First cohomology for finite groups of Lie type: simple modules with small dominant weights

Let $k$ be an algebraically closed field of characteristic $p > 0$, and let $G$ be a simple, simply connected algebraic group defined over $\mathbb{F}_p$. Given $r \geq 1$, set $q=p^r$, and let $G(\mathbb{F}_q)$ be the corresponding finite Chevalley group. In this paper we investigate the structure of the first cohomology group $H^1(G(\mathbb{F}_q),L(\lambda))$ where $L(\lambda)$ is the simple $G$-module of highest weight $\lambda$. Under certain very mild conditions on $p$ and $q$, we are able to completely describe the first cohomology group when $\lambda$ is less than or equal to a fundamental dominant weight. In particular, in the cases we consider, we show that the first cohomology group has dimension at most one. Our calculations significantly extend, and provide new proofs for, earlier results of Cline, Parshall, Scott, and Jones, who considered the special case when $\lambda$ is a minimal nonzero dominant weight.Comment: 24 pages, 5 figures, 6 tables. Typos corrected and some proofs streamlined over previous versio

Second cohomology for finite groups of Lie type

Let $G$ be a simple, simply-connected algebraic group defined over $\mathbb{F}_p$. Given a power $q = p^r$ of $p$, let $G(\mathbb{F}_q) \subset G$ be the subgroup of $\mathbb{F}_q$-rational points. Let $L(\lambda)$ be the simple rational $G$-module of highest weight $\lambda$. In this paper we establish sufficient criteria for the restriction map in second cohomology $H^2(G,L(\lambda)) \rightarrow H^2(G(\mathbb{F}_q),L(\lambda))$ to be an isomorphism. In particular, the restriction map is an isomorphism under very mild conditions on $p$ and $q$ provided $\lambda$ is less than or equal to a fundamental dominant weight. Even when the restriction map is not an isomorphism, we are often able to describe $H^2(G(\mathbb{F}_q),L(\lambda))$ in terms of rational cohomology for $G$. We apply our techniques to compute $H^2(G(\mathbb{F}_q),L(\lambda))$ in a wide range of cases, and obtain new examples of nonzero second cohomology for finite groups of Lie type.Comment: 29 pages, GAP code included as an ancillary file. Rewritten to include the adjoint representation in types An, B2, and Cn. Corrections made to Theorem 3.1.3 and subsequent dependent results in Sections 3-4. Additional minor corrections and improvements also implemente

Protonation of the Binuclear Metal Center within the Active Site of Phosphotriesterase †

ABSTRACT: Phosphotriesterase (PTE) is a binuclear metalloenzyme that catalyzes the hydrolysis of organophosphates, including pesticides and chemical warfare agents, at rates approaching the diffusion controlled limit. The catalytic mechanism of this enzyme features a bridging solvent molecule that is proposed to initiate nucleophilic attack at the phosphorus center of the substrate. X-band EPR spectroscopy is utilized to investigate the active site of Mn/Mn-substituted PTE. Simulation of the dominant EPR spectrum from the coupled binuclear center of Mn/Mn-PTE requires slightly rhombic zero-field splitting parameters. Assuming that the signal arises from the S ) 2 manifold, an exchange coupling constant of J ) -2.7 ( 0.2 cm -1 (H ex ) -2JS 1 ‚S 2 ) is calculated. A kinetic pK a of 7.1 ( 0.1 associated with loss in activity at low pH indicates that a protonation event is responsible for inhibition of catalysis. Analysis of changes in the EPR spectrum as a function of pH provides a pK a of 7.3 ( 0.1 that is assigned as the protonation of the hydroxyl bridge. From the comparison of kinetic and spectral pK a values, it is concluded that the loss of catalytic activity at acidic pH results from the protonation of the hydroxide that bridges the binuclear metal center. Phosphotriesterase (PTE) 1 catalyzes the hydrolysis of a wide range of organophosphate esters, including agricultural pesticides and chemical warfare agents (1-3). The enzyme has been isolated from soil bacteria, but the natural substrate for PTE is not known. PTE is a member of the amidohydrolase superfamily, which also includes urease, dihydroorotase, and approximately 30 other enzymes of known specificity (4). The high-resolution X-ray crystal structure of Zn/Zn-PTE reveals that it is a homodimeric protein containing an active site with two divalent metal ions embedded within a ( /R) 8 -barrel motif (5). The R-metal ion is ligated by His-55, His-57, and Asp-301 while the -metal ion is coordinated to His-201 and His-230 as illustrated i

