Neuroimaging prognostic factors for treatment response to motor imagery training after stroke.

The efficacy of motor imagery training for motor recovery is well acknowledged, but with substantial inter-individual variability in stroke patients. To help optimize motor imagery training therapy plans and screen suitable patients, this study aimed to explore neuroimaging biomarkers explaining variability in treatment response. Thirty-nine stroke patients were randomized to a motor imagery training group (n = 22, received a combination of conventional rehabilitation therapy and motor imagery training) and a control group (n = 17, received conventional rehabilitation therapy and health education) for 4 weeks of interventions. Their demography and clinical information, brain lesion from structural MRI, spontaneous brain activity and connectivity from rest fMRI, and sensorimotor brain activation from passive motor task fMRI were acquired to identify prognostic factors. We found that the variability of outcomes from sole conventional rehabilitation therapy could be explained by the reserved sensorimotor neural function, whereas the variability of outcomes from motor imagery training + conventional rehabilitation therapy was related to the spontaneous activity in the ipsilesional inferior parietal lobule and the local connectivity in the contralesional supplementary motor area. The results suggest that additional motor imagery training treatment is also efficient for severe patients with damaged sensorimotor neural function, but might be more effective for patients with impaired motor planning and reserved motor imagery.

Grass-specific ABERRANT MICROSPORE DEVELOPMENT 1 is required for maintaining pollen fertility in rice.

Pollen development includes a series of biological events that require precise gene regulation. Although several transcription factors (TFs) have been shown to play roles in maintaining pollen fertility, the major regulatory networks underlying tapetum development and pollen wall formation are largely unknown. Herein, we report that ABERRANT MICROSPORE DEVELOPMENT1 (AMD1), a protein annotated previously as unknown protein, is required for tapetum development and pollen exine patterning in rice (Oryza sativa L.). AMD1 encodes a grass-specific protein exhibiting transactivation activity in the nucleus and is spatiotemporally expressed in the tapetum and microspores during pollen development. Further biochemical assays indicate that AMD1 directly activates the transcription of DEFECTIVE POLLEN WALL (DPW) and POLYKETIDE SYNTHASE2 (OsPKS2), which are both implicated in sporopollenin biosynthesis during exine formation. Additionally, AMD1 directly interacts with TAPETUM DEGENERATION RETARDATION (TDR), a key TF involved in the regulation of tapetum degradation and exine formation. Taken together, we demonstrate that AMD1 is an important regulatory component involved in the TDR-mediated regulatory pathway to regulate sporopollenin biosynthesis, tapetum degradation, and exine formation for pollen development. Our work provides insights into the regulatory network of rice sexual reproduction and a useful target for genetic engineering of new male-sterile lines for hybrid rice breeding.

The Key Metabolites in Rice Quality Formation of Conventional japonica Varieties.

To understand differences in the quality of different conventional japonica rice varieties and variations in metabolites related to rice quality, the quality of three conventional japonica varieties was determined, and the metabolites of the milled rice were investigated using nontargeted metabolomics technology. The results showed that the taste value (TV) of Yangda 4Hao (YD4) was significantly higher than that of Yangda 3Hao (YD3) and Huaidao 5Hao (HD5). The protein content (PC) of HD5 was significantly higher than that of YD3 and YD4. PC was significantly negatively correlated with TV. Ninety-one differential metabolites (59 increased and 32 decreased) were identified between YD3 and HD5. A total of 144 differential metabolites (96 upregulated and 48 downregulated) were identified between YD4 and HD5. A total of 114 differential metabolites (40 increased and 74 decreased) were identified between YD3 and YD4. The metabolites with a high correlation to rice quality were mostly involved in the amino acid metabolism pathway. Amino acid metabolites play an important role in the formation of rice quality. The key metabolites in the synthesis and regulation of metabolic pathways are sucrose, levan, and amylose, which are carbohydrates, and L-glutamine, L-aspartic acid, and L-asparagine, which are amino acid metabolites. It can be seen from this study that the metabolites of sucrose, levan, amylose, L-glutamine, L-aspartic acid, and L-asparagine may be the key metabolites in the quality formation of high-quality rice varieties.

