Aspergillus nidulans Septa Are Indispensable for Surviving Cell Wall Stress

Septation in filamentous fungi is a normal part of development, which involves the formation of cross-hyphal bulkheads, typically containing pores, allowing cytoplasmic streaming between compartments. Based on previous findings regarding septa and cell wall stress, we hypothesized that septa are critical for survival during cell wall stress. To test this hypothesis, we used known Aspergillus nidulans septation-deficient mutants (ΔsepH, Δbud3, Δbud4, and Δrho4) and six antifungal compounds. Three of these compounds (micafungin, Congo red, and calcofluor white) are known cell wall stressors which activate the cell wall integrity signaling pathway (CWIS), while the three others (cycloheximide, miconazole, and 2,3-butanedione monoxime) perturb specific cellular processes not explicitly related to the cell wall. Our results show that deficiencies in septation lead to fungi which are more susceptible to cell wall-perturbing compounds but are no more susceptible to other antifungal compounds than a control. This implies that septa play a critical role in surviving cell wall stress

Microscopic simulation of membrane molecule diffusion on corralled membrane surfaces

The current understanding of how receptors diffuse and cluster in the plasma membrane is limited. Data from single-particle tracking and laser tweezer experiments have suggested that membrane molecule diffusion is affected by the presence of barriers dividing the membrane into corrals. Here, we have developed a stochastic spatial model to simulate the effect of corrals on the diffusion of molecules in the plasma membrane. The results of this simulation confirm that a fence barrier (the ratio of the transition probability for diffusion across a boundary to that within a corral) on the order of 103–104 recreates the experimentally measured difference in diffusivity between artificial and natural plasma membranes. An expression for the macroscopic diffusivity of receptors on corralled membranes is derived to analyze the effects of the corral parameters on diffusion rate. We also examine whether the lattice model is an appropriate description of the plasma membrane and look at three different sets of boundary conditions that describe diffusion over the barriers and whether diffusion events on the plasma membrane may occur with a physically relevant length scale. Finally, we show that to observe anomalous (two-timescale) diffusion, one needs high temporal (microsecond) resolution along with sufficiently long (more than milliseconds) trajectories

SAND, a New Protein Family: From Nucleic Acid to Protein Structure and Function Prediction

As a result of genome, EST and cDNA sequencing projects, there are huge numbers of predicted and/or partially characterised protein sequences compared with a relatively small number of proteins with experimentally determined function and structure. Thus, there is a considerable attention focused on the accurate prediction of gene function and structure from sequence by using bioinformatics. In the course of our analysis of genomic sequence from Fugu rubripes, we identified a novel gene, SAND, with significant sequence identity to hypothetical proteins predicted in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans, a Drosophila melanogaster gene, and mouse and human cDNAs. Here we identify a further SAND homologue in human and Arabidopsis thaliana by use of standard computational tools. We describe the genomic organisation of SAND in these evolutionarily divergent species and identify sequence homologues from EST database searches confirming the expression of SAND in over 20 different eukaryotes. We confirm the expression of two different SAND paralogues in mammals and determine expression of one SAND in other vertebrates and eukaryotes. Furthermore, we predict structural properties of SAND, and characterise conserved sequence motifs in this protein family

A longitudinal investigation of the role of parental responses in predicting children’s post-traumatic distress

Background While parental post-trauma support is considered theoretically important for child adjustment, empirical evidence concerning the specific aspects of parental responding that influence child post-traumatic distress, or the processes via which any such impacts occur, is extremely limited. We conducted a longitudinal examination of whether parental post-trauma appraisals, trauma-specific support style and general parenting style predicted child post-traumatic stress symptom severity (PTSS) following trauma; and whether such influences operated via the child's own appraisals and coping style. Method We recruited 132 parent–child pairs following children's experience of acute trauma. We examined whether parental responses assessed at 1-month post-trauma, predicted child PTSS at 6-month follow-up. Parental trauma-specific appraisals and responses, and general parenting style, were assessed via both self-report and direct observations. Child-report questionnaires were used to assess PTSS and potential mediators. Results Initial parent negative appraisals and encouragement of avoidant coping were associated with higher child-reported PTSS at 6-month follow-up. Predictive effects were maintained even when controlling for initial child symptom levels. Observational assessments broadly supported conclusions from self-report. There was evidence that parental influences may operate, in part, by influencing the child's own appraisals and coping responses. In contrast, there was no evidence for an influence of more “adaptive” support or general parenting style on child PTSS. Conclusions Findings provide important insight into how elements of social support may influence child post-trauma outcomes

