A novel superior factor widely controlling the rice grain quality

Synthesis of storage starch and protein accumulation is the main action of endosperm organogenesis in term of the economic importance of rice. This event is strongly disturbed by abiotic stresses such as high temperature; thus, the upcoming global warming will cause a crisis with a great impact on food production^1,2^. The enzymes for the protein storage and starch synthesis pathway should work in concert to carry out the organogenesis of rice endosperm^3-5^, but the regulatory mechanism is largely unknown. Here we show that a novel regulatory factor, named OsCEO1, acts as the conductor of endosperm organogenesis during the rice grain filling stage. The physiological properties of _floury-endosperm-2_ (_flo2_) mutants showed many similarities to symptoms of grains developed under high-temperature conditions, suggesting important roles of the responsible gene in sensitivity to high-temperature stress. Our map-based cloning identified the responsible gene for the _flo2_ mutant, _OsCEO1_, which has no homology to any genes of known function. The _OsCEO1_ belongs to a novel conserved gene family and encodes a protein composed of 1,720 amino acid residues containing a TPR (tetratricopeptide repeat) motif, which is considered to mediate a protein-protein interaction. The yeast two-hybrid analysis raised an unknown protein showing homology to a late embryogenesis abundant protein and a putative basic helix-loop-helix protein as candidates for the direct interactor for _OsCEO1_, whereas no enzyme genes for the synthesis of storage substances were detected. The _flo2_ mutant exhibited reduced expression of several genes for putative regulatory proteins as well as many enzymes involved in storage starch and proteins. These results suggest that _OsCEO1_ is a superior conductor of the novel regulatory cascade of endosperm organogenesis and may have important roles in the response to high-temperature stress

SnRK1 Kinase and the NAC Transcription Factor SOG1 Are Components of a Novel Signaling Pathway Mediating the Low Energy Response Triggered by ATP Depletion

Plant growth is strictly controlled by cell division, elongation, and differentiation for which adequate supplies of intracellular ATP are required. However, it is unclear how changes in the amount of intracellular ATP affect cell division and growth. To reveal the specific pathway dependent on ATP concentration, we performed analyses on the Arabidopsis mitochondria mutation sd3. The mutant is tiny, a result of a low amount of ATP caused by the disruption of Tim21, a subunit of the TIM23 protein complex localized in the inner membrane of the mitochondria. Loss of function of suppressor of gamma response 1 (SOG1) also restored the dwarf phenotype of wild type treated with antimycin A, a blocker of ATP synthesis in mitochondria. The sd3 phenotype is partially restored by the introduction of sog1, suppressor of gamma response 1, and kin10/kin11, subunits of Snf1-related kinase 1 (SnRK1). Additionally, SOG1 interacted with SnRK1, and was modified by phosphorylation in planta only after treatment with antimycin A. Transcripts of several negative regulators of the endocycle were up-regulated in the sd3 mutant, and this high expression was not observed in sd3sog1 and sd3kin11. We suggest that there is a novel regulatory mechanism for the control of plant cell cycle involving SnRK1 and SOG1, which is induced by low amounts of intracellular ATP, and controls plant development

The Effects of Maxillomandibular Advancement and Genioglossus Advancement on Sleep Quality

Maxillomandibular advancement (MMA) using a standardized surgical procedure consisting of a LeFort I osteotomy and bilateral sagittal split ramus osteotomy and genioglossus advancement (GA) using a genioplasty improve airway volume, oxygen desaturation, and the AHI in patients with OSA. However, there are few reports on changes in sleep quality following MMA and GA. We assessed the effects of MMA and GA on sleep quality by comparing oxygen desaturation, AHI, and sleep architecture before and after surgery. Methods: Eight patients underwent polysomnography (PSG) and CT scan before and after surgery. Conclusions: Our study finds that %TST and %REM were both increased, while %S1 and NA both decreased. Based on these results, it appears that both the quality and quantity of sleep were improved. MMA and GA improve sleep respiratory disturbance and can also improve sleep quality

