State resolved rotational excitation cross sections and rates in H2+H2 collisions

Rotational transitions in molecular hydrogen collisions are computed. The two most recently developed potential energy surfaces for the H2-H2 system are used from the following works: 1) A.I. Boothroyd, P.G. Martin, W.J. Keogh, M.J. Peterson, J. Chem. Phys., 116 (2002) 666, and 2) P. Diep, J.K. Johnson, J. Chem. Phys., 113 (2000) 3480; ibid. 112, 4465. Cross sections for rotational transitions 00->20, 22, 40, 42, 44 and corresponding rate coefficients are calculated using a quantum-mechanical approach. Results are compared for a wide range of kinetic temperatures 300 K < T < 3000 K.Comment: 9 pages, 3 figures, 3 table

Structural analysis of the Ras-like G protein MglA and its cognate GAP MglB and implications for bacterial polarity

The small G protein MglA and its cognate GAP MglB exemplify a new type of GTPase activation mechanism. In contrast to other Ras-like proteins, the key 'arginine finger' is provided not by the GAP, but by MglA itself

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells

Association of whole-genome and NETRIN1 signaling pathway-derived polygenic risk scores for Major Depressive Disorder and white matter microstructure in UK Biobank

Background: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter microstructure. Methods: We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390). Results: We found significantly lower FA in the superior longitudinal fasciculus (β = −.035, p =.029) and significantly higher MD in a global measure of thalamic radiations (β =.029, p =.021), as well as higher MD in the superior (β =.034, p =.039) and inferior (β =.029, p =.043) longitudinal fasciculus and in the anterior (β =.025, p =.046) and superior (β =.027, p =.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts. Conclusions: Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for major depressive disorder through effects on a number of white matter tracts

Comparative effectiveness of mandates and financial policies targeting COVID-19 vaccine hesitancy: A randomized, controlled survey experiment

Experts debate whether COVID-19 vaccine mandates or financial incentives will reduce, rather than increase, interest in vaccination. Among 3,698 unvaccinated U.S. residents, we conducted a randomized, controlled survey-embedded experiment to estimate the absolute and relative psychological effects of vaccine policies specifying: mandates by employers or airlines, bars, and restaurants; lotteries for $1 million,$200,000, or $100,000; guaranteed cash for$1000, $200, or$100; and $1,000 as either a tax credit or penalty. Vaccine intention —the study outcome— predicts uptake and provides insight into the psychological mechanism that is most proximal to behavior (i.e., vaccination). Compared to controls, those who learned about the$1,000 cash reward policy were 17.1 (±5.3)% more likely to want vaccination. Employer mandates are more promising than other mandate policies (8.6 [+/- 7.4]% vs. 1.4 [+/- 6.0]%). The full results suggest that neither mandates nor financial incentives are likely to have counterproductive psychological effects. These policies are not mutually exclusive and, if implemented well, they may increase vaccine uptake

Comparative effectiveness of mandates and financial policies targeting COVID-19 vaccine hesitancy: A randomized, controlled survey experiment

Experts debate whether COVID-19 vaccine mandates or financial incentives will reduce, rather than increase, interest in vaccination. Among 3,698 unvaccinated U.S. residents, we conducted a randomized, controlled survey-embedded experiment to estimate the absolute and relative psychological effects of vaccine policies specifying: mandates by employers or airlines, bars, and restaurants; lotteries for $1 million,$200,000, or $100,000; guaranteed cash for$1000, $200, or$100; and $1,000 as either a tax credit or penalty. Vaccine intention —the study outcome— predicts uptake and provides insight into the psychological mechanism that is most proximal to behavior (i.e., vaccination). Compared to controls, those who learned about the$1,000 cash reward policy were 17.1 (±5.3)% more likely to want vaccination. Employer mandates are more promising than other mandate policies (8.6 [+/- 7.4]% vs. 1.4 [+/- 6.0]%). The full results suggest that neither mandates nor financial incentives are likely to have counterproductive psychological effects. These policies are not mutually exclusive and, if implemented well, they may increase vaccine uptake

Prenatal diagnosis of HNF1B-associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?

OBJECTIVE 17q12 microdeletions containing HNF1B and intragenic variants within this gene are associated with variable developmental, endocrine, and renal anomalies, often already noted prenatally as hyperechogenic/cystic kidneys. Here, we describe prenatal and postnatal phenotypes of seven individuals with HNF1B aberrations and compare their clinical and genetic data to those of previous studies. METHODS Prenatal sequencing and postnatal chromosomal microarray analysis were performed in seven individuals with renal and/or neurodevelopmental phenotypes. We evaluated HNF1B-related clinical features from 82 studies and reclassified 192 reported intragenic HNF1B variants. RESULTS In a prenatal case, we identified a novel in-frame deletion p.(Gly239del) within the HNF1B DNA-binding domain, a mutational hot spot as demonstrated by spatial clustering analysis and high computational prediction scores. The six postnatally diagnosed individuals harbored 17q12 microdeletions. Literature screening revealed variable reporting of HNF1B-associated clinical traits. Overall, both mutation groups showed a high phenotypic heterogeneity. The reclassification of all previously reported intragenic HNF1B variants provided an up-to-date overview of the mutational spectrum. CONCLUSIONS We highlight the value of prenatal HNF1B screening in renal developmental diseases. Standardized clinical reporting and systematic classification of HNF1B variants are necessary for a more accurate risk quantification of prenatal and postnatal clinical features, improving genetic counseling and prenatal decision making

Prenatal diagnosis of HNF1B‐associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?

Objective 17q12 microdeletions containing HNF1B and intragenic variants within this gene are associated with variable developmental, endocrine, and renal anomalies, often already noted prenatally as hyperechogenic/cystic kidneys. Here, we describe prenatal and postnatal phenotypes of seven individuals with HNF1B aberrations and compare their clinical and genetic data to those of previous studies. Methods Prenatal sequencing and postnatal chromosomal microarray analysis were performed in seven individuals with renal and/or neurodevelopmental phenotypes. We evaluated HNF1B‐related clinical features from 82 studies and reclassified 192 reported intragenic HNF1B variants. Results In a prenatal case, we identified a novel in‐frame deletion p.(Gly239del) within the HNF1B DNA‐binding domain, a mutational hot spot as demonstrated by spatial clustering analysis and high computational prediction scores. The six postnatally diagnosed individuals harbored 17q12 microdeletions. Literature screening revealed variable reporting of HNF1B‐associated clinical traits. Overall, both mutation groups showed a high phenotypic heterogeneity. The reclassification of all previously reported intragenic HNF1B variants provided an up‐to‐date overview of the mutational spectrum. Conclusions We highlight the value of prenatal HNF1B screening in renal developmental diseases. Standardized clinical reporting and systematic classification of HNF1B variants are necessary for a more accurate risk quantification of prenatal and postnatal clinical features, improving genetic counseling and prenatal decision making