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131.
Background: Snow and ice melt provide sensitive indicators of climate change and serve as the primary source of stream flow in alpine basins.

Aims: We synthesise the results of hydrological and hydrochemical studies during the period 1995–2014, building on a long history of earlier work focused on snow and water on Niwot Ridge and the adjacent Green Lakes Valley (GLV), which is part of the Niwot Ridge Long Term Ecological Research site (NWT LTER).

Methods: These studies are discussed in the context of how snow, snowmelt and runoff reflect changing local climate. We review recent results of snow, snowmelt, hydrology and hydrochemistry from the plot to the basin scale, utilising new tools such as continuous global positioning system (GPS) measurements of snow depth, along with remotely-sensed measurements of snow-covered area and melt, combined with long-term measurements of snow properties, discharge and solute and isotopic content of water.

Results and Conclusions: Surface–groundwater interactions are important components of water quantity and quality in alpine basins. Some or most snowmelt infiltrates underlying soils and bedrock, transporting soil and bedrock products to surface waters. Infiltrating snowmelt, along with increased melt of stored ice, increases the hydrologic connectivity between the terrestrial and aquatic systems. Alpine basins are being impacted by increases in atmospheric nitrogen deposition, which has caused changes in soil microbial processes such as nitrification. Nitrate, dissolved organic carbon and dissolved organic nitrogen are thus flushed from soils and talus to streams. Our long-term results show that alpine catchments, such as Green Lake 4 at NWT LTER+, have the greatest sensitivity and least resilience to climate warming, with any warming leading to increased water yields.  相似文献   
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Modern DNA sequencing technologies enable geneticists to rapidly identify genetic variation among many human genomes. However, isolating the minority of variants underlying disease remains an important, yet formidable challenge for medical genetics. We have developed GEMINI (GEnome MINIng), a flexible software package for exploring all forms of human genetic variation. Unlike existing tools, GEMINI integrates genetic variation with a diverse and adaptable set of genome annotations (e.g., dbSNP, ENCODE, UCSC, ClinVar, KEGG) into a unified database to facilitate interpretation and data exploration. Whereas other methods provide an inflexible set of variant filters or prioritization methods, GEMINI allows researchers to compose complex queries based on sample genotypes, inheritance patterns, and both pre-installed and custom genome annotations. GEMINI also provides methods for ad hoc queries and data exploration, a simple programming interface for custom analyses that leverage the underlying database, and both command line and graphical tools for common analyses. We demonstrate GEMINI''s utility for exploring variation in personal genomes and family based genetic studies, and illustrate its ability to scale to studies involving thousands of human samples. GEMINI is designed for reproducibility and flexibility and our goal is to provide researchers with a standard framework for medical genomics.This is a PLOS Computational Biology Software Article.  相似文献   
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Salmonella enterica is a bacterial pathogen that causes enteric fever and gastroenteritis in humans and animals. Although its population structure was long described as clonal, based on high linkage disequilibrium between loci typed by enzyme electrophoresis, recent examination of gene sequences has revealed that recombination plays an important evolutionary role. We sequenced around 10% of the core genome of 114 isolates of enterica using a resequencing microarray. Application of two different analysis methods (Structure and ClonalFrame) to our genomic data allowed us to define five clear lineages within S. enterica subspecies enterica, one of which is five times older than the other four and two thirds of the age of the whole subspecies. We show that some of these lineages display more evidence of recombination than others. We also demonstrate that some level of sexual isolation exists between the lineages, so that recombination has occurred predominantly between members of the same lineage. This pattern of recombination is compatible with expectations from the previously described ecological structuring of the enterica population as well as mechanistic barriers to recombination observed in laboratory experiments. In spite of their relatively low level of genetic differentiation, these lineages might therefore represent incipient species.  相似文献   
137.
To understand how miRNAs contribute to the molecular phenotype of adipose tissues and related traits, we performed global miRNA expression profiling in subcutaneous abdominal and gluteal adipose tissue of 70 human subjects and characterised which miRNAs were differentially expressed between these tissues. We found that 12% of the miRNAs were significantly differentially expressed between abdominal and gluteal adipose tissue (FDR adjusted p<0.05) in the primary study, of which 59 replicated in a follow-up study of 40 additional subjects. Further, 14 miRNAs were found to be associated with metabolic syndrome case-control status in abdominal tissue and three of these replicated (primary study: FDR adjusted p<0.05, replication: p<0.05 and directionally consistent effect). Genome-wide genotyping was performed in the 70 subjects to enable miRNA expression quantitative trait loci (eQTL) analysis. Candidate miRNA eQTLs were followed-up in the additional 40 subjects and six significant, independent cis-located miRNA eQTLs (primary study: p<0.001; replication: p<0.05 and directionally consistent effect) were identified. Finally, global mRNA expression profiling was performed in both tissues to enable association analysis between miRNA and target mRNA expression levels. We find 22% miRNAs in abdominal and 9% miRNAs in gluteal adipose tissue with expression levels significantly associated with the expression of corresponding target mRNAs (FDR adjusted p<0.05). Taken together, our results indicate a clear difference in the miRNA molecular phenotypic profile of abdominal and gluteal adipose tissue, that the expressions of some miRNAs are influenced by cis-located genetic variants and that miRNAs are associated with expression levels of their predicted mRNA targets.  相似文献   
138.

