Reversibility of Red blood Cell deformation

The ability of cells to undergo reversible shape changes is often crucial to their survival. For Red Blood Cells (RBCs), irreversible alteration of the cell shape and flexibility often causes anemia. Here we show theoretically that RBCs may react irreversibly to mechanical perturbations because of tensile stress in their cytoskeleton. The transient polymerization of protein fibers inside the cell seen in sickle cell anemia or a transient external force can trigger the formation of a cytoskeleton-free membrane protrusion of micrometer dimensions. The complex relaxation kinetics of the cell shape is shown to be responsible for selecting the final state once the perturbation is removed, thereby controlling the reversibility of the deformation. In some case, tubular protrusion are expected to relax via a peculiar "pearling instability".Comment: 4 pages, 3 figure

Novel mutations in CACNA1F and NYX in Dutch families with X-linked congenital stationary night blindness

PURPOSE: To describe the clinical features and genetic analysis of eight X-linked congenital stationary night blindness (XLCSNB) Dutch patients. METHODS: Electroretinogram (ERG) measurements were assessed in Dutch patients. Molecular genetic testing by denaturing high performance liquid chromatography (DHPLC), single stranded conformation polymorphism (SSCP) analysis, and direct sequencing of the CACNA1F and NYX genes were performed in the patients possessing a negative Schubert Bornschein ERG. RESULTS: Molecular genetic testing of CACNA1F and NYX revealed three novel and two known CACNA1F sequence variants as well as two novel sequence alterations in the NYX gene. While one of the CACNA1F sequence variants (5756G>A, R1919H) has been previously described as a common polymorphism in Japanese families, we did not found this transition in 100 European control alleles. CONCLUSIONS: In a pool of eight diagnosed XLCSNB patients, five showed a sequence variation in the CACNA1F and two in the NYX gene. In only one of the eight patients no sequence alteration could be detected. This might be explained by a mutation in other, as yet unidentified coding or regulatory sequences of NYX or CACNA1F or additional genes

Genotype-Phenotype Associations of the CD-Associated Single Nucleotide Polymorphism within the Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 22 in Patients of the Swiss IBD Cohort.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) plays an important role in immune cell function and intestinal homeostasis. The single nucleotide polymorphism (SNP) rs2476601 within the PTPN22 gene locus results in aberrant function of PTPN22 protein and protects from Crohn's disease (CD). Here, we investigated associations of PTPN22 SNP rs2476601 in inflammatory bowel disease (IBD) patients in the Swiss IBD Cohort Study (SIBDCS). 2'028 SIBDCS patients (1173 CD and 855 ulcerative colitis (UC) patients) were included. The clinical characteristics were analysed for an association with the presence of the PTPN22 SNP rs2476601 genotypes 'homozygous variant' (AA), 'heterozygous' (GA) and 'homozygous wild-type' (GG). 13 patients (0.6%) were homozygous variant (AA) for the PTPN22 polymorphism, 269 (13.3%) heterozygous variant (GA) and 1'746 (86.1%) homozygous wild-type (GG). In CD, AA and GA genotypes were associated with less use of steroids and antibiotics, and reduced prevalence of vitamin D and calcium deficiency. In UC the AA and GA genotype was associated with increased use of azathioprine and anti-TNF antibodies, but significantly less patients with the PTPN22 variant featured malabsorption syndrome (p = 0.026). Our study for the first time addressed how presence of SNP rs2476601 within the PTPN22 gene affects clinical characteristics in IBD-patients. Several factors that correlate with more severe disease were found to be less common in CD patients carrying the A-allele, pointing towards a protective role for this variant in affected CD patients. In UC patients however, we found the opposite trend, suggesting a disease-promoting effect of the A-allele

