African green monkey kidney Vero cells require de novo protein synthesis for efficient herpes simplex virus 1-dependent apoptosis

AbstractDuring HSV-1 infection, IE gene expression triggers apoptosis, but subsequent synthesis of infected cell proteins blocks apoptotic death from ensuing. This “HSV-1-dependent” apoptosis was identified in HEp-2/HeLa cells infected with wild-type HSV-1 in the presence of an inhibitor of protein synthesis or a virus lacking ICP27 {HSV-1(vBSΔ27)}. Unlike HEp-2/HeLa cells, vBSΔ27-infected Vero cells fail to exhibit dramatic apoptotic morphologies at times prior to 24 hpi. Here, we examined the basis of these different apoptotic responses to HSV-1. We found that infected Vero cells take substantially longer than HEp-2/HeLa cells to display membrane blebbing, chromatin condensation, DNA laddering, and PARP cleavage. Vero, but not HEp-2/HeLa, cells required de novo protein synthesis to exhibit efficient HSV-1-dependent apoptosis, which included changes in mitochondrial membrane potential, and these factors were produced prior to 3 hpi. Vero cells infected with recombinant viruses devoid of the ICP27 and ICP4 proteins alone or both the ICP27 and ICP22 proteins were apoptotic. These results indicate a requirement for cellular or other viral protein synthesis in Vero cells and provide insight into cell type differences in HSV-1-dependent apoptosis

Alteration of rumen bacteria and protozoa through grazing regime as a tool to enhance the bioactive fatty acid content of bovine milk

Rumen microorganisms are the origin of many bioactive fatty acids (FA) found in ruminant-derived food products. Differences in plant leaf anatomy and chemical composition between cool- and warm-season pastures may alter rumen microorganisms, potentially enhancing the quantity/profile of bioactive FA available for incorporation into milk. The objective of this study was to identify rumen bacteria and protozoa and their cellular FA when cows grazed a warm-season annual, pearl millet (PM), in comparison to a diverse cool-season pasture (CSP). Individual rumen digesta samples were obtained from five Holstein cows in a repeated measures design with 28-day periods. The treatment sequence was PM, CSP, then PM. Microbial DNA was extracted from rumen digesta and sequence reads were produced with Illumina MiSeq. Fatty acids (FA) were identified in rumen bacteria and protozoa using gas-liquid chromatography/mass spectroscopy. Microbial communities shifted in response to grazing regime. Bacteria of the phylum Bacteroidetes were more abundant during PM than CSP (P \u3c 0.05), while protozoa of the genus Eudiplodinium were more abundant during CSP than PM (P \u3c 0.05). Microbial cellular FA profiles differed between treatments. Bacteria and protozoa from cows grazing CSP contained more n-3 FA (P \u3c 0.001) and vaccenic acid (P \u3c 0.01), but lower proportions of branched-chain FA (P \u3c 0.05). Microbial FA correlated with microbial taxa and levels of vaccenic acid, rumenic acid, and a-linolenic acid in milk. In conclusion, grazing regime can potentially be used to alter microbial communities shifting the FA profile of microbial cells, and subsequently, alter the milk FA profile

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

Methods for colloid transport visualization in pore networks

Prediction of colloid transport in the subsurface is relevant to researchers in a variety of fields such as contaminant transport, wastewater treatment, and bioremediation. Investigations have traditionally relied on column studies whereby mechanistic inferences must be drawn on the basis of colloid behavior at the outlet. Over the past decade, development of noninvasive visualization techniques based on visible light, magnetic resonance, and X rays have provided insight into a number of colloid transport mechanisms by enabling direct observation of individual colloids at the pore scale and colloid concentrations at longer length scales. As research focus shifts from transport of ideal colloids in ideal media such as glass beads to natural colloids in natural porous media, these noninvasive techniques will become increasingly useful for studying the collection of mechanisms at work in heterogeneous pore systems. It is useful at this juncture to review recent progress in colloid transport visualization as a starting point for further development of visualization tools to support investigation of colloids in natural systems. We briefly discuss characteristics of visualization systems currently used to study colloid transport in porous media and review representative microscale and mesoscale visualization studies conducted over the past decade, with additional attention given to two optical visualization systems being developed by the authors.Keywords: Review, Methods, Colloids, Visualization, Porous medi

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

The Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) Collaborative Quality Improvement Initiative in Percutaneous Coronary Interventions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72388/1/j.1540-8183.2002.tb01071.x.pd