thereby helping to coordinate the behavior of the four mitochondrial membranes during fusion

Interaction of Streptavidin-Based Peptide-MHC Oligomers (Tetramers) with Cell-Surface T Cell Receptors

he binding of oligomeric peptide–MHC (pMHC) complexes to cell surface TCR can be considered to approximate TCR–pMHC interactions at cell-cell interfaces. In this study, we analyzed the equilibrium binding of streptavidin-based pMHC oligomers (tetramers) and their dissociation kinetics from CD8[superscript pos] T cells from 2C-TCR transgenic mice and from T cell hybridomas that expressed the 2C TCR or a high-affinity mutant (m33) of this TCR. Our results show that the tetramers did not come close to saturating cell-surface TCR (binding only 10–30% of cell-surface receptors), as is generally assumed in deriving affinity values (K[subscript D]), in part because of dissociative losses from tetramer-stained cells. Guided by a kinetic model, the oligomer dissociation rate and equilibrium constants were seen to depend not only on monovalent association and dissociation rates (k[subscript off] and k[subscript on]), but also on a multivalent association rate (μ) and TCR cell-surface density. Our results suggest that dissociation rates could account for the recently described surprisingly high frequency of tetramer-negative, functionally competent T cells in some T cell responses.National Institutes of Health (U.S.) (Grant P01 CA097296)National Institutes of Health (U.S.) (Grant R01 GM55767)National Institutes of Health (U.S.) (Grant PO1-AI071195)National Institutes of Health (U.S.). Pioneer Awar

Impact of HCV testing and treatment on HCV transmission among men who have sex with men and who inject drugs in San Francisco: A modelling analysis

BACKGROUND: Men who have sex with men who ever injected drugs (ever MSM-IDU) carry a high hepatitis C virus (HCV) burden. We estimated whether current HCV testing and treatment in San Francisco can achieve the 2030 World Health Organization (WHO) HCV elimination target on HCV incidence among ever MSM-IDU. METHODS: A dynamic HCV/HIV transmission model among MSM was calibrated to San Francisco data, including HCV antibody (15.5%, 2011) and HIV prevalence (32.8%, 2017) among ever MSM-IDU. MSM had high HCV testing (79%-86% ever tested, 2011-2019) and diagnosed MSM had high HCV treatment (65% ever treated, 2018). Following coronavirus disease 2019 (COVID-19)-related lockdowns, HCV testing and treatment decreased by 59%. RESULTS: Among all MSM, 43% of incident HCV infections in 2022 were IDU-related. Among ever MSM-IDU in 2015, HCV incidence was 1.2/100 person-years (95% credibility interval [CrI], 0.8-1.6). Assuming COVID-19-related declines in HCV testing/treatment persist until 2030, HCV incidence among ever MSM-IDU will decrease by 84.9% (95% CrI, 72.3%-90.8%) over 2015-2030. This decline is largely attributed to HCV testing and treatment (75.8%; 95% CrI, 66.7%-89.5%). Slightly greater decreases in HCV incidence (94%-95%) are projected if COVID-19 disruptions recover by 2025 or 2022. CONCLUSIONS: We estimate that HCV incidence will decline by >80% over 2015-2030 among ever MSM-IDU in San Francisco, achieving the WHO target

Ecosystem Consequences of Plant Genetic Divergence with Colonization of New Habitat

When plants colonize new habitats altered by natural or anthropogenic disturbances, those individuals may encounter biotic and abiotic conditions novel to the species, which can cause plant functional trait divergence. Over time, site-driven adaptation can give rise to population-level genetic variation, with consequences for plant community dynamics and ecosystem processes. We used a series of 3000-yr-old, lava-created forest fragments on the Island of Hawai`i to examine whether disturbance and subsequent colonization can lead to genetically differentiated populations, and where differentiation occurs, if there are ecosystem consequences of trait-driven changes. These fragments are dominated by a single tree species, Metrosideros polymorpha (Myrtaceae) or ʻohiʻa, which have been actively colonizing the surrounding lava flow created in 1858. To test our ideas about differentiation of genetically determined traits, we (1) created rooted cuttings of ʻohiʻa individuals sampled from fragment interiors and open lava sites, raised these individuals in a greenhouse, and then used these cuttings to create a common garden where plant growth was monitored for three years; and (2) assessed genetic variation and made QST/FST comparisons using microsatellite repeat markers. Results from the greenhouse showed quantitative trait divergence in plant height and pubescence across plants sampled from fragment interior and matrix sites. Results from the subsequent common garden study confirmed that the matrix environment can select for individuals with 9.1% less shoot production and 17.3% higher leaf pubescence. We found no difference in molecular genetic variation indicating gene flow among the populations. The strongest QST level was greater than the FST estimate, indicating sympatric genetic divergence in growth traits. Tree height was correlated with ecosystem properties such as soil carbon and nitrogen storage, soil carbon turnover rates, and soil phosphatase activity, indicating that selection for growth traits will influence structure, function, and dynamics of developing ecosystems. These data show that divergence can occur on centennial timescales of early colonization

Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6×10−10, odds ratio (OR) = 0.74, 95% CI:0.68–0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6×10−4. OR = 0.86 (95% CI:0.79–0.93); rs744166, P = 2.6×10−5, OR = 0.84 (95% CI:0.77–0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2×10−5, OR = 0.65 (95% CI:0.54–0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2×10−5, OR = 0.83 (95% CI:0.76–0.91)), CDKAL1 (rs6908425, P = 1.1×10−4, OR = 0.82 (95% CI:0.74–0.91)), LRRK2/MUC19 (rs11175593, P = 9.9×10−5, OR = 1.92 (95% CI: 1.38–2.67)), and chr13q14 (rs3764147, P = 5.9×10−4, OR = 1.19 (95% CI: 1.08–1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases