Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model

Background

Repeated adaptive radiations are evident when phenotypic divergence occurs within lineages, but this divergence into different forms is convergent when compared across lineages. Classic examples of such repeated adaptive divergence occur in island (for example, Caribbean Anolis lizards) and lake systems (for example, African cichlids). Host-parasite systems in many respects are analogous to island systems, where host species represent isolated islands for parasites whose life cycle is highly tied to that of their hosts. Thus, host-parasite systems might exhibit interesting cases of repeated adaptive divergence as seen in island and lake systems. The feather lice of birds spend their entire life cycle on the body of the host and occupy distinct microhabitats on the host: head, wing, body and generalist. These microhabitat specialists show pronounced morphological differences corresponding to how they escape from host preening. We tested whether these different microhabitat specialists were a case of repeated adaptive divergence by constructing both morphological and molecular phylogenies for a diversity of avian feather lice, including many examples of head, wing, body and generalist forms.

Results

Morphological and molecular based phylogenies were highly incongruent, which could be explained by rampant convergence in morphology related to microhabitat specialization on the host. In many cases lice from different microhabitat specializations, but from the same group of birds, were sister taxa.

Conclusions

This pattern indicates a process of repeated adaptive divergence of these parasites within host group, but convergence when comparing parasites across host groups. These results suggest that host-parasite systems might be another case in which repeated adaptive radiations could be relatively common, but potentially overlooked, because morphological convergence can obscure evolutionary relationships.     

Induction of endothelial apoptosis by 4-hydroxyhexenal.

Lipid peroxidation and its products such as 4-hydroxy-2-nonenal (HNE) and 4-hydroxyhexenal (HHE) are known to affect redox balance during aging and various degenerative processes, including vascular dysfunction. Deterioration of the endothelial cells that line the vascular wall is known to be an underlying cause of vascular dysfunction. At present, little is known about the mechanism by which HHE induces endothelial cell death (i.e. apoptosis), although HNE-induced apoptotic cell death has been reported. The aim of this study was to determine whether apoptosis induced by HHE in endothelial cells involves peroxynitrite (ONOO(-)). Our results show that in endothelial cells HHE triggers apoptotic cell death by inducing apoptotic Bax coupled with a decrease in anti-apoptotic Bcl-2. Results show that HHE induces reactive oxygen species (ROS), nitric oxide, and ONOO(-) generation, leading to redox imbalance. Furthermore, the antioxidant N-acetyl cysteine, ROS scavenger, and penicillamine, an ONOO(-) scavenger, were found to block HHE-mediated apoptosis. We used confocal laser microscopy to estimate the ability of these inhibitors to attenuate HHE-induced intracellular ONOO(-) levels thus confirming the oxidative mediation of apoptosis in endothelial cells. These findings strongly suggest that accumulated HHE triggers reactive species-mediated endothelial apoptosis, leading to vascular dysfunction as well as vascular aging. During aging, increased lipid peroxidation and its associated production of HHE may exacerbate the weakened redox balance, leading to various chronic degenerative processes including vascular dysfunction.     

Prevalence of cardiovascular disease risk factors by habitat: a study on adult Asian Indians in West Bengal, India

The present community based cross-sectional study was aimed to investigate whether or not increasing prevalence of cardiovascular disease (CVD) risk factors in adult Asian Indian population are associated with increasing urbanization. The 'urban group' was comprised of 224 individuals including 122 males and 102 females being inhabitants of Kolkata (erstwhile Calcutta) under the Kolkata Metropolitan Development Authority (KMDA) area. The 'rural group' comprised 224 individuals including 135 males and 89 females and was living in a village council located about 80 kilometers from Kolkata. Therefore, a total of 448 adult (> or = 30 years) individuals (257 males and 191 females) participated in the study. Anthropometric measures, lipids profiles, fasting blood glucose and blood pressure measures were taken from participants. Obesity and body composition measures were subsequently calculated from the anthropometric measures. Accepted cut-offs were used to define metabolic syndrome (MS), lipids abnormalities, increased adiposity and high blood pressure in the study. It was found that 58.7% participants were engaged in sedentary work which includes 60.7% males and 56% females. It was further observed that the prevalence of high blood pressure was as high as 70.6% in urban females compared to 55.1% in rural females. However, the prevalence of low HDLc was remarkably high in females ofboth rural and urban areas. The prevalence ofMS was significantly higher in urban females (57.8%) than in their rural counterparts (34.8%). It seems reasonable to argue that people with changing lifestyles due to growing urbanization are associated with adverse CVD risk factors irrespective of their habitat (rural vs. urban). This in turn warranted a comprehensive risk stratification protocol at the national level for the effective management of CVD risk factors in this part of the world.     

Nickel tolerance and accumulation by bacteria from rhizosphere of nickel hyperaccumulators in serpentine soil ecosystem of Andaman, India

Rhizosphere microorganisms harboring nickel hyperaccumulators, Rinorea bengalensis (Wall.) O. K. and Dichapetalum gelonioides ssp. andamanicum (King) Leenh. endemic to serpentine outcrops of Andaman Islands, India, were screened for their tolerance and accumulation of Ni. The rhizosphere soils from both the plants were rich in total and available Ni along with Co, Cr, Fe and Mg but poor in microbial density and were dominated by bacteria. Out of total 123 rhizosphere microorganisms (99 bacteria and 24 fungi), bacteria were more tolerant to Ni than fungi. Viable cells of selected Ni-tolerant bacterial isolates (MIC = 13.6–28.9 mM Ni) belonging to Pseudomonas, Bacillus and Cupriavidus were capable of accumulating nickel (209.5–224.0 μM Ni g⁻¹ protein) from aqueous solution. Cupriavidus pauculus KPS 201 (MTCC 6280), showing highest degree of nickel tolerance (MIC 28.9 mM Ni) and uptake (224.0 μM Ni g⁻¹ protein, 60 min) was used for detailed study. Kinetics of nickel uptake in C. pauculus KPS 201 followed a linearized Lineweaver-Burk plot. The K _m and V _max for nickel uptake by minimal medium grown-cells approximated 1.5 mM Ni and 636.9 μM Ni g⁻¹ protein, respectively. The uptake process was inhibited by Co, Cu, Cd, Mg, Mn and Zn, however, complete inhibition was not achieved even in presence of 500 mM Mg. Metabolic inhibitors, sodium azide (1.0 mM) and carbonyl cyanide m-chlorophenylhydrazone (0.4 mM) strongly inhibited nickel uptake suggesting the process as an energy dependent one. The present study clearly shows that bacteria in the rhizosphere of Ni-hyperaccumulators are capable of tolerating high concentration of Ni and also possesses nickel uptake potential. The Ni-hyperaccumulators in combination with these Ni-resistant bacteria could be an ideal tool for nickel bioremediation.     

Binding of YC-1/BAY 41-2272 to soluble guanylate cyclase: A new perspective to the mechanism of activation

Soluble guanylate cyclase (sGC), a heterodimeric heme protein, catalyses the conversion of GTP in to cyclic GMP, which acts as a second messenger in cellular signaling. Nitric oxide activates this enzyme several hundred folds over its basal level. Carbon monoxide, along with some activator molecules like YC-1 and BAY, also synergistically activate sGC. Mechanism of this synergistic activation is a matter of debate. Here we review the existing literature to identify the possible binding site for YC-1 and BAY on bovine lung sGC and its mechanism of activation. These two exogenous compounds bind sGC on α subunit inside a pocket and thus exert allosteric effect via subunit interface, which is relayed to the catalytic site. We used docking studies to further validate this hypothesis. We propose that the binding of YC-1/BAY inside the sensory domain of the α subunit modulates the interactions on the subunit interface resulting in rearrangements in the catalytic site into active conformation and this partly induces the cleavage of Fe-His bond.     

