Pre-anthesis ovary development determines genotypic differences in potential kernel weight in sorghum

Kernel weight is an important factor determining grain yield and nutritional quality in sorghum, yet the developmental processes underlying the genotypic differences in potential kernel weight remain unclear. The aim of this study was to determine the stage in development at which genetic effects on potential kernel weight were realized, and to investigate the developmental mechanisms by which potential kernel weight is controlled in sorghum. Kernel development was studied in two field experiments with five genotypes known to differ in kernel weight at maturity. Pre-fertilization floret and ovary development was examined and post-fertilization kernel-filling characteristics were analysed. Large kernels had a higher rate of kernel filling and contained more endosperm cells and starch granules than normal-sized kernels. Genotypic differences in kernel development appeared before stamen primordia initiation in the developing florets, with sessile spikelets of large-seeded genotypes having larger floret apical meristems than normal-seeded genotypes. At anthesis, the ovaries for large-sized kernels were larger in volume, with more cells per layer and more vascular bundles in the ovary wall. Across experiments and genotypes, there was a significant positive correlation between kernel dry weight at maturity and ovary volume at anthesis. Genotypic effects on meristem size, ovary volume, and kernel weight were all consistent with additive genetic control, suggesting that they were causally related. The pre-fertilization genetic control of kernel weight probably operated through the developing pericarp, which is derived from the ovary wall and potentially constrains kernel expansion

Weak pairwise correlations imply strongly correlated network states in a neural population

Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher order interactions among large groups of elements play an important role. In the vertebrate retina, we show that weak correlations between pairs of neurons coexist with strongly collective behavior in the responses of ten or more neurons. Surprisingly, we find that this collective behavior is described quantitatively by models that capture the observed pairwise correlations but assume no higher order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behavior. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.Comment: Full account of work presented at the conference on Computational and Systems Neuroscience (COSYNE), 17-20 March 2005, in Salt Lake City, Utah (http://cosyne.org

Pre-anthesis ovary development determines genotypic differences in potential kernel weight in sorghum

Kernel weight is an important factor determining grain yield and nutritional quality in sorghum, yet the developmental processes underlying the genotypic differences in potential kernel weight remain unclear. The aim of this study was to determine the stage in development at which genetic effects on potential kernel weight were realized, and to investigate the developmental mechanisms by which potential kernel weight is controlled in sorghum. Kernel development was studied in two field experiments with five genotypes known to differ in kernel weight at maturity. Pre-fertilization floret and ovary development was examined and post-fertilization kernel-filling characteristics were analysed. Large kernels had a higher rate of kernel filling and contained more endosperm cells and starch granules than normal-sized kernels. Genotypic differences in kernel development appeared before stamen primordia initiation in the developing florets, with sessile spikelets of large-seeded genotypes having larger floret apical meristems than normal-seeded genotypes. At anthesis, the ovaries for large-sized kernels were larger in volume, with more cells per layer and more vascular bundles in the ovary wall. Across experiments and genotypes, there was a significant positive correlation between kernel dry weight at maturity and ovary volume at anthesis. Genotypic effects on meristem size, ovary volume, and kernel weight were all consistent with additive genetic control, suggesting that they were causally related. The pre-fertilization genetic control of kernel weight probably operated through the developing pericarp, which is derived from the ovary wall and potentially constrains kernel expansion

Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types

Measurement of the Spectral Shape of the beta-decay of 137Xe to the Ground State of 137Cs in EXO-200 and Comparison with Theory

We report on a comparison between the theoretically predicted and experimentally measured spectra of the first-forbidden non-unique $\beta$-decay transition ^{137}\textrm{Xe}(7/2^-)\to\,^{137}\textrm{Cs}(7/2^+). The experimental data were acquired by the EXO-200 experiment during a deployment of an AmBe neutron source. The ultra-low background environment of EXO-200, together with dedicated source deployment and analysis procedures, allowed for collection of a pure sample of the decays, with an estimated signal-to-background ratio of more than 99-to-1 in the energy range from 1075 to 4175 keV. In addition to providing a rare and accurate measurement of the first-forbidden non-unique $\beta$-decay shape, this work constitutes a novel test of the calculated electron spectral shapes in the context of the reactor antineutrino anomaly and spectral bump.Comment: Version as accepted by PR

Exogenous transforming growth factor-β1 and its helminth-derived mimic attenuate the heart's inflammatory response to ischemic injury and reduce mature scar size

