Glacier contribution to the North and South Saskatchewan Rivers

The hydrological model WATFLOOD and a volume-area scaling relationship are applied to estimate glacier wastage and seasonal Melt contribution to the headwaters of the North and South Saskatchewan Rivers on the eastern slopes of the Canadian Rocky Mountains from 1975-1998. Wastage is defined as the annual volume of glacier ice melt that exceeds the annual volume of snow accumulation into the glacier system, causing an annual net loss of glacier volume. Melt is defined as the annual volume of glacier ice melt that is equal to, or less than, the annual volume of snow that does not melt from the glacier and instead accumulates into the glacier system. It is proposed that the distinction between these two components of glacier runoff is important in studies of the impact of glacier variations on flow. A comparison of similar glacierised and non-glacierised basin hydrographs shows that glacierised basins have greater specific streamflow in the late summer months of otherwise low flow, and the presence of glaciers in a basin results in a lower coefficient of variation of the July to September and annual streamflow as a result of the natural regulating impact of glaciers on streamflow. Glacier wastage and Melt are estimated from a hydrological-hypsometric comparison of glacierised and non-glacierised basins, mass balance data from Peyto Glacier and the published work of other researchers. The similarity of these results to those from the volume-area scaling approach indicates that this is a suitable method for estimating glacier wastage on a regional scale. Whilst the WATFLOOD results were similar to those from the hydrological-hypsometric approach regionally, there were considerable differences between the estimates of combined glacier wastage and Melt from different methods in the small, highly glacierised Peyto Glacier basin. The WATFLOOD results, and thus the estimates of Melt, are therefore treated with caution and it is proposed that glacier runoff data is collected with which to improve the model calibration, verify results and make uncertainty estimations, currently prevented by the severe lack of data on glaciers in the North and South Saskatchewan River basins. The results show that glacier wastage was smaller than Melt and varied between glaciers, though contributed over 10% to streamflow in a number of basins in the July to September period 1975-1998. Melt was positively correlated with basin glacier cover and contributed over 25% to streamflow from basins with glacier cover as little as 1% in the July to September period. The significance of Melt is manifest in its timing since it is equal to the annual volume of snow that accumulates into the glacier system, the volume of which melts as ice instead of snow thus entering the stream in the later summer months after snowmelt. Future glacier decline is therefore expected to result in an advancement of peak flow towards a snowmelt regime hydrograph, assuming that post glacial basin conditions do not similarly delay snowmelt runoff. The resulting reduced late summer flow, compounded by decreasing wastage contributions, is a concern for agricultural and industrial streamflow users, such as hydropower plants, and threatens ecological habitats. Downstream at Edmonton and Calgary, glacier wastage contributed approximately 3% of streamflow 1975-1998; however, Melt supplied over double this volume of flow thus the concern here is whether reservoir capacities are large enough to store a sufficient volume of the spring peak flow to meet supply needs in the late summer months of decreasing flows

eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro which was capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n = 5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n = 5). Despite the xenograft nature of the scaffold, the TEBV structure remained well preserved in seeded grafts. In sum, this study demonstrates that upregulation of NO expression within adult stem cells differentiated towards an endothelial-like lineage imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications

A Happy Abundance : Tales, Memoirs and More Past and Present in Wayne, Maine

https://digitalmaine.com/wayne_books/1002/thumbnail.jp

New Algorithm to Determine True Colocalization in Combination with Image Restoration and Time-Lapse Confocal Microscopy to Map Kinases in Mitochondria

The subcellular localization and physiological functions of biomolecules are closely related and thus it is crucial to precisely determine the distribution of different molecules inside the intracellular structures. This is frequently accomplished by fluorescence microscopy with well-characterized markers and posterior evaluation of the signal colocalization. Rigorous study of colocalization requires statistical analysis of the data, albeit yet no single technique has been established as a standard method. Indeed, the few methods currently available are only accurate in images with particular characteristics. Here, we introduce a new algorithm to automatically obtain the true colocalization between images that is suitable for a wide variety of biological situations. To proceed, the algorithm contemplates the individual contribution of each pixel's fluorescence intensity in a pair of images to the overall Pearsońs correlation and Manders' overlap coefficients. The accuracy and reliability of the algorithm was validated on both simulated and real images that reflected the characteristics of a range of biological samples. We used this algorithm in combination with image restoration by deconvolution and time-lapse confocal microscopy to address the localization of MEK1 in the mitochondria of different cell lines. Appraising the previously described behavior of Akt1 corroborated the reliability of the combined use of these techniques. Together, the present work provides a novel statistical approach to accurately and reliably determine the colocalization in a variety of biological images

A population-based study of ambulatory and surgical services provided by orthopaedic surgeons for musculoskeletal conditions

