Utilizing differences in bTH tolerance between the parents of two-line hybrid rice to improve the purity of hybrid rice seed.

Introduction: Two-line hybrid rice based on Photoperiod/thermo-sensitive genic male sterile (P/TGMS) lines has been developed and applied widely in agriculture due to the freedom in making hybrid combinations, less difficulty in breeding sterile lines, and simpler procedures for breeding and producing hybrid seed. However, there are certain risks associated with hybrid seed production; if the temperature during the P/TGMS fertility-sensitive period is lower than the critical temperature, seed production will fail due to self-pollination. In a previous study, we found that the issue of insufficient purity of two-line hybrid rice seed could be initially addressed by using the difference in tolerance to ß-triketone herbicides (bTHs) between the female parent and the hybrid seeds. Methods: In this study, we further investigated the types of applicable herbicides, application methods, application time, and the effects on physiological and biochemical indexes and yield in rice. Results: The results showed that this method could be used for hybrid purification by soaking seeds and spraying plants with the bTH benzobicylon (BBC) at safe concentrations in the range of 37.5-112.5 mg/L, and the seeds could be soaked in BBC at a treatment rate of 75.0 mg/L for 36-55 h without significant negative effects. The safe concentration for spraying in the field is 50.0-400.0 mg/L BBC at the three-leaf stage. Unlike BBC, Mesotrione (MST) can only be sprayed to achieve hybrid purification at concentrations between 10.0 and 70.0 mg/L without affecting yield. The three methods of hybrid seed purification can reach 100% efficiency without compromising the nutritional growth and yield of hybrid rice. Moreover, transcriptome sequencing revealed that 299 up-regulated significant differentially expressed genes (DEGs) in the resistant material (Huazhan) poisoned by BBC, were mainly enriched in phenylalanine metabolism and phenylpropanoid biosynthesis pathway, it may eliminate the toxic effects of herbicides through this way. Discussion: Our study establishes a foundation for the application of the bTH seed purification strategy and the three methods provide an effective mechanism for improving the purity of two-line hybrid rice seeds.

OsMADS17 simultaneously increases grain number and grain weight in rice.

During the processes of rice domestication and improvement, a trade-off effect between grain number and grain weight was a major obstacle for increasing yield. Here, we identify a critical gene COG1, encoding the transcription factor OsMADS17, with a 65-bp deletion in the 5' untranslated region (5' UTR) presented in cultivated rice increasing grain number and grain weight simultaneously through decreasing mRNA translation efficiency. OsMADS17 controls grain yield by regulating multiple genes and that the interaction with one of them, OsAP2-39, has been characterized. Besides, the expression of OsMADS17 is regulated by OsMADS1 directly. It indicates that OsMADS1-OsMADS17-OsAP2-39 participates in the regulatory network controlling grain yield, and downregulation of OsMADS17 or OsAP2-39 expression can further improve grain yield by simultaneously increasing grain number and grain weight. Our findings provide insights into understanding the molecular basis co-regulating rice yield-related traits, and offer a strategy for breeding higher-yielding rice varieties.

Dissecting the genetic basis of heterosis in elite super-hybrid rice.

Y900 is one of the top hybrid rice (Oryza sativa) varieties, with its yield exceeding 15 t·hm-2. To dissect the mechanism of heterosis, we sequenced the male parent line R900 and female parent line Y58S using long-read and Hi-C technology. High-quality reference genomes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 single-nucleotide polymorphisms, 299,149 insertions/deletions, and 4,757 structural variations. The level of variation between Y58S and R900 was the lowest among the comparisons of Y58S with other rice genomes. More than 75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the portion of Geng/japonica (GJ)-type genetic components from different male parents increased with yield increasing in their corresponding hybrids. Transcriptome analysis revealed that the partial dominance effect was the main genetic effect that constituted the heterosis of Y900. In the hybrid, both alleles from the two parents were expressed, and their expression patterns were dynamically regulated in different tissues. The cis-regulation was dominant for young panicle tissues, while trans-regulation was more common in leaf tissues. Overdominance was surprisingly prevalent in stems and more likely regulated by the trans-regulation mechanism. Additionally, R900 contained many excellent GJ haplotypes, such as NARROW LEAF1, Oryza sativa SQUAMOSA PROMOTER BINDING PROTEIN-LIKE13, and Grain number, plant height, and heading date8, making it a good complement to Y58S. The fine-tuned mechanism of heterosis involves genome-wide variation, GJ introgression, key functional genes, and dynamic gene/allele expression and regulation pattern changes in different tissues and growth stages.

Allelic Diversification of the Wx and ALK Loci in Indica Restorer Lines and Their Utilisation in Hybrid Rice Breeding in China over the Last 50 Years.

Hybrid rice technology has been used for more than 50 years, and eating and cooking quality (ECQ) has been a major focus throughout this period. Waxy (Wx) and alkaline denaturation (ALK) genes have received attention owing to their pivotal roles in determining rice characteristics. However, despite significant effort, the ECQ of restorer lines (RLs) has changed very little. By contrast, obvious changes have been seen in inbred rice varieties (IRVs), and the ECQ of IRVs is influenced by Wx, which reduces the proportion of Wxa and increases the proportion of Wxb, leading to a decrease in amylose content (AC) and an increase in ECQ. Meanwhile, ALK is not selected in the same way. We investigated Wx alleles and AC values of sterile lines of female parents with the main mating combinations in widely used areas. The results show that almost all sterile lines were Wxa-type with a high AC, which may explain the low ECQ of hybrid rice. Analysis of hybrid rice varieties and RLs in the last 5 years revealed serious homogenisation among hybrid rice varieties.

Mapping brain-wide excitatory projectome of primate prefrontal cortex at submicron resolution and comparison with diffusion tractography.

Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here, we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic, and subcortical areas, relatively weak projections to parietal and insular regions but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative green fluorescent protein-labeled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.

In the brain is a web of interconnected nerve cells that send messages to one another via spindly projections called axons. These axons join together at junctions called synapses to create circuits of nerve cells which connect neighboring or distant brain regions. Notably, long-range neural connections underpin higher-order cognitive skills (such as planning and emotion regulation) which make humans distinct from our primate relatives. Only by untangling these far-reaching networks can researchers begin to delineate what sets the human brain apart from other species. Researchers deploy a range of imaging techniques to map neural networks: scanning entire brains using MRI machines, or imaging thin slices of fluorescently labelled brain tissue using powerful microscopes. However, tracing long-range axons at a high resolution is challenging, and has stirred up debate about whether some neural tracts, such as the inferior fronto-occipital fasciculus, are present in all primates or only humans. To address these discrepancies, Yan, Yu et al. employed a two-pronged approach to map neural circuits in the brains of macaques. First, two techniques ­ called viral tracing and two-photon microscopy ­ were used to create a three-dimensional, fine-grain map showing how the ventrolateral prefrontal cortex (vlPFC), which regulates complex behaviors, connects to the rest of the brain. This revealed prominent axons from the vlPFC projecting via a single synapse to distant brain regions involved in higher-order functions, such as encoding memories and processing emotion. However, there were no direct, monosynaptic connections between the vlPFC and the occipital lobe, the brain's visual processing center at the back of the head. Next, Yan, Yu et al. used a specialized MRI scanner to create an atlas of neural circuits connected to the vlPFC, and compared these results to a technique tracing axons stained with a fluorescent dye. In general, there was good agreement between the two methods, except for major differences in the rear-end projections that typically form the inferior fronto-occipital fasciculus. This suggests that this long-range neural pathway exists in monkeys, but it connects via multiple synapses instead of a single junction as was previously thought. The findings of Yan, Yu et al. provide new insights on the far-reaching neural pathways connecting distant parts of the macaque brain. It also suggests that atlases of neural circuits from whole brain scans should be taken with caution and validated using neural tracing experiments.

Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms.

OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP5 on Cd and Mn accumulation, as well as Cd tolerance of rice plants in response to varying environmental Cd concentrations, and to uncover the underlying mechanism, which until now, has remained largely unexplored. This study showed that knockout of OsNRAMP5 decreased Cd uptake, but simultaneously facilitated Cd translocation from roots to shoots. The effect of OsNRAMP5 knockout on reducing root Cd uptake weakened, however its effect on improving root-to-shoot Cd translocation was constant with increasing environmental Cd concentrations. As a result, its mutation dramatically reduced Cd accumulation in shoots under low and moderate Cd stress, but inversely increased that under high Cd conditions. Interestingly, Cd tolerance of its knockout mutants was persistently enhanced, irrespective of lower or higher Cd concentrations in shoots, compared with that of wild-type plants. Knockout of OsNRAMP5 mitigated Cd toxicity by dramatically diminishing Cd uptake at low or moderate external Cd concentrations. Remarkably, its knockout effectively complemented deficient mineral nutrients in shoots, thereby indirectly enhancing rice tolerance to severe Cd stress. Additionally, its mutation conferred preferential delivery of Mn to young leaves and grains. These results have important implications for the application of the OsNRAMP5 mutation in mitigating Cd toxicity and lowering the risk of excessive Cd accumulation in rice grains.

Common and differential connectivity profiles of deep brain stimulation and capsulotomy in refractory obsessive-compulsive disorder.

Neurosurgical interventions including deep brain stimulation (DBS) and capsulotomy have been demonstrated effective for refractory obsessive-compulsive disorder (OCD), although treatment-shared/-specific network mechanisms remain largely unclear. We retrospectively analyzed resting-state fMRI data from three cohorts: a cross-sectional dataset of 186 subjects (104 OCD and 82 healthy controls), and two longitudinal datasets of refractory patients receiving ventral capsule/ventral striatum DBS (14 OCD) and anterior capsulotomy (27 OCD). We developed a machine learning model predictive of OCD symptoms (indexed by the Yale-Brown Obsessive Compulsive Scale, Y-BOCS) based on functional connectivity profiles and used graphic measures of network communication to characterize treatment-induced profile changes. We applied a linear model on 2 levels treatments (DBS or capsulotomy) and outcome to identify whether pre-surgical network communication was associated with differential treatment outcomes. We identified 54 functional connectivities within fronto-subcortical networks significantly predictive of Y-BOCS score in patients across 3 independent cohorts, and observed a coexisting pattern of downregulated cortico-subcortical and upregulated cortico-cortical network communication commonly shared by DBS and capsulotomy. Furthermore, increased cortico-cortical communication at ventrolateral and centrolateral prefrontal cortices induced by DBS and capsulotomy contributed to improvement of mood and anxiety symptoms, respectively (p < 0.05). Importantly, pretreatment communication of ventrolateral and centrolateral prefrontal cortices were differentially predictive of mood and anxiety improvements by DBS and capsulotomy (effect sizes = 0.45 and 0.41, respectively). These findings unravel treatment-shared and treatment-specific network characteristics induced by DBS and capsulotomy, which may facilitate the search of potential evidence-based markers for optimally selecting among treatment options for a patient.

Overexpression of OsLCT2, a Low-Affinity Cation Transporter Gene, Reduces Cadmium Accumulation in Shoots and Grains of Rice.

Cadmium (Cd)-contaminated rice is a serious issue affecting food safety. Understanding the molecular regulatory mechanisms of Cd accumulation in rice grains is crucial to minimizing Cd concentrations in grains. We identified a member of the low-affinity cation transporter family, OsLCT2 in rice. It was a membrane protein. OsLCT2 was expressed in all tissues of the elongation and maturation zones in roots, with the strongest expression in pericycle and stele cells adjacent to the xylem. When grown in Cd-contaminated paddy soils, rice plants overexpressing OsLCT2 significantly reduced Cd concentrations in the straw and grains. Hydroponic experiment demonstrated its overexpression decreased the rate of Cd translocation from roots to shoots, and reduced Cd concentrations in xylem sap and in shoots of rice. Moreover, its overexpression increased Zn concentrations in roots by up-regulating the expression of OsZIP9, a gene responsible for Zn uptake. Overexpression of OsLCT2 reduces Cd accumulation in rice shoots and grains by limiting the amounts of Cd loaded into the xylem and restricting Cd translocation from roots to shoots of rice. Thus, OsLCT2 is a promising genetic resource to be engineered to reduce Cd accumulation in rice grains.

