The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae

Intracellular membrane trafficking pathways must be tightly regulated to ensure proper functioning of all eukaryotic cells. Central to membrane trafficking is the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor attachment protein receptor) complexes between proteins on opposing lipid bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE-mediated membrane fusion, and like the SNAREs are conserved through evolution from yeast to humans. The SM protein Vps45 is required for the formation of yeast endosomal SNARE complexes and is thus essential for traffic through the endosomal system. Here we report that, in addition to its role in regulating SNARE complex assembly, Vps45 regulates cellular levels of its SNARE binding partners: the syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant increases in the levels of both Tlg2 and Snc2. As well as regulating traffic through the endosomal system, the Snc v-SNAREs are also required for exocytosis. Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes. Here we report that these can be reversed by selectively restoring Snc2 levels in vps45 mutant cells. Our data indicate that as well as functioning as part of the machinery that controls SNARE complex assembly, Vps45 also plays a key role in determining the levels of its cognate SNARE proteins; another key factor in regulation of membrane traffic

Direct interaction between the Gulf Stream and the shelfbreak south of New England

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 2 (2012): 553, doi:10.1038/srep00553.Sea surface temperature imagery, satellite altimetry, and a surface drifter track reveal an unusual tilt in the Gulf Stream path that brought the Gulf Stream to 39.9°N near the Middle Atlantic Bight shelfbreak—200 km north of its mean position—in October 2011, while a large meander brought Gulf Stream water within 12 km of the shelfbreak in December 2011. Near-bottom temperature measurements from lobster traps on the outer continental shelf south of New England show distinct warming events (temperature increases exceeding 6°C) in November and December 2011. Moored profiler measurements over the continental slope show high salinities and temperatures, suggesting that the warm water on the continental shelf originated in the Gulf Stream. The combination of unusual water properties over the shelf and slope in late fall and the subsequent mild winter may affect seasonal stratification and habitat selection for marine life over the continental shelf in 2012.Profiler data were made available by the Ocean Observatory Initiative (OOI) during the construction phase of the project. The OOI is funded by the National Science Foundation and managed by the Consortium for Ocean Leadership. Drifter data were provided by Tim Shaw and David Calhoun at Cape Fear Community College.GGGwas supported by NSFGrant OCE-1129125. RET was supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Cooperative Institute for the North Atlantic Region. MA was supported by the Penzance Endowed Fund in Support of Assistant Scientists

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

Could salvage surgery after chemotherapy have clinical impact on cancer survival of patients with metastatic urothelial carcinoma?

The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy. Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery. All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test). Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival

Ras GTPase-like protein MglA, a controller of bacterial social-motility in Myxobacteria, has evolved to control bacterial predation by Bdellovibrio

Bdellovibrio bacteriovorus invade Gram-negative bacteria in a predatory process requiring Type IV pili (T4P) at a single invasive pole, and also glide on surfaces to locate prey. Ras-like G-protein MglA, working with MglB and RomR in the deltaproteobacterium Myxococcus xanthus, regulates adventurous gliding and T4P-mediated social motility at both M. xanthus cell poles. Our bioinformatic analyses suggested that the GTPase activating protein (GAP)-encoding gene mglB was lost in Bdellovibrio, but critical residues for MglABd GTP-binding are conserved. Deletion of mglABd abolished prey-invasion, but not gliding, and reduced T4P formation. MglABd interacted with a previously uncharacterised tetratricopeptide repeat (TPR) domain protein Bd2492, which we show localises at the single invasive pole and is required for predation. Bd2492 and RomR also interacted with cyclic-di-GMP-binding receptor CdgA, required for rapid prey-invasion. Bd2492, RomRBd and CdgA localize to the invasive pole and may facilitate MglA-docking. Bd2492 was encoded from an operon encoding a TamAB-like secretion system. The TamA protein and RomR were found, by gene deletion tests, to be essential for viability in both predatory and non-predatory modes. Control proteins, which regulate bipolar T4P-mediated social motility in swarming groups of deltaproteobacteria, have adapted in evolution to regulate the anti-social process of unipolar prey-invasion in the “lone-hunter” Bdellovibrio. Thus GTP-binding proteins and cyclic-di-GMP inputs combine at a regulatory hub, turning on prey-invasion and allowing invasion and killing of bacterial pathogens and consequent predatory growth of Bdellovibrio

Dissection of a QTL Hotspot on Mouse Distal Chromosome 1 that Modulates Neurobehavioral Phenotypes and Gene Expression

A remarkably diverse set of traits maps to a region on mouse distal chromosome 1 (Chr 1) that corresponds to human Chr 1q21–q23. This region is highly enriched in quantitative trait loci (QTLs) that control neural and behavioral phenotypes, including motor behavior, escape latency, emotionality, seizure susceptibility (Szs1), and responses to ethanol, caffeine, pentobarbital, and haloperidol. This region also controls the expression of a remarkably large number of genes, including genes that are associated with some of the classical traits that map to distal Chr 1 (e.g., seizure susceptibility). Here, we ask whether this QTL-rich region on Chr 1 (Qrr1) consists of a single master locus or a mixture of linked, but functionally unrelated, QTLs. To answer this question and to evaluate candidate genes, we generated and analyzed several gene expression, haplotype, and sequence datasets. We exploited six complementary mouse crosses, and combed through 18 expression datasets to determine class membership of genes modulated by Qrr1. Qrr1 can be broadly divided into a proximal part (Qrr1p) and a distal part (Qrr1d), each associated with the expression of distinct subsets of genes. Qrr1d controls RNA metabolism and protein synthesis, including the expression of ∼20 aminoacyl-tRNA synthetases. Qrr1d contains a tRNA cluster, and this is a functionally pertinent candidate for the tRNA synthetases. Rgs7 and Fmn2 are other strong candidates in Qrr1d. FMN2 protein has pronounced expression in neurons, including in the dendrites, and deletion of Fmn2 had a strong effect on the expression of few genes modulated by Qrr1d. Our analysis revealed a highly complex gene expression regulatory interval in Qrr1, composed of multiple loci modulating the expression of functionally cognate sets of genes

The Long Term Response of Birds to Climate Change: New Results from a Cold Stage Avifauna in Northern England

The early MIS 3 (55–40 Kyr BP associated with Middle Palaeolithic archaeology) bird remains from Pin Hole, Creswell Crags, Derbyshire, England are analysed in the context of the new dating of the site’s stratigraphy. The analysis is restricted to the material from the early MIS 3 level of the cave because the upper fauna is now known to include Holocene material as well as that from the Late Glacial. The results of the analysis confirm the presence of the taxa, possibly unexpected for a Late Pleistocene glacial deposit including records such as Alpine swift, demoiselle crane and long-legged buzzard with southern and/or eastern distributions today. These taxa are accompanied by more expected ones such as willow ptarmigan /red grouse and rock ptarmigan living today in northern and montane areas. Finally, there are temperate taxa normally requiring trees for nesting such as wood pigeon and grey heron. Therefore, the result of the analysis is that the avifauna of early MIS 3 in England included taxa whose ranges today do not overlap making it a non-analogue community similar to the many steppe-tundra mammalian faunas of the time. The inclusion of more temperate and woodland taxa is discussed in the light that parts of northern Europe may have acted as cryptic northern refugia for some such taxa during the last glacial. These records showing former ranges of taxa are considered in the light of modern phylogeographic studies as these often assume former ranges without considering the fossil record of those taxa. In addition to the anomalous combination of taxa during MIS 3 living in Derbyshire, the individuals of a number of the taxa are different in size and shape to members of the species today probably due to the high carrying capacity of the steppe-tundra

Heritable symbionts in a world of varying temperature

Heritable microbes represent an important component of the biology, ecology and evolution of many plants, animals and fungi, acting as both parasites and partners. In this review, we examine how heritable symbiont–host interactions may alter host thermal tolerance, and how the dynamics of these interactions may more generally be altered by thermal environment. Obligate symbionts, those required by their host, are considered to represent a thermally sensitive weak point for their host, associated with accumulation of deleterious mutations. As such, these symbionts may represent an important determinant of host thermal envelope and spatial distribution. We then examine the varied relationship between thermal environment and the frequency of facultative symbionts that provide ecologically contingent benefits or act as parasites. We note that some facultative symbionts directly alter host thermotolerance. We outline how thermal environment will alter the benefits/costs of infection more widely, and additionally modulate vertical transmission efficiency. Multiple patterns are observed, with symbionts being cold sensitive in some species and heat sensitive in others, with varying and non-coincident thresholds at which phenotype and transmission are ablated. Nevertheless, it is clear that studies aiming to predict ecological and evolutionary dynamics of symbiont–host interactions need to examine the interaction across a range of thermal environments. Finally, we discuss the importance of thermal sensitivity in predicting the success/failure of symbionts to spread into novel species following natural/engineered introduction

A Bayesian hierarchical approach for spatial analysis of climate model bias in multi-model ensembles

Coupled atmosphere–ocean general circulation models are key tools to investigate climate dynamics and the climatic response to external forcings, to predict climate evolution and to generate future climate projections. Current general circulation models are, however, undisputedly affected by substantial systematic errors in their outputs compared to observations. The assessment of these so-called biases, both individually and collectively, is crucial for the models’ evaluation prior to their predictive use. We present a Bayesian hierarchical model for a unified assessment of spatially referenced climate model biases in a multi-model framework. A key feature of our approach is that the model quantifies an overall common bias that is obtained by synthesizing bias across the different climate models in the ensemble, further determining the contribution of each model to the overall bias. Moreover, we determine model-specific individual bias components by characterizing them as non-stationary spatial fields. The approach is illustrated based on the case of near-surface air temperature bias in the tropical Atlantic and bordering regions from a multi-model ensemble of historical simulations from the fifth phase of the Coupled Model Intercomparison Project. The results demonstrate the improved quantification of the bias and interpretative advantages allowed by the posterior distributions derived from the proposed Bayesian hierarchical framework, whose generality favors its broader application within climate model assessment