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

An Emerging Model of Creative Game-based Learning

We consider the integration of creative approaches to problem solving into pervasive games is a natural extension of play for creative thinking – one that can innovatively drive technology-led changes to the facilitation of creative thinking and pose a new genre in serious gaming for learning. This paper presents an initial proposal of a new model of creative game-base learning (CGBL), which emerged through mapping of established characteristics of climates that encourage creativity and innovation to characteristics of effective serious games

Single Feature Polymorphism Discovery in Rice

The discovery of nucleotide diversity captured as single feature polymorphism (SFP) by using the expression array is a high-throughput and effective method in detecting genome-wide polymorphism. The efficacy of such method was tested in rice, and the results presented in the paper indicate high sensitivity in predicting SFP. The sensitivity of polymorphism detection was further demonstrated by the fact that no biasness was observed in detecting SFP with either single or multiple nucleotide polymorphisms. The high density SFP data that can be generated quite effectively by the current method has promise for high resolution genetic mapping studies, as physical location of features are well-defined on rice genome

Increased Soil Frost Versus Summer Drought as Drivers of Plant Biomass Responses To Reduced Precipitation: Results from A Globally-Coordinated Field Experiment

Reduced precipitation treatments often are used in field experiments to explore the effects of drought on plant productivity and species composition. However, in seasonally snow-covered regions reduced precipitation also reduces snow cover, which can increase soil frost depth, decrease minimum soil temperatures and increase soil freeze-thaw cycles. Therefore, in addition to the effects of reduced precipitation on plants via drought, freezing damage to overwintering plant tissues at or below the soil surface could further affect plant productivity and relative species abundances during the growing season. We examined the effects of both reduced rainfall (via rain-out shelters) and reduced snow cover (via snow removal) at 13 sites globally (primarily grasslands) within the framework of the International Drought Experiment, a coordinated distributed experiment. Plant cover was estimated at the species level and aboveground biomass was quantified at the functional group level. Among sites, we observed a negative correlation between the snow removal effect on minimum soil temperature and plant biomass production the next growing season. Three sites exhibited significant rain-out shelter effects on plant productivity, but there was no correlation among sites between the rain-out shelter effect on minimum soil moisture and plant biomass. There was no interaction between snow removal and rain-out shelters for plant biomass, although these two factors only exhibited significant effects simultaneously for a single site. Overall, our results reveal that reduced snowfall, when it decreases minimum soil temperatures, can be an important component of the total effect of reduced precipitation on plant productivity

Stimulation of Midbrain Dopaminergic Structures Modifies Firing Rates of Rat Lateral Habenula Neurons

Ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) are midbrain structures known to be involved in mediating reward in rodents. Lateral habenula (LHb) is considered as a negative reward source and it is reported that stimulation of the LHb rapidly induces inhibition of firing in midbrain dopamine neurons. Interestingly, the phasic fall in LHb neuronal activity may follow the excitation of dopamine neurons in response to reward-predicting stimuli. The VTA and SNpc give rise to dopaminergic projections that innervate the LHb, which is also known to be involved in processing painful stimuli. But it's unclear what physiological effects these inputs have on habenular function. In this study we distinguished the LHb pain-activated neurons of the Wistar rats and assessed their electrophysiological responsiveness to the stimulation of the VTA and SNpc with either single-pulse stimulation (300 µA, 0.5 Hz) or tetanic stimulation (80 µA, 25 Hz). Single-pulse stimulation that was delivered to either midbrain structure triggered transient inhibition of firing of ∼90% of the LHb pain-activated neurons. However, tetanic stimulation of the VTA tended to evoke an elevation in neuronal firing rate. We conclude that LHb pain-activated neurons can receive diverse reward-related signals originating from midbrain dopaminergic structures, and thus participate in the regulation of the brain reward system via both positive and negative feedback mechanisms

Genomic Diversity and Introgression in O. sativa Reveal the Impact of Domestication and Breeding on the Rice Genome

The domestication of Asian rice (Oryza sativa) was a complex process punctuated by episodes of introgressive hybridization among and between subpopulations. Deep genetic divergence between the two main varietal groups (Indica and Japonica) suggests domestication from at least two distinct wild populations. However, genetic uniformity surrounding key domestication genes across divergent subpopulations suggests cultural exchange of genetic material among ancient farmers.In this study, we utilize a novel 1,536 SNP panel genotyped across 395 diverse accessions of O. sativa to study genome-wide patterns of polymorphism, to characterize population structure, and to infer the introgression history of domesticated Asian rice. Our population structure analyses support the existence of five major subpopulations (indica, aus, tropical japonica, temperate japonica and GroupV) consistent with previous analyses. Our introgression analysis shows that most accessions exhibit some degree of admixture, with many individuals within a population sharing the same introgressed segment due to artificial selection. Admixture mapping and association analysis of amylose content and grain length illustrate the potential for dissecting the genetic basis of complex traits in domesticated plant populations.Genes in these regions control a myriad of traits including plant stature, blast resistance, and amylose content. These analyses highlight the power of population genomics in agricultural systems to identify functionally important regions of the genome and to decipher the role of human-directed breeding in refashioning the genomes of a domesticated species

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Genetic Architecture of Aluminum Tolerance in Rice (Oryza sativa) Determined through Genome-Wide Association Analysis and QTL Mapping

Aluminum (Al) toxicity is a primary limitation to crop productivity on acid soils, and rice has been demonstrated to be significantly more Al tolerant than other cereal crops. However, the mechanisms of rice Al tolerance are largely unknown, and no genes underlying natural variation have been reported. We screened 383 diverse rice accessions, conducted a genome-wide association (GWA) study, and conducted QTL mapping in two bi-parental populations using three estimates of Al tolerance based on root growth. Subpopulation structure explained 57% of the phenotypic variation, and the mean Al tolerance in Japonica was twice that of Indica. Forty-eight regions associated with Al tolerance were identified by GWA analysis, most of which were subpopulation-specific. Four of these regions co-localized with a priori candidate genes, and two highly significant regions co-localized with previously identified QTLs. Three regions corresponding to induced Al-sensitive rice mutants (ART1, STAR2, Nrat1) were identified through bi-parental QTL mapping or GWA to be involved in natural variation for Al tolerance. Haplotype analysis around the Nrat1 gene identified susceptible and tolerant haplotypes explaining 40% of the Al tolerance variation within the aus subpopulation, and sequence analysis of Nrat1 identified a trio of non-synonymous mutations predictive of Al sensitivity in our diversity panel. GWA analysis discovered more phenotype–genotype associations and provided higher resolution, but QTL mapping identified critical rare and/or subpopulation-specific alleles not detected by GWA analysis. Mapping using Indica/Japonica populations identified QTLs associated with transgressive variation where alleles from a susceptible aus or indica parent enhanced Al tolerance in a tolerant Japonica background. This work supports the hypothesis that selectively introgressing alleles across subpopulations is an efficient approach for trait enhancement in plant breeding programs and demonstrates the fundamental importance of subpopulation in interpreting and manipulating the genetics of complex traits in rice