Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

Background The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.Children’s Discovery InstituteMarch of Dimes Birth Defects FoundationNational Institute of General Medical Sciences (U.S.) (grant T32 GM081739)Washington University (Saint Louis, Mo.) (Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study)Sigrid Jusélius FoundationSigne and Anne Gyllenberg FoundationAcademy of FinlandVanderbilt University (Turner-Hazinski grant award

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

The Use of DMA to Reduce Robin Depredation on Cherries

The use of a biorational pesticide, Dimethyl Anthrantlate (DMA), was investigated for possible use as a robin repellant in an Eastern Washington Research orchard. Applied in low concentrations (2, 4, and 8% with surfactant), robin depredation was reduced an average of 75%. A double-blind taste test showed no consumer aversion for fresh fruit sprayed with DMA two weeks before harvest

Biochemical description of fresh produce quality factors

Purpose of review: Consumer appreciation of nutritional value and putative disease prevention roles has fostered worldwide increases in fresh fruit consumption. Preservation of fresh fruit quality remains a postharvest challenge for the perishables industry. Many biochemical factors influence the consumer's perception of quality. Using examples from widely studied fruits, this review focuses on recent developments in general areas associated with quality assessment, and quality changes in the postharvest environment. Recent findings: The principal biochemical components that contribute to the consumer perception of quality can be separated into three major classes: (1) those associated with “mouth feel”, ie, firmness and texture; (2) those associated with taste, eg, sweetness, acidity, aroma/flavor, and astringency ; and (3) those components that contribute to appearance, notably color and surface finish. Objective measurement of texture is possible using a variety of destructive instrumentation, with progress in development of non-destructive technologies with possible on-line applications. Our understanding of cell wall architecture and biochemical components therein has advanced, establishing the relationship between cell wall modifying enzymes and textural softening. Sensory correlations between several types of objective measurements are still being investigated. Advanced sweetness and acidity measurement technologies are well-developed, with many studies regarding postharvest changes and the influence on sensory quality. Volatile aroma production remains an active area of investigation, both in the analytical and sensory disciplines. Postharvest storage and handling influence volatile development. Phenolic substance measurement has enjoyed renewed popularity due to the putative neutraceutical benefits, with more emphasis on radical scavenging capability. Exploitation of genomic and biotechnological tools (gene isolation, cloning and expression studies) has resulted in initial quality trait heritability studies. Limitations: Challenges still remain. Fruit eating quality factors are very complex traits that are influenced by the interaction of genome, growing conditions, and harvest maturity, as well as postharvest handling and storage. Fundamental mechanisms responsible for changes in quality are not completely understood, as most biochemical pathways that determine quality traits are still being identified. Directions for future research: Consumer perception of fruit quality by consumer sensory analysis, combined with instrumental analysis should further define the relationship of individual components responsible for texture, taste and aroma to the total “quality experience”. This includes the role of changes in cell wall components, turgor, sugar and acid transformations, and volatile aroma compound changes in relation to instrumental and sensory testing. Through application of biochemical, genomic, proteomic and microscopic methods to determine fundamental metabolism and its control, the true nature of "ripeness", "eating quality" and "freshness" of fruit products will be revealed, facilitating employment of modern storage and handling technologies for preservation of same

Abstract

ii ACKNOWLEDGEMENT I express my greatest gratitude to my advisor Dr. Juming Tang for his guidance, support, consistent encouragement, and great patience throughout my studies and research. Because of his insightful advices, understanding and moral support, I could stay focused on my PhD research. I also express my sincere thanks to my doctoral committee members: Drs