MATE transporter GFD1 cooperates with sugar transporters, mediates carbohydrate partitioning and controls grain-filling duration, grain size and number in rice.

More than half of the world's food is provided by cereals, as humans obtain >60% of daily calories from grains. Producing more carbohydrates is always the final target of crop cultivation. The carbohydrate partitioning pathway directly affects grain yield, but the molecular mechanisms and biological functions are poorly understood, including rice (Oryza sativa L.), one of the most important food sources. Here, we reported a prolonged grain filling duration mutant 1 (gfd1), exhibiting a long grain-filling duration, less grain number per panicle and bigger grain size without changing grain weight. Map-based cloning and molecular biological analyses revealed that GFD1 encoded a MATE transporter and expressed high in vascular tissues of the stem, spikelet hulls and rachilla, but low in the leaf, controlling carbohydrate partitioning in the stem and grain but not in the leaf. GFD1 protein was partially localized on the plasma membrane and in the Golgi apparatus, and was finally verified to interact with two sugar transporters, OsSWEET4 and OsSUT2. Genetic analyses showed that GFD1 might control grain-filling duration through OsSWEET4, adjust grain size with OsSUT2 and synergistically modulate grain number per panicle with both OsSUT2 and OsSWEET4. Together, our work proved that the three transporters, which are all initially classified in the major facilitator superfamily family, could control starch storage in both the primary sink (grain) and temporary sink (stem), and affect carbohydrate partitioning in the whole plant through physical interaction, giving a new vision of sugar transporter interactome and providing a tool for rice yield improvement.

SWOLLEN TAPETUM AND STERILITY 1 is required for tapetum degeneration and pollen wall formation in rice.

The pollen wall is important for protecting the male gametophyte and for fertilization. The lipid components of the pollen wall are mainly synthesized and transported from the sporophytic tapetum. Although several factors related to lipid biosynthesis have been characterized, the molecular mechanisms underlying lipid biosynthesis during pollen development in rice (Oryza sativa L.) remain elusive. Here, we showed that mutation in the SWOLLEN TAPETUM AND STERILITY 1 (STS1) gene causes delayed tapetum degradation and aborted pollen wall formation in rice. STS1 encodes an endoplasmic reticulum (ER)-localized protein that contains domain of unknown function (DUF) 726 and exhibits lipase activity. Lipidomic and transcriptomic analyses showed that STS1 is involved in anther lipid homeostasis. Moreover, STS1 interacts with Polyketide Synthase 2 (OsPKS2) and Acyl-CoA Synthetase 12 (OsACOS12), two enzymes crucial in lipidic sporopollenin biosynthesis in pollen wall formation, suggesting a potentially lipidic metabolon for sporopollenin biosynthesis in rice. Collectively, our results indicate that STS1 is an important factor for lipid biosynthesis in reproduction, providing a target for the artificial control of male fertility in hybrid rice breeding and insight into the function of DUF726-containing protein in plants.

A ubiquitin-specific protease functions in regulating cell death and immune responses in rice.

Ubiquitin-specific proteases (UBPs) process deubiquitination in eukaryotic organisms and are widely involved in plant development and responses to environmental stress. However, their role in cell death and plant immunity remains largely unknown. Here, we identified a rice lesion mimic mutant (LMM) and cloned its causative gene, LMM22. Both dysfunction and overexpression of LMM22 gave rise to the hypersensitive response-like cell death, reactive oxygen species bursts, and activated defence responses. LMM22 encodes an active UBP that is localised to the endoplasmic reticulum (ER) and displays a constitutive expression pattern in rice. LMM22 interacts with SPOTTED LEAF 35 (SPL35), a coupling of ubiquitin conjugation to ER degradation domain-containing protein that is known to participate in ubiquitination and the regulation of cell death and disease response in rice. Additional analyses suggest that LMM22 can positively regulate and stabilise the abundance of SPL35 protein likely through its deubiquitination activity. These data therefore improve our understanding of the function of UBP in rice innate immune responses by demonstrating that LMM22 functions as a critical regulator of SPL35 in cell death and disease resistance.