<p>Abstract</p> <p>Background</p> <p>The ongoing process of population aging is associated with an increase in prevalence of musculoskeletal conditions with a concomitant increase in the demand of orthopaedic services. Shortages of orthopaedic services have been documented in Canada and elsewhere. This population-based study describes the number of patients seen by orthopaedic surgeons in office and hospital settings to set the scene for the development of strategies that could maximize the availability of orthopaedic resources.</p> <p>Methods</p> <p>Administrative data from the Ontario Health Insurance Plan and Canadian Institute for Health Information hospital separation databases for the 2005/06 fiscal year were used to identify individuals accessing orthopaedic services in Ontario, Canada. The number of patients with encounters with orthopaedic surgeons, the number of encounters and the number of surgeries carried out by orthopaedic surgeons were estimated according to condition groups, service location, patient's age and sex.</p> <p>Results</p> <p>In 2005/06, over 520,000 Ontarians (41 per 1,000 population) had over 1.3 million encounters with orthopaedic surgeons. Of those 86% were ambulatory encounters and 14% were in hospital encounters. The majority of ambulatory encounters were for an injury or related condition (44%) followed by arthritis and related conditions (37%). Osteoarthritis accounted for 16% of all ambulatory encounters. Orthopaedic surgeons carried out over 140,000 surgeries in 2005/06: joint replacement accounted for 25% of all orthopaedic surgeries, whereas closed repair accounted for 16% and reductions accounted for 21%. Half of the orthopaedic surgeries were for arthritis and related conditions.</p> <p>Conclusion</p> <p>The large volume of ambulatory care points to the significant contribution of orthopaedic surgeons to the medical management of chronic musculoskeletal conditions including arthritis and injuries. The findings highlight that surgery is only one component of the work of orthopaedic surgeons in the management of these conditions. Policy makers and orthopaedic surgeons need to be creative in developing strategies to accommodate the growing workload of orthopaedic surgeons without sacrificing quality of care of patients with musculoskeletal conditions.</p

Lupus risk variants in the PXK locus alter B-cell receptor internalization

Genome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7 cells, mechanisms linking PXK to lupus pathophysiology have remained undefined. In an effort to uncover the mechanism at this locus that increases lupus-risk, we undertook a fine-mapping analysis in a large multi-ancestral study of lupus patients and controls. We define a large (257kb) common haplotype marking a single causal variant that confers lupus risk detected only in European ancestral populations and spans the promoter through the 3' UTR of PXK. The strongest association was found at rs6445972 with P &lt; 4.62 × 10-10, OR 0.81 (0.75 - 0.86). Using stepwise logistic regression analysis, we demonstrate that one signal drives the genetic association in the region. Bayesian analysis confirms our results, identifying a 95% credible set consisting of 172 variants spanning 202 kb. Functionally, we found that PXK operates on the B-cell antigen receptor (BCR); we confirmed that PXK influenced the rate of BCR internalization. Furthermore, we demonstrate that individuals carrying the risk haplotype exhibited a decreased rate of BCR internalization, a process known to impact B cell survival and cell fate. Taken together, these data define a new candidate mechanism for the genetic association of variants around PXK with lupus risk and highlight the regulation of intracellular trafficking as a genetically regulated pathway mediating human autoimmunity

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE

Gene Expression Changes in the Motor Cortex Mediating Motor Skill Learning

The primary motor cortex (M1) supports motor skill learning, yet little is known about the genes that contribute to motor cortical plasticity. Such knowledge could identify candidate molecules whose targeting might enable a new understanding of motor cortical functions, and provide new drug targets for the treatment of diseases which impair motor function, such as ischemic stroke. Here, we assess changes in the motor-cortical transcriptome across different stages of motor skill acquisition. Adult rats were trained on a gradually acquired appetitive reach and grasp task that required different strategies for successful pellet retrieval, or a sham version of the task in which the rats received pellet reward without needing to develop the reach and grasp skill. Tissue was harvested from the forelimb motor-cortical area either before training commenced, prior to the initial rise in task performance, or at peak performance. Differential classes of gene expression were observed at the time point immediately preceding motor task improvement. Functional clustering revealed that gene expression changes were related to the synapse, development, intracellular signaling, and the fibroblast growth factor (FGF) family, with many modulated genes known to regulate synaptic plasticity, synaptogenesis, and cytoskeletal dynamics. The modulated expression of synaptic genes likely reflects ongoing network reorganization from commencement of training till the point of task improvement, suggesting that motor performance improves only after sufficient modifications in the cortical circuitry have accumulated. The regulated FGF-related genes may together contribute to M1 remodeling through their roles in synaptic growth and maturation.McGovern Institute for Brain Research at MITNational Institutes of Health (U.S.) ((NIH grant 1-RC1-NS068103-01)National Institutes of Health (U.S.) (NIH grant R01-MH084966)Roberto Rocca Education Program (Fellowship)Massachusetts Institute of Technology. Undergraduate Research Opportunities Program (Fellowship)Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR grant RBIN04H5AS)Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR grant RBLA03FLJC)Italy. Ministero dell'istruzione, dell'università e della ricerca (FIRB n. RBAP10L8TY

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE