Vaginal microbiome-hormonal contraceptive interactions associate with the mucosal proteome and HIV acquisition

Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24–11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44–2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.     

Deciphering role of technical bioprocess parameters for bioethanol production using microalgae

Microalgae biomass is considered an important feedstock for biofuels and other bioactive compounds due to its faster growth rate, high biomass production and high biomolecules accumulation over first and second-generation feedstock. This research aimed to maximize the specific growth rate of fresh water green microalgae Closteriopsis acicularis, a member of family Chlorellaceae under the effect of pH and phosphate concentration to attain enhanced biomass productivity. This study investigates the individual and cumulative effect of phosphate concentration and pH on specific growth characteristics of Closteriopsis acicularis in autotrophic mode of cultivation for bioethanol production. Central-Composite Design (CCD) strategy and Response Surface Methodology (RSM) was used for the optimization of microalga growth and ethanol production under laboratory conditions. The results showed that high specific growth rate and biomass productivity of 0.342 day⁻¹ and 0.497 g L⁻¹ day⁻¹ respectively, were achieved at high concentration of phosphate (0.115 g L⁻¹) and pH (9) at 21st day of cultivation. The elemental composition of optimized biomass has shown enhanced elemental accumulation of certain macro (C, O, P) and micronutrients (Na, Mg, Al, K, Ca and Fe) except for nitrogen and sulfur. The Fourier transform infrared spectroscopic analysis has revealed spectral peaks and high absorbance in spectral range of carbohydrates, lipids and proteins, in optimized biomass. The carbohydrates content of optimized biomass was observed as 58%, with 29.3 g L⁻¹ of fermentable sugars after acid catalyzed saccharification. The bioethanol yield was estimated as 51 % g ethanol/g glucose with maximum of 14.9 g/L of bioethanol production. In conclusion, it can be inferred that high specific growth rate and biomass productivity can be achieved by varying levels of phosphate concentration and pH during cultivation of Closteriopsis acicularis for improved yield of microbial growth, biomass and bioethanol production.     

Optimization of the demineralization process for the extraction of chitin from Omani Portunidae segnis

Chitin is an organic polymer and it is the most frequent marine natural polysaccharide after cellulose. The main natural sources of chitin are exoskeletons of insects, mollusks, the cell walls of certain fungi and crustaceans such as crabs, shrimps and lobsters. The waste of these marine exoskeletons are pollutant for the environment, but these waste raw materials could be useful for production of commercial products like chitin. Chitin is an important raw material used for water treatment, agricultural, biomedical, biotechnological purposes, food and paper industry and cosmetics. Based on the variety of importance, the present targets of this study are to optimize the demineralization process for the removal of calcium and phosphate contents from the waste of Portunidae segnis (P. segnis) by using acid at ambient temperature and to characterize the isolated demineralized sample as well as the percentage of remaining calcium and phosphorus contents by using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). The prepared waste carbs coarse powder samples of P. segnis were demineralized with seven different concentrations of hydrochloric acid at ambient temperature for 1 h. All the demineralization samples by the different concentrations were analyzed by using sensitive ICP-OES. The results based on ICP-OES showed that among the seven different concentrations used in the demineralization process for the isolation of chitin, the best was 2 M of HCl concentration for the production of chitin. The results also showed that the optimized concentration 2 M HCl gave the minimum concentration of calcium and phosphorus compared to other concentrations applied in this experiment. In conclusion, the optimized concentration for demineralization process could be used commercially for the isolation or commercial production of chitin for agricultural, biomedical and biotechnological purposes.     

Rings and ribbons in protein structures: Characterization using helical parameters and Ramachandran plots for repeating dipeptides

Helical parameters displayed on a Ramachandran plot allow peptide structures with successive residues having identical main chain conformations to be studied. We investigate repeating dipeptide main chain conformations and present Ramachandran plots encompassing the range of possible structures. Repeating dipeptides fall into the categories: rings, ribbons, and helices. Partial rings occur in the form of “nests” and “catgrips”; many nests are bridged by an oxygen atom hydrogen bonding to the main chain NH groups of alternate residues, an interaction optimized by the ring structure of the nest. A novel recurring feature is identified that we name unpleated β, often situated at the ends of a β‐sheet strand. Some are partial rings causing the polypeptide to curve gently away from the sheet; some are straight. They lack β‐pleat and almost all incorporate a glycine. An example is the first glycine in the GxxxxGK motif of P‐loop proteins. Ribbons in repeating dipeptides can be either flat, as seen in repeated type II and type II′ β‐turns, or twisted, as in multiple type I and type I′ β‐turns. Hexa‐ and octa‐peptides in such twisted ribbons occur frequently in proteins, predominantly with type I β‐turns, and are the same as the “β‐bend ribbons” hitherto identified only in short peptides. One is seen in the GTPase‐activating protein for Rho in the active, but not the inactive, form of the enzyme. It forms a β‐bend ribbon, which incorporates the catalytic arginine, allowing its side chain guanidino group to approach the active site and enhance enzyme activity. Proteins 2014; 82:230–239. © 2013 Wiley Periodicals, Inc.     