Coronary reperfusion after acute ST-elevation myocardial infarction (STEMI) is standard therapy to salvage ischemic heart muscle. However, subsequent inflammatory responses within the infarct lead to further loss of viable myocardium. Transforming growth factor (TGF)-β1 is a potent anti-inflammatory cytokine released in response to tissue injury. The aim of this study was to investigate the protective effects of TGF-β1 after MI. In patients with STEMI, there was a significant correlation (P = 0.003) between higher circulating TGF-β1 levels at 24 hours after MI and a reduction in infarct size after 3 months, suggesting a protective role of early increase in circulating TGF-β1. A mouse model of cardiac ischemia reperfusion was used to demonstrate multiple benefits of exogenous TGF-β1 delivered in the acute phase. It led to a significantly smaller infarct size (30% reduction, P = 0.025), reduced inflammatory infiltrate (28% reduction, P = 0.015), lower intracardiac expression of inflammatory cytokines IL-1β and chemokine (C-C motif) ligand 2 (>50% reduction, P = 0.038 and 0.0004, respectively) at 24 hours, and reduced scar size at 4 weeks (21% reduction, P = 0.015) after reperfusion. Furthermore, a low-fibrogenic mimic of TGF-β1, secreted by the helminth parasite Heligmosomoides polygyrus, had an almost identical protective effect on injured mouse hearts. Finally, genetic studies indicated that this benefit was mediated by TGF-β signaling in the vascular endothelium

Genetic Variation in VEGF Does Not Contribute Significantly to the Risk of Congenital Cardiovascular Malformation

Several previous studies have investigated the role of common promoter variants in the vascular endothelial growth factor (VEGF) gene in causing congenital cardiovascular malformation (CVM). However, results have been discrepant between studies and no study to date has comprehensively characterised variation throughout the gene. We genotyped 771 CVM cases, of whom 595 had the outflow tract malformation Tetralogy of Fallot (TOF), and carried out TDT and case-control analyses using haplotype-tagging SNPs in VEGF. We carried out a meta-analysis of previous case-control or family-based studies that had typed VEGF promoter SNPs, which included an additional 570 CVM cases. To identify rare variants potentially causative of CVM, we carried out mutation screening in all VEGF exons and splice sites in 93 TOF cases. There was no significant effect of any VEGF haplotype-tagging SNP on the risk of CVM in our analyses of 771 probands. When the results of this and all previous studies were combined, there was no significant effect of the VEGF promoter SNPs rs699947 (OR 1.05 [95% CI 0.95–1.17]); rs1570360 (OR 1.17 [95% CI 0.99–1.26]); and rs2010963 (OR 1.04 [95% CI 0.93–1.16]) on the risk of CVM in 1341 cases. Mutation screening of 93 TOF cases revealed no VEGF coding sequence variants and no changes at splice consensus sequences. Genetic variation in VEGF appears to play a small role, if any, in outflow tract CVM susceptibility

Genotype at the P554L Variant of the Hexose-6 Phosphate Dehydrogenase Gene Is Associated with Carotid Intima-Medial Thickness

Objective: The combined thickness of the intima and media of the carotid artery (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease and stroke. Previous studies indicate that carotid intima-medial thickness is a significantly heritable phenotype, but the responsible genes are largely unknown. Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity regulates corticosteroid metabolism in the liver and adipose tissue; variability in measures of corticosteroid metabolism within the normal range have been associated with risk factors for cardiovascular disease. We performed a genetic association study in 854 members of 224 families to assess the relationship between polymorphisms in the gene coding for hexose-6 phosphate dehydrogenase (H6PD) and carotid intima-medial thickness. Methods: Families were ascertained via a hypertensive proband. CIMT was measured using B-mode ultrasound. Single nucleotide polymorphisms (SNPs) tagging common variation in the H6PD gene were genotyped. Association was assessed following adjustment for significant covariates including "classical" cardiovascular risk factors. Functional studies to determine the effect of particular SNPs on H6PDH were performed. Results: There was evidence of association between the single nucleotide polymorphism rs17368528 in exon five of the H6PD gene, which encodes an amino-acid change from proline to leucine in the H6PDH protein, and mean carotid intima-medial thickness (p = 0.00065). Genotype was associated with a 5% (or 0.04 mm) higher mean carotid intima-medial thickness measurement per allele, and determined 2% of the population variability in the phenotype. Conclusions: Our results suggest a novel role for the H6PD gene in atherosclerosis susceptibility