A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.

Cell-cell fusion is essential for fertilization. For fusion of walled cells, the cell wall must be degraded at a precise location but maintained in surrounding regions to protect against lysis. In fission yeast cells, the formin Fus1, which nucleates linear actin filaments, is essential for this process. In this paper, we show that this formin organizes a specific actin structure-the actin fusion focus. Structured illumination microscopy and live-cell imaging of Fus1, actin, and type V myosins revealed an aster of actin filaments whose barbed ends are focalized near the plasma membrane. Focalization requires Fus1 and type V myosins and happens asynchronously always in the M cell first. Type V myosins are essential for fusion and concentrate cell wall hydrolases, but not cell wall synthases, at the fusion focus. Thus, the fusion focus focalizes cell wall dissolution within a broader cell wall synthesis zone to shift from cell growth to cell fusion.

Percutaneous coronary interventions prior to coronary artery bypass surgery.

BACKGROUND AND AIM OF THE STUDY: Percutaneous coronary interventions (PCI) are frequently performed before coronary artery bypass graft (CABG) surgery. This study sought to evaluate postoperative outcomes, and incidence of recurrent target ischemia in vessels with prior PCI in patients who had PCI prior to CABG compared to only CABG patients. METHODS: A review included CABG patients operated from 2000 to 2012. PCI prior to CABG patients were compared with patients having had CABG on native coronary arteries. Demographic and risk factors, including hospital morbidity, mortality, and recurrent target vessel ischemia at follow-up (FU), were compared. Major end-points were statistical differences of postoperative morbidity and reintervention rates due to symptomatic graft failure or target vessel ischemia during FU. RESULTS: Twenty-four percent of 1669 isolated CABG patients had PCI prior to CABG, with an increasing percentage during recent years. Demographics, risk factors, comorbidities and mortality rates were similar. Incidence of postoperative hemorrhage (OR 1.9; 95% CI 1.1-3.2; p = 0.02), perioperative myocardial infarction rate (p = 0.02), neurological deficits (OR 3.5; 95% CI 1.2-9.7; p = 0.02) and re-intervention rate for symptomatic graft or target vessel occlusion were higher in pretreated patients (OR 1.8; 95% CI 1.1-3.0; p = 0.01). CONCLUSIONS: PCI prior to CABG increases the risk for postoperative morbidity. Increased postoperative hemorrhage could be attributed to ongoing double anti-platelet therapy. doi: 10.1111/jocs.12514 (J Card Surg 2015;30:313-318).

Schonlandia XIII nova tabula - Schonlandia XIII nova tabula

Basel : H. Petri 1540

Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress.

Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in the energy homeostasis of all tissues. The AK2 isoenzyme is expressed in the mitochondrial intermembrane space and is mutated in reticular dysgenesis (RD), a rare form of severe combined immunodeficiency (SCID) in humans. RD is characterized by a maturation arrest in the myeloid and lymphoid lineages, leading to early onset, recurrent, and overwhelming infections. To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient. In zebrafish, Ak2 deficiency affected hematopoietic stem and progenitor cell (HSPC) development with increased oxidative stress and apoptosis. AK2-deficient iPSCs recapitulated the characteristic myeloid maturation arrest at the promyelocyte stage and demonstrated an increased AMP/ADP ratio, indicative of an energy-depleted adenine nucleotide profile. Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish and restored differentiation of AK2-deficient iPSCs into mature granulocytes. Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD.

Short-Term Heparin Kinetics during Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Percutaneous catheter ablation of atrial fibrillation (CA-AF) is a treatment option for symptomatic drug-refractory atrial fibrillation (AF). CA-AF carries a risk for thromboembolic complications that has been minimized by the use of intraprocedural intravenous unfractionated heparin (UFH). The optimal administration of UFH as well as its kinetics are not well established and need to be precisely determined. METHODS AND RESULTS: A total 102 of consecutive patients suffering from symptomatic drug-refractory AF underwent CA-AF. The mean age was 61 ± 10 years old. After transseptal puncture of the fossa ovalis, weight-adjusted UFH bolus (100 U/kg) was infused. A significant increase in activated clotting time (ACT) was observed from an average value of 100 ± 27 seconds at baseline, to 355 ± 94 seconds at 10 min (T10), to 375 ± 90 seconds at 20 min (T20). Twenty-four patients failed to reach the targeted ACT value of ≥300 seconds at T10 and more than half of these remained with subtherapeutic ACT values at T20. This subset of patients showed similar clinical characteristics and amount of UFH but were more frequently prescribed preprocedural vitamin K1 than the rest of the study population. CONCLUSIONS: In a typical intervention setting, UFH displays unexpected slow anticoagulation kinetics in a significant proportion of procedures up to 20 minutes after infusion. These findings support the infusion of UFH before transseptal puncture or any left-sided catheterization with early ACT measurements to identify patients with delayed kinetics. They are in line with recent guidelines to perform CA-AF under therapeutic anticoagulation.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

What Role Does Sleep Play in Weight Gain in the First Semester of University?

We hypothesized that shorter sleep durations and greater variability in sleep patterns are associated with weight gain in the first semester of university. Students (N = 132) completed daily sleep diaries for 9 weeks, completed the MEQ (chronotype) and CES-D (depressed mood) at week 9, and self-reported weight/height (weeks 1 & 9). Mean and variability scores were calculated for sleep duration (TST, TSTv), bedtime (BT, BTv), and wake time (WT, WTv). An initial hierarchical regression evaluated (block 1) sex, ethnicity; (block 2) depressed mood, chronotype; (block 3) TST; (block 4) BT, WT; and (block 5; R(2) change = 0.09, p = 0.005) TSTv, BTv, WTv with weight change. A sex-by-TSTv interaction was found. A final model showed that ethnicity, TST, TSTv, and BTv accounted for 31% of the variance in weight change for males; TSTv was the most significant contributor (R(2) change = 0.21, p < 0.001). Daily variability in sleep duration contributes to males' weight gain. Further investigation needs to examine sex-specific outcomes for sleep and weight.

The DYRK-family kinase Pom1 phosphorylates the F-BAR protein Cdc15 to prevent division at cell poles.

Division site positioning is critical for both symmetric and asymmetric cell divisions. In many organisms, positive and negative signals cooperate to position the contractile actin ring for cytokinesis. In rod-shaped fission yeast Schizosaccharomyces pombe cells, division at midcell is achieved through positive Mid1/anillin-dependent signaling emanating from the central nucleus and negative signals from the dual-specificity tyrosine phosphorylation-regulated kinase family kinase Pom1 at the cell poles. In this study, we show that Pom1 directly phosphorylates the F-BAR protein Cdc15, a central component of the cytokinetic ring. Pom1-dependent phosphorylation blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics. This promotes ring sliding from cell poles, which prevents septum assembly at the ends of cells with a displaced nucleus or lacking Mid1. Pom1 also slows down ring constriction. These results indicate that a strong negative signal from the Pom1 kinase at cell poles converts Cdc15 to its closed state, destabilizes the actomyosin ring, and thus promotes medial septation.

Turhan kunnianhimoinen yleisesitys

Kirjallisuusarvostelu

Philipp Melanchthon als Verfasser von Briefen, als Dichter und als Ethiker

Kirjallisuusarvostelu

Philipp Melanchthon i backspegeln : 450 år efter hans död

Kirjallisuusarvostelu