Anterior limb of the internal capsule tractography: relationship with capsulotomy outcomes in obsessive-compulsive disorder.

OBJECTIVES: Surgical procedures targeting the anterior limb of the internal capsule (aLIC) can be effective in patients with selected treatment-refractory obsessive-compulsive disorder (OCD). The aLIC consists of white-matter tracts connecting cortical and subcortical structures and show a topographical organisation. Here we assess how aLIC streamlines are affected in OCD compared with healthy controls (HCs) and which streamlines are related with post-capsulotomy improvement. METHODS: Diffusion-weighted MRI was used to compare white-matter microstructure via the aLIC between patients with OCD (n=100, 40 women, mean of age 31.8 years) and HCs (n=88, 39 women, mean of age 29.6 years). For each individual, the fractional anisotropy (FA) and streamline counts were calculated for each white-matter fibre bundle connecting a functionally defined prefrontal and subcortical region. Correlations between tractography measures and pre-capsulotomy and post-capsulotomy clinical outcomes (in obsessive-compulsive, anxiety and depression scores 6 months after surgery) were assessed in 41 patients with OCD. RESULTS: Hierarchical clustering dendrograms show an aLIC organisation clustering lateral and dissociating ventral and dorsal prefrontal-thalamic streamlines, findings highly relevant to surgical targeting. Compared with HCs, patients with OCD had lower aLIC FA across multiple prefrontal cortical-subcortical regions (p<0.0073, false discovery rate-adjusted). Greater streamline counts of the dorsolateral prefrontal-thalamic tracts in patients with OCD predicted greater post-capsulotomy obsessive-compulsive improvement (p=0.016). In contrast, greater counts of the dorsal cingulate-thalamic streamlines predicted surgical outcomes mediated by depressive and anxiety improvements. CONCLUSIONS: These findings shed light on the critical role of the aLIC in OCD and may potentially contribute towards precision targeting to optimise outcomes in OCD.

Exploring Natural Allelic Variations of the ß-Triketone Herbicide Resistance Gene HIS1 for Application in indica Rice and Particularly in Two-Line Hybrid Rice.

BACKGROUND: Benzobicyclon (BBC) is a ß-triketone herbicide (bTH) used in rice paddy fields. It has the advantages of high efficiency, low toxicity, high crop safety, and good environmental compatibility, and shows efficacy against paddy weeds resistant to other types of herbicides. However, as some important indica rice varieties are susceptible to BBC, BBC is currently only registered and applied in japonica rice cultivation areas. RESULTS: By analyzing haplotypes of the bTHs broad-spectrum resistance gene HIS1 and phenotypes for BBC in 493 major indica rice accessions in China, we identified a novel non-functional allelic variant of HIS1 in addition to the previously reported 28-bp deletion. Through detection with markers specific to the two non-functional mutations, it was clear that 25.4% of indica conventional varieties, 59.9% of fertility restorers, and 15.9% of sterile lines were susceptible to BBC. In addition, due to natural allelic variations of the HIS1 gene in the sterile and restorer lines, some two-line hybrid sterile lines were sensitive to bTHs, and the corresponding restorers were resistant. We showed the potential effectiveness of using bTHs to address the issue of two-line hybrid rice seed purity stemming from the self-crossing of sterile lines during hybrid rice seed production. Finally, allelic variations of the HIS1 gene may also play an important role in the mechanized seed production of hybrid rice. CONCLUSIONS: Our findings offer guidance for the application of BBC in indica rice areas and provide a non-transgenic approach to address the seed purity issue of two-line hybrid rice.

Forecasting rice latitude adaptation through a daylength-sensing-based environment adaptation simulator.

Global climate change necessitates crop varieties with good environmental adaptability. As a proxy for climate adaptation, crop breeders could select for adaptability to different latitudes, but the lengthy procedures for that slow development. Here, we combined molecular technologies with a streamlined in-house screening method to facilitate rapid selection for latitude adaptation. We established the daylength-sensing-based environment adaptation simulator (DEAS) to assess rice latitude adaptation status via the transcriptional dynamics of florigen genes at different latitudes. The DEAS predicted the florigen expression profiles in rice varieties with high accuracy. Furthermore, the DEAS showed potential for application in different crops. Incorporating the DEAS into conventional breeding programmes would help to develop cultivars for climate adaptation.

Normative Analysis of Individual Brain Differences Based on a Population MRI-Based Atlas of Cynomolgus Macaques.

The developmental trajectory of the primate brain varies substantially with aging across subjects. However, this ubiquitous variability between individuals in brain structure is difficult to quantify and has thus essentially been ignored. Based on a large-scale structural magnetic resonance imaging dataset acquired from 162 cynomolgus macaques, we create a species-specific 3D template atlas of the macaque brain, and deploy normative modeling to characterize individual variations of cortical thickness (CT) and regional gray matter volume (GMV). We observed an overall decrease in total GMV and mean CT, and an increase in white matter volume from juvenile to early adult. Specifically, CT and regional GMV were greater in prefrontal and temporal cortices relative to early unimodal areas. Age-dependent trajectories of thickness and volume for each cortical region revealed an increase in the medial temporal lobe, and decreases in all other regions. A low percentage of highly individualized deviations of CT and GMV were identified (0.0021%, 0.0043%, respectively, P < 0.05, false discovery rate [FDR]-corrected). Our approach provides a natural framework to parse individual neuroanatomical differences for use as a reference standard in macaque brain research, potentially enabling inferences regarding the degree to which behavioral or symptomatic variables map onto brain structure in future disease studies.

Neuroanatomical Substrates and Predictors of Response to Capsulotomy in Intractable Obsessive-Compulsive Disorder.

BACKGROUND: Anterior capsulotomy that surgically targets fiber tracts connecting prefrontal cortex and subcortical nuclei is a therapeutic option for a subgroup of patients with treatment-refractory obsessive-compulsive disorder. The goal of this study was to investigate neural correlates to anterior capsulotomy and find predictors of clinical improvement following this procedure. METHODS: Structural and diffusion imaging data and clinical evaluation were acquired from 31 patients with refractory obsessive-compulsive disorder who underwent anterior capsulotomy. Of the 31 patients, 16 were clinical responders defined by a ≥35% reduction in the Yale-Brown Obsessive Compulsive Scale scores. Analysis of variance was applied on 2 levels (surgery and response) to examine alterations of gray matter volume and fiber tract integrity (measured by generalized fractional anisotropy). The correlation between preoperative data and clinical response was further investigated. RESULTS: After surgery, generalized fractional anisotropy was significantly decreased in the bilateral anterior limb of the internal capsule and anterior thalamic radiation, accompanied by a decrease in gray matter volume in the prefrontal cortex, anterior cingulate cortex, striatum, thalamus, and cerebellum. Moreover, atrophy of the right caudate was greater in responders than in nonresponders, which correlated with alteration in Yale-Brown Obsessive Compulsive Scale score. In addition, preoperative gray matter volume in the right inferior frontal gyrus and generalized fractional anisotropy in the left superior longitudinal fasciculus and right cingulum predicted improved response. More anterior location of the lesion area predicted better clinical response. CONCLUSIONS: These results demonstrate that reduced volume of the right caudate might be associated with therapeutic response of capsulotomy and might offer a potential predictor of treatment outcome and a guide for lesion site.

Resequencing of 1,143 indica rice accessions reveals important genetic variations and different heterosis patterns.

