Diabetes (db/db) mutation-induced endometrial epithelial lipoapoptosis: Ultrastructural and cytochemical analysis of reproductive tract atrophy

BACKGROUND: The diabetes (db/db) mutation in C57BL/KsJ mice promotes a progressive cytolipidemia within the endometrial epithelial (EE) layer of the female reproductive tract which results in premature cellular and organ atrophy. The current studies focus on the ultrastructural and cytochemical changes which promote nuclear apoptosis and cytostructural disruption following the expression of endometrial hypercytolipidemia which promotes diabetes-associated organoinvolution and manifest infertility. METHODS: Control (normal:+/+) and diabetes (db/db) genotype groups were prepared for high resolution light microscopic analysis of cytolipidemia and nuclear apoptosis (TUNEL-labeled 3'-DNA fragmentation) indices and compared to the transmission electron (TEM) microscopic analysis of endometrial tissue samples collected from 8–16 week-old groups. RESULTS: Compared to controls, db/db mutation expression induced a dramatic increase in EE cytolipid vacuole volume and density within the epithelial endometrial layer. TEM analysis revealed that cytolipid vacuole accumulations initially aggregated at the baso-polar regions of UEE cells in response to the systemic hyperglycemic/hypertriglyceridemic conditions which characterized the (db/db) groups. Progressive cytoplasmic movement of the lipid pools into perinuclear compartments of affected EE cells induced nuclear isolation from organelles that were displaced towards peripheral cytoplasmic compartments. Cytochemical analysis of lipid vacuole accumulations indicated attraction towards, and incorporation within, the nuclear envelope of hyperlipidemic cells. Co-localization of nuclear apoptotic 3'-DNA fragments within identified hyperlipidemic EE cells was coincident with the cytochemical and ultrastructural identification of lipid penetration through the nuclear envelope in db/db mutants. CONCLUSION: These results are the first cytochemical indication that the metabolic disturbances in db/db mutants which promote hypercytolipidemia are coincident with lipoapoptosis-induced nuclear dissolution, as denoted by DNA fragmentation analysis. The lipidemia-induced alterations in intracellular organelle and nuclear architectures suggests that the metabolic disturbances in glucose and lipid metabolic cascades in diabetes (db/db) mutants disrupts cytointegrity, culminating in nuclear disregulation (as indicated by lipoapoptosis) and eventual premature reproductive tract organoinvolution and resultant, manifest, reproductive sterility

Influences of obese (ob/ob) and diabetes (db/db) genotype mutations on lumber vertebral radiological and morphometric indices: Skeletal deformation associated with dysregulated systemic glucometabolism

BACKGROUND: Both diabetes and obesity syndromes are recognized to promote lumbar vertebral instability, premature osteodegeneration, exacerbate progressive osteoporosis and increase the propensity towards vertebral degeneration, instability and deformation in humans. METHODS: The influences of single-gene missense mutations, expressing either diabetes (db/db) or obese (ob/ob) metabolic syndromes on vertebral maturation and development in C57BL/KsJ mice were evaluated by radiological and macro-morphometric analysis of the resulting variances in osteodevelopment indices relative to control parameters between 8 and 16 weeks of age (syndrome onset @ 4 weeks), and the influences of low-dose 17-B-estradiol therapy on vertebral growth expression evaluated. RESULTS: Associated with the indicative genotypic obesity and hyper-glycemic/-insulinemic states, both db/db and ob/ob mutants demonstrated a significant (P ≤ 0.05) elongation of total lumbar vertebrae column (VC) regional length, and individual lumbar vertebrae (LV1-5) lengths, relative to control VC and LV parameters. In contrast, LV1-5 width indices were suppressed in db/db and ob/ob mutants relative to control LV growth rates. Between 8 and 16 weeks of age, the suppressed LV1-5 width indices were sustained in both genotype mutant groups relative to control osteomaturation rates. The severity of LV1-5 width osteosuppression correlated with the severe systemic hyperglycemic and hypertriglyceridemic conditions sustained in ob/ob and db/db mutants. Low-dose 17-B-estradiol therapy (E2-HRx: 1.0 ug/ 0.1 ml oil s.c/3.5 days), initiated at 4 weeks of age (i.e., initial onset phase of db/db and ob/ob expressions) re-established control LV 1–5 width indices without influencing VC or LV lengths in db/db groups. CONCLUSION: These data demonstrate that the abnormal systemic endometabolic states associated with the expression of db/db and ob/ob genomutation syndromes suppress LV 1–5 width osteomaturation rates, but enhanced development related VC and LV length expression, relative to control indices in a progressive manner similar to recognized human metabolic syndrome conditions. Therapeutic E2 modulation of the hyperglycemic component of diabetes-obesity syndrome protected the regional LV from the mutation-induced osteopenic width-growth suppression. These data suggest that these genotype mutation models may prove valuable for the evaluation of therapeutic methodologies suitable for the treatment of human diabetes- or obesity-influenced, LV degeneration-linked human conditions, which demonstrate amelioration from conventional replacement therapies following diagnosis of systemic syndrome-induced LV osteomaturation-associated deformations

