Yeast sterol esters and their relationship to the growth of yeast.

Variation in the percentage of sterols esterified to long-chain fatty acids during cellular growth has been examined. Under all conditions, a constant percentage of sterol esters was maintained during exponential growth. This maintenance level was found to vary with different growth conditions. A sharp increase in the rate of esterification was observed upon entry of the culture into the stationary growth phase. The minor cellular sterol components were found to accumulate after this period of rapid sterol ester synthesis, with a relative decrease in the size of the ergosterol pool. Evidence is presented that sterol esters of ergosterol precursors are unable to be metabolized to ergosterol. Once esterified, the fatty acids do not appear to be scavenged during starvation conditions.     

Comparison of infrared coagulation and rubber band ligation for first and second degree haemorrhoids: a randomised prospective clinical trial.

One hundred and thirty seven previously untreated out-patients with first and second degree haemorrhoids were allocated at random to treatment by infrared coagulation (n=66) or rubber band ligation (n=71). Complete follow up was obtained in 122 patients (60 who had undergone infrared coagulation (group 1), and 62 rubber band ligation (group 2)) at periods from three months to one year after completion of treatment. Infrared coagulation produced a satisfactory outcome in 51 patients (85%): 34 were rendered asymptomatic and 17 improved. Rubber band ligation produced a satisfactory outcome in 57 patients (92%): 33 were rendered asymptomatic and 24 improved. Both methods were equally effective in first and second degree haemorrhoids. The incidence of side effects, particularly discomfort, during and after treatment was significantly higher in those treated by rubber band ligation (p less than 0.001). This appeared to be an appreciable deterrent to future patient compliance. The number of patients losing more than 24 hours from work was higher after rubber band ligation than after infrared coagulation. The number of treatments necessary to cure symptoms did not differ significantly between the two methods. Infrared coagulation was significantly faster than rubber band ligation (p less than 0.001). Infrared coagulation is a simple, fast, and effective outpatient method for the treatment of first and second degree haemorrhoids with fewer troublesome side effects and higher patient acceptability than rubber band ligation.     

Human land uses reduce climate connectivity across North America

Climate connectivity, the ability of a landscape to promote or hinder the movement of organisms in response to a changing climate, is contingent on multiple factors including the distance organisms need to move to track suitable climate over time (i.e. climate velocity) and the resistance they experience along such routes. An additional consideration which has received less attention is that human land uses increase resistance to movement or alter movement routes and thus influence climate connectivity. Here we evaluate the influence of human land uses on climate connectivity across North America by comparing two climate connectivity scenarios, one considering climate change in isolation and the other considering climate change and human land uses. In doing so, we introduce a novel metric of climate connectivity, ‘human exposure’, that quantifies the cumulative exposure to human activities that organisms may encounter as they shift their ranges in response to climate change. We also delineate potential movement routes and evaluate whether the protected area network supports movement corridors better than non‐protected lands. We found that when incorporating human land uses, climate connectivity decreased; climate velocity increased on average by 0.3 km/year and cumulative climatic resistance increased for ~83% of the continent. Moreover, ~96% of movement routes in North America must contend with human land uses to some degree. In the scenario that evaluated climate change in isolation, we found that protected areas do not support climate corridors at a higher rate than non‐protected lands across North America. However, variability is evident, as many ecoregions contain protected areas that exhibit both more and less representation of climate corridors compared to non‐protected lands. Overall, our study indicates that previous evaluations of climate connectivity underestimate climate change exposure because they do not account for human impacts.     

Exploring movement patterns and changing distributions of baleen whales in the western North Atlantic using a decade of passive acoustic data

Six baleen whale species are found in the temperate western North Atlantic Ocean, with limited information existing on the distribution and movement patterns for most. There is mounting evidence of distributional shifts in many species, including marine mammals, likely because of climate‐driven changes in ocean temperature and circulation. Previous acoustic studies examined the occurrence of minke (Balaenoptera acutorostrata) and North Atlantic right whales (NARW; Eubalaena glacialis). This study assesses the acoustic presence of humpback (Megaptera novaeangliae), sei (B. borealis), fin (B. physalus), and blue whales (B. musculus) over a decade, based on daily detections of their vocalizations. Data collected from 2004 to 2014 on 281 bottom‐mounted recorders, totaling 35,033 days, were processed using automated detection software and screened for each species' presence. A published study on NARW acoustics revealed significant changes in occurrence patterns between the periods of 2004–2010 and 2011–2014; therefore, these same time periods were examined here. All four species were present from the Southeast United States to Greenland; humpback whales were also present in the Caribbean. All species occurred throughout all regions in the winter, suggesting that baleen whales are widely distributed during these months. Each of the species showed significant changes in acoustic occurrence after 2010. Similar to NARWs, sei whales had higher acoustic occurrence in mid‐Atlantic regions after 2010. Fin, blue, and sei whales were more frequently detected in the northern latitudes of the study area after 2010. Despite this general northward shift, all four species were detected less on the Scotian Shelf area after 2010, matching documented shifts in prey availability in this region. A decade of acoustic observations have shown important distributional changes over the range of baleen whales, mirroring known climatic shifts and identifying new habitats that will require further protection from anthropogenic threats like fixed fishing gear, shipping, and noise pollution.     

