A Protease Isolated from the Latex of Plumeria rubra Linn (Apocynaceae) 2: Anti-inflammatory and Wound- Healing Activities

Purpose: The aim of this study was to investigate the anti-inflammatory and wound-healing activities of the protease isolated from the latex of Plumeria rubra Linn.Methods: The protease was isolated from the latex of the plant by acetone precipitation method and given a trivial name, Plumerin-R. The anti-inflammatory activity of the protease was based on its effects on carrageenan-induced paw oedema in rats. Its wound healing effect was investigated using an excision wound rat model.Results: Four hours after treatment, the reduction in carrageenan-induced rat paw oedema by 20, 40 and 80 mg/kg body weight of plumerin-R was 21.6, 33.8 and 48.8 %, respectively, while oedema reduction by indomethacin (10 mg/kg) was 58.0 %. Plumerin-R showed significant (p < 0.05) wound closure and epithelialization time compared with control.Conclusion: This study demonstrates that the protease, Plumerin-R, has significant anti-inflammatory and wound-healing properties.Keywords: Protease, Plumerin-R, Anti-inflammatory, Excision wound, Healing

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Origin of the Spin-Orbital Liquid State in a Nearly J=0 Iridate Ba3ZnIr2O9

We show using detailed magnetic and thermodynamic studies and theoretical calculations that the ground state of Ba3ZnIr2O9 is a realization of a novel spin-orbital liquid state. Our results reveal that Ba3ZnIr2O9 with Ir5+ (5d(4)) ions and strong spin-orbit coupling (SOC) arrives very close to the elusive J = 0 state but each Ir ion still possesses a weak moment. Ab initio density functional calculations indicate that this moment is developed due to superexchange, mediated by a strong intradimer hopping mechanism. While the Ir spins within the structural Ir2O9 dimer are expected to form a spin-orbit singlet state (SOS) with no resultant moment, substantial frustration arising from interdimer exchange interactions induce quantum fluctuations in these possible SOS states favoring a spin-orbital liquid phase down to at least 100 mK

The Financial Burden of Non-Communicable Chronic Diseases in Rural Nigeria: Wealth and Gender Heterogeneity in Health Care Utilization and Health Expenditures

Objectives Better insights into health care utilization and out-of-pocket expenditures for non-communicable chronic diseases (NCCD) are needed to develop accessible health care and limit the increasing financial burden of NCCDs in Sub-Saharan Africa. Methods A household survey was conducted in rural Kwara State, Nigeria, among 5,761 individuals. Data were obtained using biomedical and socio-economic questionnaires. Health care utilization, NCCD-related health expenditures and distances to health care providers were compared by sex and by wealth quintile, and a Heckman regression model was used to estimate health expenditures taking selection bias in health care utilization into account. Results The prevalence of NCCDs in our sample was 6.2%. NCCD-affected individuals from the wealthiest quintile utilized formal health care nearly twice as often as those from the lowest quintile (87.8% vs 46.2%, p = 0.002). Women reported foregone formal care more often than men (43.5% vs. 27.0%, p = 0.058). Health expenditures relative to annual consumption of the poorest quintile exceeded those of the highest quintile 2.2-fold, and the poorest quintile exhibited a higher rate of catastrophic health spending (10.8% among NCCD-affected households) than the three upper quintiles (4.2% to 6.7%). Long travel distances to the nearest provider, highest for the poorest quintile, were a significant deterrent to seeking care. Using distance to the nearest facility as instrument to account for selection into health care utilization, we estimated out-of-pocket health care expenditures for NCCDs to be significantly higher in the lowest wealth quintile compared to the three upper quintiles. Conclusions Facing potentially high health care costs and poor accessibility of health care facilities, many individuals suffering from NCCDs—particularly women and the poor—forego formal care, thereby increasing the risk of more severe illness in the future. When seeking care, the poor spend less on treatment than the rich, suggestive of lower quality care, while their expenditures represent a higher share of their annual household consumption. This calls for targeted interventions that enhance health care accessibility and provide financial protection from the consequences of NCCDs, especially for vulnerable populations

Hydrogeological typologies of the Indo-Gangetic basin alluvial aquifer, South Asia

The Indo-Gangetic aquifer is one of the world’s most important transboundary water resources, and the most heavily exploited aquifer in the world. To better understand the aquifer system, typologies have been characterized for the aquifer, which integrate existing datasets across the Indo-Gangetic catchment basin at a transboundary scale for the first time, and provide an alternative conceptualization of this aquifer system. Traditionally considered and mapped as a single homogenous aquifer of comparable aquifer properties and groundwater resource at a transboundary scale, the typologies illuminate significant spatial differences in recharge, permeability, storage, and groundwater chemistry across the aquifer system at this transboundary scale. These changes are shown to be systematic, concurrent with large-scale changes in sedimentology of the Pleistocene and Holocene alluvial aquifer, climate, and recent irrigation practices. Seven typologies of the aquifer are presented, each having a distinct set of challenges and opportunities for groundwater development and a different resilience to abstraction and climate change. The seven typologies are: (1) the piedmont margin, (2) the Upper Indus and Upper-Mid Ganges, (3) the Lower Ganges and Mid Brahmaputra, (4) the fluvially influenced deltaic area of the Bengal Basin, (5) the Middle Indus and Upper Ganges, (6) the Lower Indus, and (7) the marine-influenced deltaic areas

Nerve growth factor induces neurite outgrowth of PC12 cells by promoting Gβγ-microtubule interaction

Background: Assembly and disassembly of microtubules (MTs) is critical for neurite outgrowth and differentiation. Evidence suggests that nerve growth factor (NGF) induces neurite outgrowth from PC12 cells by activating the receptor tyrosine kinase, TrkA. G protein-coupled receptors (GPCRs) as well as heterotrimeric G proteins are also involved in regulating neurite outgrowth. However, the possible connection between these pathways and how they might ultimately converge to regulate the assembly and organization of MTs during neurite outgrowth is not well understood. Results: Here, we report that Gβγ, an important component of the GPCR pathway, is critical for NGF-induced neuronal differentiation of PC12 cells. We have found that NGF promoted the interaction of Gβγ with MTs and stimulated MT assembly. While Gβγ-sequestering peptide GRK2i inhibited neurite formation, disrupted MTs, and induced neurite damage, the Gβγ activator mSIRK stimulated neurite outgrowth, which indicates the involvement of Gβγ in this process. Because we have shown earlier that prenylation and subsequent methylation/demethylation of γ subunits are required for the Gβγ-MTs interaction in vitro, small-molecule inhibitors (L-28 and L-23) targeting prenylated methylated protein methyl esterase (PMPMEase) were tested in the current study. We found that these inhibitors disrupted Gβγ and ΜΤ organization and affected cellular morphology and neurite outgrowth. In further support of a role of Gβγ-MT interaction in neuronal differentiation, it was observed that overexpression of Gβγ in PC12 cells induced neurite outgrowth in the absence of added NGF. Moreover, overexpressed Gβγ exhibited a pattern of association with MTs similar to that observed in NGF-differentiated cells. Conclusions: Altogether, our results demonstrate that βγ subunit of heterotrimeric G proteins play a critical role in neurite outgrowth and differentiation by interacting with MTs and modulating MT rearrangement. Electronic supplementary material The online version of this article (doi:10.1186/s12868-014-0132-4) contains supplementary material, which is available to authorized users