Estrogen Modulation of Uterine Adrenergic-Cholinergic Interaction: Effects on Vasoactivity and Adrenergic Receptors in the Guinea Pig1

ABSTRACT ABBREVIATIONS: UBF, uterine blood flow; NE, norepinephrine; DHA, dihydroalprenolol; DHE, dihydroergocryptine; OVX, ovanectomized; ACh, acetylchohine; 5-HT, 5-hydroxytryptamine

Worldwide genetic diversity for mineral element concentrations in rice grain

With the aim of identifying rice (Oryza spp.) germplasm having enhanced grain nutritional value, the mineral nutrient and trace element concentrations (or ionome) of whole (unmilled) grains from a set of 1763 rice accessions of diverse geographic and genetic origin were evaluated. Seed for analysis of P, Mg, K, S, Ca, As, Cd, Co, Cu, Fe, Mn, Mo, Ni, Rb, Sr, and Zn concentrations by inductively coupled plasma mass spectrometry was produced over 2 yr in Beaumont, TX, under both flooded and unflooded watering regimes. The distributions of all element concentrations analyzed were skewed toward higher concentration. A significant portion of this ionomic variation has a genetic basis (broad sense heritabilities 0.14–0.75), indicating an ability to breed for improved grain concentration of all elements except possibly Ni. Variation in grain elemental concentrations was not strongly associated with plant height, heading time, or grain shape, suggesting these physiological factors are not of primary importance in controlling ionomic variation in rice grain. Accessions high in specific elements were sometimes found to have similar genetic or geographic origins, suggesting they share a heritable mechanism underlying their enhanced ionomes. For example, accessions with high Ca, Mg, or K were more common in the indica than in the japonica subgroup; low As was most common among temperate japonica accessions; and several lines high in Mo originated in Malaysia or adjacent Brunei

Next Generation Mapping of Enological Traits in an F2 Interspecific Grapevine Hybrid Family

In winegrapes (Vitis spp.), fruit quality traits such as berry color, total soluble solids content (SS), malic acid content (MA), and yeast assimilable nitrogen (YAN) affect fermentation or wine quality, and are important traits in selecting new hybrid winegrape cultivars. Given the high genetic diversity and heterozygosity of Vitis species and their tendency to exhibit inbreeding depression, linkage map construction and quantitative trait locus (QTL) mapping has relied on F1 families with the use of simple sequence repeat (SSR) and other markers. This study presents the construction of a genetic map by single nucleotide polymorphisms identified through genotyping-by-sequencing (GBS) technology in an F2 mapping family of 424 progeny derived from a cross between the wild species V. riparia Michx. and the interspecific hybrid winegrape cultivar, ‘Seyval’. The resulting map has 1449 markers spanning 2424 cM in genetic length across 19 linkage groups, covering 95% of the genome with an average distance between markers of 1.67 cM. Compared to an SSR map previously developed for this F2 family, these results represent an improved map covering a greater portion of the genome with higher marker density. The accuracy of the map was validated using the well-studied trait berry color. QTL affecting YAN, MA and SS related traits were detected. A joint MA and SS QTL spans a region with candidate genes involved in the malate metabolism pathway. We present an analytical pipeline for calling intercross GBS markers and a high-density linkage map for a large F2 family of the highly heterozygous Vitis genus. This study serves as a model for further genetic investigations of the molecular basis of additional unique characters of North American hybrid wine cultivars and to enhance the breeding process by marker-assisted selection. The GBS protocols for identifying intercross markers developed in this study can be adapted for other heterozygous species

Game feature and expertise effects on experienced richness, control and engagement in game play

The extent to which game play is experienced as engaging is an important criterion for the playability of video games. This study investigates how video games can be designed towards increased levels of experienced engagement over time. For this purpose, two experiments were conducted in which a total of 35 participants repeatedly played a video game. Results indicate that experienced engagement is based on the extent to which the game provides rich experiences as well as by the extent to which the game provides a sense of control. In view of the influence of both game features and players’ expertise on the levels of experienced richness and control, it is concluded that game features should be modified over time to maintain optimal levels of engagement