Smoking,Suicidality and Psychosis: A Systematic Meta-Analysis

The aim of this study is to systematically review the literature that explored the association between smoking and suicidal risk among those with serious mental illness and to estimate the risk of suicidal behaviors attributable to smoking among this patient group. Multiple databases (CINAHL, PsycINFO, EMBASE, Informit Health Collection and the Cochrane Library databases) were searched from 1 January 1975 through 15 January 2014, along with references from relevant articles for observational studies that ascertained the association between smoking and suicidal behaviors among patients with psychotic disorders conducted in adult patients. Thirteen studies involving 6813 patients with severe mental illness were included. We found that smoking was significantly associated with suicidality in psychosis with an Odds Ratio of 2.12 (95% CI 1.67–2.7). Smoking is associated with suicidal risk amongst individuals with a severe mental illness; however, it is still unclear whether this represents a true risk factor or a confounder or a mediator via mechanisms, hitherto unknown, needs to be studied further.     

Use of sustainable chemistry to produce an acyl amino acid surfactant

Surfactants find wide commercial use as foaming agents, emulsifiers, and dispersants. Currently, surfactants are produced from petroleum, or from seed oils such as palm or coconut oil. Due to concerns with CO₂ emissions and the need to protect rainforests, there is a growing necessity to manufacture these chemicals using sustainable resources In this report, we describe the engineering of a native nonribosomal peptide synthetase pathway (i.e., surfactin synthetase), to generate a Bacillus strain that synthesizes a highly water-soluble acyl amino acid surfactant, rather than the water insoluble lipopeptide surfactin. This novel product has a lower CMC and higher water solubility than myristoyl glutamate, a commercial surfactant. This surfactant is produced by fermentation of cellulosic carbohydrate as feedstock. This method of surfactant production provides an approach to sustainable manufacturing of new surfactants.     

Global regulation of alternative splicing during myogenic differentiation

Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons of splice isoforms between differentiated tissues. However, regulated splicing changes are likely to be important in biological transitions such as cellular differentiation, or response to environmental stimuli. To assess the extent and significance of AS in myogenesis, we used splicing-sensitive microarray analysis of differentiating C2C12 myoblasts. We identified 95 AS events that undergo robust splicing transitions during C2C12 differentiation. More than half of the splicing transitions are conserved during differentiation of avian myoblasts, suggesting the products and timing of transitions are functionally significant. The majority of splicing transitions during C2C12 differentiation fall into four temporal patterns and were dependent on the myogenic program, suggesting that they are integral components of myogenic differentiation. Computational analyses revealed enrichment of many sequence motifs within the upstream and downstream intronic regions near the alternatively spliced regions corresponding to binding sites of splicing regulators. Western analyses demonstrated that several splicing regulators undergo dynamic changes in nuclear abundance during differentiation. These findings show that within a developmental context, AS is a highly regulated and conserved process, suggesting a major role for AS regulation in myogenic differentiation.     

Sphingosine kinase 1 is a negative regulator of CD4+ Th1 cells

CD4+ Th1 cells produce IFN-gamma, TNF-alpha, and IL-2. These Th1 cytokines play critical roles in both protective immunity and inflammatory responses. In this study we report that sphingosine kinase 1 (SPHK1), but not SPHK2, is highly expressed in DO11.10 Th1 cells. The expression of SPHK1 in Th1 cells requires TCR signaling and new protein synthesis. SPHK1 phosphorylates sphingosine to form sphingosine-1-phosphate. Sphingosine-1-phosphate plays important roles in inhibition of apoptosis, promotion of cell proliferation, cell migration, calcium mobilization, and activation of ERK1/2. When SPHK1 expression was knocked down by SPHK1 short interfering RNA, the production of IL-2, TNF-alpha, and IFN-gamma by Th1 cells in response to TCR stimulation was enhanced. Consistently, overexpression of dominant-negative SPHK1 increased the production of IL-2, TNF-alpha, and IFN-gamma in Th1 cells. Furthermore, overexpression of SPHK1 in Th1 and Th0 cells decreased the expression of IL-2, TNF-alpha, and IFN-gamma. Several chemokines, including Th2 chemokines CCL17 and CCL22, were up-regulated by SPHK1 short interfering RNA and down-regulated by overexpression of SPHK1. We also showed that Th2 cells themselves express CCL17 and CCL22. Finally, we conclude that SPHK1 negatively regulates the inflammatory responses of Th1 cells by inhibiting the production of proinflammatory cytokines and chemokines.     

Membrane position of a basic aromatic peptide that sequesters phosphatidylinositol 4,5 bisphosphate determined by site-directed spin labeling and high-resolution NMR

The membrane interactions and position of a positively charged and highly aromatic peptide derived from a secretory carrier membrane protein (SCAMP) are examined using magnetic resonance spectroscopy and several biochemical methods. This peptide (SCAMP-E) is shown to bind to membranes containing phosphatidylinositol 4,5-bisphosphate, PI(4,5)P2, and sequester PI(4,5)P2 within the plane of the membrane. Site-directed spin labeling of the SCAMP-E peptide indicates that the position and structure of membrane bound SCAMP-E are not altered by the presence of PI(4,5)P2, and that the peptide backbone is positioned within the lipid interface below the level of the lipid phosphates. A second approach using high-resolution NMR was used to generate a model for SCAMP-E bound to bicelles. This approach combined oxygen enhancements of nuclear relaxation with a computational method to dock the SCAMP-E peptide at the lipid interface. The model for SCAMP generated by NMR is consistent with the results of site-directed spin labeling and places the peptide backbone in the bilayer interfacial region and the aromatic side chains within the lipid hydrocarbon region. The charged side chains of SCAMP-E lie well within the interface with two arginine residues lying deeper than a plane defined by the position of the lipid phosphates. These data suggest that SCAMP-E interacts with PI(4,5)P2 through an electrostatic mechanism that does not involve specific lipid-peptide contacts. This interaction may be facilitated by the position of the positively charged side chains on SCAMP-E within a low-dielectric region of the bilayer interface.     

