An In-Vitro Comparison of Steady State Leakage Rates through Introducer Sheaths Used for Fenestrated Endovascular Aortic Aneurysm Repair.

Background: Fenestrated Endovascular Aneurysm Repair (fEVAR) involves deploying a covered stent into the aorta followed by multiple visceral stents through fenestrations in the main body of graft. The most commonly used large sheaths for cannulation of visceral vessels are the Gore DrySeal Flex, Cook Performer Check-Flo, and Medtronic Sentrant. None of these sheaths were designed for the insertion of multiple sheaths, and so a slow but steady leakage of blood occurs during the procedure.

Disordered C-terminal domain drives spatiotemporal confinement of RNAPII to enhance search for chromatin targets.

Efficient gene expression requires RNA polymerase II (RNAPII) to find chromatin targets precisely in space and time. How RNAPII manages this complex diffusive search in three-dimensional nuclear space remains largely unknown. The disordered carboxy-terminal domain (CTD) of RNAPII, which is essential for recruiting transcription-associated proteins, forms phase-separated droplets in vitro, hinting at a potential role in modulating RNAPII dynamics.

Disordered C-terminal domain drives spatiotemporal confinement of RNAPII to enhance search for chromatin targets.

Efficient gene expression requires RNA Polymerase II (RNAPII) to find chromatin targets precisely in space and time. How RNAPII manages this complex diffusive search in 3D nuclear space remains largely unknown. The disordered carboxy-terminal domain (CTD) of RNAPII, which is essential for recruiting transcription-associated proteins, forms phase-separated droplets , hinting at a potential role in modulating RNAPII dynamics.

Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events.

Background: The Ccr4-Not complex is mostly known as the major eukaryotic deadenylase. However, several studies have uncovered roles of the complex, in particular of the Not subunits, unrelated to deadenylation and relevant for translation. In particular, the existence of Not condensates that regulate translation elongation dynamics has been reported.

An assessment of techniques and practices used to elevate intra-abdominal pressure when assessing pelvic floor dysfunction.

Aims: To determine terminology and methods for raising intra-abdominal pressure (IAP) currently used by clinicians to assess pelvic floor dysfunction (PFD) and to measure the effect of these maneuvers on IAP.

Methods: Three-hundred questionnaires were distributed at two scientific meetings in the United Kingdom to determine methods clinicians used to raise IAP and their perceptions of these methods. Twenty healthy volunteers were also recruited to measure the effect of two methods of raising IAP: Valsalva maneuver (VM) and bear down maneuver (BDM).

Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress-dependent mRNAs.

RNA-binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four-RNA recognition motif (RRM)-containing RBP, as a functional and physical interactor of the export factor Mex67. Mip6-RRM4 directly interacts with the ubiquitin-associated (UBA) domain of Mex67 through a loop containing tryptophan 442.

An Arginine Nexus in the RNA Polymerase II CTD.

In this issue of Molecular Cell,Sharma et al. (2019) show that normal cell growth requires conversion of an arginine residue in the RNA polymerase II C-terminal domain (CTD) to citrulline, uncovering a potential regulatory pathway involving opposing arginine modifications.

In Vivo Measurement of Surface Pressures and Retraction Distances Applied on Abdominal Organs During Surgery.

This study undertook the in vivo measurement of surface pressures applied by the fingers of the surgeon during typical representative retraction movements of key human abdominal organs during both open and hand-assisted laparoscopic surgery. Surface pressures were measured using a flexible thin-film pressure sensor for 35 typical liver retractions to access the gall bladder, 36 bowel retractions, 9 kidney retractions, 8 stomach retractions, and 5 spleen retractions across 12 patients undergoing open and laparoscopic abdominal surgery. The maximum and root mean square surface pressures were calculated for each organ retraction.

Yeast RNA-Binding Protein Nab3 Regulates Genes Involved in Nitrogen Metabolism.

Termination of RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while noncoding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex.

Pol II CTD Code Light.

In this issue of Molecular Cell, Schüller et al. (2016) and Suh et al. (2016) describe genetic and mass spectrometry methodologies for mapping phosphorylation sites on the tandem repeats of the RNA polymerase II CTD.

Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains.

The low-complexity (LC) domains of the products of the fused in sarcoma (FUS), Ewings sarcoma (EWS), and TAF15 genes are translocated onto a variety of different DNA-binding domains and thereby assist in driving the formation of cancerous cells. In the context of the translocated fusion proteins, these LC sequences function as transcriptional activation domains. Here, we show that polymeric fibers formed from these LC domains directly bind the C-terminal domain (CTD) of RNA polymerase II in a manner reversible by phosphorylation of the iterated, heptad repeats of the CTD.

The Saccharomyces cerevisiae Nrd1-Nab3 transcription termination pathway acts in opposition to Ras signaling and mediates response to nutrient depletion.

The Saccharomyces cerevisiae Nrd1-Nab3 pathway directs the termination and processing of short RNA polymerase II transcripts. Despite the potential for Nrd1-Nab3 to affect the transcription of both coding and noncoding RNAs, little is known about how the Nrd1-Nab3 pathway interacts with other pathways in the cell. Here we present the results of a high-throughput synthetic lethality screen for genes that interact with NRD1 and show roles for Nrd1 in the regulation of mitochondrial abundance and cell size.

Transcriptome-wide binding sites for components of the Saccharomyces cerevisiae non-poly(A) termination pathway: Nrd1, Nab3, and Sen1.

RNA polymerase II synthesizes a diverse set of transcripts including both protein-coding and non-coding RNAs. One major difference between these two classes of transcripts is the mechanism of termination. Messenger RNA transcripts terminate downstream of the coding region in a process that is coupled to cleavage and polyadenylation reactions.

Simplified electrocardiogram sampling maintains high diagnostic capability for atrial fibrillation: implications for opportunistic atrial fibrillation screening in primary care.

Aims: Atrial fibrillation (AF) is a major cause of morbidity, mortality, and health resource consumption. However, as many patients with chronic AF are asymptomatic, rapid, accurate opportunistic screening is needed in primary care to detect AF. Conventional electrocardiogram (ECG) technology is too clumsy and time consuming for mass opportunistic screening, thus technology that allows easy, rapid, yet accurate AF screening is required.

Yeast Nrd1, Nab3, and Sen1 transcriptome-wide binding maps suggest multiple roles in post-transcriptional RNA processing.

RNA polymerase II transcribes both coding and noncoding genes, and termination of these different classes of transcripts is facilitated by different sets of termination factors. Pre-mRNAs are terminated through a process that is coupled to the cleavage/polyadenylation machinery, and noncoding RNAs in the yeast Saccharomyces cerevisiae are terminated through a pathway directed by the RNA-binding proteins Nrd1, Nab3, and the RNA helicase Sen1. We have used an in vivo cross-linking approach to map the binding sites of components of the yeast non-poly(A) termination pathway.

Going nuclear: transcribers in transit.

Recent experiments have identified novel RNA polymerase-associated proteins with roles in assembly and nuclear transport of multisubunit eukaryotic RNA polymerases. In this issue of Molecular Cell, Czeko et al. (2011) characterize a novel Pol II transport factor that is conserved from yeast to humans.

Epidemic asthma and the role of the fungal mold Alternaria alternata.

Background: After July 29, 2002, an epidemic of asthma admissions was associated with a thunderstorm in the United Kingdom.

Objective: We sought to study the cause of epidemics of asthma associated with thunderstorms.

Methods: We performed a case-control study of 26 patients presenting to Cambridge University Hospital with asthma after the thunderstorm.

Interaction of yeast RNA-binding proteins Nrd1 and Nab3 with RNA polymerase II terminator elements.

Yeast RNA-binding proteins Nrd1 and Nab3 direct transcription termination of sn/snoRNA transcripts, some mRNA transcripts, and a class of intergenic and anti-sense transcripts. Recognition of Nrd1- and Nab3-binding sites is a critical first step in the termination and subsequent processing or degradation of these transcripts. In this article, we describe the purification and characterization of an Nrd1-Nab3 heterodimer.