Cobalt Oxide Arrays Anchored to Copper Foam as Efficient Binder-free Anode for Lithium Ion Batteries.

The development of lithium-ion batteries with simplified assembling steps and fast charge capability is crucial for current battery applications. In this study, we propose a simple in-situ strategy for the construction of high-dispersive cobalt oxide (CoO) nanoneedle arrays, which grow vertically on a copper foam substrate. It is demonstrated that this nanoneedle CoO electrodes provide abundant electrochemical surface area. The resulting CoO arrays directly act as binder-free anodes in lithium-ion batteries with the copper foam functioning as the current collector. The highly-dispersed feature of the nanoneedle arrays enhances the effectiveness of active materials, leading to outstanding rate capability and superior long-term cycling stability. These impressive electrochemical properties are attributed to the highly-dispersed self-standing nanoarrays, the advantages of binder-free constituent, and the high exposed surface area of the copper foam substrate compared to copper foil, which enrich active surface area and facilitate charge transfer. The proposed approach to prepare binder-free lithium-ion battery anodes streamlines the electrode fabrication steps and holds significant promise for the future development of the battery industry.

Ef-cd locus shortens rice maturity duration without yield penalty.

The contradiction between "high yielding" and "early maturing" hampers further improvement of annual rice yield. Here we report the positional cloning of a major maturity duration regulatory gene, Early flowering-completely dominant (Ef-cd), and demonstrate that natural variation in Ef-cd could be used to overcome the above contradictory. The Ef-cd locus gives rise to a long noncoding RNA (lncRNA) antisense transcript overlapping the OsSOC1 gene. Ef-cd lncRNA expression positively correlates with the expression of OsSOC1 and H3K36me3 deposition. Field test comparisons of early maturing Ef-cd near-isogenic lines with their wild types as well as of the derivative early maturing hybrids with their wild-type hybrids conducted under different latitudes determined that the early maturing Ef-cd allele shortens maturity duration (ranging from 7 to 20 d) without a concomitant yield penalty. Ef-cd facilitates nitrogen utilization and also improves the photosynthesis rate. Analysis of 1,439 elite hybrid rice varieties revealed that the 16 homozygotes and 299 heterozygotes possessing Ef-cd matured significantly earlier. Therefore, Ef-cd could be a vital contributor of elite early maturing hybrid varieties in balancing grain yield with maturity duration.

Transcriptome and Metabolome Analysis Provides Insights into the Heterosis of Yield and Quality Traits in Two Hybrid Rice Varieties (Oryza sativa L.).

Heterosis is a common biological phenomenon that is useful for breeding superior lines. Using heterosis to increase the yield and quality of crops is one of the main achievements of modern agricultural science. In this study, we analysed the transcriptome and metabolome of two three-line hybrid rice varieties, Taiyou 871 (TY871), and Taiyou 398 (TY398) and the parental grain endosperm using RNA-seq (three biological repeats per variety) and untargeted metabolomic (six biological repeats per variety) methods. TY871 and TY398 showed specific heterosis in yield and quality. Transcriptome analysis of the hybrids revealed 638 to 4059 differentially expressed genes in the grain when compared to the parents. Metabolome analysis of the hybrids revealed 657 to 3714 differential grain metabolites when compared to the parents. The honeydew1 and grey60 module core genes Os04g0350700 and Os05g0154700 are involved in the regulation of awn development, grain size, and grain number, as well as the regulation of grain length and plant height, respectively. Rice grain length may be an important indicator for improving the quality of three-line hybrid rice. In addition, the rice quality-related metabolite NEG_M341T662 was highly connected to the module core genes Os06g0254300 and Os03g0168100. The functions of Os06g0254300 and Os03g0168100 are EF-hand calcium binding protein and late embroideries absolute protein repeat containing protein, respectively. These genes may play a role in the formation of rice quality. We constructed a gene and metabolite coexpression network, which provides a scientific basis for the utilization of heterosis in producing high-yield and high-quality hybrid rice.