Obtaining genetic variation information from indica rice hybrid parents and identification of loci associated with heterosis are important for hybrid rice breeding. Here, we resequence 1,143 indica accessions mostly selected from the parents of superior hybrid rice cultivars of China, identify genetic variations, and perform kinship analysis. We find different hybrid rice crossing patterns between 3- and 2-line superior hybrid lines. By calculating frequencies of parental variation differences (FPVDs), a more direct approach for studying rice heterosis, we identify loci that are linked to heterosis, which include 98 in superior 3-line hybrids and 36 in superior 2-line hybrids. As a proof of concept, we find two accessions harboring a deletion in OsNramp5, a previously reported gene functioning in cadmium absorption, which can be used to mitigate rice grain cadmium levels through hybrid breeding. Resource of indica rice genetic variation reported in this study will be valuable to geneticists and breeders.

Allelic variations of the Wx locus in cultivated rice and their use in the development of hybrid rice in China.

To make better use of global germplasm resources for improving the eating quality of hybrid rice, using the resequencing data from the 3,000 rice genomes project (3K RGP), the allelic variations of the rice Wx locus were analysed. With the exception of five rare alleles discovered for the first time in our study, most of these alleles were known alleles of Wx. Furthermore, a set of Kompetitive allele-specific PCR (KASP) markers based on these Wx alleles have been developed, and thirty-six main parents of hybrid rice from 1976 to 2018 were selected for Wx genotyping. The results showed that only three Wx alleles existed in the main parents of hybrids, and the allelic combination of the hybrids changed from Wxa/Wxb and Wxlv/Wxb to Wxb/Wxb with the development of hybrid rice. Wxb is widely used in the male parents of hybrid rice. Wxa and Wxlv were used in the female parents of early hybrid rice, and they were gradually replaced by Wxb. In the future, more favourable Wx alleles from cultivated rice should be identified, introduced, and effectively used to improve hybrid rice quality.

Expression of heat shock protein 70 and Annexin A1 in serum of patients with acutely severe traumatic brain injury.

Trends of early expression levels of heat shock protein 70 (Hsp70) and Annexin A1 (ANXA1) in serum of patients with acutely severe traumatic brain injury and the effects on clinical prognosis were investigated. Eighty-four patients with severe traumatic brain injury admitted to Binzhou Center Hospital from June 2014 to July 2017 were selected as the experimental group. Glasgow coma scale and acute physiology and chronic health evaluation II (APACHE II) score were obtained after admission. A further 75 healthy subjects were selected as the control group. Serum expression of Hsp70 and ANXA1 in the two groups was detected by enzyme-linked immunosorbent assay on the 1st, 2nd, 3rd and 4th day after admission. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of Hsp70 and ANXA1 for the death of patients with acutely severe traumatic brain injury. Compared with the control group, expression of Hsp70 in the experimental group was significantly increased on the 1st, 2nd, 3rd and 4th day after admission (P<0.05), while expression of ANXA1 was significantly decreased (P<0.05). Expression levels of serum Hsp70 in the experimental group reached the peak on the 3rd day after admission, and the difference was statistically significant compared with the 1st, 2nd and 4th day (P<0.05). Expression of ANXA1 was the lowest on the 3rd day, and the difference was statistically significant compared with the 1st, 2nd and 4th day (P<0.05). The ROC curve analysis showed that the area under the curve of serum Hsp70 and ANXA1 was, respectively, 0.721 (95% CI: 0.611-0.829) and 0.684 (95% CI: 0.569-0.799). In conclusion, Hsp70 and ANXA1 may be involved in the occurrence and progression of acutely severe traumatic brain injury. The detection of serum Hsp70 and ANXA1 has certain diagnostic value for the death of patients with acutely severe traumatic brain injury.

Importance of OsRac1 and RAI1 in signalling of nucleotide-binding site leucine-rich repeat protein-mediated resistance to rice blast disease.

