HUNK Phosphorylates Rubicon to Support Autophagy

Background: Autophagy is a catabolic cellular recycling pathway that is essential for maintaining intracellular homeostasis. Autophagosome formation is achieved via the coordination of the Beclin-1 protein complex. Rubicon is a Beclin-1 associated protein that suppresses autophagy by impairing the activity of the class III PI3K, Vps34. However, very little is known about the molecular mechanisms that regulate Rubicon function. Methods: In this study, co-immunoprecipitation and kinase assays were used to investigate the ability of Hormonally Upregulated Neu-associated Kinase (HUNK) to bind to and phosphorylate Rubicon. LC3B was monitored by immunofluorescence and immunoblotting to determine whether phosphorylation of Rubicon by HUNK controls the autophagy suppressive function of Rubicon. Results: Findings from this study identify Rubicon as a novel substrate of HUNK and show that phosphorylation of Rubicon inhibits its function, promoting autophagy

Double Balloon Cervical Ripening Catheter for Control of Massive Hemorrhage in a Cervical Ectopic Pregnancy

Cervical pregnancy can be complicated by perfuse vaginal bleeding. Mechanical compression directed at tamponing the cervical vessels can control hemostasis. There are several types of balloon catheters that have been described for cervical compression. However use of a double balloon catheter is a novel approach for cervical tamponade, as one balloon is positioned below the external cervical os and the second balloon is situated above in the internal cervical os. This compresses the cervix from internal os to external os between the two balloons, forming a cervical sandwich. We describe this method of cervical tamponade using a silicone double balloon cervical ripening catheter that rapidly controlled hemorrhage in a patient that failed conservative management with methotrexate

Smartphone-based pathogen diagnosis in urinary sepsis patients.

BackgroundThere is an urgent need for rapid, sensitive, and affordable diagnostics for microbial infections at the point-of-care. Although a number of innovative systems have been reported that transform mobile phones into potential diagnostic tools, the translational challenge to clinical diagnostics remains a significant hurdle to overcome.MethodsA smartphone-based real-time loop-mediated isothermal amplification (smaRT-LAMP) system was developed for pathogen ID in urinary sepsis patients. The free, custom-built mobile phone app allows the phone to serve as a stand-alone device for quantitative diagnostics, allowing the determination of genome copy-number of bacterial pathogens in real time.FindingsA head-to-head comparative bacterial analysis of urine from sepsis patients revealed that the performance of smaRT-LAMP matched that of clinical diagnostics at the admitting hospital in a fraction of the time (~1 h vs. 18-28 h). Among patients with bacteremic complications of their urinary sepsis, pathogen ID from the urine matched that from the blood - potentially allowing pathogen diagnosis shortly after hospital admission. Additionally, smaRT-LAMP did not exhibit false positives in sepsis patients with clinically negative urine cultures.InterpretationThe smaRT-LAMP system is effective against diverse Gram-negative and -positive pathogens and biological specimens, costs less than $100 US to fabricate (in addition to the smartphone), and is configurable for the simultaneous detection of multiple pathogens. SmaRT-LAMP thus offers the potential to deliver rapid diagnosis and treatment of urinary tract infections and urinary sepsis with a simple test that can be performed at low cost at the point-of-care. FUND: National Institutes of Health, Chan-Zuckerberg Biohub, Bill and Melinda Gates Foundation

Human genetics and genomics research in Ecuador: historical survey, current state, and future directions

Background: In South America, the history of human genetics is extensive and its beginnings go back to the onset of the twentieth century. In Ecuador, the historical record of human genetics and genomics research is limited. In this context, our work analyzes the current status and historical panorama of these fields, based on bibliographic searches in Scopus, Google Scholar, PubMed, and Web of Science. Results: Our results determined that the oldest paper in human genetics coauthored by an Ecuadorian institution originates from the Central University of Ecuador in 1978. From a historical standpoint, the number of articles has increased since the 1990s. This growth has intensified and it is reflected in 137 manuscripts recorded from 2010 to 2019. Areas such as human population genetics, phylogeography, and forensic sciences are the core of genetics and genomics-associated research in Ecuador. Important advances have been made in the understanding of the bases of cancer, some genetic diseases, and congenital disorders. Fields such as pharmacogenetics and pharmacogenomics have begun to be explored during the last years. Conclusions: This work paints a comprehensive picture and provides additional insights into the future panorama of human genetic and genomic research in Ecuador as an example of an emerging, resource-limited country with interesting phylogeographic characteristics and public health implications

