Исследование кинетики процесса полимеризации 5-норборнен-2,3дикарбоксимид-n-метил ацетата

Previous family studies revealed a large number of calpain 3 (CAPN3) mutations that cause recessive forms of limb girdle muscular dystrophy (LGMD2A) with selective atrophy of the proximal limb muscles. Correlations between the nature and site of a particular mutation and its corresponding phenotype, however, can only be established from homozygous mutations, which are particularly rare in the alternatively spliced NS, IS1 and IS2 regions of CAPN3. Here we identified a sibling pair with LGMD2A-type muscular dystrophy caused by a homozygous Ser606Leu (S606L) substitution in the IS2 linker domain. Normal protein levels, unaltered myofibrillar targeting and conserved calcium-induced autocatalytic activity of the mutated protein could be demonstrated in muscle biopsies from one patient. Despite this inconspicuous modification of the IS2 linker between domains III and IV, both patients developed signs and symptoms of the disease within their second decade of life. The unexpected severity of the clinical manifestation points to the high relevance of the calpain 3-specific IS2 segment between domains III and IV. We conclude that the structural motif around the Ser606 residue represents an important functional site that may regulate the transient activation and limited proteolysis of calpain 3

Pitt Political Review: GSPIA Edition (Spring 2011, Volume 3)

This volume of the Pitt Political Review: GSPIA Edition includes "Legal and Societal Injustice: Gender Inequality and Land Rights in Tanzania" and "The Transformation of Philanthropy in Sub-Saharan Africa: from Traditional Practices to the Establishment of Grantmaking Foundations." The aim of "Legal and Societal Injustice: Gender Inequality and Land Rights in Tanzania" is to increase awareness of the problems surrounding land rights and gender inequality in Tanzania's Karagwe District. "The Transformation of Philanthropy in Sub-Saharan Africa: from Traditional Practices to the Establishment of Grantmaking Foundations" discusses the effectiveness of African foundations in development over the long-term

A meta-analysis of water quality and aquatic macrophyte responses in 18 lakes treated with lanthanum modified bentonite (PHOSLOCK®)

Lanthanum (La) modified bentonite is being increasingly used as a geo-engineering tool for the control of phosphorus (P) release from lake bed sediments to overlying waters. However, little is known about its effectiveness in controlling P across a wide range of lake conditions or of its potential to promote rapid ecological recovery. We combined data from 18 treated lakes to examine the lake population responses in the 24 months following La-bentonite application (range of La-bentonite loads: 1.4 to 6.7 tonnes ha-1) in concentrations of surface water total phosphorus (TP; data available from 15 lakes), soluble reactive phosphorus (SRP; 14 lakes), and chlorophyll a (15 lakes), and in Secchi disk depths (15 lakes), aquatic macrophyte species numbers (6 lakes) and aquatic macrophyte maximum colonisation depths (4 lakes) across the treated lakes. Data availability varied across the lakes and variables, and in general monitoring was more frequent closer to the application dates. Median annual TP concentrations decreased significantly across the lakes, following the La-bentonite applications (from 0.08 mg L-1 in the 24 months pre-application to 0.03 mg L-1 in the 24 months post-application), particularly in autumn (0.08 mg L-1 to 0.03 mg L-1) and winter (0.08 mg L-1 to 0.02 mg L-1). Significant decreases in SRP concentrations over annual (0.019 mg L-1 to 0.005 mg L-1), summer (0.018 mg L-1 to 0.004 mg L-1), autumn (0.019 mg L-1 to 0.005 mg L-1) and winter (0.033 mg L-1 to 0.005 mg L-1) periods were also reported. P concentrations following La-bentonite application varied across the lakes and were correlated positively with dissolved organic carbon concentrations. Relatively weak, but significant responses were reported for summer chlorophyll a concentrations and Secchi disk depths following La-bentonite applications, the 75th percentile values decreasing from 119 μg L-1 to 74 μg L-1 and increasing from 398 cm to 506 cm, respectively. Aquatic macrophyte species numbers and maximum colonisation depths increased following La-bentonite application from a median of 5.5 species to 7.0 species and a median of 1.8 m to 2.5 m, respectively. The aquatic macrophyte responses varied significantly between lakes. La-bentonite application resulted in a general improvement in water quality leading to an improvement in the aquatic macrophyte community within 24 months. However, because, the responses were highly site-specific, we stress the need for comprehensive pre- and post-application assessments of processes driving ecological structure and function in candidate lakes to inform future use of this and similar products

A secondary ionization mass spectrometry calibration of Cibicidoides pachyderma Mg/Ca with temperature

