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.     

The Effect of Lubricants on Powder Flowability for Pharmaceutical Application

Pharmaceutical tablets are manufactured through a series of batch steps finishing with compression into a form using a tablet press. Lubricants are added to the powder mixture prior to the tabletting step to ensure that the tablet is ejected properly from the press. The addition of lubricants also affects tablet properties and can affect the behavior of the powder mixture. The objective of this research was to investigate the effect of lubricants on powder flowability as flowability into the tablet press is critical. Four lubricants (magnesium stearate, magnesium silicate, stearic acid, and calcium stearate) were mixed, in varying amounts, with spray-dried lactose. In addition, magnesium stearate was also mixed with placebo granules from a high-shear granulator. Measurements based on avalanche behavior indicated flowability potential and dynamic density and were more sensitive to changes in the mixture and provided a more accurate and reproducible indication of flowability than traditional static measurements. Of the tested lubricants, magnesium stearate provided the best increase in flowability even in the low amounts commonly added in formulations.     

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders

Induction of phosphorylated extracellular-regulated kinase (pERK) is a reliable molecular readout of learning-dependent neuronal activation. Here, we describe a pERK immunohistochemistry protocol to study the profile of hippocampal neuron activation following exposure to a spatial learning task in a mouse model characterized by cognitive deficits of neurodevelopmental origin. Specifically, we used pERK immunostaining to study neuronal activation following Morris water maze (MWM, a classical hippocampal-dependent learning task) in Engrailed-2 knockout (En2^-/-) mice, a model of autism spectrum disorders (ASD). As compared to wild-type (WT) controls, En2^-/- mice showed significant spatial learning deficits in the MWM. After MWM, significant differences in the number of pERK-positive neurons were detected in specific hippocampal subfields of En2^-/- mice, as compared to WT animals. Thus, our protocol can robustly detect differences in pERK-positive neurons associated to hippocampal-dependent learning impairment in a mouse model of ASD. More generally, our protocol can be applied to investigate the profile of hippocampal neuron activation in both genetic or pharmacological mouse models characterized by cognitive deficits.     

NATIVE MICHIGAN PLANTS STIMULATE SOIL MICROBIAL SPECIES CHANGES AND PAH REMEDIATION AT A LEGACY STEEL MILL

A 1.3-acre phytoremediation site was constructed to mitigate polyaromatic hydrocarbon (PAH) contamination from a former steel mill in Michigan. Soil was amended with 10% (v/v) compost and 5% (v/v) poultry litter. The site was divided into twelve 11.89 m X 27.13 m plots, planted with approximately 35,000 native Michigan perennials, and soils sampled for three seasons. Soil microbial density generally increased in subplots of Eupatorium perfoliatum (boneset), Aster novae-angliae (New England aster), Andropogon gerardii (big bluestem), and Scirpus atrovirens (green bulrush) versus unplanted subplots. Using enumeration assays with root exudates, PAH degrading bacteria were greatest in soils beneath plants. Initially predominant, Arthrobacter were found capable of degrading a PAH cocktail in vitro, especially upon the addition of root exudate. Growth of some Arthrobacter isolates was stimulated by root exudate. The frequency of Arthrobacter declined in planted subplots with a concurrent increase in other species, including secondary PAH degraders Bacillus and Nocardioides. In subplots supporting only weeds, an increase in Pseudomonas density and little PAH removal were observed. This study supports the notion that a dynamic interplay between the soil, bacteria, and native plant root secretions likely contributes to in situ PAH phytoremediation.     

Fcμ receptor as a Costimulatory Molecule for T Cells

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A Comparison of Granules Produced by High-Shear and Fluidized-Bed Granulation Methods

Placebo granules were manufactured by both wet high-shear and fluidized-bed techniques. The granules were compared based on size, shape, surface morphology, and a variety of different flowability measurements. This comparison showed that granule formation and growth were different, with induction growth for high-shear granulation and steady growth for fluidized-bed granulation. Final granules from high-shear granulation were more spherical and dense compared with the irregular granules from fluidized-bed granulation. The high-shear granules demonstrated better overall flow properties.     