A quantitative trait variant in Gabra2 underlies increased methamphetamine stimulant sensitivity

Psychostimulant (methamphetamine, cocaine) use disorders have a genetic component that remains mostly unknown. We conducted genome-wide quantitative trait locus (QTL) analysis of methamphetamine stimulant sensitivity. To facilitate gene identification, we employed a Reduced Complexity Cross between closely related C57BL/6 mouse substrains and examined maximum speed and distance traveled over 30 min following methamphetamine (2 mg/kg, i.p.). For maximum methamphetamine-induced speed following the second and third administration, we identified a single genome-wide significant QTL on chromosome 11 that peaked near the Cyfip2 locus (LOD = 3.5, 4.2; peak = 21 cM [36 Mb]). For methamphetamine-induced distance traveled following the first and second administration, we identified a genome-wide significant QTL on chromosome 5 that peaked near a functional intronic indel in Gabra2 coding for the alpha-2 subunit of the GABA-A receptor (LOD = 3.6–5.2; peak = 34–35 cM [66–67 Mb]). Striatal cis-expression QTL mapping corroborated Gabra2 as a functional candidate gene underlying methamphetamine-induced distance traveled. CRISPR/Cas9-mediated correction of the mutant intronic deletion on the C57BL/6J background to the wild-type C57BL/6NJ allele was sufficient to reduce methamphetamine-induced locomotor activity toward the wild-type C57BL/6NJ-like level, thus validating the quantitative trait variant (QTV). These studies show the power and efficiency of Reduced Complexity Crosses in identifying causal variants underlying complex traits. Functionally restoring Gabra2 expression decreased methamphetamine stimulant sensitivity and supports preclinical and human genetic studies implicating the GABA-A receptor in psychostimulant addiction-relevant traits. Importantly, our findings have major implications for studying psychostimulants in the C57BL/6J strain—the gold standard strain in biomedical research.     

Functional evidence of distinct electrophile-induced activation states of the ion channel TRPA1

Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective cation channel expressed on nociceptive sensory nerves whose activation elicits nocifensive responses (e.g. pain). TRPA1 is activated by electrophiles found in foods and pollution, or produced during inflammation and oxidative stress, via covalent modification of reactive cysteines, but the mechanism underlying electrophilic activation of TRPA1 is poorly understood. Here we studied TRPA1 activation by the irreversible electrophiles iodoacetamide and N-ethylmaleimide (NEM) following transient expression in HEK293 cells. We found that in Ca²⁺ imaging studies C621 is critical for electrophile-induced TRPA1 activation, but the role of C665 in TRPA1 activation is dependent on the size of the electrophile. We identified slower TRPA1 activation in whole-cell recordings compared to studies with intact cells, which is rescued by pipette solution supplementation with the antioxidant glutathione. Single-channel recordings identified two distinct electrophilic-induced TRPA1 activation phases: a partial activation that, in some channels, switched to full activation with continued electrophile exposure. Full activation but not the initial activation was regulated by C665. Fitting of open time distributions suggests that full activation correlated with an additional (and long) exponential component, thus suggesting the phases are manifestations of distinct activation states. Our results suggest that distinct NEM-induced TRPA1 activation states are evoked by sequential modification of C621 then C665.     

Small geographic range but not panmictic: how forests structure the endangered Point Arena mountain beaver (Aplodontia rufa nigra)

The landscape genetics framework is typically applied to broad regions that occupy only small portions of a species’ range. Rarely is the entire range of a taxon the subject of study. We examined the landscape genetic structure of the endangered Point Arena mountain beaver (Aplodontia rufa nigra), whose isolated geographic range is found in a restricted (85 km²) but heterogenous region in California. Based on its diminutive range we may predict widespread gene flow and a relatively weak role for landscape variation in defining genetic structure. We used skin, bone, tissue and noninvasively collected hair samples to describe genetic substructure and model gene flow. We examined spatial partitioning of multilocus DNA genotypes and mitochondrial DNA haplotypes. We identified 3 groups from microsatellite data, all of which had low estimates of effective population size consistent with significant tests for historical bottlenecks. We used least-cost-path analysis with the microsatellites to examine how vegetation type affects gene flow in a landscape genetics framework. Gene flow was best predicted by a model with “Forest” as the most permeable, followed by “Riparian”. Agricultural lands demonstrated the highest resistance. MtDNA data revealed only two haplotypes: one was represented in all 57 individuals that occurred north of the east–west flowing Garcia River. South of the river, however, both haplotypes occurred, often at the same site suggesting that the river may have affected historical patterns of genetic divergence.