Phytosterol feeding induces alteration in testosterone metabolism in rat tissues

The objective of the present study was to examine the metabolism of testosterone in rat tissues as influenced by dietary phytosterols. Testosterone metabolism includes reductions to more active metabolites or aromatization to estrogen. Both higher levels of androgens and estrogens are implicated as risk factors in the development of prostate cancer. Tissues studied included liver, testis, and prostate. Feeding 2% phytosterols with 0.2% cholic acid to rats for 22 days resulted in a 33% reduction in serum testosterone compared with controls, which received only 0.2% cholic acid in the diet. 5-α-Reductase was reduced by 41 to 44% and 33% in the liver and prostate, respectively. No effect of phytosterols was observed in the testis. Only aromatase activity of the prostate was reduced by 55% upon feeding phytosterols. It was concluded that dietary phytosterols may reduce the risk of prostate cancer by lowering the activities of the enzymes of testosterone metabolism.     

High Connectivity in Rastrelliger kanagurta: Influence of Historical Signatures and Migratory Behaviour Inferred from mtDNA Cytochrome b

Phylogeographic patterns and population structure of the pelagic Indian mackerel, Rastrelliger kanagurta were examined in 23 populations collected from the Indonesian-Malaysian Archipelago (IMA) and the West Indian Ocean (WIO). Despite the vast expanse of the IMA and neighbouring seas, no evidence for geographical structure was evident. An indication that R. kanagurta populations across this region are essentially panmictic. This study also revealed that historical isolation was insufficient for R. kanagurta to attain migration drift equilibrium. Two distinct subpopulations were detected between the WIO and the IMA (and adjacent populations); interpopulation genetic variation was high. A plausible explanation for the genetic differentiation observed between the IMA and WIO regions suggest historical isolation as a result of fluctuations in sea levels during the late Pleistocene. This occurrence resulted in the evolution of a phylogeographic break for this species to the north of the Andaman Sea.     

Using Isolated Mitochondria from Minimal Quantities of Mouse Skeletal Muscle for High throughput Microplate Respiratory Measurements

Skeletal muscle mitochondria play a specific role in many disease pathologies. As such, the measurement of oxygen consumption as an indicator of mitochondrial function in this tissue has become more prevalent. Although many technologies and assays exist that measure mitochondrial respiratory pathways in a variety of cells, tissue and species, there is currently a void in the literature in regards to the compilation of these assays using isolated mitochondria from mouse skeletal muscle for use in microplate based technologies. Importantly, the use of microplate based respirometric assays is growing among mitochondrial biologists as it allows for high throughput measurements using minimal quantities of isolated mitochondria. Therefore, a collection of microplate based respirometric assays were developed that are able to assess mechanistic changes/adaptations in oxygen consumption in a commonly used animal model. The methods presented herein provide step-by-step instructions to perform these assays with an optimal amount of mitochondrial protein and reagents, and high precision as evidenced by the minimal variance across the dynamic range of each assay.     

A Reevaluation of the Voluntary Medical Male Circumcision Scale-Up Plan in Zimbabwe

Background

The voluntary medical male circumcision (VMMC) program in Zimbabwe aims to circumcise 80% of males aged 13–29 by 2017. We assessed the impact of actual VMMC scale-up to date and evaluated the impact of potential alterations to the program to enhance program efficiency, through prioritization of subpopulations.

Methods and Findings

We implemented a recently developed analytical approach: the age-structured mathematical (ASM) model and accompanying three-level conceptual framework to assess the impact of VMMC as an intervention. By September 2014, 364,185 males were circumcised, an initiative that is estimated to avert 40,301 HIV infections by 2025. Through age-group prioritization, the number of VMMCs needed to avert one infection (effectiveness) ranged between ten (20–24 age-group) and 53 (45–49 age-group). The cost per infection averted ranged between $811 (20–24 age-group) and $5,518 (45–49 age-group). By 2025, the largest reductions in HIV incidence rate (up to 27%) were achieved by prioritizing 10–14, 15–19, or 20–24 year old. The greatest program efficiency was achieved by prioritizing 15–24, 15–29, or 15–34 year old. Prioritizing males 13–29 year old was programmatically efficient, but slightly inferior to the 15–24, 15–29, or 15–34 age groups. Through geographic prioritization, effectiveness varied from 9–12 VMMCs per infection averted across provinces. Through risk-group prioritization, effectiveness ranged from one (highest sexual risk-group) to 60 (lowest sexual risk-group) VMMCs per infection averted.