Trade-off and adaptive cost in a multiple-resistant strain of the invasive potato tuber moth Tecia solanivora

EntomologiaResistance to pesticides is an evolutionary process that entails, in most cases, substantial consequences to the biology of the resistant populations. In this study we focus on the life history traits of the potato tuber moth Tecia solanivora, an invasive and voracious pest for which resistance to pyrethroid insecticides was recently reported. Marginally resistant and multiple‐resistant populations were selected from eight sampled localities in Colombia; the use of a fully susceptible population was not possible since none was recognized in the laboratory or field. The multiple‐resistant Siachoque population exhibited a 42‐fold resistance to the carbamate insecticide carbofuran, and low levels of resistance to chlorpyrifos, a trend observed in six of the eight tested populations. This population also exhibits 24‐fold resistance to permethrin. The marginally resistant population of Gualmatán showed 4‐fold resistance to chlorpyrifos. The multiple-resistant population exhibited a 3.8-day shorter developmental time than the susceptible population, but with higher larval mortality. The peak of egg-laying was delayed in the resistant population in 9 days and the population growth rate was lower than that of the susceptible population.We hypothesize that the short developmental time of the multiple-resistant population may be an adaptation to minimize exposure to insecticides, which are applied to the soil. This adaptation is likely to require the surviving adults to compensate for the smaller nutrient amounts accumulated by the larvae in investing part of its adult life in securing the necessary resources for late-life egg production

Ingestión de lípidos oxidados: efecto sobre actividad enzimática antioxidativa en trucha arcoiris Oncorhynchus mykiss (Walbaum)

RESUMEN Objetivo. Evaluar el efecto de la ingestión de lípidos durante períodos cortos (20 días) ylargos (90 días) sobre la actividad hepática y en tracto gastrointestinal (TGI) de las enzimascatalasa (CAT), superóxido dismutasa (SOD) y glutatión peroxidasa (GPx). Materiales ymétodos. Se utilizó el Índice peróxidos (VP) y el índice anisidina (VA) para detectar lapresencia de productos de la oxidación en las raciones. Se realizó un análisis de varianzabajo un modelo de parcelas divididas en el tiempo. Cuando se encontraron diferencias(p<0.05) las medias fueron comparadas mediante la prueba de Tukey (5%). Resultados.Las raciones presentaron altos niveles de oxidación durante todo el experimento y hubodiferencias significativas entre tratamientos. La actividad SOD presentó niveles decrecientesa nivel hepático durante los dos períodos de exposición, sin embargo, en TGI se generóun incremento significativo de actividad SOD (175%) en individuos sometidos a todoslos tratamientos. La actividad CAT presentó un alto nivel de correlación con la actividadSOD en todos los períodos de exposición y órganos. La actividad GPx presentó diferenciassignificativas para los dos períodos de exposición en hígado y al día 90 en TGI, indicandoalta sensibilidad de la enzima ante la ingestión de peróxidos. Conclusiones. La actividadGPx en TGI mostró coeficientes de correlación superiores a 0.95, sugiriendo que es buenindicador del estado oxidativo de las raciones

Path Integral Quantization of Generalized Quantum Electrodynamics

In this paper, a complete covariant quantization of generalized electrodynamics is shown through the path integral approach. To this goal, we first studied the hamiltonian structure of system following Dirac's methodology and, then, we followed the Faddeev-Senjanovic procedure to obtain the transition amplitude. The complete propagators (Schwinger-Dyson-Fradkin equations) of the correct gauge fixation and the generalized Ward-Fradkin-Takahashi identities are also obtained. Afterwards, an explicit calculation of one-loop approximation of all Green's functions and a discussion about the obtained results are presented.Comment: 25 pages, 5 figure