Aortic Pathology Determines Midterm Outcome After Endovascular Repair of the Thoracic Aorta Report From the Medtronic Thoracic Endovascular Registry (MOTHER) Database

Background—Endovascular repair of the thoracic aorta has become an increasingly utilized therapy. Although the short-term mortality advantage over open surgery is well documented, late mortality and the impact of presenting pathology on long-term outcomes remain poorly reported. Methods and Results—A database was built from 5 prospective studies and a single institutional series. Rates of perioperative adverse events were calculated, as were midterm death and reintervention rates. Multivariate analysis was performed with the use of logistic regression modeling. Kaplan-Meier survival curves were drawn for midterm outcomes. The database contained 1010 patients: 670 patients with thoracic aortic aneurysm, 195 with chronic type B aortic dissection, and 114 with acute type B aortic dissection. Lower elective mortality was observed in patients with chronic dissections (3%) compared with patients with aneurysms (5%). Multivariate analysis identified age, mode of admission, American Society of Anesthesiologists grade, and pathology as independent predictors of 30-day death (P < 0.05). In the midterm, the all-cause mortality rate was 8, 4.9, and 3.2 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively. The rates of aortic-related death were 0.6, 1.2, and 0.4 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively. Conclusions—This study indicated that the midterm outcomes of endovascular repair of the thoracic aorta are defined by presenting pathology, associated comorbidities, and mode of admission. Nonaortic mortality is high in the midterm for patients with thoracic aortic aneurysm, and managing modifiable risk factors appears vital. Endovascular repair of the thoracic aorta results in excellent midterm protection from aortic-related mortality, regardless of presenting pathology

The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase

Copyright: © 2013 Gwynn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust project grant to MD (Reference: 077368), an ERC starting grant to MD (Acronym: SM-DNA-REPAIR) and a BBSRC project grant to PM, NS and MD (Reference: BB/I003142/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Crystal Structure of the Minimalist Max-E47 Protein Chimera

Max-E47 is a protein chimera generated from the fusion of the DNA-binding basic region of Max and the dimerization region of E47, both members of the basic region/helix-loop-helix (bHLH) superfamily of transcription factors. Like native Max, Max-E47 binds with high affinity and specificity to the E-box site, 5′-CACGTG, both in vivo and in vitro. We have determined the crystal structure of Max-E47 at 1.7 Å resolution, and found that it associates to form a well-structured dimer even in the absence of its cognate DNA. Analytical ultracentrifugation confirms that Max-E47 is dimeric even at low micromolar concentrations, indicating that the Max-E47 dimer is stable in the absence of DNA. Circular dichroism analysis demonstrates that both non-specific DNA and the E-box site induce similar levels of helical secondary structure in Max-E47. These results suggest that Max-E47 may bind to the E-box following the two-step mechanism proposed for other bHLH proteins. In this mechanism, a rapid step where protein binds to DNA without sequence specificity is followed by a slow step where specific protein:DNA interactions are fine-tuned, leading to sequence-specific recognition. Collectively, these results show that the designed Max-E47 protein chimera behaves both structurally and functionally like its native counterparts

Vasa-Like DEAD-Box RNA Helicases of Schistosoma mansoni

Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of primordial germ cells and the germ line in the Metazoa. Using bioinformatics, 33 putative DEAD-box RNA helicases exhibiting conserved motifs that characterize helicases of this family were identified in the S. mansoni genome. Moreover, three of the helicases exhibited vasa-like sequences; phylogenetic analysis confirmed the three vasa-like genes—termed Smvlg1, Smvlg2, and Smvlg3—were members of the Vasa/PL10 DEAD-box subfamily. Transcripts encoding Smvlg1, Smvlg2, and Smvlg3 were cloned from cDNAs from mixed sex adult worms, and quantitative real time PCR revealed their presence in developmental stages of S. mansoni with elevated expression in sporocysts, adult females, eggs, and miracidia, with strikingly high expression in the undeveloped egg. Whole mount in situ hybridization (WISH) analysis revealed that Smvlg1, Smvlg2 and Smvlg3 were transcribed in the posterior ovary where the oocytes mature. Germ cell specific expression of schistosome vasa-like genes should provide an informative landmark for germ line transgenesis of schistosomes, etiologic agents of major neglected tropical diseases

Phylogenetic Distribution and Evolutionary History of Bacterial DEAD-Box Proteins