Background

Augmentation cystoplasty (AC) with autogenous ileum remains the current gold standard surgical treatment for many patients with end-stage bladder disease. However, the presence of mucus-secreting epithelium within the bladder is associated with debilitating long-term complications. Currently, decellularised biological materials derived from porcine extracellular matrix (ECM) are under investigation as potential augmentation scaffolds. Important biomechanical limitations of ECMs are decreased bladder capacity and poor compliance after implantation.

Methodology/Principal Findings

In the present ex vivo study a novel concept was investigated where a two-fold increase in ECM scaffold surface-area relative to the resected ileal segment was compared in ovine bladder models after AC. Results showed that bladder capacity increased by 40±4% and 37±11% at 10 mmHg and compliance by 40.4±4% and 39.7±6% (ΔP = 0–10 mmHg) after AC with ileum and porcine urinary bladder matrix (UBM) respectively (p<0.05). Comparative assessment between ileum and UBM demonstrated no significant differences in bladder capacity or compliance increases after AC (p>0.05).

Conclusions

These findings may have important clinical implications as metabolic, infective and malignant complications precipitated by mucus-secreting epithelium are potentially avoided after augmentation with ECM scaffolds.  相似文献   
139.
Four evolutionarily conserved proteins are required for mammalian regulated exocytosis: three SNARE proteins, syntaxin, SNAP-25, and synaptobrevin, and the SM protein, Munc18-1. Here, using single-molecule imaging, we measured the spatial distribution of large cohorts of single Munc18-1 molecules correlated with the positions of single secretory vesicles in a functionally rescued Munc18-1-null cellular model. Munc18-1 molecules were nonrandomly distributed across the plasma membrane in a manner not directed by mode of interaction with syntaxin1, with a small mean number of molecules observed to reside under membrane resident vesicles. Surprisingly, we found that the majority of vesicles in fully secretion-competent cells had no Munc18-1 associated within distances relevant to plasma membrane-vesicle SNARE interactions. Live cell imaging of Munc18-1 molecule dynamics revealed that the density of Munc18-1 molecules at the plasma membrane anticorrelated with molecular speed, with single Munc18-1 molecules displaying directed motion between membrane hotspots enriched in syntaxin1a. Our findings demonstrate that Munc18-1 molecules move between membrane depots distinct from vesicle morphological docking sites.  相似文献   
140.
We understand little about the energetic costs of flight in free-ranging birds, in part because current techniques for estimating flight energetics in the wild are limited. Accelerometry is known to estimate energy expenditure through body movement in terrestrial animals, once calibrated using a treadmill with chamber respirometry. The flight equivalent, a wind tunnel with mask respirometry, is particularly difficult to instigate, and has not been applied to calibrate accelerometry. We take the first steps in exploring a novel method for calibrating accelerometers with flight energy expenditure. We collected accelerometry data for Harris's Hawks Parabuteo unicinctus flying to varying heights up to 4.1 m over a small horizontal distance; the mechanical energy expended to gain height can be estimated from physical first principles. The relationship between accelerometry and mechanical energy expenditure was strong, and while a simple wing flapping model confirmed that accelerometry is sensitive to both changes in wing beat amplitude and frequency, the relationship was explained predominately by changes in wing beat frequency, and less so by changes in amplitude. Our study provides initial, positive evidence that accelerometry can be calibrated with body power using climbing flights, potentially providing a basis for estimating flapping flight metabolic rate at least in situations of altitude gain.  相似文献   
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