DRB2 Modulates Leaf Rolling by Regulating Accumulation of MicroRNAs Related to Leaf Development in Rice.

As an important agronomic trait in rice (Oryza sativa), moderate leaf rolling helps to maintain the erectness of leaves and minimize shadowing between leaves, leading to improved photosynthetic efficiency and grain yield. However, the molecular mechanisms underlying rice leaf rolling still need to be elucidated. Here, we isolated a rice mutant, rl89, showing adaxially rolled leaf phenotype due to decreased number and size of bulliform cells. We confirmed that the rl89 phenotypes were caused by a single nucleotide substitution in OsDRB2 (LOC_Os10g33970) gene encoding DOUBLE-STRANDED RNA-BINDING2. This gene was constitutively expressed, and its encoded protein was localized to both nucleus and cytoplasm. Yeast two-hybrid assay showed that OsDRB2 could interact with DICER-LIKE1 (DCL1) and OsDRB1-2 respectively. qRT-PCR analysis of 29 related genes suggested that defects of the OsDRB2-miR166-OsHBs pathway could play an important role in formation of the rolled leaf phenotype of rl89, in which OsDRB2 mutation reduced miR166 accumulation, resulting in elevated expressions of the class III homeodomain-leucine zipper genes (such as OsHB1, 3 and 5) involved in leaf polarity and/or morphology development. Moreover, OsDRB2 mutation also reduced accumulation of miR160, miR319, miR390, and miR396, which could cause the abnormal leaf development in rl89 by regulating expressions of their target genes related to leaf development.

Mutation of Protoporphyrinogen IX Oxidase Gene Causes Spotted and Rolled Leaf and Its Overexpression Generates Herbicide Resistance in Rice.

Protoporphyrinogen IX (Protogen IX) oxidase (PPO) catalyzes the oxidation of Protogen IX to Proto IX. PPO is also the target site for diphenyl ether-type herbicides. In plants, there are two PPO encoding genes, PPO1 and PPO2. To date, no PPO gene or mutant has been characterized in monocotyledonous plants. In this study, we isolated a spotted and rolled leaf (sprl1) mutant in rice (Oryza sativa). The spotted leaf phenotype was sensitive to high light intensity and low temperature, but the rolled leaf phenotype was insensitive. We confirmed that the sprl1 phenotypes were caused by a single nucleotide substitution in the OsPPO1 (LOC_Os01g18320) gene. This gene is constitutively expressed, and its encoded product is localized to the chloroplast. The sprl1 mutant accumulated excess Proto(gen) IX and reactive oxygen species (ROS), resulting in necrotic lesions. The expressions of 26 genes associated with tetrapyrrole biosynthesis, photosynthesis, ROS accumulation, and rolled leaf were significantly altered in sprl1, demonstrating that these expression changes were coincident with the mutant phenotypes. Importantly, OsPPO1-overexpression transgenic plants were resistant to the herbicides oxyfluorfen and acifluorfen under field conditions, while having no distinct influence on plant growth and grain yield. These finding indicate that the OsPPO1 gene has the potential to engineer herbicide resistance in rice.

Crosstalk between the Circadian Clock and Histone Methylation.

The circadian clock and histone modifications could form a feedback loop in Arabidopsis; whether a similar regulatory mechanism exists in rice is still unknown. Previously, we reported that SDG724 and OsLHY are two rice heading date regulators in rice. SDG724 encodes a histone H3K36 methyltransferase, and OsLHY is a vital circadian rhythm transcription factor. Both could be involved in transcription regulatory mechanisms and could affect gene expression in various pathways. To explore the crosstalk between the circadian clock and histone methylation in rice, we studied the relationship between OsLHY and SDG724 via the transcriptome analysis of their single and double mutants, oslhy, sdg724, and oslhysdg724. Screening of overlapped DEGs and KEGG pathways between OsLHY and SDG724 revealed that they could control many overlapped pathways indirectly. Furthermore, we identified three candidate targets (OsGI, OsCCT38, and OsPRR95) of OsLHY and one candidate target (OsCRY1a) of SDG724 in the clock pathway. Our results showed a regulatory relationship between OsLHY and SDG724, which paved the way for revealing the interaction between the circadian clock and histone H3K36 methylation.

