Observed 1970-2005 cooling of summer daytime temperatures in coastal California

This study evaluated 1950–2005 summer [June–August (JJA)] mean monthly air temperatures for two California air basins: the South Coast Air Basin (SoCAB) and the San Francisco Bay Area (SFBA). The study focuses on the more rapid post-1970 warming period, and its daily minima temperature Tmin and maxima temperature Tmax values were used to produce average monthly values and spatial distributions of trends for each air basin. Additional analyses included concurrent SSTs, 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) sea level coastal pressure gradients, and GCM-downscaled average temperature Tave values. Results for all 253 California National Weather Service (NWS) Cooperative Observer Program (COOP) sites together showed increased Tave values (0.23°C decade−1); asymmetric warming, as Tmin values increase faster than Tmax values (0.27° versus 0.04°C decade−1) and thus decreased daily temperature range (DTR) values (0.15°C decade−1). The spatial distribution of observed SoCAB and SFBA Tmax values exhibited a complex pattern, with cooling (−0.30°C decade−1) in low-elevation coastal areas open to marine air penetration and warming (0.32°C decade−1) in inland areas. Results also showed that decreased DTR values in the basins arose from small increases at inland sites (0.16°C decade−1) combined with large decreases (−0.58°C decade−1) at coastal sites. It is also possible that some of the current observed temperature trends could be associated with low-frequency decadal variability, expected even with a constant radiative forcing. Previous studies suggest that cooling JJA Tmax values in coastal California were a result of increased irrigation, coastal upwelling, or cloud cover. The current hypothesis is that they arise (as a possible “reverse reaction”) from the global warming of inland areas, which results in increased sea-breeze flow activity. GCM model Tave warming decreased from 0.13°C decade−1 at inland sites to 0.08°C decade−1 in coastal areas. Sea level pressure increased in the Pacific high and decreased in the thermal low. The corresponding gradient thus showed a trend of 0.04 hPa 100 km−1 decade−1, supportive of the hypothesis of increased sea-breeze activity

2000 Ruby Yearbook

A digitized copy of the 2000 Ruby, the Ursinus College yearbook.https://digitalcommons.ursinus.edu/ruby/1103/thumbnail.jp

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological PsychiatryBackground: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.publishersversionpublishe

Mast cells: new therapeutic target in helminth immune modulation

Helminth infection and their secreted antigens have a protective role in many immune-mediated inflammatory disorders such as inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. However, studies have focused primarily on identifying immune protective mechanisms of helminth infection and their secreted molecules on dendritic cells and macrophages. Given that mast cells have been shown to be implicated in the pathogenesis and progression of many inflammatory disorders, their role should also be examined and considered as cellular target for helminth-based therapies. As there is a dearth of studies examining the interaction of helminth-derived antigens and mast cells, this review will focus on the role of mast cells during helminth infection and examine our current understanding of the involvement of mast cells in TH 1/TH 17-mediated immune disorders. In this context, potential mechanisms by which helminths could target the TH 1/TH 17 promoting properties of mast cells can be identified to unveil novel therapeutic mast cell driven targets in combating these inflammatory disorders

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Impact of TiO₂ Nanoparticles on Growth, Biofilm Formation, and Flavin Secretion in <i>Shewanella oneidensis</i>

Understanding of nanoparticle impacts on critical bacteria functions allows us to gain a mechanistic understanding of toxicity and guides us toward design rules for creating safe nanomaterials. Herein, biofilm formation, a general bacteria function, and riboflavin secretion, a species-specific function, were monitored in <i>Shewanella oneidensis</i>, a metal reducing bacterium, following exposure to a variety of TiO₂ nanoparticle types (synthesized, Aeroxide P25, and T-Eco). Transmission electron microscopy (TEM) images show that dosed nanoparticles are in close proximity to the bacteria, but they are not internalized. Using quartz crystal microbalance (QCM), it was revealed that <i>S. oneidensis</i> biofilm formation is slowed in the presence of nanoparticles. Though <i>S. oneidensis</i> grows more slowly in the presence of TiO₂ nanoparticles, riboflavin secretion, a function related to the <i>S. oneidensis</i> metal reducing capacity, was increased significantly in a nanoparticle dose-dependent manner. Both changes in biofilm formation and riboflavin secretion are supported by changes in gene expression in nanoparticle-exposed <i>S. oneidensis</i>. This broad study of bacterial nanotoxicity, including use of sensitive analytical tools for functional assessments of biofilm formation, riboflavin secretion, and gene expression, has implications for total ecosystem health as the use of engineered nanoparticles grows