Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice.

Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying the behaviors are not clearly defined. Here we show that the basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to the manifestation of compulsive-like behaviors. We revealed that the BLA neurons projecting to the DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with the neuronal population that responds to aversive predator stress, a widely used anxiogenic stressor. Specific optogenetic activation of the BLA-DMS circuit induced a strong anxiety response followed by compulsive grooming. Furthermore, we developed a mouse model for compulsivity displaying a wide spectrum of compulsive-like behaviors by chronically activating the BLA-DMS circuit. In these mice, persistent molecular changes at the BLA-DMS synapses observed were causally related to the compulsive-like phenotypes. Together, our study demonstrates the involvement of the BLA-DMS circuit in the emergence of enduring compulsive-like behaviors via its persistent synaptic changes.

Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1.

Norovirus (NV) is the most common cause of viral gastroenteritis, with the potential to develop into a fatal disease in those who are immuno-compromised, and effective vaccines and treatments are still non-existent. In this study, we aimed to elucidate the molecular mechanism of the previously identified NV replication inhibitor utilizing a vinyl-stilbene backbone, AC-1858. First, we confirmed the inhibition of the NV RNA replication by a structural analog of AC-1858, AC-2288 with its exclusive cytoplasmic subcellular localization. We further validated the induction of one specific host factor, the phosphorylated form of heat shock factor (HSF)-1, and its increased nuclear localization by AC-1858 treatment. Finally, we verified the positive and negative impact of the siRNA-mediated downregulation and lentivirus-mediated overexpression of HSF-1 on NV RNA replication. In conclusion, these data suggest the restrictive role of the host factor HSF-1 in overall viral RNA genome replication during the NV life cycle.

Genome-Wide Identification and Genetic Variations of the Starch Synthase Gene Family in Rice.

Starch is a major ingredient in rice, and the amylose content of starch significantly impacts rice quality. OsSS (starch synthase) is a gene family related to the synthesis of amylose and amylopectin, and 10 members have been reported. In the present study, a synteny analysis of a novel family member belonging to the OsSSIV subfamily that contained a starch synthase catalytic domain showed that three segmental duplications and multiple duplications were identified in rice and other species. Expression data showed that the OsSS gene family is involved in diverse expression patterns. The prediction of miRNA targets suggested that OsSS are possibly widely regulated by miRNA functions, with miR156s targeted to OsSSII-3, especially. Haplotype analysis exhibited the relationship between amylose content and diverse genotypes. These results give new insight and a theoretical basis for the improved amylose content and eating quality of rice.

Genome-Wide Association Study of Root System Development at Seedling Stage in Rice.

Root network structure plays a crucial role in growth and development processes in rice. Longer, more branched root structures help plants to assimilate water and nutrition from soil, support robust plant growth, and improve resilience to stresses such as disease. Understanding the molecular basis of root development through screening of root-related traits in rice germplasms is critical to future rice breeding programs. This study used a small germplasm collection of 137 rice varieties chosen from the Korean rice core set (KRICE_CORE) to identify loci linked to root development. Two million high-quality single nucleotide polymorphisms (SNPs) were used as the genotype, with maximum root length (MRL) and total root weight (TRW) in seedlings used as the phenotype. Genome-wide association study (GWAS) combined with Principal Components Analysis (PCA) and Kinship matrix analysis identified four quantitative trait loci (QTLs) on chromosomes 3, 6, and 8. Two QTLs were linked to MRL and two were related to TRW. Analysis of Linkage Disequilibrium (LD) decay identified a 230 kb exploratory range for detection of candidate root-related genes. Candidates were filtered using RNA-seq data, gene annotations, and quantitative real-time PCR (qRT-PCR), and five previously characterized genes related to root development were identified, as well as four novel candidate genes. Promoter analysis of candidate genes showed that LOC_Os03g08880 and LOC_Os06g13060 contained SNPs with the potential to impact gene expression in root-related promoter motifs. Haplotype analysis of candidate genes revealed diverse haplotypes that were significantly associated with phenotypic variation. Taken together, these results indicate that LOC_Os03g08880 and LOC_Os06g13060 are strong candidate genes for root development functions. The significant haplotypes identified in this study will be beneficial in future breeding programs for root improvement.