Rice ß-Glucosidase 4 (Os1ßGlu4) Regulates the Hull Pigmentation via Accumulation of Salicylic Acid.

Salicylic acid (SA) is a stress hormone synthesized in phenylalanine ammonia-lyase (PAL) and the branching acid pathway. SA has two interconvertible forms in plants: SAG (SA O-ß-glucoside) and SA (free form). The molecular mechanism of conversion of SA to SAG had been reported previously. However, which genes regulate SAG to SA remained unknown. Here, we report a cytoplasmic ß-glucosidase (ß-Glu) which participates in the SA pathway and is involved in the brown hull pigmentation in rice grain. In the current study, an EMS-generated mutant brown hull 1 (bh1) displayed decreased contents of SA in hulls, a lower photosynthesis rate, and high-temperature sensitivity compared to the wild type (WT). A plaque-like phenotype (brown pigmentation) was present on the hulls of bh1, which causes a significant decrease in the seed setting rate. Genetic analysis revealed a mutation in LOC_Os01g67220, which encodes a cytoplasmic Os1ßGlu4. The knock-out lines displayed the phenotype of brown pigmentation on hulls and decreased seed setting rate comparable with bh1. Overexpression and complementation lines of Os1ßGlu4 restored the phenotype of hulls and normal seed setting rate comparable with WT. Subcellular localization revealed that the protein of Os1ßGlu4 was localized in the cytoplasm. In contrast to WT, bh1 could not hydrolyze SAG into SA in vivo. Together, our results revealed the novel role of Os1ßGlu4 in the accumulation of flavonoids in hulls by regulating the level of free SA in the cellular pool.

DEAP1 encodes a fasciclin-like arabinogalactan protein required for male fertility in rice.

Arabinogalactan proteins (AGPs) are widely distributed in plant cells. Fasciclin-like AGPs (FLAs) belong to a subclass of AGPs that play important roles in plant growth and development. However, little is known about the biological functions of rice FLA. Herein, we report the identification of a male-sterile mutant of DEFECTIVE EXINE AND APERTURE PATTERNING1 (DEAP1) in rice. The deap1 mutant anthers produced aberrant pollen grains with defective exine formation and a flattened aperture annulus and exhibited slightly delayed tapetum degradation. DEAP1 encodes a plasma membrane-associated member of group III plant FLAs and is specifically and temporally expressed in reproductive cells and the tapetum layer during male development. Gene expression studies revealed reduced transcript accumulation of genes related to exine formation, aperture patterning, and tapetum development in deap1 mutants. Moreover, DEAP1 may interact with two rice D6 PROTEIN KINASE-LIKE3s (OsD6PKL3s), homologs of a known Arabidopsis aperture protein, to affect rice pollen aperture development. Our findings suggested that DEAP1 is involved in male reproductive development and may affect exine formation and aperture patterning, thereby providing new insights into the molecular functions of plant FLAs in male fertility.

Dual function of clock component OsLHY sets critical day length for photoperiodic flowering in rice.

