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During sexual reproduction or conjugation, ciliates form a specialized cell adhesion zone for the purpose of exchanging gametic pronuclei. Hundreds of individual membrane fusion events transform the adhesion zone into a perforated membrane curtain, the mating junction. Pronuclei from each mating partner are propelled through this fenestrated membrane junction by a web of short, cris-crossing microtubules. Pronuclear passage results in the formation of two breaches in the membrane junction. Following pronuclear exchange and karyogamy (fertilization), cells seal these twin membrane breaches thereby re-establishing cellular independence. This would seem like a straightforward problem: simply grow membrane in from the edges of each breach in a fashion similar to how animal cells "grow" their cytokinetic furrows or how plant cells construct a cell wall during mitosis. Serial section electron microscopy and 3-D electron tomography reveal that the actual mechanism is less straightforward. Each of the two membrane breaches transforms into a bowed membrane assembly platform. The resulting membrane protrusions continue to grow into the cytoplasm of the mating partner, traverse the cytoplasm in anti-parallel directions and make contact with the plasma membrane that flanks the mating junction. This investigation reveals the details of a novel, developmentally-induced mechanism of membrane disruption and restoration associated with pronuclear exchange and fertilization in the ciliate, Tetrahymena thermophila., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The Wilms' tumor gene 1 ( WT1 ) is recurrently mutated in acute myeloid leukemia. Mutations and high expression of WT1 associate with a poor prognosis. In mice, WT1 cooperates with the RUNX1/RUNX1T1 ( AML1/ETO ) fusion gene in the induction of acute leukemia, further emphasizing a role for WT1 in leukemia development. Molecular mechanisms for WT1 are, however, incompletely understood. Here, we identify the transcriptional coregulator NAB2 as a target gene of WT1. Analysis of gene expression profiles of leukemic samples revealed a positive correlation between the expression of WT1 and NAB2 , as well as a non-zero partial correlation. Overexpression of WT1 in hematopoietic cells resulted in increased NAB2 levels, while suppression of WT1 decreased NAB2 expression. WT1 bound and transactivated the proximal NAB2 promoter, as shown by ChIP and reporter experiments, respectively. ChIP experiments also revealed that WT1 can recruit NAB2 to the IRF8 promoter, thus modulating the transcriptional activity of WT1, as shown by reporter experiments. Our results implicate NAB2 as a previously unreported target gene of WT1 and that NAB2 acts as a transcriptional cofactor of WT1., Competing Interests: CONFLICTS OF INTEREST The authors report no potential conflicts of interest.

Background: A 1-h algorithm based on high-sensitivity cardiac troponin T (hs-cTnT) testing at presentation and again 1 h thereafter has been shown to accurately rule out acute myocardial infarction., Objectives: The goal of the study was to evaluate the diagnostic accuracy of the 1-h algorithm when supplemented with patient history and an electrocardiogram (ECG) (the extended algorithm) for predicting 30-day major adverse cardiac events (MACE) and to compare it with the algorithm using hs-cTnT alone (the troponin algorithm)., Methods: This prospective observational study enrolled consecutive patients presenting to the emergency department (ED) with chest pain, for whom hs-cTnT testing was ordered at presentation. Hs-cTnT results at 1 h and the ED physician's assessments of patient history and ECG were collected. The primary outcome was an adjudicated diagnosis of 30-day MACE defined as acute myocardial infarction, unstable angina, cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of a cardiac or unknown cause., Results: In the final analysis, 1,038 patients were included. The extended algorithm identified 60% of all patients for rule-out and had a higher sensitivity than the troponin algorithm (97.5% vs. 87.6%; p < 0.001). The negative predictive value was 99.5% and the likelihood ratio was 0.04 with the extended algorithm versus 97.8% and 0.17, respectively, with the troponin algorithm. The extended algorithm ruled-in 14% of patients with a higher sensitivity (75.2% vs. 56.2%; p < 0.001) but a slightly lower specificity (94.0% vs. 96.4%; p < 0.001) than the troponin algorithm. The rule-in arms of both algorithms had a likelihood ratio >10., Conclusions: A 1-h combination algorithm allowed fast rule-out and rule-in of 30-day MACE in a majority of ED patients with chest pain and performed better than the troponin-alone algorithm., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Atrial fibrillatory rate (AFR) is considered a non-invasive index of atrial remodelling. Low AFR has been associated with favourable outcome of interventions in patients with persistent atrial fibrillation (AF). However, AFR has never been studied in unselected patients with short duration of AF, prone to regain sinus rhythm (SR) spontaneously. The aim of the study was to assess if AFR can predict spontaneous conversion in patients with recent-onset AF., Methods and Results: Files of consecutive patients with AF < 48 h seeking emergency room care during a 12-month period were screened (n = 225). Patients with thyroid illness, acute ischaemic heart disease (IHD) or acute congestive heart failure, significant valvular heart disease, congenital heart disease, history of cardiac surgery or catheter ablation, or on class I/III antiarrhythmics were excluded. Atrial fibrillatory rate was obtained by QRST cancellation and time frequency analysis of electrocardiogram at admission. The study population comprised 148 patients (age 64 ± 13 years, 52 men), of whom 48 converted to SR within 18 h. Those converting spontaneously comprised more women, had a higher prevalence of first-ever AF episode, IHD, and a lower AFR. The multivariate analysis revealed: AFR < 350 fibrillations per minute [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.3-10.5, P = 0.016], IHD (OR 5.7, 95% CI 1.5-22.4, P = 0.012) and first-ever AF episode (OR 4.1, 95% CI 1.3-13.0, P = 0.015) as independent predictors of spontaneous conversion., Conclusion: A low AFR was predictive of spontaneous conversion in patients with recent-onset AF. Along with first-ever AF episode and IHD, AFR can be used in assessing likelihood of spontaneous conversion, if proven in prospective studies.