Tumor-associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma

Background

A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC.

Methodology/Principal Findings

Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a “microglia-like” appearance on these cells which we termed “Ramified TAMs” (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells.

Conclusion

ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined.     

Ribosome biogenesis is temperature‐dependent and delayed in Escherichia coli lacking the chaperones DnaK or DnaJ†

In Escherichia coli strains carrying null mutations in either the dnaK or dnaJ genes, the late stages of 30S and 50S ribosomal subunit biogenesis are slowed down in a temperature‐dependent manner. At high temperature (44°C), 32S and 45S particles (precursors to 50S subunits) and 21S particles (precursors to 30S subunits) accumulate. The latter are shown by 3′5′ rapid amplification of cDNA ends analysis to contain unprocessed or partially processed 16S ribosomal RNA at the 5′ end, but the 3′ end was never processed. This implies that maturation of 16S ribosomal RNA starts at the 5′‐terminus, and that the 3′‐terminus is only trimmed at a later step. At normal temperatures (30°C?37°C), ribosome assembly in both mutants is not arrested but is significantly delayed, as shown by pulse‐chase analysis. Assembly defects are partially compensated by an overexpression of other heat‐shock proteins, which occurs in the absence of their negative regulator DnaK, or by a plasmid‐driven overexpression of GroES/GroEL, suggesting the involvement of a network of chaperones in ribosome biogenesis.     

Identification of an endocrine disrupting agent from corn with mitogenic activity

A mitogenic agent in corncob bedding and fresh corn products disrupts sexual behavior and estrous cyclicity in rats. The mitogenic activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid. Synthetic THF-diols stimulated breast cancer cell proliferation in vitro and disrupted the estrous cycle in female rats at oral doses of approximately 0.30 mg/kg body weight/day. Exposure to THF-diols may disrupt endocrine function in experimental animals at doses approximately 200 times lower than classical phytoestrogens, promote proliferation of breast or prostate cancer, and adversely affect human health.     

Oxidative stress in cystic fibrosis patients with Burkholderia cenocepacia airway colonization: relation of 8-isoprostane concentration in exhaled breath condensate to lung function decline

The association between oxidative stress and neutrophilic inflammation in cystic fibrosis (CF) lung disease is well recognized. 8-Isoprostane is a product of non-enzymatic oxidation of arachidonic acid. The aim of the present study was to examine the relationship between lung function decline and 8-isoprostane concentrations in exhaled breath condensate (EBC) in CF patients with Burkholderia cenocepacia airway colonization. Concentrations of 8-isoprostane in EBC were measured in 24 stable CF patients with B. cenocepacia airway colonization. The median (interquartile range) age of the cohort was 23.9 (22.0; 26.6) years. All patients underwent clinical examinations and pulmonary function tests at the time of EBC collection and in 1-, 3-, and 5-year intervals. 8-Isoprostane concentrations in EBC correlated to 1- and 3-year declines of forced expiratory volume in 1 s (FEV₁) with r _S values of ?0.511 (p?=?0.0011) and ?0.495 (p?=?0.016), respectively. In multiple regression analysis, 8-isoprostane concentrations in EBC were the only independent predictor for 1-year FEV₁ decline (p?=?0.01). When the median value of 8-isoprostane concentration in EBC (10.0 pg/mL) was used as a cutoff, subgroups of patients with lower and higher level of oxidative stress had significantly different median (interquartile range) FEV₁ declines in 1-year interval, ?2.4 % (?5.3; 0.8) and ?7.3 % (?10.3; ?5.8) predicted (p?=?0.009). In conclusion, 8-isoprostane concentrations in EBC correlated to short-term lung function decline in CF patients with B. cenocepacia airway colonization. This correlation reflects the role of oxidative stress in CF lung pathogenesis and contributes to prediction of prognosis in these patients.     

Estimates of economic values for traits of Arabic sheep in village system

A deterministic bio-economic model was used to estimate the economic values of different traits in Arabic sheep native to the Khuzestan province of Iran. In the studied system, variable costs accounted for about 98.5% of the total costs and among variable costs, feed costs had the highest proportion with 70.7%. Revenue sources included meat, wool, and manure, where meat was the most important one and formed 95.5% of total revenues. Economic value for a trait was estimated as the amount of change in the profit of system as its mean increased by one unit, while the means of other traits were constant. The most important trait in this system was litter size, followed by ewe survival, dressing percentage, and wool weight, respectively. Birth weight had a negative economic value but weight at older ages especially weaning weight and 12-month weight had positive economic values. The sensitivity of economic values of traits was investigated by changing feed and non-feed costs, meat and wool prices by ±10%. Results showed that economic values for dressing percentage and wool weight are not sensitive to change in costs. In addition, changes in marketing and management costs had no effect on the economic value for traits related to body weight in different ages. In general, the economic value for traits which showed sensitivity to the changes of costs, except ewe survival, decreased due to an increase in costs. The economic value for all traits, except birth and wool weight, changed because of a change in meat price. Increasing meat price meant a higher economic importance. Among different factors, meat price fluctuations had the most effect on the economic value of traits.