Circadian clock, an endogenous time-setting mechanism, allows plants to adapt to unstable photoperiod conditions and induces flowering with proper timing. In Arabidopsis, the central clock oscillator was formed by a series of interlocked transcriptional feedback loops, but little is known in rice so far. By MutMap technique, we identified the candidate gene OsLHY from a later flowering mutant lem1 and further confirmed it through genetic complementation, RNA interference knockdown, and CRISPR/Cas9-knockout. Global transcriptome profiling and expression analyses revealed that OsLHY might be a vital circadian rhythm component. Interestingly, oslhy flowered later under ≥12 h day length but headed earlier under ≤11 h day length. qRT-PCR results exhibited that OsLHY might function through OsGI-Hd1 pathway. Subsequent one-hybrid assays in yeast, DNA affinity purification qPCR, and electrophoretic mobility shift assays confirmed OsLHY could directly bind to the CBS element in OsGI promoter. Moreover, the critical day length (CDL) for function reversal of OsLHY in oslhy (11-12 h) was prolonged in the double mutant oslhy osgi (about 13.5 h), indicating that the CDL set by OsLHY was OsGI dependent. Additionally, the dual function of OsLHY entirely relied on Hd1, as the double mutant oslhy hd1 showed the same heading date with hd1 under about 11.5, 13.5, and 14 h day lengths. Together, OsLHY could fine-tune the CDL by directly regulating OsGI, and Hd1 acts as the final effector of CDL downstream of OsLHY. Our study illustrates a new regulatory mechanism between the circadian clock and photoperiodic flowering.

A single nucleotide substitution at the 3'-end of SBPase gene involved in Calvin cycle severely affects plant growth and grain yield in rice.

BACKGROUND: Calvin cycle plays a crucial role in carbon fixation which provides the precursors of organic macromolecules for plant growth and development. Currently, no gene involved in Calvin cycle has been identified in monocotyledonous plants through mutant or/and map-based cloning approach. RESULTS: Here, we isolated a low-tillering mutant, c6635, in rice (Oryza sativa). The mutant displayed light green leaves and intensely declined pigment contents and photosynthetic capacity at early growth stage. Moreover, its individual plant showed a much smaller size, and most individuals produced only two tillers. At mature stage, its productive panicles, grain number and seed setting rate were significantly decreased, which lead to a sharp reduction of the grain yield. We confirmed that a single nucleotide mutation in LOC_Os04g16680 gene encoding sedoheptulose 1,7-bisphosphatase (SBPase) involved in Calvin cycle was responsible for the mutant phenotype of c6635 through map-based cloning, MutMap analysis and complementation experiments. Sequence analysis suggested that the point mutation caused an amino acid change from Gly-364 to Asp at the C-terminal of SBPase. In addition, OsSBPase gene was mainly expressed in leaf, and the encoded protein was located in chloroplast. The mutation of OsSBPase could significantly affect expression levels of some key genes involved in Calvin cycle. CONCLUSIONS: We successfully identified a SBPase gene in monocotyledonous plants. Meanwhile, we demonstrated that a single nucleotide substitution at the 3'-end of this gene severely affects plant growth and grain yield, implying that the Gly-364 at the C-terminal of SBPase could play an important role in SBPase function in rice.

LPS1, Encoding Iron-Sulfur Subunit SDH2-1 of Succinate Dehydrogenase, Affects Leaf Senescence and Grain Yield in Rice.

The iron-sulfur subunit (SDH2) of succinate dehydrogenase plays a key role in electron transport in plant mitochondria. However, it is yet unknown whether SDH2 genes are involved in leaf senescence and yield formation. In this study, we isolated a late premature senescence mutant, lps1, in rice (Oryza sativa). The mutant leaves exhibited brown spots at late tillering stage and wilted at the late grain-filling stage and mature stage. In its premature senescence leaves, photosynthetic pigment contents and net photosynthetic rate were reduced; chloroplasts and mitochondria were degraded. Meanwhile, lps1 displayed small panicles, low seed-setting rate and dramatically reduced grain yield. Gene cloning and complementation analysis suggested that the causal gene for the mutant phenotype was OsSDH2-1 (LOC_Os08g02640), in which single nucleotide mutation resulted in an amino acid substitution in the encoded protein. OsSDH2-1 gene was expressed in all organs tested, with higher expression in leaves, root tips, ovary and anthers. OsSDH2-1 protein was targeted to mitochondria. Furthermore, reactive oxygen species (ROS), mainly H2O2, was excessively accumulated in leaves and young panicles of lps1, which could cause premature leaf senescence and affect panicle development and pollen function. Taken together, OsSDH2-1 plays a crucial role in leaf senescence and yield formation in rice.

