The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion.

Common genetic variants at the ARL15 locus are associated with plasma adiponectin, insulin and HDL cholesterol concentrations, obesity, and coronary atherosclerosis. The ARL15 gene encodes a small GTP-binding protein whose function is currently unknown. In this study adipocyte-autonomous roles for ARL15 were investigated using conditional knockdown of Arl15 in murine 3T3-L1 (pre)adipocytes. Arl15 knockdown in differentiated adipocytes impaired adiponectin secretion but not adipsin secretion or insulin action, while in preadipocytes it impaired adipogenesis. In differentiated adipocytes GFP-tagged ARL15 localized predominantly to the Golgi with lower levels detected at the plasma membrane and intracellular vesicles, suggesting involvement in intracellular trafficking. Sequencing of ARL15 in 375 severely insulin resistant patients identified four rare heterozygous variants, including an early nonsense mutation in a proband with femorogluteal lipodystrophy and non classical congenital adrenal hyperplasia, and an essential splice site mutation in a proband with partial lipodystrophy and a history of childhood yolk sac tumour. No nonsense or essential splice site mutations were found in 2,479 controls, while five such variants were found in the ExAC database. These findings provide evidence that ARL15 plays a role in adipocyte differentiation and adiponectin secretion, and raise the possibility that human ARL15 haploinsufficiency predisposes to lipodystrophy

Clustering of gene expression data: performance and similarity analysis

BACKGROUND: DNA Microarray technology is an innovative methodology in experimental molecular biology, which has produced huge amounts of valuable data in the profile of gene expression. Many clustering algorithms have been proposed to analyze gene expression data, but little guidance is available to help choose among them. The evaluation of feasible and applicable clustering algorithms is becoming an important issue in today's bioinformatics research. RESULTS: In this paper we first experimentally study three major clustering algorithms: Hierarchical Clustering (HC), Self-Organizing Map (SOM), and Self Organizing Tree Algorithm (SOTA) using Yeast Saccharomyces cerevisiae gene expression data, and compare their performance. We then introduce Cluster Diff, a new data mining tool, to conduct the similarity analysis of clusters generated by different algorithms. The performance study shows that SOTA is more efficient than SOM while HC is the least efficient. The results of similarity analysis show that when given a target cluster, the Cluster Diff can efficiently determine the closest match from a set of clusters. Therefore, it is an effective approach for evaluating different clustering algorithms. CONCLUSION: HC methods allow a visual, convenient representation of genes. However, they are neither robust nor efficient. The SOM is more robust against noise. A disadvantage of SOM is that the number of clusters has to be fixed beforehand. The SOTA combines the advantages of both hierarchical and SOM clustering. It allows a visual representation of the clusters and their structure and is not sensitive to noises. The SOTA is also more flexible than the other two clustering methods. By using our data mining tool, Cluster Diff, it is possible to analyze the similarity of clusters generated by different algorithms and thereby enable comparisons of different clustering methods

Spin injection and spin accumulation in all-metal mesoscopic spin valves

We study the electrical injection and detection of spin accumulation in lateral ferromagnetic metal-nonmagnetic metal-ferromagnetic metal (F/N/F) spin valve devices with transparent interfaces. Different ferromagnetic metals, permalloy (Py), cobalt (Co) and nickel (Ni), are used as electrical spin injectors and detectors. For the nonmagnetic metal both aluminium (Al) and copper (Cu) are used. Our multi-terminal geometry allows us to experimentally separate the spin valve effect from other magneto resistance signals such as the anomalous magneto resistance (AMR) and Hall effects. We find that the AMR contribution of the ferromagnetic contacts can dominate the amplitude of the spin valve effect, making it impossible to observe the spin valve effect in a 'conventional' measurement geometry. In a 'non local' spin valve measurement we are able to completely isolate the spin valve signal and observe clear spin accumulation signals at T=4.2 K as well as at room temperature (RT). For aluminum we obtain spin relaxation lengths (lambda_{sf}) of 1.2 mu m and 600 nm at T=4.2 K and RT respectively, whereas for copper we obtain 1.0 mu m and 350 nm. The spin relaxation times tau_{sf} in Al and Cu are compared with theory and results obtained from giant magneto resistance (GMR), conduction electron spin resonance (CESR), anti-weak localization and superconducting tunneling experiments. The spin valve signals generated by the Py electrodes (alpha_F lambda_F=0.5 [1.2] nm at RT [T=4.2 K]) are larger than the Co electrodes (alpha_F lambda_F=0.3 [0.7] nm at RT [T=4.2 K]), whereas for Ni (alpha_F lambda_F<0.3 nm at RT and T=4.2 K) no spin signal is observed. These values are compared to the results obtained from GMR experiments.Comment: 16 pages, 12 figures, submitted to PR

Migration in the Anthropocene: how collective navigation, environmental system and taxonomy shape the vulnerability of migratory species

Recent increases in human disturbance pose significant threats to migratory species using collective movement strategies. Key threats to migrants may differ depending on behavioural traits (e.g. collective navigation), taxonomy, and the environmental system (i.e. freshwater, marine, or terrestrial) associated with migration. We quantitatively assess how collective navigation, taxonomic membership, and environmental system impact species’ vulnerability by 1) evaluating population change in migratory and no n-migratory bird, mammal, and fish species using the Living Planet Database (LPD), 2) analysing the role of collective navigation and environmental system on migrant extinction risk using International Union for Conservation of Nature (IUCN) classifications, and 3) compiling literature on geographic range change of migratory species. Likelihood of population decrease differed by taxonomic group: migratory birds were more likely to experience annual declines than non-migrants, while mammals displayed the opposite pattern. Within migratory species in IUCN, we observed that collective navigation and environmental system were important predictors of extinction risk for fishes and birds, but not for mammals, which had overall higher extinction risk than other taxa. We found high phylogenetic relatedness among collectively navigating species, which could have obscured its importance in determining extinction risk. Overall, outputs from these analyses can help guide strategic interventions to conserve the most vulnerable migrations

Host Iron Binding Proteins Acting as Niche Indicators for Neisseria meningitidis

Neisseria meningitidis requires iron, and in the absence of iron alters its gene expression to increase iron acquisition and to make the best use of the iron it has. During different stages of colonization and infection available iron sources differ, particularly the host iron-binding proteins haemoglobin, transferrin, and lactoferrin. This study compared the transcriptional responses of N. meningitidis, when grown in the presence of these iron donors and ferric iron, using microarrays

Number (mean ± 95% CI) of woody plants >1.5m tall per hectare.

Data for each habitat type, except thicket, were collected from our study site. For the thicket habitat, we used the estimate of woody plant density in Belsky (1990), hence the lack of 95% confidence intervals. (DOCX)</p

Proportional availability of different habitat types along our driving transects.

We found that artificial grasslands comprise ~10%, open canopy savanna comprise ~12%, semi-open canopy savanna comprise ~20%, woody savanna comprise ~15%, closed-canopy woody savanna comprise ~26%, and thicket comprise ~16%. The marginal differences in the proportional availability of the different habitats are unlikely to influence the observed patterns of configurations generated from our model (see main text). (DOCX)</p