Cdk1-dependent destruction of Eco1 prevents cohesion establishment after S phase

Accurate genome segregation depends on cohesion mechanisms that link duplicated sister chromatids, thereby allowing their tension-dependent biorientation in metaphase. In Saccharomyces cerevisiae, cohesion is established during DNA replication when Eco1 acetylates the cohesin subunit Smc3. Cohesion establishment is restricted to S phase of the cell cycle, but the molecular basis of this regulation is unknown. Here, we show that Eco1 is negatively regulated by the protein kinase Cdk1. Phosphorylation of Eco1 after S phase targets it to SCF(Cdc4) for ubiquitination and subsequent degradation. A nonphosphorylatable mutant of Eco1 establishes cohesion after DNA replication, suggesting that Cdk1-dependent phosphorylation of Eco1 is a key factor limiting establishment to S phase. We also show that deregulation of Eco1 results in chromosome separation defects in anaphase. We conclude that this regulatory mechanism helps optimize the level of sister chromatid cohesion, ensuring a robust and efficient anaphase.     

DMSO regulates osteoclast development in vitro

Dimethyl sulfoxide (DMSO) is routinely used in the laboratory as a solvent and vehicle for organic molecules. Although it has been used in previous studies involving myeloid cells and macrophages, we are unaware of data demonstrating the effects of DMSO alone on osteoclast development. Recently, we were using DMSO as a vehicle and included a non-vehicle control. Surprisingly, we observed a marked change in osteoclast development, and therefore designed this study to examine the effects of DMSO on osteoclast development. Osteoclasts were generated from two sources: bone marrow macrophages and an osteoclast progenitor cell line. Cells were cultured with DMSO for various durations and at differing concentrations and mature, multinucleated (>3 nuclei) TRAP(+) cells were assessed in terms of cell number, cell surface area, and number of nuclei/cell. Osteoclast surface area increased in 5 μM DMSO to a mean of 156,422 pixels from a mean of 38,510 pixels in control culture, and subsequently decreased in 10 μM DMSO to a mean of 18,994 pixels. With serial addition of DMSO over 5 d, a significant increase in mean surface area, and number of nuclei/cell was also observed, while the opposite was true when DMSO was serially removed from culture. These findings show that DMSO exerts a marked effect on osteoclast differentiation. Since many investigators use DMSO to solubilize compounds for treatment of osteoclasts, caution is warranted as altering DMSO concentrations may have a profound effect on the final data, especially if osteoclast differentiation is being assessed.     

Genetic analysis of abiotic stress tolerance in crops

Abiotic stress tolerance is complex, but as phenotyping technologies improve, components that contribute to abiotic stress tolerance can be quantified with increasing ease. In parallel with these phenomics advances, genetic approaches with more complex genomes are becoming increasingly tractable as genomic information in non-model crops increases and even whole crop genomes can be re-sequenced. Thus, genetic approaches to elucidating the molecular basis to abiotic stress tolerance in crops are becoming more easily achievable.     

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective

Background

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.

Methodology/Principal Findings

Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I² and publication bias was assessed using Begg''s funnel plot and Egger''s regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR] = 0.23; 95% confidence interval [CI] = 0.16–0.34; p<0.001) and laboratory confirmed influenza infection (OR = 0.15; 95% CI = 0.03–0.63; p = 0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified.

Conclusions/Significance

Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.