Plants depend on Resistance (R) genes, most of which encode nucleotide-binding site leucine-rich repeat (NLR) proteins, for pathogen race-specific disease resistance. However, only a few immediate downstream targets of R proteins have been characterized, and the signalling pathways for R-protein-induced immunity are largely unknown. In rice (Oryza sativa), NLR proteins serve as important immune receptors in the response to rice blast disease caused by the fungus Magnaporthe oryzae. We used site-directed mutagenesis to create an autoactive form of the NLR protein PID3 that confers blast resistance and used transgenic rice to test the resulting immunity and gene expression changes. We identified OsRac1, a known GTPase, as a signalling molecule in PID3-mediated blast resistance, implicating OsRac1 as a possible common factor downstream of rice NLR proteins. We also identified RAI1, a transcriptional activator, as a PID3 interactor required for PID3-mediated blast resistance and showed that RAI1 expression is induced by PID3 via a process mediated by OsRac1. This study describes a new signalling pathway for NLR protein-mediated blast resistance and shows that OsRac1 and RAI1 act together to play a critical role in this process.

Dissociable Frontostriatal Connectivity: Mechanism and Predictor of the Clinical Efficacy of Capsulotomy in Obsessive-Compulsive Disorder.

BACKGROUND: Little is known about the neural mechanism and response variability underlying neurosurgical interventions for intractable obsessive-compulsive disorder (OCD). METHODS: Of 81 OCD patients screened for capsulotomy identified in our institutional database, 36 patients with clinical assessment before and after capsulotomy and imaging data (9 of 36 patients without postoperative imaging data used as an independent test group), and 29 healthy control subjects were retrospectively recruited. Twenty of 36 patients (56%) responded to the lesion procedure (determined as a ≥35% reduction in Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score). Seed-based (i.e., ventral and dorsal caudate, medial dorsal thalamus, and ventral and dorsal putamen) resting-state functional connectivity was used to examine alterations in frontostriatal circuitry after capsulotomy. RESULTS: The Y-BOCS score significantly decreased (p < .001) after capsulotomy in OCD patients. Functional connectivity between the ventral striatum/nucleus accumbens and the dorsal anterior cingulate cortex was reduced (p < .05, corrected) after the surgical procedure. Moreover, change in connectivity significantly correlated with alteration in Y-BOCS score (r = .41, p = .033). In addition, preoperative connectivity between the dorsal caudate and the dorsal anterior cingulate cortex could differentiate nonresponders from responders and predict changes in Y-BOCS score (R2 = .23, F1,25 = 7.56, p = .011), which was generalized in an independent test group. CONCLUSIONS: We demonstrated that restoration of ventral frontostriatal connectivity was associated with clinical improvement in refractory OCD, suggesting a therapeutic mechanism of capsulotomy. Moreover, preoperative variations in dorsal frontostriatal connectivity predicted clinical response, which may offer a predictor of treatment outcome.

Knockout of OsNramp5 using the CRISPR/Cas9 system produces low Cd-accumulating indica rice without compromising yield.

Rice grain with excessive cadmium (Cd) is a major source of dietary Cd intake and a serious threat to health for people who consume rice as a staple food. The development of elite rice cultivars with consistently low Cd content is challenging for conventional breeding approaches, and new strategies urgently need to be developed. Here, we report the development of new indica rice lines with low Cd accumulation and no transgenes by knocking out the metal transporter gene OsNramp5 using CRISPR/Cas9 system. Hydroponic culture showed that Cd concentrations in shoots and roots of osnramp5 mutants were dramatically decreased, resulting in rescue of impaired growth in high Cd condition. Cd-contaminated paddy field trials demonstrated that Cd concentration in osnramp5 grains was consistently less than 0.05 mg/kg, in contrast to high Cd concentrations from 0.33 mg/kg to 2.90 mg/kg in grains of Huazhan (the wild-type indica rice). In particular, the plant yield was not significantly affected in osnramp5 mutants. Furthermore, we developed promising hybrid rice lines with extremely low Cd content in grains. Our work supplies a practical approach to developing Cd pollution-safe indica rice cultivars that minimizes Cd contamination risk in grains.