Response of instream animal communities to a short-term extreme event and to longer-term cumulative impacts in a strategic water resource area,South Africa

Disturbance plays an integral part in generating heterogeneity required for ecosystem persistence, but the increased amplitude and duration of disturbances linked to drivers of global change could result in ecosystem shifts or collapse. Biomonitoring over time provides insights into trajectories of ecosystem change. The responses of two instream animal taxa to two contrasting disturbance events, a major flood event and the long-term cumulative effects of land-use changes, were assessed in 1999–2012 by quantifying variation and change in abundance of functional groups based on flow rate sensitivity, water quality and metrics of ecological condition. All metrics recovered to pre-flood conditions within seven months after the flood event. Similarly, cumulative impacts of land use effected significant decreases in some but not all metrics. Indices that did not change, including SASS total score and ASPT, were the result of insufficient consideration of the decrease in the abundance of sensitive taxa specifically, and the abundance of all taxa in general. The decrease in abundance of sensitive taxa could signal imminent collapse in certain metrics. Evidence is also provided for a shift in the structure of fish assemblages linked to the decrease and loss of taxa sensitive to ecosystem degradation caused by the longer-term impacts of land-use change.     

Quantitative aspects of inhibition of virus replication by interferon in chick embryo cell cultures

Hallum, J. V. (University of Pittsburgh, Pittsburgh, Pa.), and J. S. Youngner. Quantitative aspects of inhibition of virus replication by interferon in chick embryo cell cultures. J. Bacteriol. 92:1047-1050. 1966.-The effect of interferon on single cycles of replication of vesicular stomatitis virus and Mahoney poliovirus ribonucleic acid was studied in chick embryo cell cultures. The results showed that the titer of a given interferon preparation was independent of the input multiplicity of the challenge virus. In addition, the increase in virus yield with increasing virus challenge was a function of the number of infected cells, each of which yielded progeny at a level determined by the concentration of interferon to which the cells were exposed. These findings are not compatible with the concept that increases in the size of the virus challenge reverse or overcome protection of cells by interferon.     

Aerobic training increases the expression of adiponectin receptor genes in the peripheral blood mononuclear cells of young men

Little is known about the effect of exercise training on the expression of adiponectin receptor genes in peripheral blood mononuclear cells (PBMCs). In this study, we investigated the effects of aerobic training on the expression of AdipoR1 and AidpoR2 mRNAs in PBMCs, whole body insulin sensitivity, and circulating adiponectins in men. Thirty young men were randomly assigned to either a control (n=15) or an exercise (n=15) group. Subjects assigned to the exercise group underwent a 12-week jogging and/or running programme on a motor-driven treadmill at an intensity of 60%-75% of the age-based maximum heart rate with duration of 40 minutes per session and a frequency of 5 days per week. Two-way mixed ANOVA with repeated measures was used to test any significant time-by-group interaction effects for the measured variables at p=0.05. We found significant time-by-group interaction effects for waist circumference (p=0.001), VO_2max (p<0.001), fasting insulin (p=0.016), homeostasis model assessment for insulin resistance (HOMA-IR) (p=0.010), area under the curve (AUC) for insulin response during the 75-g oral glucose tolerance test (p=0.002), high-molecular weight (HMW) adiponectin (p=0.016), and the PBMC mRNA levels of AdipoR1 (p<0.001) and AdipoR2 (p=0.001). The exercise group had significantly increased mRNA levels of AdipoR1 and AdipoR2 in PBMCs, along with increased whole body insulin sensitivity and HMW adiponectin, decreased waist circumference, and increased VO_2max compared with the control group. In summary, the current findings suggest that exercise training modulates the expression of AdipoR1 and AdipoR2 mRNAs in PBMCs, implying that manipulation of the expression of these genes could be a potential surrogate for lifestyle intervention-mediated improvements of whole body insulin sensitivity and glucose homeostasis.     

Second‐derivative synchronous spectrofluorimetric determination of nebivolol hydrochloride and amlodipine besylate in their combined dosage form

A rapid, simple, accurate and highly sensitive spectrofluorimetric method was developed for the simultaneous analysis of nebivolol hydrochloride (NEB) and amlodipine besylate (AML). The method was based on measuring the synchronous fluorescence intensity of the drugs at Δλ = 40 nm in methanol. Various experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully studied and optimized. The calibration plots were rectilinear over concentration ranges of 0.05–1.5 µg/mL and 0.5–10 µg/mL for NEB and AML with limits of detection (LOD) of 0.010 and 0.051 µg/mL and limits of quantitation (LOQ) of 0.031 and 0.156, respectively. The peak amplitudes (²D) of the second derivative synchronous fluorimetry (SDSF) were estimated at 282 nm for NEB and at 393 nm for AML. Good linearity was obtained over the concentration ranges. The proposed method was successfully applied to the determination of the studied compounds in laboratory‐prepared mixtures, commercial single and laboratory‐prepared tablets. The results were in good agreement with those obtained using the comparison method. The mean percent recoveries were found to be 100.12 ± 0.77 and 99.91 ± 0.77 for NEB and AML, respectively. Copyright © 2015 John Wiley & Sons, Ltd.     

