Additions to the Vascular Flora of the Santa Ana Mountains, California

The Santa Ana Mountains, part of the Peninsular Ranges of southern California, have been welldocumented floristically. Nevertheless, since publication of a preliminary vascular flora for the range in 1978, a significant number of additions have been reported. These are principally from studies of two subregions in the southern portion of the range and include 42 taxa from the Santa Rosa Plateau and 88 taxa from the San Mateo Canyon Wilderness Area. Documentation is provided here for an additional 66 taxa not included in other published floristic accounts of the Santa Ana Mountains. A voucher specimen and generalized distribution information are cited for each taxon

Border patrol gone awry: Lung NKT cell activation by Francisella tularensis exacerbates tularemia-like disease

The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia--because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice

A Structurally Characterized Cobalt(I) σ-Alkane Complex

The synthesis, and x-ray structure, of a cobalt s -alkane complex, [Co(Cy 2 P(CH 2 ) 4 PCy 2 )( norbornane )][BAr F 4 ], is achieved by a single-crystal to single-crystal solid/gas hydrogenation from a norbornadiene precursor. Magnetic data show this complex to be a triplet. Periodic DFT and electronic structure analyses identify weak C-H ··· Co σ -interactions, augmented by dispersive stabilisation between the alkane ligand and the anion-microenvironment. The calculations are most consistent with a η 1 : η 1 -alkane binding mode

The nsp1, nsp13, and M Proteins Contribute to the Hepatotropism of Murine Coronavirus JHM.WU

ABSTRACT Mouse hepatitis virus (MHV) isolates JHM.WU and JHM.SD promote severe central nervous system disease. However, while JHM.WU replicates robustly and induces hepatitis, JHM.SD fails to replicate or induce pathology in the liver. These two JHM variants encode homologous proteins with few polymorphisms, and little is known about which viral proteins(s) is responsible for the liver tropism of JHM.WU. We constructed reverse genetic systems for JHM.SD and JHM.WU and, utilizing these full-length cDNA clones, constructed chimeric viruses and mapped the virulence factors involved in liver tropism. Exchanging the spike proteins of the two viruses neither increased replication of JHM.SD in the liver nor attenuated JHM.WU. By further mapping, we found that polymorphisms in JHM.WU structural protein M and nonstructural replicase proteins nsp1 and nsp13 are essential for liver pathogenesis. M protein and nsp13, the helicase, of JHM.WU are required for efficient replication in vitro and in the liver in vivo . The JHM.SD nsp1 protein contains a K194R substitution of Lys194, a residue conserved among all other MHV strains. The K194R polymorphism has no effect on in vitro replication but influences hepatotropism, and introduction of R194K into JHM.SD promotes replication in the liver. Conversely, a K194R substitution in nsp1 of JHM.WU or A59, another hepatotropic strain, significantly attenuates replication of each strain in the liver and increases IFN-β expression in macrophages in culture. Our data indicate that both structural and nonstructural proteins contribute to MHV liver pathogenesis and support previous reports that nsp1 is a Betacoronavirus virulence factor. IMPORTANCE The Betacoronavirus genus includes human pathogens, some of which cause severe respiratory disease. The spread of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) into human populations demonstrates the zoonotic potential of emerging coronaviruses, and there are currently no vaccines or effective antivirals for human coronaviruses. Thus, it is important to understand the virus-host interaction that regulates coronavirus pathogenesis. Murine coronavirus infection of mice provides a useful model for the study of coronavirus-host interactions, including the determinants of tropism and virulence. We found that very small changes in coronavirus proteins can profoundly affect tropism and virulence. Furthermore, the hepatotropism of MHV-JHM depends not on the spike protein and viral entry but rather on a combination of the structural protein M and nonstructural replicase-associated proteins nsp1 and nsp13, which are conserved among betacoronaviruses. Understanding virulence determinants will aid in the design of vaccines and antiviral strategies

The Stride program: Feasibility and pre-to-post program change of an exercise service for university students experiencing mental distress

Rates of mental illness are disproportionately high for young adult and higher education (e.g., university student) populations. As such, universities and tertiary institutions often devote significant efforts to services and programs that support and treat mental illness and/or mental distress. However, within that portfolio of treatment approaches, structured exercise has been relatively underutilised and greater research attention is needed to develop this evidence base. The Stride program is a structured 12-week exercise service for students experiencing mental distress. We aimed to explore the feasibility of the program and assess pre- and post-program change, through assessments of student health, lifestyle, and wellbeing outcomes. Drawing from feasibility and effectiveness-implementation hybrid design literatures, we conducted a non-randomised feasibility trial of the Stride program. Participants were recruited from the Stride program (N = 114, Mage = 24.21 years). Feasibility results indicated the program was perceived as acceptable and that participants reported positive perceptions of program components, personnel, and sessions. Participants’ pre-to-post program change in depressive symptomatology, physical activity levels, mental health-related quality of life, and various behavioural outcomes were found to be desirable. Our results provide support for the feasibility of the Stride program, and more broadly for the delivery and potential effectiveness of structured exercise programs to support university students experiencing mental distress

A nonhuman primate model of inherited retinal disease.

Inherited retinal degenerations are a common cause of untreatable blindness worldwide, with retinitis pigmentosa and cone dystrophy affecting approximately 1 in 3500 and 1 in 10,000 individuals, respectively. A major limitation to the development of effective therapies is the lack of availability of animal models that fully replicate the human condition. Particularly for cone disorders, rodent, canine, and feline models with no true macula have substantive limitations. By contrast, the cone-rich macula of a nonhuman primate (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of heritable retinal diseases, particularly cone disorders that are predictive of human conditions, are necessary to more efficiently advance new therapies for patients. We have identified 4 related NHPs at the California National Primate Research Center with visual impairment and findings from clinical ophthalmic examination, advanced retinal imaging, and electrophysiology consistent with achromatopsia. Genetic sequencing confirmed a homozygous R565Q missense mutation in the catalytic domain of PDE6C, a cone-specific phototransduction enzyme associated with achromatopsia in humans. Biochemical studies demonstrate that the mutant mRNA is translated into a stable protein that displays normal cellular localization but is unable to hydrolyze cyclic GMP (cGMP). This NHP model of a cone disorder will not only serve as a therapeutic testing ground for achromatopsia gene replacement, but also for optimization of gene editing in the macula and of cone cell replacement in general

A New Approach to Measuring Estrogen Exposure and Metabolism in Epidemiologic Studies

Endogenous estrogen plays an integral role in the etiology of breast and endometrial cancer, and conceivably ovarian cancer. However, the underlying mechanisms and the importance of patterns of estrogen metabolism and specific estrogen metabolites have not been adequately explored. Long-standing hypotheses, derived from laboratory experiments, have not been tested in epidemiologic research because of the lack of robust, rapid, accurate measurement techniques appropriate for large-scale studies. We have developed a stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS(2)) method that can measure concurrently all 15 estrogens and estrogen metabolites (EM) in urine and serum with high sensitivity (level of detection=2.5-3.0fmol EM/mL serum), specificity, accuracy, and precision [laboratory coefficients of variation (CV\u27s) \u3c or =5% for nearly all EM]. The assay requires only extraction, a single chemical derivatization, and less than 0.5mL of serum or urine. By incorporating enzymatic hydrolysis, the assay measures total (glucuronidated+sulfated+unconjugated) EM. If the hydrolysis step is omitted, the assay measures unconjugated EM. Interindividual differences in urinary EM concentrations (pg/mL creatinine), which reflect total EM production, were consistently large, with a range of 10-100-fold for nearly all EM in premenopausal and postmenopausal women and men. Correlational analyses indicated that urinary estrone and estradiol, the most commonly measured EM, do not accurately represent levels of total urinary EM or of the other EM. In serum, all 15 EM were detected as conjugates, but only 5 were detected in unconjugated form. When we compared our assay methods with indirect radioimmunoassays for estrone, estradiol, and estriol and enzyme-linked immunosorbent assays for 2-hydroxyestrone and 16alpha-hydroxyestrone, ranking of individuals agreed well for premenopausal women [Spearman r (r(s))=0.8-0.9], but only moderately for postmenopausal women (r(s)=0.4-0.8). Our absolute readings were consistently lower, especially at the low concentrations characteristic of postmenopausal women, possibly because of improved specificity. We are currently applying our EM measurement techniques in several epidemiologic studies of premenopausal and postmenopausal breast cancer

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the International Association of Diabetes and Pregnancy Study Groups.

OBJECTIVE: Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucose and type 2 diabetes in nonpregnant populations. However, their associations with glucose levels from oral glucose tolerance tests (OGTTs) in pregnancy have not been assessed in a large sample. We hypothesized that these variants are associated with quantitative measures of glycemia in pregnancy. RESEARCH DESIGN AND METHODS: We analyzed the associations between variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24-32 weeks' gestation in 3,811 mothers of European (U.K. and Australia) and 1,706 mothers of Asian (Thailand) ancestry from the HAPO cohort. We also tested associations with offspring birth anthropometrics. RESULTS: The maternal GCK variant was associated with higher fasting glucose in Europeans (P = 0.001) and Thais (P 0.05). In both populations, both variants were associated with higher odds of gestational diabetes mellitus according to the new International Association of Diabetes and Pregnancy Study Groups recommendations (P = 0.001-0.08). CONCLUSIONS: Maternal GCK and TCF7L2 variants are associated with glucose levels known to carry an increased risk of adverse pregnancy outcome in women without overt diabetes. Further studies will be important to determine the variance in maternal glucose explained by all known genetic variants

The University of Akron Human Powered Vehicle Team

The University of Akron Human Powered Vehicle Team’s 2016 vehicle, Klokan, was designed, manufactured and tested with safety, reliability, performance and ease of use in mind. The vehicle is a fully faired tadpole trike with a lightweight aluminum frame constructed from 6061-T6 tubing having a total weight of 8.9 lbs. To complement the lightweight frame, the fairing is constructed from polycarbonate, PETG and carbon fiber strips which combine into a lightweight, easy to manufacture weather barrier and aerodynamic structure. Klokan was designed to be a safe and efficient mode of everyday transportation which ensures that riders are sufficiently protected by a rollover protection system (RPS) which was designed to meet the ASME HPVC requirements with a minimum safety factor of two. The project scope includes all aspects of design and fabrication to create a vehicle that is easy to manufacture, easy to use, safe, and low cost to facilitate its usability in everyday situations. The team completed research on how to improve the manufacturability, reliability, and performance through analysis of designs, computer based modeling, and physical testing to validate that the bike meets team goals as well as exceeding the requirements set by the ASME Human Powered Vehicle Competition. The frame was designed in a manner that reduces welding through the use of bends and allows for precision fixturing to be manufactured and used to construct multiple frames quickly and efficiently. The fairing’s modular construction reduces the need for specialized tooling while minimizing weight and construction time. The team designed and successfully implemented an innovative rollover warning system which actively monitors the percentage of vehicle load on each tire and warns the driver through audible tone and visual warning light prior to a dangerous rollover becoming imminent