Conclusion

The current VMMC program plan in Zimbabwe is targeting an efficient and impactful age bracket (13–29 year old), but program efficiency can be improved by prioritizing a subset of males for demand creation and service availability. The greatest program efficiency can be attained by prioritizing young sexually active males and males whose sexual behavior puts them at higher risk for acquiring HIV.     

Life-History Traits of the Model Organism Pristionchus pacificus Recorded Using the Hanging Drop Method: Comparison with Caenorhabditis elegans

The nematode Pristionchus pacificus is of growing interest as a model organism in evolutionary biology. However, despite multiple studies of its genetics, developmental cues, and ecology, the basic life-history traits (LHTs) of P. pacificus remain unknown. In this study, we used the hanging drop method to follow P. pacificus at the individual level and thereby quantify its LHTs. This approach allowed direct comparisons with the LHTs of Caenorhabditis elegans recently determined using this method. When provided with 5×10⁹ Escherichia coli cells ml^–1 at 20°C, the intrinsic rate of natural increase of P. pacificus was 1.125 (individually, per day); mean net production was 115 juveniles produced during the life-time of each individual, and each nematode laid an average of 270 eggs (both fertile and unfertile). The mean age of P. pacificus individuals at first reproduction was 65 h, and the average life span was 22 days. The life cycle of P. pacificus is therefore slightly longer than that of C. elegans, with a longer average life span and hatching time and the production of fewer progeny.     

The Effect of Thermophoresis on Unsteady Oldroyd-B Nanofluid Flow over Stretching Surface

There are currently only a few theoretical studies on convective heat transfer in polymer nanocomposites. In this paper, the unsteady incompressible flow of a polymer nanocomposite represented by an Oldroyd-B nanofluid along a stretching sheet is investigated. Recent studies have assumed that the nanoparticle fraction can be actively controlled on the boundary, similar to the temperature. However, in practice, such control presents significant challenges and in this study the nanoparticle flux at the boundary surface is assumed to be zero. We have used a relatively novel numerical scheme; the spectral relaxation method to solve the momentum, heat and mass transport equations. The accuracy of the solutions has been determined by benchmarking the results against the quasilinearisation method. We have conducted a parametric study to determine the influence of the fluid parameters on the heat and mass transfer coefficients.     

Effects of NaCl on surface properties,chlorophyll fluorescence and light remission,and cellular compounds of <Emphasis Type="Italic">Grewia tenax</Emphasis> (Forssk.) Fiori and <Emphasis Type="Italic">Tamarindus indica</Emphasis> L. leaves

Seedlings of the salt-tolerant plant grewia [Grewia tenax (Forssk.) Fiori] and the moderately salt-tolerant tamarind (Tamarindus indica L.) were grown under controlled conditions and treated daily with NaCl solutions to investigate mechanisms of tolerance to salinity. Leaf micromorphology, cuticular wax load, chlorophyll fluorescence and light remission, as well as antioxidative potential were evaluated. As confirmed by energy-dispersive X-ray microanalysis in both species, absorption of sodium and chlorine increased with rising NaCl concentration in the treatment solution. In parallel, accumulation of calcium in grewia leaves was strongly reduced, leading to less crystals of calcium oxalate in leaf tissue. In grewia the cuticular wax load, chlorophyll content, and electron transport rate (ETR) were significantly reduced by comparatively low NaCl concentrations. In tamarind, in contrast, wax load and ETR were not significantly affected, while the decrease of chlorophyll content was less pronounced. Measurements of the antioxidative capacity and the imbalance between values of lipophilic and hydrophilic extracts at different NaCl concentrations confirmed that grewia is more salt tolerant than tamarind. This higher tolerance degree seemed to be associated with grewias’ more efficient scavenging of free radicals and the regulation of the antioxidative potential in lipophilic and hydrophilic extracts.     

