Lipidomic analysis of human tear fluid reveals structure-specific lipid alterations in dry eye syndrome

As current diagnostic markers for dry eye syndrome (DES) are lacking in both sensitivity and specificity, a pressing concern exists to develop activity markers that closely align with the principal axes of disease progression. In this study, a comprehensive lipidomic platform designated for analysis of the human tear lipidome was employed to characterize changes in tear lipid compositions from a cohort of 93 subjects of different clinical subgroups classified based on the presence of dry eye symptoms and signs. Positive correlations were observed between the tear levels of cholesteryl sulfates and glycosphingolipids with physiological secretion of tears, which indicated the possible lacrimal (instead of meibomian) origin of these lipids. Notably, we found wax esters of low molecular masses and those containing saturated fatty acyl moieties were specifically reduced with disease and significantly correlated with various DES clinical parameters such as ocular surface disease index, tear breakup time, and Schirmer''s I test (i.e., both symptoms and signs). These structure-specific changes in tear components with DES could potentially serve as unifying indicators of disease symptoms and signs. In addition, the structurally-specific aberrations in tear lipids reported here were found in patients with or without aqueous deficiency, suggesting a common pathology for both DES subtypes.     

NAR Breakthrough Article: The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification

Histone tail modifications control many nuclear processes by dictating the dynamic exchange of regulatory proteins on chromatin. Here we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated. Four crystal structures of an extended DPF alone and in complex with unmodified or acetylated forms of the H3 tail reveal the molecular basis of crosstalk between H3K4me3 and H3K14ac. We show for the first time that MOZ DPF induces α-helical conformation of H3K4-T11, revealing a unique mode of H3 recognition. The helical structure facilitates sampling of H3K4 methylation status, and proffers H3K9 and other residues for modification. Additionally, we show that a conserved double glycine hinge flanking the H3 tail helix is required for a conformational change enabling docking of H3K14ac with the DPF. In summary, our data provide the first observations of extensive helical structure in a histone tail, revealing the inherent ability of the H3 tail to adopt alternate conformations in complex with chromatin regulators.     

Experiences of Domestic Violence and Mental Disorders: A Systematic Review and Meta-Analysis

Background

Little is known about the extent to which being a victim of domestic violence is associated with different mental disorders in men and women. We aimed to estimate the prevalence and odds of being a victim of domestic violence by diagnostic category and sex.

Methods

Study design: Systematic review and meta-analysis. Data Sources: Eighteen biomedical and social sciences databases (including MEDLINE, EMBASE, PsycINFO); journal hand searches; scrutiny of references and citation tracking of included articles; expert recommendations, and an update of a systematic review on victimisation and mental disorder. Inclusion criteria: observational and intervention studies reporting prevalence or odds of being a victim of domestic violence in men and women (aged ≥16 years), using validated diagnostic measures of mental disorder. Procedure: Data were extracted and study quality independently appraised by two reviewers. Analysis: Random effects meta-analyses were used to pool estimates of prevalence and odds.

Results

Forty-one studies were included. There is a higher risk of experiencing adult lifetime partner violence among women with depressive disorders (OR 2.77 (95% CI 1.96–3.92), anxiety disorders (OR 4.08 (95% CI 2.39–6.97), and PTSD (OR 7.34 95% CI 4.50–11.98), compared to women without mental disorders. Insufficient data were available to calculate pooled odds for other mental disorders, family violence (i.e. violence perpetrated by a non-partner), or violence experienced by men. Individual studies reported increased odds for women and men for all diagnostic categories, including psychoses, with a higher prevalence reported for women. Few longitudinal studies were found so the direction of causality could not be investigated.

Conclusions

There is a high prevalence and increased likelihood of being a victim of domestic violence in men and women across all diagnostic categories, compared to people without disorders. Longitudinal studies are needed to identify pathways to being a victim of domestic violence to optimise healthcare responses.     

High resolution genetic mapping by genome sequencing reveals genome duplication and tetraploid genetic structure of the diploid Miscanthus sinensis

We have created a high-resolution linkage map of Miscanthus sinensis, using genotyping-by-sequencing (GBS), identifying all 19 linkage groups for the first time. The result is technically significant since Miscanthus has a very large and highly heterozygous genome, but has no or limited genomics information to date. The composite linkage map containing markers from both parental linkage maps is composed of 3,745 SNP markers spanning 2,396 cM on 19 linkage groups with a 0.64 cM average resolution. Comparative genomics analyses of the M. sinensis composite linkage map to the genomes of sorghum, maize, rice, and Brachypodium distachyon indicate that sorghum has the closest syntenic relationship to Miscanthus compared to other species. The comparative results revealed that each pair of the 19 M. sinensis linkages aligned to one sorghum chromosome, except for LG8, which mapped to two sorghum chromosomes (4 and 7), presumably due to a chromosome fusion event after genome duplication. The data also revealed several other chromosome rearrangements relative to sorghum, including two telomere-centromere inversions of the sorghum syntenic chromosome 7 in LG8 of M. sinensis and two paracentric inversions of sorghum syntenic chromosome 4 in LG7 and LG8 of M. sinensis. The results clearly demonstrate, for the first time, that the diploid M. sinensis is tetraploid origin consisting of two sub-genomes. This complete and high resolution composite linkage map will not only serve as a useful resource for novel QTL discoveries, but also enable informed deployment of the wealth of existing genomics resources of other species to the improvement of Miscanthus as a high biomass energy crop. In addition, it has utility as a reference for genome sequence assembly for the forthcoming whole genome sequencing of the Miscanthus genus.     

Sex, age, and family differences in the chemical composition of owl monkey (Aotus nancymaae) subcaudal scent secretions

Numerous behavioral studies have shown that animals use olfactory cues as inbreeding avoidance or kin avoidance mechanisms, implying that scent is unique to families. However, few studies have analyzed the chemical profile of a scent and ascertained the messages that are conveyed in scent secretions. Owl monkeys (Aotus nancymaae) are socially monogamous primates that utilize scent when interacting with foreign conspecifics. This suggests there is a difference in the chemical composition of scent marks. We chemically analyzed sub-caudal gland samples from three families of captive owl monkeys (Aotus nancymaae). Samples were analyzed by capillary GC-MS and relative retention time and fragment pattern was compared with known standards. Gland samples were high in large plant-based shikikate metabolites and fatty ketones; alcohols, acids, and acetates were virtually absent. Gender, age, and family could be reliably classified using discriminant analysis (92.9, 100, and 100%, respectively). Female scent profiles were greater in concentration of aromatic plant metabolites, possibly the result of a different diet or physiological differences in female metabolism as compared to male. Offspring of adult age still living in their natal group showed a less complex chemical profile than their parents. Finally, each family had its own unique and complex chemical profile. The presence of family scent may play a role in mediating social interactions.     

Endothelial progenitor cells in cardiovascular diseases

Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome.     

Endemic infections of Parastrongylus (=Angiostrongylus) costaricensis in two species of nonhuman primates, raccoons, and an opossum from Miami, Florida

Parastrongylus (=Angiostrongylus) costaricensis was first reported in the United States from cotton rats, Sigmodon hispidus, in Texas in 1979. Here, we report the findings of P. costaricensis in a siamang (Hylobates syndactylus) from the Miami MetroZoo, in 2 Ma's night monkeys (Aotus nancymaae) from the DuMond Conservancy located at Monkey Jungle in Miami, in 4 raccoons (Procyon lotor) trapped near the MetroZoo, and in an opossum (Didelphis virginiana) trapped at the MetroZoo. These records are the first records of P. costaricensis from all 4 species of hosts. All of the primates were zoo-born, and the raccoons and opossum were native, indicating that this parasite is now endemic at these 2 sites.