Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis.

During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles.

Zika virus remodels and hijacks IGF2BP2 ribonucleoprotein complex to promote viral replication organelle biogenesis.

Zika virus (ZIKV) infection causes significant human disease that, with no approved treatment or vaccine, constitutes a major public health concern. Its life cycle entirely relies on the cytoplasmic fate of the viral RNA genome (vRNA) through a fine-tuned equilibrium between vRNA translation, replication, and packaging into new virions, all within virus-induced replication organelles (vROs). In this study, with an RNA interference (RNAi) mini-screening and subsequent functional characterization, we have identified insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a new host dependency factor that regulates vRNA synthesis.

Non-Innocent Role of Sacrificial Anodes in Electrochemical Nickel-Catalyzed C(sp)-C(sp) Cross-Electrophile Coupling.

Sacrificial anodes composed of inexpensive metals such as Zn, Fe, and Mg are widely used to support electrochemical nickel-catalyzed cross-electrophile coupling (XEC) reactions, in addition to other reductive electrochemical transformations. Such anodes are appealing because they provide a stable counter-electrode potential and typically avoid interference with the reductive chemistry. The present study outlines the development of an electrochemical Ni-catalyzed XEC reaction that streamlines access to a key pharmaceutical intermediate.

Investigating in vivo force and work production of rat medial gastrocnemius at varying locomotor speeds using a muscle avatar.

Traditional work loop studies, that use sinusoidal length trajectories with constant frequencies, lack the complexities of in vivo muscle mechanics observed in modern studies. This study refines methodology of the 'avatar' method (a modified work loop) to infer in vivo muscle mechanics using ex vivo experiments with mouse extensor digitorum longus (EDL) muscles. The 'avatar' method involves using EDL muscles to replicate in vivo time-varying force, as demonstrated by previous studies focusing on guinea fowl lateral gastrocnemius (LG).

"Avatar", a Modified Ex vivo Work Loop Experiments Using In vivo Strain and Activation.

Movement behaviors are emergent features of dynamic systems that result from muscle force production and work output. The interplay between neural and mechanical systems occurs at all levels of biological organization concurrently, from the tuning of leg muscle properties while running to the dynamics of the limbs interacting with the ground. Understanding the conditions under which animals shift their neural control strategies toward intrinsic muscle mechanics ('preflexes') in the control hierarchy would allow muscle models to predict in vivo muscle force and work more accurately.

Understanding muscle function during perturbed in vivo locomotion using a muscle avatar approach.

The work loop technique has provided key insights into in vivo muscle work and power during steady locomotion. However, for many animals and muscles, ex vivo experiments are not feasible. In addition, purely sinusoidal strain trajectories lack variations in strain rate that result from variable loading during locomotion.

A Process Chemistry Benchmark for sp-sp Cross Couplings.

As sp-sp disconnections gain acceptance in the medicinal chemist's toolbox, an increasing number of potential drug candidates containing this motif are moving into the pharmaceutical development pipeline. This raises a new set of questions and challenges around the novel, direct methodologies available for forging these bonds. These questions gain further importance in the context of process chemistry, where the focus is the development of scalable processes that enable the large-scale delivery of clinical supplies.

Total Synthesis and Computational Investigations of Sesquiterpene-Tropolones Ameliorate Stereochemical Inconsistencies and Resolve an Ambiguous Biosynthetic Relationship.

The sesquiterpene-tropolones belong to a distinctive structural class of meroterpene natural products with impressive biological activities, including anticancer, antifungal, antimalarial, and antibacterial. In this article, we describe a concise, modular, and cycloaddition-based approach to a series of sesquiterpene mono- and bistropolones, including (-)-epolone B, (+)-isoepolone B, (±)-dehydroxypycnidione, and (-)-10--pycnidione. Alongside the development of a general strategy to access this unique family of metabolites were computational modeling studies that justified the diastereoselectivity observed during key cycloadditions.

Experimental evidence of a cyclopropylcarbinyl conjugative electronic effect.

Bicyclo[3.2.0]hept-2-enes undergo thermal rearrangement to norbornenes via diradical transition structures.

Integrated approaches to improve birth outcomes: perinatal periods of risk, infant mortality review, and the Los Angeles Mommy and Baby Project.

This article provides an example of how Perinatal Periods of Risk (PPOR) can provide a framework and offer analytic methods that move communities to productive action to address infant mortality. Between 1999 and 2002, the infant mortality rate in the Antelope Valley region of Los Angeles County increased from 5.0 to 10.

Commercial sex venues: a closer look at their impact on the syphilis and HIV epidemics among men who have sex with men.

Objective: To provide insight into the role of commercial sex venues in the spread of syphilis and HIV among men who have sex with men (MSM).

Study: A cross sectional study of 1351 MSM who were diagnosed with early syphilis who did and did not encounter sexual partners at commercial sex venues.

Results: Overall, 26% MSM diagnosed with syphilis had sexual encounters at commercial sex venues.

Attempted isolation of Blastomyces dermatitidis from native shrews in northern Wisconsin, USA.

The precise ecological niche of Blastomyces dermatitidis is unknown. The related dimorphic fungus, Paracoccidioides brasiliensis, has been isolated from South American ground-dwelling insectivorous armadillos. We attempted to isolate Blastomyces from shrews, North American ground-dwelling insectivores that have been shown to harbor Histoplasma capsulatum in endemic areas.

Correlates of Internet use to meet sex partners among men who have sex with men diagnosed with early syphilis in Los Angeles County.

Objective: The objective of this study was to evaluate use of the Internet to solicit sex partners by men who have sex with men (MSM) who were diagnosed with early syphilis infection.

Study: Field interview records for syphilis patients were reviewed for factors associated with Internet use.

Results: Internet users were more likely to be of white race (prevalence ratio [PR], 1.

Use of stents to treat kinks causing obstruction in a left internal mammary artery graft.

Left internal mammary arteries (LIMA) are used routinely as grafts to the left anterior descending coronary artery (LAD) in selected patients undergoing coronary artery bypass graft (CABG) surgery because of better long-term patency rates. Pathology other than fibrointimal hyperplasia, accelerated atherosclerosis, or thrombus can sometimes cause obstructive lesions in such grafts. This report illustrates a kink in a LIMA graft to the LAD causing an obstructive lesion shortly after surgery and describes the subsequent management of this lesion with intracoronary stents.

Detachment of transluminal extraction catheter cutter head from shaft and successful retrieval.

Transluminal extraction catheter atherectomy has been shown to be a clinically effective interventional technique for the treatment of thrombotic degenerative saphenous vein bypass grafts. We will report the first case of detachment of transluminal extraction catheter cutter head from the shaft and its successful retrieval during a saphenous vein bypass graft intervention.

The role of psychological factors in cancer onset and progression.

Psychological factors have been presumed to play a role in cancer initiation and progression. This article critically reviews the literature on cancer and its potential connections to affective states, coping/defensive styles and personality traits, behaviors, and stressful life events. Much of the existing research is flawed by poor study design and analysis that have limited the reliability and validity of both negative and positive studies.