A descriptive account is given of our most recent research on the actinide dioxides with the Advanced Light Source Molecular Environmental Science (ALS-MES) Beamline 11.0.2 soft X-ray scanning transmission X-ray microscope (STXM) at the Lawrence Berkeley National Laboratory (LBNL). The ALS-MES STXM permits near-edge X-ray absorption fine structure (NEXAFS) and imaging with 30-nm spatial resolution. The first STXM spectromicroscopy NEXAFS spectra at the actinide 4d5/2 edges of the imaged transuranic particles, NpO2 and PuO2, have been obtained. Radiation damage induced by the STXM was observed in the investigation of a mixed oxidation state particle (Np(V,VI)) and was minimized during collection of the actual spectra at the 4d5/2 edge of the Np(V,VI) solid. A plutonium elemental map was obtained from an irregular PuO2 particle with the dimensions of 650 x 650 nm. The Pu 4d5/2 NEXAFS spectra were collected at several different locations from the PuO2 particle and were identical. A representative oxygen K-edge spectrum from UO2 was collected and resembles the oxygen K-edge from the bulk material. The unique and current performance of the ALS-MES STXM at extremely low energies (ca. 100 eV) that may permit the successful measurement of the actinide 5d edge is documented. Finally, the potential of STXM as a tool for actinide investigations is briefly discussed.

The immediate evaluation of patients with suspected acute coronary syndrome (ACS) in the emergency department (ED) has remained almost unchanged for decades. At the same time, therapy for established ACS has undergone a remarkable and successful change towards early active intervention. Studies show that 7 out of 10 patients admitted with a suspicion of ACS do not have it, and that 2-5% of the patients with ACS are incorrectly sent home from the ED. With new diagnostic strategies, including e.g. risk prediction algorithms, new blood samples for plaque instability, special investigations like echocardiography, myocardial perfusion imaging and magnetic resonance imaging, as well as the Chest Pain Unit concept, improvements should definitely be possible. With the structured and evidence-based use of such strategies, it is our belief that more patients can be managed as outpatients, that length of stay can be shortened for those admitted, and that some patients with ACS can get an earlier adequate intervention.

BACKGROUND: Improved diagnostics in suspected acute coronary syndrome (ACS) are considered to be needed. To help clarify the current situation and the improvement potential, judged risk in the emergency department (ED) and outcome were analyzed among patients with suspected ACS at a university hospital. METHODS: 157 consecutive patients with symptoms of ACS were included at the ED during 10 days. Risk of ACS was estimated in the ED for each patient based on history, physical examination and ECG by assigning them to one of four risk categories; I (obvious myocardial infarction, MI), II (strong suspicion of ACS), III (vague suspicion of ACS), and IV (no suspicion of ACS). RESULTS: 4, 17, 29 and 50% of the patients were allocated to risk categories I-IV respectively. 74 patients (47%) were hospitalized but only 19 (26%) had ACS as the discharge diagnose. In risk categories I-IV, ACS rates were 100, 37, 12 and 0%, respectively. Of those admitted without ACS, at least 37% could probably, given perfect ED diagnostics, have been immediately discharged. 83 patients were discharged from the ED, and among them there were no hospitalizations for ACS or cardiac mortality at 6 months. Only about three patients per 24 h were considered eligible for a potential ED chest pain unit. CONCLUSIONS: Almost 75% of the patients hospitalized with suspected ACS did not have it, and some 40% of these patients could probably, given perfect immediate diagnostics, have been managed as outpatients. The potential for diagnostic improvement in the ED seems large.