BMJ Open Ophthalmol

Objective: Explore relationships between systemic exposure to intravitreal aflibercept injection (IAI) and systemic pharmacodynamic effects via post hoc analyses of clinical trials of IAI for neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DME). Methods and analysis: Adults from VGFT-OD-0702.PK (n=6), VGFT-OD-0512 (n= 5), VIEW 2 (n=1204) and VIVID-DME (n=404) studies were included. Validated ELISAs were used to measure concentrations of free and bound aflibercept (reported as adjusted bound) in plasma at predefined time points in each study. Non-compartmental analysis of concentration-time data was obtained with dense sampling in VGFT-OD-0702.PK and VGFT-OD-0512. Sparse sampling was used in VIEW 2 and VIVID-DME. Blood pressure or intrarenal function changes were also investigated. Results: Following intravitreal administration, free aflibercept plasma concentrations quickly decreased once maximum concentrations were achieved at 1-3 days postdose; pharmacologically inactive adjusted bound aflibercept concentrations increased over a longer period and reached plateau 7 days postdose. Ratios of free and adjusted bound aflibercept decreased over time. There were no meaningful changes in systolic/diastolic blood pressure over the duration of each study at all systemic aflibercept exposure levels. For all treatment arms in VIEW 2, there was no clinically relevant change in mean intrarenal function from baseline at week 52. Overall, incidence of systemic adverse events in VIEW 2 and VIVID-DME was low and consistent with the known safety profile of IAI. Conclusion: IAI administration was not associated with systemic effects in patients with nAMD or DME as measured by blood pressure or intrarenal function, two known pharmacologically relevant effects of anti-vascular endothelial growth factor

Assessing exposure to disinfection by-products in women of reproductive age living in Corpus Christi, Texas, and Cobb county, Georgia: descriptive results and methods.

We conducted a field study in Corpus Christi, Texas, and Cobb County, Georgia, to evaluate exposure measures for disinfection by-products, with special emphasis on trihalomethanes (THMs). Participants were mothers living in either geographic area who had given birth to healthy infants from June 1998 through May 1999. We assessed exposure by sampling blood and water and obtaining information about water use habits and tap water characteristics. Two 10-mL whole blood samples were collected from each participant before and immediately after her shower. Levels of individual THM species (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) were measured in whole blood [parts per trillion (pptr)] and in water samples (parts per billion). In the Corpus Christi water samples, brominated compounds accounted for 71% of the total THM concentration by weight; in Cobb County, chloroform accounted for 88%. Significant differences in blood THM levels were observed between study locations. For example, the median baseline blood level of bromoform was 0.3 pptr and 3.5 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). Differences were most striking in blood obtained after showering. For bromoform, the median blood levels were 0.5 pptr and 17 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). These results suggest that blood levels of THM species vary substantially across populations, depending on both water quality characteristics and water use activities. Such variation has important implications for epidemiologic studies of the potential health effects of disinfection by-products

Physical and hydrological properties of peat as proxies for degradation of South African peatlands: Implications for conservation and restoration

The physical and hydrological properties of peat from seven peatlands in northern Maputaland (South Africa) were investigated and related to the degradation processes of peatlands in different hydrogeomorphic settings. The selected peatlands are representative of typical hydrogeomorphic settings and different stages of human modification from natural to severely degraded. Nineteen transects (141 soil corings in total) were examined in order to describe peat properties typical of the distinct hydrogeomorphic settings. We studied degree of decomposition, organic matter content, bulk density, water retention, saturated hydraulic conductivity and hydrophobicity of the peats. From these properties we derived pore size distribution, unsaturated hydraulic conductivity and maximum capillary rise. We found that, after drainage, degradation advances faster in peatlands containing wood peat than in peatlands containing radicell peat. Eucalyptus plantations in catchment areas are especially threatening to peatlands in seeps, interdune depressions and unchannelled valley bottoms. All peatlands and their recharge areas require wise management, especially valley-bottom peatlands with swamp forest vegetation. Blocking drainage ditches is indispensable as a first step towards achieving the restoration of drained peatland areas, and further measures may be necessary to enhance the distribution of water. The sensitive swamp forest ecosystems should be given conservation priority

Matrin 3 and HIV Rev Regulation of mRNA

The nuclear matrix protein, MATR3, is a newly-described Rev cofactor whose mechanism of action is only starting to be revealed

Optimal Path Planning for Unmanned Combat Aerial Vehicles to Defeat Radar Tracking

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76140/1/AIAA-14303-218.pd