The importance of physiological ecology in conservation biology

Many of the threats to the persistence of populations of sensitivespecies have physiological or pathological mechanisms, and thosemechanisms are best understood through the inherently integrativediscipline of physiological ecology. The desert tortoise waslisted under the Endangered Species Act largely due to a newlyrecognized upper respiratory disease thought to cause mortalityin individuals and severe declines in populations. Numeroushypotheses about the threats to the persistence of desert tortoisepopulations involve acquisition of nutrients, and its connectionto stress and disease. The nutritional wisdom hypothesis positsthat animals should forage not for particular food items, butinstead, for particular nutrients such as calcium and phosphorusused in building bones. The optimal foraging hypothesis suggeststhat, in circumstances of resource abundance, tortoises shouldforage as dietary specialists as a means of maximizing intakeof resources. The optimal digestion hypothesis suggests thattortoises should process ingesta in ways that regulate assimilationrate. Finally, the cost-of-switching hypothesis suggests thatherbivores, like the desert tortoise, should avoid switchingfood types to avoid negatively affecting the microbe communityresponsible for fermenting plants into energy and nutrients.Combining hypotheses into a resource acquisition theory leadsto novel predictions that are generally supported by data presentedhere. Testing hypotheses, and synthesizing test results intoa theory, provides a robust scientific alternative to the popularuse of untested hypotheses and unanalyzed data to assert theneeds of species. The scientific approach should focus on hypothesesconcerning anthropogenic modifications of the environment thatimpact physiological processes ultimately important to populationphenomena. We show how measurements of such impacts as nutrientstarvation, can cause physiological stress, and that the endocrinemechanisms involved with stress can result in disease. Finally,our new syntheses evince a new hypothesis. Free molecules ofthe stress hormone corticosterone can inhibit immunity, andthe abundance of "free corticosterone" in the blood (thoughtto be the active form of the hormone) is regulated when thecorticosterone molecules combine with binding globulins. Thesex hormone, testosterone, combines with the same binding globulin.High levels of testosterone, naturally occurring in the breedingseason, may be further enhanced in populations at high densities,and the resulting excess testosterone may compete with bindingglobulins, thereby releasing corticosterone and reducing immunityto disease. This sequence could result in physiological andpathological phenomena leading to population cycles with a periodthat would be essentially impossible to observe in desert tortoise.Such cycles could obscure population fluctuations of anthropogenicorigin.     

Establishment of baseline susceptibility data to various insecticides for Homalodisca coagulata (Homoptera: Cicadellidae) by comparative bioassay techniques

Homalodisca coagulata Say, adults from three locations in California were subjected to insecticide bioassays to establish baseline toxicity. Initially, two bioassay techniques, petri dish and leaf dip, were compared to determine the most useful method to establish baseline susceptibility data under laboratory and greenhouse conditions. Comparative dose-response data were determined by both techniques to endosulfan, dimethoate, cyfluthrin, and acetamiprid. Toxic values were similar to some insecticides with both techniques but not for all insecticides, revealing susceptibility differences among the three populations of H. coagulata. In subsequent tests, the petri dish technique was selected to establish baseline susceptibility data to various contact insecticides. A systemic uptake bioassay was adapted to estimate dose-mortality responses to a systemic insecticide, imidacloprid. A 2-yr comparison of toxicological responses showed all three populations of H. coagulata to be highly susceptible to 10 insecticides, including chlorpyrifos, dimethoate, endosulfan, bifenthrin, cyfluthrin, esfenvalerate, fenpropathrin, acetamiprid, imidacloprid, and thiamethoxam. In general, two pyrethroids, bifenthrin and esfenvalerate, were the most toxic compounds, followed by two neonicotinoids, acetamiprid and imidacloprid. The LC50 values for all insecticides tested were lower than concentrations used as recommended field rates. Baseline data varied for the three geographically distinct H. coagulata populations with the petri dish technique. Adult H. coagulata collected from San Bernardino County were significantly more susceptible to select pyrethroids compared with adults from Riverside or Kern counties. Adults from San Bernardino County also were more sensitive to two neonicotinoids, acetamiprid and imidacloprid. The highest LC50 values were to endosulfan, which nonetheless proved highly toxic to H. coagulata from all three regions. In the majority of the tests, mortality increased over time resulting in increased susceptibility at 48 h compared with 24 h. These results indicate a wide selection of highly effective insecticides that could aid in managing H. coagulata populations in California.     

Heritability and phenotypic variation of canine hip dysplasia radiographic traits in a cohort of Australian German shepherd dogs

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14-0.24 (ordinal models), 0.14-0.25 (linear models) and 0.12-0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30 ± 0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.