Fission yeast Ags1 confers the essential septum strength needed for safe gradual cell abscission

[EN]Fungal cytokinesis requires the assembly of a dividing septum wall. In yeast, the septum has to be selectively digested during the critical cell separation process. Fission yeast cell wall alpha (1-3) glucan is essential, but nothing is known about its localization and function inthe cell wall or about cooperation between the alpha - and beta (1-3) glucan synthases Ags1 and Bgs for cell wall and septum assembly. Here, we generate a physiological Ags1-GFP variant and demonstrate a tight colocalization with Bgs1, suggesting a cooperation in the important early steps of septum construction. Moreover, we define the essential functions of alpha(1-3) glucan in septation and cell separation. We show that alpha (1-3) glucan is essential for both secondary septum formation and the primary septum structural strength needed to support the physical forces of the cell turgor pressure during cell separation. Consequently, the absence of Ags1 and therefore alpha(1-3)glucan generates a special and unique side-explosive cell separation due to an instantaneous primary septum tearing caused by the turgor pressure

Improving the effectiveness of psychological interventions for depression and anxiety in the cardiac rehabilitation pathway using group-based metacognitive therapy (PATHWAY Group MCT) : study protocol for a randomised controlled trial

BACKGROUND: Anxiety and depression are prevalent among cardiac rehabilitation patients but pharmacological and psychological treatments have limited effectiveness in this group. Furthermore, psychological interventions have not been systematically integrated into cardiac rehabilitation services despite being a strategic priority for the UK National Health Service. A promising new treatment, metacognitive therapy, may be well-suited to the needs of cardiac rehabilitation patients and has the potential to improve outcomes. It is based on the metacognitive model, which proposes that a thinking style dominated by rumination, worry and threat monitoring maintains emotional distress. Metacognitive therapy is highly effective at reducing this thinking style and alleviating anxiety and depression in mental health settings. This trial aims to evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy for cardiac rehabilitation patients with elevated anxiety and/or depressive symptoms. METHODS/DESIGN: The PATHWAY Group-MCT trial is a multicentre, two-arm, single-blind, randomised controlled trial comparing the clinical- and cost-effectiveness of group-based metacognitive therapy plus usual cardiac rehabilitation to usual cardiac rehabilitation alone. Cardiac rehabilitation patients (target sample n = 332) with elevated anxiety and/or depressive symptoms will be recruited across five UK National Health Service Trusts. Participants randomised to the intervention arm will receive six weekly sessions of group-based metacognitive therapy delivered by either cardiac rehabilitation professionals or research nurses. The intervention and control groups will both be offered the usual cardiac rehabilitation programme within their Trust. The primary outcome is severity of anxiety and depressive symptoms at 4-month follow-up measured by the Hospital Anxiety and Depression Scale total score. Secondary outcomes are severity of anxiety/depression at 12-month follow-up, health-related quality of life, severity of post-traumatic stress symptoms and strength of metacognitive beliefs at 4- and 12-month follow-up. Qualitative interviews will help to develop an account of barriers and enablers to the effectiveness of the intervention. DISCUSSION: This trial will evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy in alleviating anxiety and depression in cardiac rehabilitation patients. The therapy, if effective, offers the potential to improve psychological wellbeing and quality of life in this large group of patients. TRIAL REGISTRATION: UK Clinical Trials Gateway, ISRCTN74643496 , Registered on 8 April 2015