Structural insights of resveratrol with its binding partners in the toll-like receptor 4 pathway

The benefits associated with resveratrol (Resv; 3,4′,5-trihydroxy-trans-stilbene) are known for a long time. The therapeutic properties of Resv are observed in diseases like cancer, neurological disorders, atherosclerosis, aging, inflammation, etc. Multiple studies suggest that the beneficial properties of Resv are due to its binding to targets in multiple pathways. The same has been reflected in inflammation, where Resv has been shown to inhibit nuclear factor κ light-chain enhancer of activated B cells in the toll-like receptor 4 (TLR4) pathway. There are multiple cellular targets which bind to Resv, however the mode and the key interactions involved remain elusive for many of them. In the current work, we have investigated the structural insights of Resv with three of its binding partners involved in the inflammatory TLR4 signaling pathway. Through a structure-based modelling and molecular dynamics study, we have unraveled the molecular and atomic interactions involved in the Resv-binary complexes of inhibitor of κB kinase, cyclooxygeanse-2, and tank-binding kinase I, all three of which are key players in TLR4 inflammatory signaling. This study is the latest addition to the investigations of the structural partners of Resv and its molecular interactions.     

Genetic diversity of hop stunt viroid from symptomatic and asymptomatic citrus trees in Iran

Hop stunt viroid as the causal agent of cachexia disease has detected from citrus trees in different areas in Iran. Although cachexia has not been reported as a decline disease for citrus trees, it can impair crop quality and reduce plant yields. This study was undertaken to molecularly detect HSVd among different commercial citrus cultivars and determine genetic diversity of this viroid in Mazandaran province of Iran. Sampling was performed from symptomatic and symptomless citrus cultivars in Mazandaran province. HSVd specific primers were used for molecular detection. SSCP and sequencing were applied to assay HSVd genetic diversity. Results showed the detection of HSVd in all symptomatic Satsuma (25 out of 25), Clementine (25 out of 25), sweet lime (20 out of 20) and sweet orange cv. Valencia (7 out of 7), as well as, 31% (14 out of 22), 100% (12 out of 12) and 33% (5 out of 15) of page mandarin, lemon and grapefruit trees, respectively. 10 different HSVd genomes were identified by sequencing the SSCP profiles among which HSVd‐IR1 had the most frequency.     

Whole-genome sequencing and gene sharing network analysis powered by machine learning identifies antibiotic resistance sharing between animals,humans and environment in livestock farming

Anthropogenic environments such as those created by intensive farming of livestock, have been proposed to provide ideal selection pressure for the emergence of antimicrobial-resistant Escherichia coli bacteria and antimicrobial resistance genes (ARGs) and spread to humans. Here, we performed a longitudinal study in a large-scale commercial poultry farm in China, collecting E. coli isolates from both farm and slaughterhouse; targeting animals, carcasses, workers and their households and environment. By using whole-genome phylogenetic analysis and network analysis based on single nucleotide polymorphisms (SNPs), we found highly interrelated non-pathogenic and pathogenic E. coli strains with phylogenetic intermixing, and a high prevalence of shared multidrug resistance profiles amongst livestock, human and environment. Through an original data processing pipeline which combines omics, machine learning, gene sharing network and mobile genetic elements analysis, we investigated the resistance to 26 different antimicrobials and identified 361 genes associated to antimicrobial resistance (AMR) phenotypes; 58 of these were known AMR-associated genes and 35 were associated to multidrug resistance. We uncovered an extensive network of genes, correlated to AMR phenotypes, shared among livestock, humans, farm and slaughterhouse environments. We also found several human, livestock and environmental isolates sharing closely related mobile genetic elements carrying ARGs across host species and environments. In a scenario where no consensus exists on how antibiotic use in the livestock may affect antibiotic resistance in the human population, our findings provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. Moreover, our original data analysis method has the potential to uncover AMR transmission pathways when applied to the study of other pathogens active in other anthropogenic environments characterised by complex interconnections between host species.     

Neutral space analysis for a Boolean network model of the fission yeast cell cycle network

Background

Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gene expression, such as the cell cycle, which can be analyzed through its GRN, where deregulation can lead to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast. An approach to study the robustness of GRN is through the neutral space. In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks that share the same state sequences of the fission yeast cell cycle.

Results

Through simulations it was found that in the generated neutral graph, the functional networks that are not in the wildtype connected component have in general a Hamming distance more than 3 with the wildtype, and more than 10 between the other disconnected functional networks. Significant differences were found between the functional networks in the connected component of the wildtype network and the rest of the network, not only at a topological level, but also at the state space level, where significant differences in the distribution of the basin of attraction for the G₁ fixed point was found for deterministic updating schemes.

Conclusions

In general, functional networks in the wildtype network connected component, can mutate up to no more than 3 times, then they reach a point of no return where the networks leave the connected component of the wildtype. The proposed method to construct a neutral graph is general and can be used to explore the neutral space of other biologically interesting networks, and also formulate new biological hypotheses studying the functional networks in the wildtype network connected component.     

Oxidative stress indicators and trace elements in the blue shark (Prionace glauca) off the east coast of the Mexican Pacific Ocean

Trace element concentrations and oxidative stress indicators (including production of reactive oxygen species (ROS), antioxidant enzyme activities and oxidative damage) were measured in muscle of blue sharks collected along the west coast of Baja California Sur to determine potential differences by sex and maturity cohorts. Mercury (Hg) concentration in muscle samples from larger sharks (>200 cm LT) exceeded the permissible limit (>1 ppm wet weight) for human consumption set by numerous international agencies. Significant differences were found in Hg concentrations (mature>immature; males>females), and in protein carbonyl concentrations (male>female); however, except for carbonyl protein levels, no significant differences by sex or maturity stage were found in the oxidative stress indicators. Differences between sexes and maturity stages in trace element concentration and carbonyl protein levels in blue shark muscle may be related to variations in diet within different cohorts.     

Factors associated with early initiation of breastfeeding among Nepalese mothers: further analysis of Nepal Demographic and Health Survey, 2011

Background

Timely initiation of breastfeeding has been reported to reduce neonatal mortality by 19.1%. The World Health Organisation recommends early initiation of breastfeeding i.e. breastfeeding a newborn within the first hour of life. Knowledge on the rate and the determinants of early initiation of breastfeeding may help health program managers to design and implement effective breastfeeding promotion programs. The aim of this study was to determine the rate and the determinants of early initiation of breastfeeding in Nepal.

Methods

This study used the data from Nepal Demographic and Health Survey (NDHS) 2011 which is a nationally representative sample study. Chi square test and multiple logistic regression analysis were used to examine the factors associated with early initiation of breastfeeding (within one hour of birth).

Results

Of 4079 mothers, 66.4% initiated breastfeeding within one hour of delivery. Mothers with higher education (Odds Ratio (OR) 2.56; 95% CI : 1.26, 5.21), mothers of disadvantaged Janjati ethnicity (OR 1.43; 95% CI : 1.04, 1.94), mothers who were involved in agriculture occupation (OR 1.51; 95% CI : 1.16, 1.97), mothers who delivered in a health facility (OR 1.67; 95% CI : 1.25, 2.23), whose children were large at birth (OR 1.46; 95% CI : 1.07, 1.99) were more likely to initiate breastfeeding within the first hour of child birth.

Conclusions

Results suggest that two thirds of children in Nepal were breastfed within the first hour after birth. Although there was a higher prevalence of early initiation of breastfeeding among mothers who delivered in health facilities compared to mothers who delivered at home, universal practice of early initiation of breastfeeding should be a routine practice. The findings suggest the need of breastfeeding promotion programs among the mothers who are less educated, and not working. Such breastfeeding promotion programmes could be implemented via Nepal’s extensive network of community-based workers.

     

Isolation and 16S rRNA sequence analysis of the beneficial bacteria from the rhizosphere of rice

The present study deals with the isolation of plant growth promoting rhizobacteria (PGPR) from rice (variety NIAB IRRI-9) and the beneficial effects of these inoculants on two Basmati rice varieties. Nitrogen-fixing activity (acetylene-reduction activity) was detected in the roots and submerged shoots of field-grown rice variety NIAB IRRI-9. Estimation of the population size of diazotrophic bacteria by ARA-based MPN (acetylene reduction assay-based most probable number) in roots and shoots indicated about 10(5)-10(6) counts/g dry weight at panicle initiation and grain filling stages. Four bacterial isolates from rice roots and shoots were obtained in pure culture which produced phytohormone indoleacetic acid (IAA) in the growth medium. Among these, three isolates S1, S4, and R3 reduced acetylene to ethylene in nitrogen-free semi-solid medium. Morphological and physiological characteristics of the isolates indicated that three nitrogen-fixing isolates S1, S4, and R3 belonged to the genus Enterobacter, while the non-fixing isolate R8 belonged to the genus Aeromonas. 16S rRNA sequence of one isolate from root (R8) and one isolate from shoot (S1) was obtained which confirmed identification of the isolates as Aeromonas veronii and Enterobacter cloacae, respectively. The 1517-nucleotide-long sequence of the isolate R8 showed 99% similarity with Aeromonas veronii (accession No. AF099023) while partial 16S rRNA sequence (two stretches of total 1271 nucleotide length) of S1 showed 97% similarity with the sequence of Enterobacter cloacae (accession No. AJ251469). The seedlings of two rice varieties Basmati 385 and Super Basmati were inoculated with the four bacterial isolates from rice and one Azospirillum brasilense strain Wb3, which was isolated from wheat. In the rice variety Basmati 385, maximum increase in root area and plant biomass was obtained in plants inoculated with Enterobacter S1 and Azospirillum Wb3, whereas in the rice variety Super Basmati, inoculation with Enterobacter R3 resulted in maximum increase of root area and plant biomass. Nitrogen fixation was quantified by using 15N isotopic dilution method. Maximum fixation was observed in Basmati 385 with the inoculants Azospirillum Wb3 and Enterobacter S1 where nearly 46% and 41% of the nitrogen was derived from atmosphere (%Ndfa), respectively. In general, higher nitrogen fixation was observed in variety Basmati 385 than in Super Basmati, and different bacterial strains were found more effective as inoculants for the rice varieties Basmati 385 and Super Basmati.     

Thyroid hormone status regulates the expression of secretory phospholipases

Thyroid hormone (T3) stimulates various metabolic pathways and the hepatic actions of T3 are mediated primarily through the thyroid hormone receptor beta (TRβ). Hypothyroidism has been linked with low grade inflammation, elevated risk of hepatic steatosis and atherosclerosis. Secretory phospholipases (sPLA2) are associated with inflammation, hyperlipidemia and atherosclerosis. Due to potential linkage between thyroid hormone and sPLA2, we investigated the effect of thyroid hormone status on the regulation of secretory phospholipases in mice, rats and human liver. T3 suppressed the expression of the sPLA2 group IIa (PLA2g2a) gene in the liver of BALB/c mice and C57BL/6 transgenic mice expressing the human PLA2g2a. PLA2g2a was elevated with hypothyroidism and high fat diets which may contribute to the low grade inflammation associated with hypothyroidism and diet induced obesity. We also examined the effects of the TRβ agonist eprotirome on hepatic gene regulation. We observed that eprotirome inhibited the expression of selected sPLA2 genes and furthermore the cytokine mediated induction PLA2g2a was suppressed. In addition, eprotirome induced genes involved in fatty acid oxidation and cholesterol clearance while inhibiting lipogenic genes. Our results indicate that in vivo thyroid hormone status regulates the abundance of sPLA2 and the inhibition of PLA2g2a by T3 is conserved across species. By regulating sPLA2 genes, T3 may impact processes associated with atherosclerosis and inflammation and TRβ agonists may ameliorate inflammation and hyperlipidemia.     

Historical,Observed, and Modeled Wildfire Severity in Montane Forests of the Colorado Front Range

Large recent fires in the western U.S. have contributed to a perception that fire exclusion has caused an unprecedented occurrence of uncharacteristically severe fires, particularly in lower elevation dry pine forests. In the absence of long-term fire severity records, it is unknown how short-term trends compare to fire severity prior to 20^th century fire exclusion. This study compares historical (i.e. pre-1920) fire severity with observed modern fire severity and modeled potential fire behavior across 564,413 ha of montane forests of the Colorado Front Range. We used forest structure and tree-ring fire history to characterize fire severity at 232 sites and then modeled historical fire-severity across the entire study area using biophysical variables. Eighteen (7.8%) sites were characterized by low-severity fires and 214 (92.2%) by mixed-severity fires (i.e. including moderate- or high-severity fires). Difference in area of historical versus observed low-severity fire within nine recent (post-1999) large fire perimeters was greatest in lower montane forests. Only 16% of the study area recorded a shift from historical low severity to a higher potential for crown fire today. An historical fire regime of more frequent and low-severity fires at low elevations (<2260 m) supports a convergence of management goals of ecological restoration and fire hazard mitigation in those habitats. In contrast, at higher elevations mixed-severity fires were predominant historically and continue to be so today. Thinning treatments at higher elevations of the montane zone will not return the fire regime to an historic low-severity regime, and are of questionable effectiveness in preventing severe wildfires. Based on present-day fuels, predicted fire behavior under extreme fire weather continues to indicate a mixed-severity fire regime throughout most of the montane forest zone. Recent large wildfires in the Front Range are not fundamentally different from similar events that occurred historically under extreme weather conditions.