The Functions of Myosin II and Myosin V Homologs in Tip Growth and Septation in Aspergillus nidulans

Because of the industrial and medical importance of members of the fungal genus Aspergillus, there is considerable interest in the functions of cytoskeletal components in growth and secretion in these organisms. We have analyzed the genome of Aspergillus nidulans and found that there are two previously unstudied myosin genes, a myosin II homolog, myoB (product = MyoB) and a myosin V homolog, myoE (product = MyoE). Deletions of either cause significant growth defects. MyoB localizes in strings that coalesce into contractile rings at forming septa. It is critical for septation and normal deposition of chitin but not for hyphal extension. MyoE localizes to the Spitzenkörper and to moving puncta in the cytoplasm. Time-lapse imaging of SynA, a v-SNARE, reveals that in myoE deletion strains vesicles no longer localize to the Spitzenkörper. Tip morphology is slightly abnormal and branching occurs more frequently than in controls. Tip extension is slower than in controls, but because hyphal diameter is greater, growth (increase in volume/time) is only slightly reduced. Concentration of vesicles into the Spitzenkörper before incorporation into the plasma membrane is, thus, not required for hyphal growth but facilitates faster tip extension and a more normal hyphal shape

Checkpoint-Dependent and -Independent Roles of Swi3 in Replication Fork Recovery and Sister Chromatid Cohesion in Fission Yeast

Multiple genome maintenance processes are coordinated at the replication fork to preserve genomic integrity. How eukaryotic cells accomplish such a coordination is unknown. Swi1 and Swi3 form the replication fork protection complex and are involved in various processes including stabilization of replication forks, activation of the Cds1 checkpoint kinase and establishment of sister chromatid cohesion in fission yeast. However, the mechanisms by which the Swi1–Swi3 complex achieves and coordinates these tasks are not well understood. Here, we describe the identification of separation-of-function mutants of Swi3, aimed at dissecting the molecular pathways that require Swi1–Swi3. Unlike swi3 deletion mutants, the separation-of-function mutants were not sensitive to agents that stall replication forks. However, they were highly sensitive to camptothecin that induces replication fork breakage. In addition, these mutants were defective in replication fork regeneration and sister chromatid cohesion. Interestingly, unlike swi3-deleted cell, the separation-of-functions mutants were proficient in the activation of the replication checkpoint, but their fork regeneration defects were more severe than those of checkpoint mutants including cds1Δ, chk1Δ and rad3Δ. These results suggest that, while Swi3 mediates full activation of the replication checkpoint in response to stalled replication forks, Swi3 activates a checkpoint-independent pathway to facilitate recovery of collapsed replication forks and the establishment of sister chromatid cohesion. Thus, our separation-of-function alleles provide new insight into understanding the multiple roles of Swi1-Swi3 in fork protection during DNA replication, and into understanding how replication forks are maintained in response to different genotoxic agents

The effectiveness of health interventions in cardiovascular risk reduction among emergency service personnel

PurposeThe physical demands and hazards associated with emergency service work place particular stress on responders&rsquo; cardiovascular systems. Indeed, cardiovascular disease (CVD) is a significant problem for emergency service personnel. Although it may be difficult to alter the cardiovascular health hazards associated with the work environment, it is possible for personnel to control their modifiable CVD risk factors, cardiovascular fitness levels and subsequently, reduce their CVD risk. This review aimed to determine the effectiveness and methodological quality of health interventions designed to mitigate CVD risk in emergency service personnel.MethodsA literature search of electronic journal databases was performed. Sixteen relevant studies were assessed for methodological quality using a standardised assessment tool. Data regarding the effectiveness of each intervention were extracted and synthesised in a narrative format.ResultsFifteen studies were rated &lsquo;Weak&rsquo; and one study was rated &lsquo;Strong&rsquo;. Interventions which combined behavioural counselling, exercise and nutrition were more effective in improving cardiovascular health than nutrition, exercise or CVD risk factor assessment-based interventions alone. Further, CVD risk factor assessment in isolation proved to be an ineffective intervention type to reduce CVD risk.ConclusionCombined interventions appear most effective in improving the cardiovascular health of emergency service personnel. Accordingly, fire and emergency service agencies should consider trialling multifaceted interventions to improve the cardiovascular health of personnel and avoid interventions focused only on one of nutrition, exercise or CVD risk factor assessment. However, as most studies were methodologically weak, further studies of a higher methodological quality are needed.<br /