A foldable CFTR{Delta}F508 biogenic intermediate accumulates upon inhibition of the Hsc70-CHIP E3 ubiquitin ligase

CFTRDeltaF508 exhibits a correctable protein-folding defect that leads to its misfolding and premature degradation, which is the cause of cystic fibrosis (CF). Herein we report on the characterization of the CFTRDeltaF508 biogenic intermediate that is selected for proteasomal degradation and identification of cellular components that polyubiquitinate CFTRDeltaF508. Nonubiquitinated CFTRDeltaF508 accumulates in a kinetically trapped, but folding competent conformation, that is maintained in a soluble state by cytosolic Hsc70. Ubiquitination of Hsc70-bound CFTRDeltaF508 requires CHIP, a U box containing cytosolic cochaperone. CHIP is demonstrated to function as a scaffold that nucleates the formation of a multisubunit E3 ubiquitin ligase whose reconstituted activity toward CFTR is dependent upon Hdj2, Hsc70, and the E2 UbcH5a. Inactivation of the Hsc70-CHIP E3 leads CFTRDeltaF508 to accumulate in a nonaggregated state, which upon lowering of cell growth temperatures, can fold and reach the cell surface. Inhibition of CFTRDeltaF508 ubiquitination can increase its cell surface expression and may provide an approach to treat CF.     

Improved reduced representation bisulfite sequencing for epigenomic profiling of clinical samples

Background

DNA methylation plays crucial roles in epigenetic gene regulation in normal development and disease pathogenesis. Efficient and accurate quantification of DNA methylation at single base resolution can greatly advance the knowledge of disease mechanisms and be used to identify potential biomarkers. We developed an improved pipeline based on reduced representation bisulfite sequencing (RRBS) for cost-effective genome-wide quantification of DNA methylation at single base resolution. A selection of two restriction enzymes (Taq^αI and MspI) enables a more unbiased coverage of genomic regions of different CpG densities. We further developed a highly automated software package to analyze bisulfite sequencing results from the Solexa GAIIx system.

Results

With two sequencing lanes, we were able to quantify ~1.8 million individual CpG sites at a minimum sequencing depth of 10. Overall, about 76.7% of CpG islands, 54.9% of CpG island shores and 52.2% of core promoters in the human genome were covered with at least 3 CpG sites per region.

Conclusions

With this new pipeline, it is now possible to perform whole-genome DNA methylation analysis at single base resolution for a large number of samples for understanding how DNA methylation and its changes are involved in development, differentiation, and disease pathogenesis.     

Excess Cardiovascular Risk Burden in Jamaican Women Does Not Influence Predicted 10-Year CVD Risk Profiles of Jamaica Adults: An Analysis of the 2007/08 Jamaica Health and Lifestyle Survey

Background

Black Caribbean women have a higher burden of cardiovascular disease (CVD) risk factors than their male counterparts. Whether this results in a difference in incident cardiovascular events is unknown. The aim of this study was to estimate the 10 year World Health Organization/International Society for Hypertension (WHO/ISH) CVD risk score for Jamaica and explore the effect of sex as well as obesity, physical activity and socioeconomic status on these estimates.

Methods and Findings

Data from 40–74 year old participants in the 2007/08 Jamaica Health and Lifestyle Survey were used. Trained interviewers administered questionnaires and measured anthropometrics, blood pressure, fasting glucose and cholesterol. Education and occupation were used to assess socioeconomic status. The Americas B tables were used to estimate the WHO/ISH 10 year CVD risk scores for the population. Weighted prevalence estimates were calculated. Data from 1,432 (450 men, 982 women) participants were analysed, after excluding those with self-reported heart attack and stroke. The women had a higher prevalence of diabetes (19%W;12%M), hypertension (49%W;47%M), hypercholesterolemia (25%W;11%M), obesity (46%W;15%M) and physical inactivity (59%W;29%M). More men smoked (6%W;31%M). There was good agreement between the 10-year cardiovascular risk estimates whether or not cholesterol measurements were utilized for calculation (kappa –0.61). While 90% had a 10 year WHO/ISH CVD risk of less than 10%, approximately 2% of the population or 14,000 persons had a 10 year WHO/ISH CVD risk of ≥30%. As expected CVD risk increased with age but there was no sex difference in CVD risk distribution despite women having a greater risk factor burden. Women with low socioeconomic status had the most adverse CVD risk profile.

Conclusion

Despite women having a higher prevalence of CVD risk factors there was no sex difference in 10-year WHO/ISH CVD risk in Jamaican adults.     

Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons

Axons and dendrites differ in both microtubule organization and in the organelles and proteins they contain. Here we show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented uniformly plus-end-distal; however, without dynein, axons contain both plus- and minus-end distal microtubules. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal microtubules are no longer uniform in polarity.