The transcriptional cycle of HIV-1 in real-time and live cells

RNA polymerase II ( RNAPII) is a fundamental enzyme, but few studies have analyzed its activity in living cells. Using human immunodeficiency virus ( HIV) type 1 reporters, we study real- time messenger RNA ( mRNA) biogenesis by photobleaching nascent RNAs and RNAPII at specific transcription sites. Through modeling, the use of mutant polymerases, drugs, and quantitative in situ hybridization, we investigate the kinetics of the HIV- 1 transcription cycle. Initiation appears efficient because most polymerases demonstrate stable gene association. We calculate an elongation rate of approximately 1.9 kb/ min, and, surprisingly, polymerases remain at transcription sites 2.5 min longer than nascent RNAs. With a total polymerase residency time estimated at 333 s, 114 are assigned to elongation, and 63 are assigned to 3'- end processing and/ or transcript release. However, mRNAs were released seconds after polyadenylation onset, and analysis of polymerase density by chromatin immunoprecipitation suggests that they pause or lose processivity after passing the polyA site. The strengths and limitations of this kinetic approach to analyze mRNA biogenesis in living cells are discussed

EMS Systems: Foundations for the Future

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73462/1/j.1553-2712.1999.tb00094.x.pd

Possible mineral contributions to the diet and health of wild chimpanzees in three East African forests

For financial support, the authors acknowledge the Mohamed bin Zayed Species Conservation Fund grant numbers 0925272, 10251055, 11252562, 12254904, the Royal Zoological Society of Scotland, the Leverhulme Trust grant number ECF‐2013‐507, and the Boise Fund.We present new data on the ingestion of minerals from termite mound soil by East African chimpanzees (Pan troglodytes schweinfurthii) living in the Budongo Forest Reserve, Uganda, the Gombe National Park and the Mahale Mountains National Park, Tanzania. Termite mound soil is here shown to be a rich source of minerals, containing high concentrations of iron and aluminum. Termite mound soil is not, however, a source of sodium. The concentrations of iron and aluminum are the highest yet found in any of the mineral sources consumed. Levels of manganese and copper, though not so high as for iron and aluminum, are also higher than in other dietary sources. We focus on the contribution of termite mound soil to other known sources of mineral elements consumed by these apes, and compare the mineral content of termite soil with that of control forest soil, decaying wood, clay, and the normal plant‐based chimpanzee diet at Budongo. Samples obtained from Mahale Mountains National Park and Gombe National Park, both in Tanzania, show similar mineral distribution across sources. We suggest three distinct but related mechanisms by which minerals may come to be concentrated in the above‐mentioned sources, serving as potentially important sources of essential minerals in the chimpanzee diet.PostprintPeer reviewe

Modeling Initiation of Ewing Sarcoma in Human Neural Crest Cells

Ewing sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC) and/or neural crest (NCSC) stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC). Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC) progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

After jail scandal, spotlight on growing role of women officers

The 19-year-old felt sick to her stomach when she stepped into the Baltimore prison once nicknamed Supermax for her first day of work as a corrections officer. The place was dark and dingy, and she had never been around so many men before

After jail scandal, spotlight on growing role of women officers

The 19-year-old felt sick to her stomach when she stepped into the Baltimore prison once nicknamed Supermax for her first day of work as a corrections officer. The place was dark and dingy, and she had never been around so many men before

A unified model for soil shrinkage, subsidence, and cracking

Many clayey soils shrink as they dry, causing a shift of porosity from inside to outside the soil aggregates and leading to the formation of shrinkage cracks and/or surface subsidence. During swelling, shrinkage cracks begin to seal and/or the soil surface rises. Previous models have focused on describing shrinkage at the aggregate level, with little success in predicting soil cracking and subsidence. To remedy this shortcoming, we provide a unified, physically based set of governing equations for these three pore domains (aggregates, cracks, and subsidence) and predict the porosity distribution among domains as a function of soil water content and minimal (up to six) additional parameters. Examples collected from a variety of soils show how these functions describe shrinkage of soil samples in the laboratory; quantify the relationships among soil suction, soil shrinkage, and water content using the same set of parameters; and predict sealing of soil cracks in the field. This approach provides the framework for accurate and unified hydromechanical modeling of swelling soils

Prima segnalazione di Klebsiella pneumoniae produttrice di KPC nell'area di Trieste.

Introduzione Una delle emergenze nell'ambito della terapia antibiotica \ue8 rappresentata dall'aumento di Enterobacteriaceae resistenti ai carbapenemi. Questa \ue8 dovuta all'espressione di geni che codificano per enzimi definiti carbapenemasi. La diffusione di ceppi resistenti \ue8 un problema epidemiologico attuale nei confronti del quale i Laboratori di Microbiologia sono tenuti alla sorveglianza. Metodi Nel maggio 2012 \ue8 stata ricoverata presso il Reparto di Oncoematologia del nostro Istituto una paziente di 3 anni, proveniente dal Venezuela, sottoposta a trapianto di midollo osseo. Dal tampone rettale di sorveglianza \ue8 stata isolata una Klebsiella pneumoniae resistente ai carbapenemi che ha richiesto ulteriori accertamenti: sono state confermate le MIC per i carbapenemi mediante Etest ; effettuati i test fenotipici (test di sinergia con inibitori delle carbapenemasi, test NP); il ceppo \ue8 stato sottoposto a PCR con primers specifici per le principali carbapenemasi. Un successivo campione per emocoltura inviatoci per l'insorgere di una sepsi \ue8 risultato positivo per Klebsiella pneumoniae resistente ai carbapenemi; il ceppo \ue8 stato sottoposto agli stessi test fenotipici e molecolari. Si \ue8 proceduto ad uno screening dei pazienti del Reparto di Oncoematologia mediante tampone rettale, con semina su agar McKonkey con dischetto di meropenem, per verificare che il ceppo non fosse presente e circolante. Risultati I test fenotipici sui ceppi isolati da tampone e da emocoltura hanno indicato che la resistenza ai carbapenemi fosse dovuta alla presenza di una KPC (test di sinergia con a.boronico positivo); il risultato \ue8 stato confermato dalla positivit\ue0 della PCR per il gene blaKPC. Lo screening sugli altri pazienti ricoverati ha dato esito negativo. Conclusioni Questa, a nostra conoscenza, \ue8 la prima segnalazione di Klebsiella pneumoniae produttrice di KPC in provincia di Trieste, verosimilmente di importazione in paziente proveniente dal Venezuela. Il microrganismo non si \ue8 diffuso ulteriormente, anche grazie alla tempestiva segnalazione ed alle misure di contenimento