Ehrlichia chaffeensis tandem repeat proteins and Ank200 are type1 secretion system substrates related to the repeats-in-toxin exoprotein family

Plant science

Agrobacterium tumefaciens VirC2 enhances T-DNA transfer and virulence through its C-terminal ribbon– helix– helix DNA-binding fold

Plant sciencesMicrobial Biotechnolog

Analysis of Vir protein translocation from Agrobacterium tumefaciens using Saccharomyces cerevisiae as a model: evidence for transport of a novel effector protein VirE3

Plant sciencesMicrobial Biotechnolog

SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and inactivation of its human homologue, SRPK1, induces cisplatin resistance in a human ovarian carcinoma cell line

The therapeutic potential of cisplatin, one of the most active and widely used anticancer drugs, is severely limited by the occurrence of cellular resistance. In this study, using budding yeast Saccharomyces cerevisiae as a model organism to identify novel drug resistance genes, we found that disruption of the yeast gene SKY1 (serine/arginine-rich protein-specific kinase from budding yeast) by either transposon insertion or one-step gene replacement conferred cellular resistance to cisplatin. Heterologous expression of the human SKY1 homologue SRPK1 (serine/arginine-rich protein-specific kinase) in SKY1 deletion mutant yeast cells restored cisplatin sensitivity, suggesting that SRPK1 is a cisplatin sensitivity gene, the inactivation of which could lead to cisplatin resistance. Subsequently, we investigated the role of SRPK1 in cisplatin sensitivity and resistance in human ovarian carcinoma A2780 cells using antisense oligodeoxynucleotides. Treatment of A2780 cells with antisense oligodeoxynucleotides directed against the translation initiation site of SRPK1 led to down-regulation of SRPK1 protein and conferred a 4-fold resistance to cisplatin. The human SRPK1 gene has not been associated with drug resistance before. Our new findings strongly suggest that SRPK1 is involved in cisplatin-induced cell kill and indicate that SRPK1 might potentially be of importance for studying clinical drug resistance

Exploring the relation between preoperative physical functioning and the impact of major complications in patients following pancreatic resection

BACKGROUND: This study aimed to evaluate the association between preoperative level of physical functioning and time to recovery of physical functioning, postoperative complications, and the impact of postoperative major complications in patients undergoing elective pancreatic resection. Additionally, prediction models to identify high-risk patients for developing a major complication were externally validated. METHODS: Perioperative data of patients who underwent pancreatic resection were analysed. Primary outcomes were time to recovery of physical functioning and postoperative major complications. Impact of a major complication was explored by evaluating its effect on time to recovery of physical functioning. Risk-prediction models were retrieved following a systematic review. RESULTS: Multivariable analysis (n = 63) showed that ASA grade III (OR 3.498) and preoperative platelet count (OR 1.005) were associated with major complications, whereas aerobic capacity (OR 0.347) was associated with time to recovery of physical functioning. Age, preoperative aerobic capacity, functional mobility, and perceived level of functional capacity were associated with the impact of a major complication. The AUC of two risk prediction models were 0.556 and 0.701. CONCLUSION: Preoperative parameters of physical function were associated with postoperative outcomes and may be useful in outcome prediction, although future approaches should not only register the incidence of major complications but also take the impact of a complication on a patient's physical functioning into account

National-level family policies and the access to schedule control in a European comparative perspective: crowding out or in, and for whom?

This paper examines national-level family policies in a comparative perspective, to see whether they ‘crowd out’ company-level family-friendly policies, namely schedule control. Further, it examines whether this relationship varies for different types of family policies, and for different groups of workers – i.e. distinguished by gender, parenthood status and skill divisions. The paper uses data from 27 European countries in 2010, and applies multilevel random slopes models with cross-level interaction terms. Results show that generous national-level family policies, in particular work-facilitating policies, ‘crowd in’ company-level schedule control provisions, especially for high-skilled workers. However, very generous leaves seem to crowdout schedule control provision

Is green space in the living environment associated with people's feelings of social safety?

Abstract. The authors investigate whether the percentage of green space in people's living environ- ment affects their feelings of social safety positively or negatively. More specifically they investigate the extent to which this relationship varies between urban and rural areas, between groups in the community that can be identified as more or less vulnerable, and the extent to which different types of green space exert different influences. The study includes 83736 Dutch citizens who were interviewed about their feelings of social safety. The percentage of green space in the living environment of each respondent was calculated, and data analysed by use of a three-level latent variable model, controlled for individual and environmental background characteristics. The analyses suggest that more green space in people's living environment is associated with enhanced feelings of social safetyöexcept in very strongly urban areas, where enclosed green spaces are associated with reduced feelings of social safety. Contrary to the common image of green space as a dangerous hiding place for criminal activity which causes feelings of insecurity, the results suggest that green space generally enhances feelings of social safety. The results also suggest, however, that green space in the most urban areas is a matter of concern with respect to social safety.

Two-step activity-based protein profiling of diacylglycerol lipase

Diacylglycerol lipases (DAGL) produce the endocannabinoid 2-arachidonoylglycerol, a key modulator of neurotransmitter release. Chemical tools that visualize endogenous DAGL activity are desired. Here, we report the design, synthesis and application of a triazole urea probe for DAGL equipped with a norbornene as a biorthogonal handle. The activity and selectivity of the probe was assessed with activity-based protein profiling. This probe was potent against endogenous DAGLα (IC50 = 5 nM) and it was successfully applied as a two-step activity-based probe for labeling of DAGLα using an inverse electron-demand Diels–Alder ligation in living cells.Bio-organic SynthesisMolecular Physiolog