Aberrant DNA Methylation: Implications in Racial Health Disparity

BackgroundIncidence and mortality rates of colorectal carcinoma (CRC) are higher in African Americans (AAs) than in Caucasian Americans (CAs). Deficient micronutrient intake due to dietary restrictions in racial/ethnic populations can alter genetic and molecular profiles leading to dysregulated methylation patterns and the inheritance of somatic to germline mutations.ResultsDNA from the tumor of AA CRC patients, compared to adjacent normal tissues, contained 1,588 hypermethylated and 100 hypomethylated differentially methylated regions (DMRs). Whereas, 109 hypermethylated and 4 hypomethylated DMRs were observed in DNA from the tumor of CA CRC patients; representing a 14.6-fold and 25-fold change, respectively. Specifically; CHL1, 4 anti-inflammatory genes (i.e., NELL1, GDF1, ARHGEF4, and ITGA4), and 7 miRNAs (of which miR-9-3p and miR-124-3p have been implicated in CRC) were hypermethylated in DNA samples from AA patients with CRC. From the same sample set, RNAseq analysis revealed 108 downregulated genes (including 14 ribosomal proteins) and 34 upregulated genes (including POLR2B and CYP1B1 [targets of miR-124-3p]) in AA patients with CRC versus CA patients.ConclusionDNA methylation profile and/or products of its downstream targets could serve as biomarker(s) addressing racial health disparity.     

C-reactive Protein Exists in an NaCl Concentration-dependent Pentamer-Decamer Equilibrium in Physiological Buffer

C-reactive protein (CRP) is an acute phase protein of the pentraxin family that binds ligands in a Ca²⁺-dependent manner, and activates complement. Knowledge of its oligomeric state in solution and at surfaces is essential for functional studies. Analytical ultracentrifugation showed that CRP in 2 mm Ca²⁺ exhibits a rapid pentamer-decamer equilibrium. The proportion of decamer decreased with an increase in NaCl concentration. The sedimentation coefficients s_20,w⁰ of pentameric and decameric CRP were 6.4 S and in excess of 7.6 S, respectively. In the absence of Ca²⁺, CRP partially dissociates into its protomers and the NaCl concentration dependence of the pentamer-decamer equilibrium is much reduced. By x-ray scattering, the radius of gyration R_G values ranged from 3.7 nm for the pentamer to above 4.0 nm for the decamer. An averaged K_D value of 21 μm in solution (140 mm NaCl, 2 mm Ca²⁺) was determined by x-ray scattering and modeling based on crystal structures for the pentamer and decamer. Surface plasmon resonance showed that CRP self-associates on a surface with immobilized CRP with a similar K_D value of 23 μm (140 mm NaCl, 2 mm Ca²⁺), whereas CRP aggregates in low salt. It is concluded that CRP is reproducibly observed in a pentamer-decamer equilibrium in physiologically relevant concentrations both in solution and on surfaces. Both 2 mm Ca²⁺ and 140 mm NaCl are essential for the integrity of CRP in functional studies and understanding the role of CRP in the acute phase response.     

Adiponectin Protein Exists in Aortic Endothelial Cells

Aims

Inflammation is closely associated with the development of atherosclerosis and metabolic syndrome. Adiponectin, an adipose-derived secretory protein, possesses an anti-atherosclerotic property. The present study was undertaken to elucidate the presence and significance of adiponectin in vasculature.

Methods and Results

Immunofluorescence staining was performed in aorta of wild-type (WT) mice and demonstrated that adiponectin was co-stained with CD31. Thoracic aorta was cut through and then aortic intima was carefully shaved from aorta. Western blotting showed the existence of adiponectin protein in aortic intima, while there was no adiponectin mRNA expression. Adiponectin knockout (Adipo-KO) and WT mice were administered with a low-dose and short-term lipopolysaccharide (LPS) (1 mg/kg of LPS for 4 hours). The endothelium vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were highly increased in Adipo-KO mice compared to WT mice after LPS administration.

Conclusions

Adiponectin protein exists in aortic endothelium under steady state and may protect vasculature from the initiation of atherosclerosis.     

Phylogenomic Analysis Reveals Deep Divergence and Recombination in an Economically Important Grapevine Virus

The evolutionary history of the exclusively grapevine (Vitis spp.) infecting, grapevine leafroll-associated virus 3 (GLRaV-3) has not been studied extensively, partly due to limited available sequence data. In this study we trace the evolutionary history of GLRaV-3, focussing on isolate GH24, a newly discovered variant. GH24 was discovered through the use of next-generation sequencing (NGS) and the whole genome sequence determined and validated with Sanger sequencing. We assembled an alignment of all 13 available whole genomes of GLRaV-3 isolates and all other publicly available GLRaV-3 sequence data. Using multiple recombination detection methods we identified a clear signal for recombination in one whole genome sequence and further evidence for recombination in two more, including GH24. We inferred phylogenetic trees and networks and estimated the ages of common ancestors of GLRaV-3 clades by means of relaxed clock models calibrated with asynchronous sampling dates. Our results generally confirm previously identified variant groups as well as two new groups (VII and VIII). Higher order groups were defined as supergroups designated A to D. Supergroup A includes variant groups I-V and supergroup B group VI and its related unclassified isolates. Supergroups C and D are less well known, including the newly identified groups VII (including isolate GH24) and VIII respectively. The inferred node ages suggest that the origins of the major groups of GLRaV-3, including isolate GH24, may have occurred prior to worldwide cultivation of grapevines, whilst the current diversity represents closely related isolates that diverged from common ancestors within the last century.     

Public Health Risks of Multiple-Drug-Resistant Enterococcus spp. in Southeast Asia

Enterococci rank as one of the leading causes of nosocomial infections, such as urinary tract infections, surgical wound infections, and endocarditis, in humans. These infections can be hard to treat because of the rising incidence of antibiotic resistance. Enterococci inhabiting nonhuman reservoirs appear to play a critical role in the acquisition and dissemination of antibiotic resistance determinants. The spread of antibiotic resistance has become a major concern in both human and veterinary medicine, especially in Southeast Asia, where many developing countries have poor legislation and regulations to control the supply and excessive use of antimicrobials. This review addresses the occurrence of antibiotic-resistant enterococci in Association of Southeast Asian Nations countries and proposes infection control measures that should be applied to limit the spread of multiple-drug-resistant enterococci.     

Ruminant‐mediated Seed Dispersal of an Economically Valuable Tree in Indian Dry Forests1

Ruminant‐mediated seed dispersal, an understudied process in tropical forests, was examined via Phyllanthus emblica–Axis axis interaction. A captive Axis deer regurgitated intact P. emblica seeds after retaining them in the rumen for 7–27 h. At Rajaji National Park, a considerable fraction (22%) of deer‐regurgitated P. emblica seeds germinated, although lower than unconsumed seeds (72%). The size and strength of seeds like P. emblica might ensure that ruminants regurgitate them intact instead of defecating them.     

Introducing One Health to the Ethical Debate About Zoonotic Diseases in Southeast Asia

Pandemic plans recommend phases of response to an emergent infectious disease (EID) outbreak, and are primarily aimed at preventing and mitigating human‐to‐human transmission. These plans carry presumptive weight and are increasingly being operationalized at the national, regional and international level with the support of the World Health Organization (WHO). The conventional focus of pandemic preparedness for EIDs of zoonotic origin has been on public health and human welfare. However, this focus on human populations has resulted in strategically important disciplinary silos. As the risks of zoonotic diseases have implications that reach across many domains outside traditional public health, including anthropological, environmental, and veterinary fora, a more inclusive ecological perspective is paramount for an effective response to future outbreaks.