Clinical impact of albuminuria and glomerular filtration rate on renal and cardiovascular events, and all-cause mortality in Japanese patients with type 2 diabetes

Background: The number of patients suffering from diabetic nephropathy resulting in end-stage kidney disease is increasing worldwide. In clinical settings, there are limited data regarding the impact of the urinary albumin-to-creatinine ratio (UACR) and reduced estimated glomerular filtration rate (eGFR) on renal and cardiovascular outcomes and all-cause mortality. Methods: We performed a historical cohort study of 4328 Japanese participants with type 2 diabetes from 10 centers. Risks for renal events (requirement for dialysis or transplantation, or half reduction in eGFR), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), and all-cause mortality were assessed according to UACR and eGFR levels. Results: During follow-up (median 7.0 years, interquartile range 3.0-8.0 years), 419 renal events, 605 cardiovascular events and 236 deaths occurred. The UACR levels increased the risk and the adjusted hazard ratios for these three events. In addition to the effects of UACR levels, eGFR stages significantly increased the adjusted hazard ratios for renal events and all-cause mortality, especially in patients with macroalbuminuria. Diabetic nephropathy score, based on the prognostic factors, well predicted incidence rates per 1000 patient/year for each event. Conclusions: Increased UACR levels were closely related to the increase in risks for renal, cardiovascular events and all-cause mortality in Japanese patients with type 2 diabetes, whereas the association between high levels of UACR and reduced eGFR was a strong predictor for renal events. © 2013 Japanese Society of Nephrology

A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of <it>KRAS </it>are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells.</p> <p>Methods</p> <p>DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for <it>KRAS </it>amplification by quantitative PCR, and investigated <it>KRAS </it>amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of <it>KRAS </it>knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively.</p> <p>Results</p> <p>DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the <it>KRAS </it>gene locus. Amplification of the <it>KRAS </it>locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). <it>KRAS </it>mutations were identified in two of the three cell lines in which <it>KRAS </it>was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased <it>KRAS </it>copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type <it>KRAS</it>, but not in cells with amplified mutant <it>KRAS</it>. Knock-down of <it>KRAS </it>in gastric cancer cells that carried amplified wild-type <it>KRAS </it>resulted in the inhibition of cell growth and suppression of p44/42 MAP kinase and AKT activity.</p> <p>Conclusion</p> <p>Our study highlights the utility of DGS for identification of copy-number alterations. Using DGS, we identified <it>KRAS </it>as a gene that is amplified in human gastric cancer. We demonstrated that gene amplification likely forms the molecular basis of overactivation of KRAS in gastric cancer. Additional studies using a larger cohort of gastric cancer specimens are required to determine the diagnostic and therapeutic implications of <it>KRAS </it>amplification and overexpression.</p

Enhanced Characterization of the Smell of Death by Comprehensive Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry (GCxGC-TOFMS)

Soon after death, the decay process of mammalian soft tissues begins and leads to the release of cadaveric volatile compounds in the surrounding environment. The study of postmortem decomposition products is an emerging field of study in forensic science. However, a better knowledge of the smell of death and its volatile constituents may have many applications in forensic sciences. Domestic pigs are the most widely used human body analogues in forensic experiments, mainly due to ethical restrictions. Indeed, decomposition trials on human corpses are restricted in many countries worldwide. This article reports on the use of comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) for thanatochemistry applications. A total of 832 VOCs released by a decaying pig carcass in terrestrial ecosystem, i.e. a forest biotope, were identified by GCxGC-TOFMS. These postmortem compounds belong to many kinds of chemical class, mainly oxygen compounds (alcohols, acids, ketones, aldehydes, esters), sulfur and nitrogen compounds, aromatic compounds such as phenolic molecules and hydrocarbons. The use of GCxGC-TOFMS in study of postmortem volatile compounds instead of conventional GC-MS was successful