Identification of novel non-nucleoside vinyl-stilbene analogs as potent norovirus replication inhibitors with a potential host-targeting mechanism.

Norovirus (NV), is the most common cause of acute gastroenteritis worldwide. To date, there is no specific anti-NV drug or vaccine to treat NV infections. In this study, we evaluated the inhibitory effect of different stilbene-based analogs on RNA genome replication of human NV (HNV) using a virus replicon-bearing cell line (HG23). Initial screening of our in-house chemical library against NV led to the identification of a hit containing stilbene scaffold 5 which on initial optimization gave us a vinyl stilbene compound 16c (EC50 = 4.4 µM). Herein we report our structure-activity relationship study of the novel series of vinyl stilbene analogs that inhibits viral RNA genome replication in a human NV-specific manner. Among these newly synthesized compounds, several amide derivatives of vinyl stilbenes exhibited potent anti-NV activity with EC50 values ranging from 1 to 2 µM. A trans-vinyl stilbenoid with an appended substituted piperazine amide (18k), exhibited potent anti-NV activity and also displayed favorable metabolic stability. Compound 18k demonstrated an excellent safety profile, the highest suppressive effect, and was selective for HNV replication via a viral RNA polymerase-independent manner. Its potential host-targeting antiviral mechanism was further supported by specific activation of heat shock factor 1-dependent stress-inducible pathway by 18k. These results suggest that 18k might be a promising lead compound for developing novel NV inhibitors with the novel antiviral mechanism.

Genome-wide association study reveals candidate genes related to low temperature tolerance in rice (Oryza sativa) during germination.

In this study, relative germination percentage (RGP) and delayed mean germination time (DMGT) were measured in various rice accessions at the germination stage and carried out association analysis to identify candidate genes related to low temperature germination (LTG) using a natural population comprising 137 rice cultivars and inbred lines selected from the Korean rice core set. Genome-wide association study using ~ 1.44 million high-quality SNPs, which were identified by re-sequencing all rice collections, revealed 48 candidate genes on chromosome 10 and 55 candidate genes on chromosome 11 in the high peak SNP sites of associated loci for RGP and DMGT, respectively. By detecting highly associated variations located inside genic regions and performing functional annotation of the genes, we detected 23 candidate genes for RGP and 18 genes for DMGT for LTG. In addition, the haplotype and sequence analysis of the candidate gene (Os10g0371100) with RGP trait and the candidate gene (Os11t0104240-00) with DMGT revealed correlation between sequences of functional variations and phenotypes. Several novel LTG-related candidate genes previously were known for the function during rice germination and uncovered their substantial natural variations. These candidate genes represent valuable resources for molecular breeding and genetic improvement of cold tolerance during rice germination.

Next-generation sequencing yields the complete chloroplast genome of C. goeringii acc. smg222 and phylogenetic analysis.

Spring orchid (Cymbidium goeringii) is one of the most important species belonging to Orchidaceae owing to its aesthetic appeal, fragrant flowers and ideal characteristics for using as a houseplant. In this study, the complete chloroplast genome of Korean C. goeringii acc. smg222 was determined by Illumina sequencing. The circular double-stranded DNA of 148,441 bp consisted of two inverted repeat regions of 25,610 bp each, a large single copy region of 83,311 bp, and a small single copy region of 13,910 bp. The genome contained 122 genes, of which 104 were unique and 18 were duplicated within the IRs. The 104 unique genes included 70 protein-coding genes, 30 distinct tRNA genes, and four rRNA genes. Phylogenetic tree analysis revealed that C. goeringii acc. smg222 was clustered with Cymbidium kanran, a cymbidium species native to Korea.