DEAD-box proteins are found in all domains of life and participate in almost all cellular processes that involve RNA. The presence of DEAD and Helicase_C conserved domains distinguish these proteins. DEAD-box proteins exhibit RNA-dependent ATPase activity in vitro, and several also show RNA helicase activity. In this study, we analyzed the distribution and architecture of DEAD-box proteins among bacterial genomes to gain insight into the evolutionary pathways that have shaped their history. We identified 1,848 unique DEAD-box proteins from 563 bacterial genomes. Bacterial genomes can possess a single copy DEAD-box gene, or up to 12 copies of the gene, such as in Shewanella. The alignment of 1,208 sequences allowed us to perform a robust analysis of the hallmark motifs of DEAD-box proteins and determine the residues that occur at high frequency, some of which were previously overlooked. Bacterial DEAD-box proteins do not generally contain a conserved C-terminal domain, with the exception of some members that possess a DbpA RNA-binding domain (RBD). Phylogenetic analysis showed a separation of DbpA-RBD-containing and DbpA-RBD-lacking sequences and revealed a group of DEAD-box protein genes that expanded mainly in the Proteobacteria. Analysis of DEAD-box proteins from Firmicutes and γ-Proteobacteria, was used to deduce orthologous relationships of the well-studied DEAD-box proteins from Escherichia coli and Bacillus subtilis. These analyses suggest that DbpA-RBD is an ancestral domain that most likely emerged as a specialized domain of the RNA-dependent ATPases. Moreover, these data revealed numerous events of gene family expansion and reduction following speciation

Novel ATP-Independent RNA Annealing Activity of the Dengue Virus NS3 Helicase

The flavivirus nonstructural protein 3 (NS3) bears multiple enzymatic activities and represents an attractive target for antiviral intervention. NS3 contains the viral serine protease at the N-terminus and ATPase, RTPase, and helicase activities at the C-terminus. These activities are essential for viral replication; however, the biological role of RNA remodeling by NS3 helicase during the viral life cycle is still unclear. Secondary and tertiary RNA structures present in the viral genome are crucial for viral replication. Here, we used the NS3 protein from dengue virus to investigate functions of NS3 associated to changes in RNA structures. Using different NS3 variants, we characterized a domain spanning residues 171 to 618 that displays ATPase and RNA unwinding activities similar to those observed for the full-length protein. Interestingly, we found that, besides the RNA unwinding activity, dengue virus NS3 greatly accelerates annealing of complementary RNA strands with viral or non-viral sequences. This new activity was found to be ATP-independent. It was determined that a mutated NS3 lacking ATPase activity retained full-RNA annealing activity. Using an ATP regeneration system and different ATP concentrations, we observed that NS3 establishes an ATP-dependent steady state between RNA unwinding and annealing, allowing modulation of the two opposing activities of this enzyme through ATP concentration. In addition, we observed that NS3 enhanced RNA-RNA interactions between molecules representing the ends of the viral genome that are known to be necessary for viral RNA synthesis. We propose that, according to the ATP availability, NS3 could function regulating the folding or unfolding of viral RNA structures

Autoregulation in resistance training : addressing the inconsistencies

Autoregulation is a process that is used to manipulate training based primarily on the measurement of an individual's performance or their perceived capability to perform. Despite being established as a training framework since the 1940s, there has been limited systematic research investigating its broad utility. Instead, researchers have focused on disparate practices that can be considered specific examples of the broader autoregulation training framework. A primary limitation of previous research includes inconsistent use of key terminology (e.g., adaptation, readiness, fatigue, and response) and associated ambiguity of how to implement different autoregulation strategies. Crucially, this ambiguity in terminology and failure to provide a holistic overview of autoregulation limits the synthesis of existing research findings and their dissemination to practitioners working in both performance and health contexts. Therefore, the purpose of the current review was threefold: first, we provide a broad overview of various autoregulation strategies and their development in both research and practice whilst highlighting the inconsistencies in definitions and terminology that currently exist. Second, we present an overarching conceptual framework that can be used to generate operational definitions and contextualise autoregulation within broader training theory. Finally, we show how previous definitions of autoregulation fit within the proposed framework and provide specific examples of how common practices may be viewed, highlighting their individual subtleties

Enfermeiras americanas do Serviço Especial de Saúde Pública e a formação de recursos humanos na Enfermagem Brasileira

RESUMO Objetivo Historicizar as mudanças na formação de recursos humanos em enfermagem no Brasil, no período de 1942 a 1961, a partir da presença de 35 enfermeiras americanas designadas para trabalhar em cooperação com o SESP. Método O estudo utilizou como fontes relatórios redigidos pelas enfermeiras, que descrevem suas impressões, sugestões e atividades desenvolvidas no país, e foram analisadas a partir da análise de discurso de Michel Foucault. Resultados O período mencionado foi marcado pela presença americana nos projetos de enfermagem desenvolvidos pelo Serviço Especial de Saúde Pública (SESP). Os discursos indicaram que o período foi marcado por muitas mudanças na enfermagem brasileira, em especial no que diz respeito à captação e formação de recursos humanos para a profissão. Conclusão Pode-se afirmar que elas, através de seus discursos e influência, foram centrais para a consolidação de um novo paradigma na formação de profissionais de enfermagem no Brasil