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

The community engagement course and action network: strengthening community and academic research partnerships to advance health equity

BackgroundHistorically Black Colleges and Universities and Minority Serving Institutions are uniquely positioned to implement community-campus research partnerships based on a history of service, the pursuit of community trustworthiness and student demographics often similar to surrounding marginalized communities. The Morehouse School of Medicine Prevention Research Center collaborates with members of Historically Black Colleges and Universities, Minority Serving Institutes, and community organizations on the Community Engaged Course and Action Network. This network is the first of its kind and aims to strengthen members’ ability to implement Community-Based Participatory Research (CBPR) principles and partnerships. Projects address public health priorities including mental health among communities of color, zoonotic disease prevention, and urban food deserts.Materials and methodsTo assess the effectiveness of the network, a Participatory Evaluation framework was implemented to conduct process evaluation which included review of partnership structures, operations, project implementation processes, and preliminary outcomes of the research collaborations. A focus group of Community Engagement Course and Action Network members (community and academic) was also conducted to identify benefits and challenges of the network with emphasis on key areas for improvement to further enhance the relationships between partners and to facilitate their subsequent community-campus research.ResultsNetwork improvements were tied to themes strengthening community-academic partnerships including sharing and fellowship, coalition building and collaboration, and greater connections and awareness of community needs through their current community-academic partnerships. The need to conduct ongoing evaluation during and after implementation, for determining the early adoption of CBPR approaches was also identified.ConclusionEvaluation of the network’s processes, infrastructure, and operation provides early lessons learned to strengthen the network. Ongoing assessment is also essential for ensuring continuous quality improvement across partnerships such as determining CBPR fidelity, assessing partnership synergy, and dynamics, and for quality improvement of research protocol. The implications and potential for advancing implementation science through this and similar networks are great towards advancing leadership in modeling how foundations in community service can advance to CBPR partnership formation and ultimately, health equity approaches, that are local defined and assessed

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

Modulation of the expression of components of the stress response by dietary arachidonic acid in European sea bass (Dicentrarchus labrax) larvae

This study reports for the first time in European sea bass, Dicentrarchus labrax (L.), larvae, the effect of different levels of dietary arachidonic acid (ARA; 20:4n-6) on the expression of genes related to the fish stress response. Copies of mRNA from genes related to steroidogenesis (StAR (steroidogenic acute regulatory protein), c-Fos, and CYP11β (11β- hydroxylase gene)), glucocorticoid receptor complex (GR (glucorticoid receptor) and HSP (heat shock proteins) 70 and 90) and antioxidative stress (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX)) were quantified. Eighteen day-old larvae were fed for 14 days with three experimental diets with increasing levels of ARA (0.3, 0.6 and 1.2% d.w.) and similar levels of docosahexaenoic (DHA; 22:6n-3) and eicosapentaenoic (EPA; 20:5n-3) acids (5 and 3%, respectively). The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real time RT-PCR with the standard curve method (absolute quantification). Increase dietary levels of ARA induced a significantly (p<0.05) down-regulation of genes related to cortisol synthesis, such as StAR and CYP11β and up-regulated genes related to glucocorticoid receptor complex, such as HSP70 and GR. No effects were observed on antioxidant enzymes gene expression. These results revealed the regulatory role of dietary ARA on the expression of stress-related genes in European sea bass larvae