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q04009, doi:10.1029/2007GC001620.An evaluation of C. pachyderma Mg/Ca using a new suite of warm water multicores from the Florida Straits shows that the slope of Mg/Ca with temperature is shallower than previously thought. Using secondary ionization mass spectrometry, we have documented that the distribution of magnesium within the polished walls of foraminiferal tests is Gaussian, suggesting that the Mg/Ca in these samples is not affected by the addition of a secondary high-magnesium calcite in the walls. The Mg/Ca within a typical C. pachyderma test varies by about ±20% (1σ/μ · 100), and the variability increases slightly in tests with higher Mg/Ca. The regression of C. pachyderma Mg/Ca with temperature has a slope of 0.13 ± 0.05 mmol mol−1 per °C, indistinguishable from the slope observed in inductively coupled plasma–mass spectrometry measurements from a different subset of the same multicores, but about one half the slope of previously published calibrations. The largest differences between the calibrations comes at the warm water end of the regression, where previously published C. pachyderma Mg/Ca values from Little Bahama Bank are at least 3 mmol mol−1 higher than observed in these new cores. The reasons for this difference are not fully known but are most likely related to diagenesis at Little Bahama Bank.This research was supported by several grants from the National Science Foundation: OCE0096469 to W.B.C. for cruise support to collect the Florida Straits cores; ATM0502428 and OCE0550271 to W. B. C. for support to obtain the Mg/Ca data on the ion probe; and OCE0425522 and OCE0550150 to T. M. for the core top calibration study using ICP-MS

Power estimation of tests in log-linear non-uniform association models for ordinal agreement

<p>Abstract</p> <p>Background</p> <p>Log-linear association models have been extensively used to investigate the pattern of agreement between ordinal ratings. In 2007, log-linear non-uniform association models were introduced to estimate, from a cross-classification of two independent raters using an ordinal scale, varying degrees of distinguishability between distant and adjacent categories of the scale.</p> <p>Methods</p> <p>In this paper, a simple method based on simulations was proposed to estimate the power of non-uniform association models to detect heterogeneities across distinguishabilities between adjacent categories of an ordinal scale, illustrating some possible scale defects.</p> <p>Results</p> <p>Different scenarios of distinguishability patterns were investigated, as well as different scenarios of marginal heterogeneity within rater. For sample size of N = 50, the probabilities of detecting heterogeneities within the tables are lower than .80, whatever the number of categories. In additition, even for large samples, marginal heterogeneities within raters led to a decrease in power estimates.</p> <p>Conclusion</p> <p>This paper provided some issues about how many objects had to be classified by two independent observers (or by the same observer at two different times) to be able to detect a given scale structure defect. Our results also highlighted the importance of marginal homogeneity within raters, to ensure optimal power when using non-uniform association models.</p

Pre-Diagnostic Circulating Vitamin D and Risk of Melanoma in Men

PURPOSE: Various studies have examined the association between serum vitamin D levels and different cancers; however, this is the first prospective study of this association with melanoma risk. The aim of this study is to investigate the association between serum vitamin D [25(OH)D] levels and melanoma in a cohort of older, middle-aged Finnish male smokers. METHODS: We conducted a nested case-control study within the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. From the ATBC cohort, 368 subjects were chosen for our study; 92 participants that developed melanoma and 276 matched control subjects. At study baseline, lifestyle questionnaires and blood samples were collected. Serum 25(OH)D was modeled as three sets of categorical variables: clinically-defined categories, season-specific quartiles and season-adjusted residual quartiles. Conditional logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs) to estimate the association between circulating vitamin D and melanoma risk. RESULTS: Overall no association of serum 25(OH)D and melanoma risk was observed. A decreased risk of developing melanoma was observed in the middle categories compared to the lowest category, albeit not significant. CONCLUSION: Results indicate no association between serum 25(OH)D levels and melanoma. Additional studies, including possibly consortium efforts, are needed to investigate the association between serum 25(OH)D levels and risk of melanoma in larger, more diverse study populations

CHD2 variants are a risk factor for photosensitivity in epilepsy

Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2·17 × 10−5). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3·50 × 10−4). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research into human cortical excitability

Prioritization and Evaluation of Depression Candidate Genes by Combining Multidimensional Data Resources

Large scale and individual genetic studies have suggested numerous susceptible genes for depression in the past decade without conclusive results. There is a strong need to review and integrate multi-dimensional data for follow up validation. The present study aimed to apply prioritization procedures to build-up an evidence-based candidate genes dataset for depression.Depression candidate genes were collected in human and animal studies across various data resources. Each gene was scored according to its magnitude of evidence related to depression and was multiplied by a source-specific weight to form a combined score measure. All genes were evaluated through a prioritization system to obtain an optimal weight matrix to rank their relative importance with depression using the combined scores. The resulting candidate gene list for depression (DEPgenes) was further evaluated by a genome-wide association (GWA) dataset and microarray gene expression in human tissues.A total of 5,055 candidate genes (4,850 genes from human and 387 genes from animal studies with 182 being overlapped) were included from seven data sources. Through the prioritization procedures, we identified 169 DEPgenes, which exhibited high chance to be associated with depression in GWA dataset (Wilcoxon rank-sum test, p = 0.00005). Additionally, the DEPgenes had a higher percentage to express in human brain or nerve related tissues than non-DEPgenes, supporting the neurotransmitter and neuroplasticity theories in depression.With comprehensive data collection and curation and an application of integrative approach, we successfully generated DEPgenes through an effective gene prioritization system. The prioritized DEPgenes are promising for future biological experiments or replication efforts to discover the underlying molecular mechanisms for depression

Author Correction: Defective Gpsm2/G alpha(i3) signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome (vol 8, 14907, 2017)

Author Correction: Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrom