Impact of template backbone heterogeneity on RNA polymerase II transcription.

Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3'-5' or 2'-5' orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary 'imperfect' DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA

Double Secret Protection: Bridging Federal and State Law To Protect Privacy Rights for Telemental and Mobile Health Users

Mental health care in the United States is plagued by stigma, cost, and access issues that prevent many people from seeking and continuing treatment for mental health conditions. Emergent technology, however, may offer a solution. Through telemental health, patients can connect with providers remotely—avoiding stigmatizing situations that can arise from traditional healthcare delivery, receiving more affordable care, and reaching providers across geographic boundaries. And with mobile health technology, people can use smart phone applications both to self-monitor their mental health and to communicate with their doctors. But people do not want to take advantage of telemental and mobile health unless their privacy is protected. After evaluating the applicability of current health information privacy law to these new forms of treatment, this Note proposes changes to the federal regime to protect privacy rights for telemental and mobile health users

A Rare Isolated Trapezoid Fracture

<p>[West J Emerg Med. 2011;12(4):523–524.]</p

AQP2 is Necessary for Vasopressin- and Forskolin-Mediated Filamentous Actin Depolymerization in Renal Epithelial Cells

Remodeling of the actin cytoskeleton is required for vasopressin (VP)‐induced aquaporin 2 (AQP2) trafficking. Here, we asked whether VP and forskolin (FK)‐mediated F‐actin depolymerization depends on AQP2 expression. Using various MDCK and LLC‐PK1 cell lines with different AQP2 expression levels, we performed F‐actin quantification and immunofluorescence staining after VP/FK treatment. In MDCK cells, in which AQP2 is delivered apically, VP/FK mediated F‐actin depolymerization was significantly correlated with AQP2 expression levels. A decrease of apical membrane associated F‐actin was observed upon VP/FK treatment in AQP2 transfected, but not in untransfected cells. There was no change in basolateral actin staining under these conditions. In LLC‐PK1 cells, which deliver AQP2 basolaterally, a significant VP/FK mediated decrease in F‐actin was also detected only in AQP2 transfected cells. This depolymerization response to VP/FK was significantly reduced by siRNA knockdown of AQP2. By immunofluorescence, an inverse relationship between plasma membrane AQP2 and membrane‐associated F‐actin was observed after VP/FK treatment again only in AQP2 transfected cells. This is the first report showing that VP/FK mediated F‐actin depolymerization is dependent on AQP2 protein expression in renal epithelial cells, and that this is not dependent on the polarity of AQP2 membrane insertion

Influence of First and Second Coordination Environment on Structural Fe(II) Sites in MIL-101 for C–H Bond Activation in Methane

Divalent iron sites in tri-iron oxo-centered metal nodes in metal–organic frameworks (MOFs) catalyze light alkane oxidation. The first two steps of the reaction sequence, which are also the most en..

Defining functional classes of Barth syndrome mutation in humans

The X-linked disease Barth syndrome (BTHS) is caused by mutations in TAZ; TAZ is the main determinant of the final acyl chain composition of the mitochondrial-specific phospholipid, cardiolipin. To date, a detailed characterization of endogenous TAZ has only been performed in yeast. Further, why a given BTHS-associated missense mutation impairs TAZ function has only been determined in a yeast model of this human disease. Presently, the detailed characterization of yeast tafazzin harboring individual BTHS mutations at evolutionarily conserved residues has identified seven distinct loss-of-function mechanisms caused by patient-associated missense alleles. However, whether the biochemical consequences associated with individual mutations also occur in the context of human TAZ in a validated mammalian model has not been demonstrated. Here, utilizing newly established monoclonal antibodies capable of detecting endogenous TAZ, we demonstrate that mammalian TAZ, like its yeast counterpart, is localized to the mitochondrion where it adopts an extremely protease-resistant fold, associates non-integrally with intermembrane space-facing membranes and assembles in a range of complexes. Even though multiple isoforms are expressed at the mRNA level, only a single polypeptide that co-migrates with the human isoform lacking exon 5 is expressed in human skin fibroblasts, HEK293 cells, and murine heart and liver mitochondria. Finally, using a new genome-edited mammalian BTHS cell culture model, we demonstrate that the loss-of-function mechanisms for two BTHS alleles that represent two of the seven functional classes of BTHS mutation as originally defined in yeast, are the same when modeled in human TAZ

Modelling the urban heat island in Birmingham, UK at the neighbourhood scale

Cities have higher peak temperatures compared to surrounding rural areas. The urban-rural surface air temperature difference is known as the urban heat island (UHI). As extreme heat exposure can lead to adverse health effects, information on UHI characteristics of cities is important for future urban climate planning strategies. This study applied the ADMS-Urban Temperature and Humidity model to investigate the key processes driving the UHI in Birmingham, UK, at the neighbourhood scale. This model was configured with a range of input datasets (such as meteorological data, landuse data, building data, anthropogenic heat sources etc) and run on the University of Birmingham’s BlueBEAR HPC. This urban climate modelling was evaluated against the temperature measurement datasets from UK Met Office and Weather Underground. The spatiotemporal variations of surface air temperature in Birmingham, UK were captured by this model. This modelling study can be further applied to explore the impacts of local urban head island mitigation strategies

Unraveling the optimum latent structure of attention-deficit/hyperactivity disorder : evidence supporting ICD and HiTOP frameworks

Attention Deficit/hyperactivity disorder (ADHD) is conceptualized differently in the Diagnostic and Statistical Manual (DSM-5), the International Classification of Diseases-10 (ICD-10), and the Hierarchical Taxonomy of Psychopathology (HiTOP) frameworks. This study applied independent cluster confirmatory factor analysis (ICM-CFA), exploratory structure equation model with target rotation (ESEM), and the S-1 bi-factor CFA approaches to evaluate seven ADHD models yielded by different combinations of these taxonomic frameworks. Parents and teachers of a community sample of children (between 6 and 12 years of age) completed the Disruptive Behavior Rating Scale (for ADHD symptoms) and the Strengths and Difficulties Questionnaire (for validation). Our findings for both parent and teacher ratings provided the most support for the S-1 bi-factor CFA model comprised of (i) a g-factor based on ICD-10 impulsivity symptoms as the reference indicators and (ii) inattention and hyperactivity as specific factors. However, the hyperactivity-specific factor lacked clarity and reliability. Thus, our findings indicate that ADHD is best viewed as a disorder primarily reflecting impulsivity, though with a separable inattention (but no hyperactivity) component, i.e., “ADID (attention deficit/impulsivity disorder).” This model aligns with the HiTOP proposals. © Copyright © 2021 Gomez, Liu, Krueger, Stavropoulos, Downs, Preece, Houghton and Chen