Echinocystic acid 3,16-O-bisglycosides from Albizia procera

Three triterpene glycosides and two known ones were isolated from the bark of Albizia procera by using chromatographic techniques. The structures of the compounds were determined to be 3-O-β-d-xylopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 6)-2-acetamido-2-deoxy-β-d-glucopyranosyl echinocystic acid 16-O-β-d-glucopyranoside, 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-arabinopyranosyl-(1 → 6)-2-acetamido-2-deoxy-β-d-glucopyranosyl echinocystic acid 16-O-β-d-glucopyranoside and 3-O-α-l-arabinopyranosyl-(1 → 2)-α-l-arabinopyranosyl-(1 → 6)-2-acetamido-2-deoxy-β-d-glucopyranosyl echinocystic acid 16-O-β-d-glucopyranoside. Their structures were determined by NMR techniques including HOHAHA, ¹H-¹H COSY, ROE, HMQC and HMBC experiments together with FABMS as well as acid hydrolysis. To the best of our knowledge, the new compounds are considered the first examples of echinocystic acid 3,16-O-bisglycosides. In contrast to other cytotoxic echinocystic acid glycosides with N-acetyl glucosamine unit, the new glycosides were found inactive when assayed by MTT method for their cytotoxicities against the human tumor cell lines HEPG2, A549, HT29 and MCF7. The results showed the importance of the free hydroxyl group at the aglycone C-16 for exhibiting cytotoxic properties.     

Cyclic AMP signaling contributes to neural plasticity and hyperexcitability in AH sensory neurons following intestinal Trichinella spiralis-induced inflammation

Trichinella spiralis infection causes hyperexcitability in enteric after-hyperpolarising (AH) sensory neurons that is mimicked by neural, immune or inflammatory mediators known to stimulate adenylyl cyclase (AC)/cyclic 3',5'-adenosine monophosphate (cAMP) signaling. The hypothesis was tested that ongoing modulation and sustained amplification in the AC/cAMP/phosphorylated cAMP related element binding protrein (pCREB) signaling pathway contributes to hyperexcitability and neuronal plasticity in gut sensory neurons after nematode infection. Electrophysiological, immunological, molecular biological or immunochemical studies were done in T. spiralis-infected guinea-pigs (8000 larvae or saline) after acute-inflammation (7 days) or 35 days p.i., after intestinal clearance. Acute-inflammation caused AH-cell hyperexcitability and elevated mucosal and neural tissue levels of myeloperoxidase, mast cell tryptase, prostaglandin E2, leukotrine B4, lipid peroxidation, nitric oxide and gelatinase; lower level inflammation persisted 35 days p.i. Acute exposure to blockers of AC, histamine, cyclooxygenase or leukotriene pathways suppressed AH-cell hyperexcitability in a reversible manner. Basal cAMP responses or those evoked by forskolin (FSK), Ro-20-1724, histamine or substance P in isolated myenteric ganglia were augmented after T. spiralis infection; up-regulation also occurred in AC expression and AC-immunoreactivity in calbindin (AH) neurons. The cAMP-dependent slow excitatory synaptic transmission-like responses to histamine (mast cell mediator) or substance P (neurotransmitter) acting via G-protein coupled receptors (GPCR) in AH neurons were augmented by up to 2.5-fold after T. spiralis infection. FSK, histamine, substance P or T. spiralis acute infection caused a 5- to 30-fold increase in cAMP-dependent nuclear CREB phosphorylation in isolated ganglia or calbindin (AH) neurons. AC and CREB phosphorylation remained elevated 35 days p.i.. Ongoing immune activation, AC up-regulation, enhanced phosphodiesterase IV activity and facilitation of the GPCR-AC/cAMP/pCREB signaling pathway contributes to T. spiralis-induced neuronal plasticity and AH-cell hyperexcitability. This may be relevant in gut nematode infections and inflammatory bowel diseases, and is a potential therapeutic target.