A lil3 chlp double mutant with exclusive accumulation of geranylgeranyl chlorophyll displays a lethal phenotype in rice.

BACKGROUND: Phytyl residues are the common side chains of chlorophyll (Chl) and tocopherols. Geranylgeranyl reductase (GGR), which is encoded by CHLP gene, is responsible for phytyl biosynthesis. The light-harvesting like protein LIL3 was suggested to be required for stability of GGR and protochlorophyllide oxidoreductase in Arabidopsis. RESULTS: In this study, we isolated a yellow-green leaf mutant, 637ys, in rice (Oryza sativa). The mutant accumulated majority of Chls with unsaturated geranylgeraniol side chains and displayed a yellow-green leaf phenotype through the whole growth period. The development of chloroplasts was suppressed, and the major agronomic traits, especially No. of productive panicles per plant and of spikelets per panicle, dramatically decreased in 637ys. Besides, the mutant exhibited to be sensitive to light intensity and deficiency of tocopherols without obvious alteration in tocotrienols in leaves and grains. Map-based cloning and complementation experiment demonstrated that a point mutation on the OsLIL3 gene accounted for the mutant phenotype of 637ys. OsLIL3 is mainly expressed in green tissues, and its encoded protein is targeted to the chloroplast. Furthermore, the 637ys 502ys (lil3 chlp) double mutant exclusively accumulated geranylgeranyl Chl and exhibited lethality at the three-leaf stage. CONCLUSIONS: We identified the OsLIL3 gene through a map-based cloning approach. Meanwhile, we demonstrated that OsLIL3 is of extreme importance to the function of OsGGR, and that the complete replacement of phytyl side chain of chlorophyll by geranylgeranyl chain could be fatal to plant survival in rice.

5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy.

We describe the discovery and optimization of 5-substituted-N-pyridazinylbenzamide derivatives as potent and selective LRRK2 inhibitors. Extensive SAR studies led to the identification of compounds 18 and 23, which demonstrated good in vitro pharmacokinetic profile and excellent selectivity over 140 other kinases. Both compounds demonstrated high unbound fractions in both blood and brain. Compound 18 proved to be brain penetrant, and the high unbound fraction of compound 18 in brain enabled its in vivo efficacy in CNS, wherein a significant inhibition of LRRK2 Ser935 phosphorylation was observed in rat brain following intravenous infusion at 5 mg/kg/h.

Transcriptome and Proteome Profiling of Different Colored Rice Reveals Physiological Dynamics Involved in the Flavonoid Pathway.

Black and red rice are rich in both anthocyanin and proanthocyanin content, which belong to a large class of flavonoids derived from a group of phenolic secondary metabolites. However, the molecular pathways and mechanisms underlying the flavonoid biosynthetic pathway are far from clear. Therefore, this study was undertaken to gain insight into physiological factors that are involved in the flavonoid biosynthetic pathway in rice cultivars with red, black, and white colors. RNA sequencing of caryopsis and isobaric tags for relative and absolute quantification (iTRAQ) analyses have generated a nearly complete catalog of mRNA and expressed proteins in different colored rice cultivars. A total of 31,700 genes were identified, of which 3417, 329, and 227 genes were found specific for red, white, and black rice, respectively. A total of 13,996 unique peptides corresponding to 3916 proteins were detected in the proteomes of black, white, and red rice. Coexpression network analyses of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) among the different rice cultivars showed significant differences in photosynthesis and flavonoid biosynthesis pathways. Based on a differential enrichment analysis, 32 genes involved in the flavonoid biosynthesis pathway were detected, out of which only CHI, F3H, ANS, and FLS were detected by iTRAQ. Taken together, the results point to differences in flavonoid biosynthesis pathways among different colored rice cultivars, which may reflect differences in physiological functions. The differences in contents and types of flavonoids among the different colored rice cultivars are related to changes in base sequences of Os06G0162500, Os09G0455500, Os09G0455500, and Os10G0536400. Current findings expand and deepen our understanding of flavonoid biosynthesis and concurrently provides potential candidate genes for improving the nutritional qualities of rice.