Influence of the change in stem length on the load transfer and bone remodelling for a cemented resurfaced femur

The effect of a short-stem femoral resurfacing component on load transfer and potential failure mechanisms has rarely been studied. The stem length has been reduced by approximately 50% as compared to the current long-stem design. Using 3-D FE models of natural and resurfaced femurs, the study is aimed at investigating the influence of a short-stem resurfacing component on load transfer and bone remodelling. Applied loading conditions include normal walking and stair climbing. The mechanical role of the stem along with implant–cement and stem–bone contact conditions was observed to be crucial. Shortening the stem length to half of the current length (long-stem) led to several favourable effects, even though the stress distributions in the implant and the cement were similar in both the cases. The short-stem implant led not only to a more physiological stress distribution but also to bone apposition (increase of 20–70% bone density) in the superior resurfaced head, when the stem–bone contact prevailed. This also led to a reduction in strain concentration in the cancellous bone around the femoral neck–component junction. The normalised peak strain in this region was lower for the short-stem design as compared to that of the long-stem one, thereby reducing the initial risk of neck fracture. The effect of strain shielding (50–75% reduction) was restricted to a small bone volume underlying the cement, which was approximately half of that of the long-stem design. Consequently, bone resorption was considerably less for the short-stem design. The short-stem design offers better prospects than the long-stem resurfacing component.     

A newly synthesized,potent tyrosinase inhibitor: 5-(6-Hydroxy-2-naphthyl)-1,2,3-benzenetriol

In searching for new agents with a depigmenting effect, we synthesized a derivative of resveratrol, 5-(6-hydroxy-2-naphthyl)-1,2,3-benzenetriol (5HNB) with a potent tyrosinase inhibitory activity. 5HNB inhibited mushroom tyrosinase with an IC₅₀ value of 2.95 μM, which is more potent than the well-known anti-tyrosinase activity of kojic acid (IC₅₀ = 38.24). The results of the enzymatic inhibition kinetics by Lineweaver–Burk analysis indicated 5HNB inhibits tyrosinase non-competitively when l-tyrosine was used as the substrate. Based on the strong inhibitory action of 5HNB, it is expected that 5HNB can suppress melanin production in which tyrosinase plays the essential role. Our expectation was confirmed by the experimentations with B16 melanoma cells in which 5HNB inhibited melanin production. We propose that 5HNB might have skin-whitening effects as well as therapeutic potential for treating skin pigmentation disorders.     

Chromium stress mitigation by polyamine-brassinosteroid application involves phytohormonal and physiological strategies in Raphanus sativus L

Brassinosteroids (BRs) and polyamines (PAs) are well-established growth regulators playing key roles in stress management among plants. In the present study, we evaluated the effects of epibrassinolide (EBL, an active BR) and spermidine (Spd, an active PA) on the tolerance of radish to oxidative stress induced by Cr (VI) metal. Our investigation aimed to study the impacts of EBL (10(-9) M) and/or Spd (1 mM) on the biochemical and physiological responses of radish (Raphanus sativus L.) under Cr-stress. Applications of EBL and/or Spd were found to improve growth of Cr-stressed seedlings in terms of root length, shoot length and fresh weight. Our data also indicated that applications of EBL and Spd have significant impacts, particularly when applied together, on the endogenous titers of PAs, free and bound forms of IAA and ABA in seedlings treated with Cr-stress. Additionally, co-applications of EBL and Spd modulated more remarkably the titers of antioxidants (glutathione, ascorbic acid, proline, glycine betaine and total phenol) and activities of antioxidant enzymes (guaicol peroxidase, catalase, superoxide dismutase and glutathione reductase) in Cr-stressed plants than their individual applications. Attenuation of Cr-stress by EBL and/or Spd (more efficient with EBL and Spd combination) was also supported by enhanced values of stress indices, such as phytochelatins, photosynthetic pigments and total soluble sugars, and reduction in malondialdehyde and H(2)O(2) levels in Cr-treated seedlings. Diminution of ROS production and enhanced ROS scavenging capacities were also noted for EBL and/or Spd under Cr-stress. However, no significant reduction in Cr uptake was observed for co-application of EBL and Spd when compared to their individual treatments in Cr-stressed seedlings. Taken together, our results demonstrate that co-applications of EBL and Spd are more effective than their independent treatments in lowering the Cr-induced oxidative stress in radish, leading to improved growth of radish seedlings under Cr-stress.