Background: MADS-box transcription factors, besides being involved in floral organ specification, have also been implicated in several aspects of plant growth and development. In recent years, there have been reports on genomic localization, protein motif structure, phylogenetic relationships, gene structure and expression of the entire MADS-box family in the model plant system, Arabidopsis. Though there have been some studies in rice as well, an analysis of the complete MADS-box family along with a comprehensive expression profiling was still awaited after the completion of rice genome sequencing. Furthermore, owing to the role of MADS-box family in flower development, an analysis involving structure, expression and functional aspects of MADS-box genes in rice and Arabidopsis was required to understand the role of this gene family in reproductive development.

F-box proteins constitute a large family in eukaryotes and are characterized by a conserved F-box motif (approximately 40 amino acids). As components of the Skp1p-cullin-F-box complex, F-box proteins are critical for the controlled degradation of cellular proteins. We have identified 687 potential F-box proteins in rice (Oryza sativa), the model monocotyledonous plant, by a reiterative database search. Computational analysis revealed the presence of several other functional domains, including leucine-rich repeats, kelch repeats, F-box associated domain, domain of unknown function, and tubby domain in F-box proteins. Based upon their domain composition, they have been classified into 10 subfamilies. Several putative novel conserved motifs have been identified in F-box proteins, which do not contain any other known functional domain. An analysis of a complete set of F-box proteins in rice is presented, including classification, chromosomal location, conserved motifs, and phylogenetic relationship. It appears that the expansion of F-box family in rice, in large part, might have occurred due to localized gene duplications. Furthermore, comprehensive digital expression analysis of F-box protein-encoding genes has been complemented with microarray analysis. The results reveal specific and/or overlapping expression of rice F-box protein-encoding genes during floral transition as well as panicle and seed development. At least 43 F-box protein-encoding genes have been found to be differentially expressed in rice seedlings subjected to different abiotic stress conditions. The expression of several F-box protein-encoding genes is also influenced by light. The structure and function of F-box proteins in plants is discussed in light of these results and the published information. These data will be useful for prioritization of F-box proteins for functional validation in rice.

Calcium-dependent protein kinases (CDPKs) are important sensors of Ca(+2) flux in plants, which control plant development and responses by regulating downstream components of calcium signaling pathways. Availability of the whole genome sequence and microarray platform allows investigation of genome-wide organization and expression profile of CDPK genes in rice with a view to ultimately define their function in plant systems. Genome-wide analysis led to identification of 31 CDPK genes in rice after a thorough annotation exercise based upon HMM profiles. Twenty-nine already identified CDPK genes were verified and two new members were added to the CDPK gene family of rice. Relative expression of all these genes has been analyzed by using Affymetrix rice genome arraytrade mark during three vegetative stages, six stages of panicle (P1-P6) and five stages of seed (S1-S5) development along with three abiotic stress conditions, viz. cold, salt and desiccation, given to seedling. Thirty-one CDPK genes were found to express in at least one of the experimental stages studied. Of these, transcripts for twenty three genes accumulated differentially during reproductive developmental stages; nine of them were preferentially up-regulated only in panicle, five were up-regulated in stages of panicles as well as seed development, whereas, expression of one gene was found to be specific to the S1 stage of seed development. Eight genes were found to be down-regulated during the panicle and seed developmental stages. Six CDPK genes were found to be induced while the expression of one gene was down-regulated under stress conditions. The differential expression of CDPK genes during reproductive development and stress is suggestive of their involvement in the underlying signal transduction pathways. Furthermore, up-regulation of common genes both during reproductive development as well as stress responses is indicative of common element between reproduction and stress.

Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2df<5×10−8 in GWAIS, and OR = 0.41, P = 3×10−8 in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients.

