Pericytes display increased CCN2 expression upon culturing

By providing a source of α-smooth muscle actin (α-SMA)-expressing myofibroblasts, microvascular pericytes contribute to the matrix remodeling that occurs during tissue repair. However, the extent to which pericytes may contribute to the fibroblast phenotype post-repair is unknown. In this report, we test whether pericytes isolated from human placenta can in principle become fibroblast-like. Pericytes were cultured in vitro for 11 passages. The Affymetrix mRNA expression profile of passage 2 and passage 11 pericytes was compared. The expression of type I collagen, thrombospondin and fibronectin mRNAs was induced by passaging pericytes in culture. This induction of a fibroblast phenotype was paralleled by induction of connective tissue growth factor (CTGF/CCN2) and type I collagen protein expression and the fibroblast marker ASO2. These results indicate that, in principle, pericytes have the capacity to become fibroblast-like and that pericytes may contribute to the population of fibroblasts in a healed wound.     

Genetic Variation at Selected SNPs in the Leptin Gene and Association of Alleles with Markers of Kidney Disease in a Xhosa Population of South Africa

Background

Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP) may be associated with markers of CKD in indigenous black Africans.

Methodology/Principal Findings

Black South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-{"type":"entrez-nucleotide","attrs":{"text":"U43653","term_id":"1226243","term_text":"U43653"}}U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482).

Conclusions/Significance

These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.     

A new gonad-infecting species of <Emphasis Type="Italic">Philometra</Emphasis> Costa, 1845 (Nematoda: Philometridae) from the marine fish <Emphasis Type="Italic">Terapon jarbua</Emphasis> (Forsskål) (Terapontidae) off the eastern coast of India

A new nematode species, Philometra terapontis n. sp. (Philometridae), is described from male and female specimens found in the ovary of the jarbua terapon Terapon jarbua (Forsskål) (Terapontidae, Perciformes) from the Bay of Bengal off the eastern coast of India. Based on light and scanning electron microscopical examination, the new species differs from most other gonad-infecting Philometra spp. in the length of the spicules (105–114 μm), a gubernaculum with dorsal, lamella-like structures and a distinct protuberance on its distal end, and a U-shaped, dorsally uninterrupted caudal mound in the male. From a few congeneric, gonad-infecting species with unknown males, it can be distinguished by morphological and biometrical features found in gravid females (i.e. length of body, length of first-stage larvae or oesophagus, and caudal structure), by the host type (fish family) and by the geographical distribution. Philometra terapontis is the first philometrid species reported from a fish belonging to the family Terapontidae. Philometra sawara Quiazon, Yoshinaga &; Ogawa, 2008 is considered a junior synonym of P. scomberomori (Yamaguti, 1935). A key to gonad-infecting species of Philometra parasitising marine and brackish-water fishes is provided.     

Plant growth promoting rhizobacteria and endophytes accelerate phytoremediation of metalliferous soils

Technogenic activities (industrial—plastic, textiles, microelectronics, wood preservatives; mining—mine refuse, tailings, smelting; agrochemicals—chemical fertilizers, farm yard manure, pesticides; aerosols—pyrometallurgical and automobile exhausts; biosolids—sewage sludge, domestic waste; fly ash—coal combustion products) are the primary sources of heavy metal contamination and pollution in the environment in addition to geogenic sources. During the last two decades, bioremediation has emerged as a potential tool to clean up the metal-contaminated/polluted environment. Exclusively derived processes by plants alone (phytoremediation) are time-consuming. Further, high levels of pollutants pose toxicity to the remediating plants. This situation could be ameliorated and accelerated by exploring the partnership of plant-microbe, which would improve the plant growth by facilitating the sequestration of toxic heavy metals. Plants can bioconcentrate (phytoextraction) as well as bioimmobilize or inactivate (phytostabilization) toxic heavy metals through in situ rhizospheric processes. The mobility and bioavailability of heavy metal in the soil, particularly at the rhizosphere where root uptake or exclusion takes place, are critical factors that affect phytoextraction and phytostabilization. Developing new methods for either enhancing (phytoextraction) or reducing the bioavailability of metal contaminants in the rhizosphere (phytostabilization) as well as improving plant establishment, growth, and health could significantly speed up the process of bioremediation techniques. In this review, we have highlighted the role of plant growth promoting rhizo- and/or endophytic bacteria in accelerating phytoremediation derived benefits in extensive tables and elaborate schematic sketches.     

Insulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training

Insulin and insulin-like growth factor 1 (IGF-1) receptor signaling pathways differentially modulate cardiac growth under resting conditions and following exercise training. These effects are mediated by insulin receptor substrate 1 (IRS1) and IRS2, which also differentially regulate resting cardiac mass. To determine the role of IRS isoforms in mediating the hypertrophic and metabolic adaptations of the heart to exercise training, we subjected mice with cardiomyocyte-specific deletion of either IRS1 (CIRS1 knockout [CIRS1KO] mice) or IRS2 (CIRS2KO mice) to swim training. CIRS1KO hearts were reduced in size under basal conditions, whereas CIRS2KO hearts exhibited hypertrophy. Following exercise swim training in CIRS1KO and CIRS2KO hearts, the hypertrophic response was equivalently attenuated, phosphoinositol 3-kinase (PI3K) activation was blunted, and prohypertrophic signaling intermediates, such as Akt and glycogen synthase kinase 3β (GSK3β), were dephosphorylated potentially on the basis of reduced Janus kinase-mediated inhibition of protein phosphatase 2a (PP2A). Exercise training increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein content, mitochondrial capacity, fatty acid oxidation, and glycogen synthesis in wild-type (WT) controls but not in IRS1- and IRS2-deficient hearts. PGC-1α protein content remained unchanged in CIRS1KO but decreased in CIRS2KO hearts. These results indicate that although IRS isoforms play divergent roles in the developmental regulation of cardiac size, these isoforms exhibit nonredundant roles in mediating the hypertrophic and metabolic response of the heart to exercise.     

Influence of Protein – Micelle Ratios and Cysteine Residues on the Kinetic Stability and Unfolding Rates of Human Mitochondrial VDAC-2

Delineating the kinetic and thermodynamic factors which contribute to the stability of transmembrane β-barrels is critical to gain an in-depth understanding of membrane protein behavior. Human mitochondrial voltage-dependent anion channel isoform 2 (hVDAC-2), one of the key anti-apoptotic eukaryotic β-barrel proteins, is of paramount importance, owing to its indispensable role in cell survival. We demonstrate here that the stability of hVDAC-2 bears a strong kinetic contribution that is dependent on the absolute micellar concentration used for barrel folding. The refolding efficiency and ensuing stability is sensitive to the lipid-to-protein (LPR) ratio, and displays a non-linear relationship, with both low and high micellar amounts being detrimental to hVDAC-2 structure. Unfolding and aggregation process are sequential events and show strong temperature dependence. We demonstrate that an optimal lipid-to-protein ratio of 2600∶1 – 13000∶1 offers the highest protection against thermal denaturation. Activation energies derived only for lower LPRs are ∼17 kcal mol⁻¹ for full-length hVDAC-2 and ∼23 kcal mol⁻¹ for the Cys-less mutant, suggesting that the nine cysteine residues of hVDAC-2 impart additional malleability to the barrel scaffold. Our studies reveal that cysteine residues play a key role in the kinetic stability of the protein, determine barrel rigidity and thereby give rise to strong micellar association of hVDAC-2. Non-linearity of the Arrhenius plot at high LPRs coupled with observation of protein aggregation upon thermal denaturation indicates that contributions from both kinetic and thermodynamic components stabilize the 19-stranded β-barrel. Lipid-protein interaction and the linked kinetic contribution to free energy of the folded protein are together expected to play a key role in hVDAC-2 recycling and the functional switch at the onset of apoptosis.     

Development and Validation of a Risk Model for Predicting Adverse Drug Reactions in Older People during Hospital Stay: Brighton Adverse Drug Reactions Risk (BADRI) Model

Background

Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model.

Methods

We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset).

Results

Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively.

Conclusions

We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported.     

Hydrolysis of cellulose derived from steam exploded bagasse by Penicillium cellulases: Comparison with commercial cellulase

A complete cellulase from Penicillium pinophilum was evaluated for the hydrolysis of α-cellulose derived from steam exploded sugarcane bagasse and other cellulosic substrates. α-Cellulose at 1% substrate concentration was completely hydrolyzed by Penicillium cellulase within 3 h wherein at 10% the hydrolysis was 100% within 24 h with an enzyme loading of 10 FPU/g. The hydrolysate yielded glucose as major end product as analyzed by HPLC. Under similar conditions, hydrolysis of Sigmacell (microcrystalline cellulose), CP-123 (pulverized cellulose powder) and ball milled Solka Floc were 42%, 56% and 52%, respectively. Further the hydrolysis performance of Penicillium sp. cellulase is compared with Trichoderma reesei cellulase (Accellerase^TM 1000) from Genencore. The kinetics of hydrolysis with respect to enzyme and substrate concentration will be presented.