C-reactive protein across the menstrual cycle

C-reactive protein (CRP) is a widely used, sensitive biomarker of inflammation. Studies conducted among users of exogenous hormones suggest that estrogen increases CRP, whereas progesterone decreases CRP. Examinations of CRP in normally cycling women suggest the opposite: CRP is negatively associated with endogenous estrogen and positively associated with endogenous progesterone. This work evaluates the association between menstrual cycle-related hormone changes and events (menstruation and ovulation) and CRP. Eight female subjects gave urine and blood samples from twelve days across the menstrual cycle, for a total of eleven cycles. Blood samples were assayed for CRP; urine samples for beta-follicle stimulating hormone (betaFSH), pregnanediol 3-glucuronide (PDG), and estrone glucuronide (E1G). Ovulation day was estimated using hormone levels. Presence or absence of menses was reported by subjects. Analyses were conducted with random-effects linear regression. All cycles were ovulatory; day of ovulation was identified for nine cycles. A ten-fold increase in progesterone was associated with a 23% increase in CRP (P = 0.01), a ten-fold increase in estrogen was associated with a 29% decrease in CRP (P = 0.05), and menses was associated with a 17% increase in CRP (P = 0.18); no association between ovulation or FSH and CRP was found. Hormone changes across the menstrual cycle should be controlled for in future studies of inflammation in reproductive-age women.     

Reduction of N2 by Fe2+ via Homogeneous and Heterogeneous Reactions

Because of their high kinetic barrier and thermodynamic favorability under moderately reducing atmospheric composition photochemical approaches appear to be ideally suited to the direct reduction of solvated nitrogen gas. Ferrous iron has been investigated as an electron donor, as it has a highly tunable redox character and is environmentally ubiquitous. Recent advances in mineralogy connected to the field of environmental remediation have led to the identification of an important class of rusts which have reductive potentials comparable to Fe(0). These materials possess redox couples that are, potentially, capable of overcoming the kinetic barrier to the production of NH₃. In this study, we attempted to produce ammonia from N₂ by oxidizing white rust both photochemically and in a dark reaction. All results indicated the reaction was inhibited by competing reactions; primarily the reduction of H₂O to H₂. However, the dark reactions showed limited potential for reduction up to 1.4 mM. As a result, we turned to the question of closure temperature; the minimum temperature of rapid reaction based on a choice of reductant, which we demonstrate a model for its estimation. Due to the high thermodynamic energy of the intermediate, we conclude that aqueous photochemical reduction under the conditions studied here is an unlikely prebiotic source for reactive, i.e. reduced, nitrogen.     

Effects of relative humidity and spraying medium on UV decontamination of filters loaded with viral aerosols

Although respirators and filters are designed to prevent the spread of pathogenic aerosols, a stockpile shortage is anticipated during the next flu pandemic. Contact transfer and reaerosolization of collected microbes from used respirators are also a concern. An option to address these potential problems is UV irradiation, which inactivates microbes by dimerizing thymine/uracil in nucleic acids. The objective of this study was to determine the effects of transmission mode and environmental conditions on decontamination efficiency by UV. In this study, filters were contaminated by different transmission pathways (droplet and aerosol) using three spraying media (deionized water [DI], beef extract [BE], and artificial saliva [AS]) under different humidity levels (30% [low relative humidity {LRH}], 60% [MRH], and 90% [HRH]). UV irradiation at constant intensity was applied for two time intervals at each relative humidity condition. The highest inactivation efficiency (IE), around 5.8 logs, was seen for DI aerosols containing MS2 on filters at LRH after applying a UV intensity of 1.0 mW/cm(2) for 30 min. The IE of droplets containing MS2 was lower than that of aerosols containing MS2. Absorption of UV by high water content and shielding of viruses near the center of the aggregate are considered responsible for this trend. Across the different media, IEs in AS and in BE were much lower than in DI for both aerosol and droplet transmission, indicating that solids present in AS and BE exhibited a protective effect. For particles sprayed in a protective medium, RH is not a significant parameter.     

High throughput engineering to revitalize a vestigial electron transfer pathway in bacterial photosynthetic reaction centers

Photosynthetic reaction centers convert light energy into chemical energy in a series of transmembrane electron transfer reactions, each with near 100% yield. The structures of reaction centers reveal two symmetry-related branches of cofactors (denoted A and B) that are functionally asymmetric; purple bacterial reaction centers use the A pathway exclusively. Previously, site-specific mutagenesis has yielded reaction centers capable of transmembrane charge separation solely via the B branch cofactors, but the best overall electron transfer yields are still low. In an attempt to better realize the architectural and energetic factors that underlie the directionality and yields of electron transfer, sites within the protein-cofactor complex were targeted in a directed molecular evolution strategy that implements streamlined mutagenesis and high throughput spectroscopic screening. The polycistronic approach enables efficient construction and expression of a large number of variants of a heteroligomeric complex that has two intimately regulated subunits with high sequence similarity, common features of many prokaryotic and eukaryotic transmembrane protein assemblies. The strategy has succeeded in the discovery of several mutant reaction centers with increased efficiency of the B pathway; they carry multiple substitutions that have not been explored or linked using traditional approaches. This work expands our understanding of the structure-function relationships that dictate the efficiency of biological energy-conversion reactions, concepts that will aid the design of bio-inspired assemblies capable of both efficient charge separation and charge stabilization.     

MicroRNA-Mediated Suppression of the TGF-β Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance

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Multiple, non-allelic, intein-coding sequences in eukaryotic RNA polymerase genes

Background  

Inteins are self-splicing protein elements. They are translated as inserts within host proteins that excise themselves and ligate the flanking portions of the host protein (exteins) with a peptide bond. They are encoded as in-frame insertions within the genes for the host proteins. Inteins are found in all three domains of life and in viruses, but have a very sporadic distribution. Only a small number of intein coding sequences have been identified in eukaryotic nuclear genes, and all of these are from ascomycete or basidiomycete fungi.