Transcription factors regulate gene expression in response to various external and internal cues by activating or suppressing downstream genes in a pathway. In this study, we provide a complete overview of the genes encoding C(2)H(2) zinc-finger transcription factors in rice, describing the gene structure, gene expression, genome localization, and phylogenetic relationship of each member. The genome of Oryza sativa codes for 189 C(2)H(2) zinc-finger transcription factors, which possess two main types of zinc-fingers (named C and Q). The Q-type zinc fingers contain a conserved motif, QALGGH, and are plant specific, whereas C type zinc fingers are found in other organisms as well. A genome-wide microarray based gene expression analysis involving 14 stages of vegetative and reproductive development along with 3 stress conditions has revealed that C(2)H(2) gene family in indica rice could be involved during all the stages of reproductive development from panicle initiation till seed maturation. A total of 39 genes are up-regulated more than 2-fold, in comparison to vegetative stages, during reproductive development of rice, out of which 18 are specific to panicle development and 12 genes are seed-specific. Twenty-six genes have been found to be up-regulated during three abiotic stresses and of these, 14 genes express specifically during the stress conditions analyzed while 12 are also up-regulated during reproductive development, suggesting that some components of the stress response pathways are also involved in reproduction.

IMPORTANCE Medical treatment of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) is an unmet need.OBJECTIVE To evaluate the efficacy and safety of ADS-5102 (amantadine) extended-release 274-mg capsules for treatment of LID in patients with PD. DESIGN, SETTING, AND PARTICIPANTSA randomized, double-blind, placebo-controlled clinical trial was conducted between May 7, 2014, and July 22, 2015, at 44 North American sites among patients with PD treated with levodopa who experienced at least 1 hour of troublesome dyskinesia per day with at least mild functional impact.INTERVENTIONS Patients were randomized to receive placebo or 274 mg of ADS-5102 administered orally at bedtime for up to 25 weeks. MAIN OUTCOMES AND MEASURESThe primary efficacy analysis was the change from baseline to week 12 in the Unified Dyskinesia Rating Scale total score for ADS-5102 vs placebo in the modified intent-to-treat population. OFF time (amount of time the PD medication is not controlling motor symptoms) was a key secondary end point. Safety analyses included all patients who received the study drug (ADS-5102 or placebo).RESULTS A total of 189 patients were screened, and 126 were randomized; the modified intent-to-treat population included 121 patients (51 women and 70 men; mean [SD] age, 64.7 [9.1] years). At week 12, the least-squares mean (SE) change in the Unified Dyskinesia Rating Scale score was -15.9 (1.6) for ADS-5102 (n = 63) and -8.0 (1.6) for placebo (n = 58) (treatment difference, -7.9; 95% CI, -12.5 to -3.3; P < .001). OFF time decreased by a mean (SE) of 0.6 (0.3) hours for ADS-5102 and increased by 0.3 (0.3) hours for placebo (treatment difference, -0.9 hours; 95% CI, -1.6 to -0.2; P = .02). Common adverse events for ADS-5102 vs placebo included visual hallucinations (15 [23.8%] vs 1 [1.7%]), peripheral edema (15 [23.8%] vs 0), and dizziness (14 [22.2%] vs 0). Adverse events led to treatment discontinuation for 13 patients receiving ADS-5102 (20.6%) vs 4 patients receiving placebo (6.9%).CONCLUSIONS AND RELEVANCE ADS-5102, 274 mg at bedtime, may be an effective treatment for LID. An additional benefit is reduced OFF time. To our knowledge, this is the first demonstration of an oral treatment reducing both LID and OFF time in patients with PD with dyskinesia.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02136914

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Seed development in this paper has been classified into the three landmark stages of cell division, organ initiation and maturation, based on morphological changes, and the available literature. The entire process proceeds at the behest of an interplay of various specific and general transcription factors (TFs). Monocots and dicots utilize overlapping, as well as distinct, TF networks during the process of seed development. The known TFs in rice and Arabidopsis have been chronologically categorized into the three stages. The main regulators of seed development contain B3 or HAP3 domains. These interact with bZIP and AP2 TFs. Other TFs that play an indispensable role during the process contain homeobox-, NAC-, MYB-, or ARF-domains. This paper is a comprehensive analysis of the TFs essential for seed development and their interactions. An understanding of this interplay will not only help unravel an integrated developmental process, but will also pave the way for biotechnological applications.