Alternative syntheses and reactivity of platinum(II) terpyridyl acetonitrile complexes

New direct syntheses of [Pt(trpy)(NCCH₃)](CF₃SO₃)₂2 (where trpy = 2,2′:6′,2′′-terpyridine) and [Pt(tBu₃-trpy)(NCCH₃)](CF₃SO₃)₂3 (where tBu₃-trpy = 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine) via the displacement of acetonitrile from [Pt(NCCH₃)₄](CF₃SO₃)₂ have been developed. The synthetic utility of 2 was investigated in reactions with triphenylphosphine (PPh₃), 2,6-dimethylphenyl isocyanide (CN-Xyl), 2,5-dimethyl-2,5-diisocyanohexane (TM4), and tert-butyl isocyanide (CN-tBu). Whereas the expected substitution products were observed for reactions with PPh₃, CN-Xyl, and CN-tBu, dealkylation of TM4 occurred to afford [Pt(trpy)(CN)](CF₃SO₃) 6. The structures of [Pt(trpy)L]²⁺ dications show little intermolecular interactions in the solid state, with the exception of the tBu₃-trpy complex 3 which exists as head-to-tail dimers with a Pt-Pt distance of 3.29 Å. The cyano product 6 was found to stack in infinite chains of cations with a Pt-Pt distance of 3.45 Å.     

2D:4D Asymmetry and Gender Differences in Academic Performance

Exposure to prenatal androgens affects both future behavior and life choices. However, there is still relatively limited evidence on its effects on academic performance. Moreover, the predicted effect of exposure to prenatal testosterone (T)–which is inversely correlated with the relative length of the second to fourth finger lengths (2D:4D)–would seem to have ambiguous effects on academic achievement since traits like aggressiveness or risk-taking are not uniformly positive for success in school. We provide the first evidence of a non-linear, quadratic, relationship between 2D:4D and academic achievement using samples from Moscow and Manila. We also find that there is a gender differentiated link between various measures of academic achievement and measured digit ratios. These effects are different depending on the field of study, choice of achievement measure, and use of the right hand or left digit ratios. The results seem to be asymmetric between Moscow and Manila where the right (left) hand generates inverted-U (U-shaped) curves in Moscow while the pattern for hands reverses in Manila. Drawing from unusually large and detailed samples of university students in two countries not studied in the digit literature, our work is the first to have a large cross country comparison that includes two groups with very different ethnic compositions.     

Influence of BMI on Health‐related Quality of Life: Comparison Between an Obese Adult Cohort and Age‐matched Population Norms

The aim of this study was to determine health‐related quality of life and fatigue measures in obese subjects and to compare scores with age‐ and gender‐matched population norms. A total of 163 obese subjects were recruited from laparoscopic‐adjustable gastric banding or exercise and diet weight loss programs between March 2006 and December 2007. All subjects completed the Medical Outcomes Study Short Form 36 (SF‐36), Assessment of Quality of Life (AQoL), and Multidimensional Assessment of Fatigue (MAF) questionnaires. One‐sample t‐tests were used to compare transformed scores with age‐ and gender‐matched population norms and controls. Obese subjects have significantly lower SF‐36 physical and emotional component scores, significantly lower AQoL utility scores and significantly higher fatigue scores compared to age‐matched population norms. Within the study cohort, the SF‐36 physical functioning, role physical and bodily pain scores, and AQoL utility index were even lower in subjects with clinical knee osteoarthritis (OA). However, obese individuals without OA still had significantly lower scores compared to population norms. Obesity is associated with impaired health‐related quality of life and disability as measured by the SF‐36, AQoL, and fatigue score (MAF) compared to matched population norms.