Haplotype-resolved genome of Prunus zhengheensis provides insight into its evolution and low temperature adaptation in apricot.

Prunus zhengheensis, an extremely rare population of apricots, originated in warm South-East China and is an excellent material for genetic breeding. However, most apricots and two related species (P. sibirica, P. mandshurica) are found in the cold northern regions in China and the mechanism of their distribution is still unclear. In addition, the classification status of P. zhengheensis is controversial. Thus, we generated a high-quality haplotype-resolved genome for P. zhengheensis, exploring key genetic variations in its adaptation and the causes of phylogenetic incongruence. We found extensive phylogenetic discordances between the nuclear and organelle phylogenies of P. zhengheensis, which could be explained by incomplete lineage sorting. A 242.22-Mb pan-genome of the Armeniaca section was developed with 13 chromosomal genomes. Importantly, we identified a 566-bp insertion in the promoter of the HSFA1d gene in apricot and showed that the activity of the HSFA1d promoter increased under low temperatures. In addition, HSFA1d overexpression in Arabidopsis thaliana indicated that HSFA1d positively regulated plant growth under chilling. Therefore, we hypothesized that the insertion in the promoter of HSFA1d in apricot improved its low-temperature adaptation, allowing it to thrive in relatively cold locations. The findings help explain the weather adaptability of Armeniaca plants.

AGAMOUS-LIKE24 controls pistil number in Japanese apricot by targeting the KNOTTED1-LIKE gene KNAT2/6-a.

The formation of multi-pistil flowers reduces the yield and quality in Japanese apricot (Prunus mume). However, the molecular mechanism underlying the formation of multi-pistil flowers remains unknown. In the current study, overexpression of PmKNAT2/6-a, a class I KNOTTED1-like homeobox (KNOX) member, in Arabidopsis (Arabidopsis thaliana) resulted in a multi-pistil phenotype. Analysis of the upstream regulators of PmKNAT2/6-a showed that AGAMOUS-like 24 (PmAGL24) could directly bind to the PmKNAT2/6-a promoter and regulate its expression. PmAGL24 also interacted with Like Heterochromatin Protein 1 (PmLHP1) to recruit lysine trimethylation at position 27 on histone H3 (H3K27me3) to regulate PmKNAT2/6-a expression, which is indirectly involved in multiple pistils formation in Japanese apricot flowers. Our study reveals that the PmAGL24 transcription factor, an upstream regulator of PmKNAT2/6-a, regulates PmKNAT2/6-a expression via direct and indirect pathways and is involved in the formation of multiple pistils in Japanese apricot.

Allelic variation of PmCBF03 contributes to the altitude and temperature adaptability in Japanese apricot (Prunus mume Sieb. et Zucc.).

Japanese apricot is an important subtropical deciduous fruit tree in China, widely distributed in different altitude areas. How does it adapt to the different temperature environments in these areas? In this study, we identified a low-temperature transcription factor PmCBF03 on chromosome 7 through adaptive analysis of populations at different altitudes, which has an early termination single nucleotide polymorphism mutation. There were two different types of variation, PmCBF03A type in high-altitude areas and PmCBF03T type in low-altitude areas. PmCBF03A gene increased the survival rate, Fv/Fm values, antioxidant enzyme activity, and expression levels of antioxidant enzyme genes, and reducing electrolyte leakage and accumulation of reactive oxygen species in transgenic Arabidopsis under low temperature and freezing stress. Simultaneously, PmCBF03A gene promoted the dormancy of transgenic Arabidopsis seeds than wild-type. Biochemical analysis demonstrated that PmCBF03A directly bound to the DRE/CRT element in the promoters of the PmCOR413, PmDAM6 and PmABI5 genes, promoting their transcription and enhanced the cold resistance and dormancy of the overexpressing PmCBF03A lines. While PmCBF03T gene is unable to bind to the promoters of PmDAM6 and PmABI5 genes, leading to early release of dormancy to adapt to the problem of insufficient chilling requirement in low-altitude areas.

The association between oral and gut microbiota in male patients with alcohol dependence.

Introduction: The relationship between oral and gut microbiota in alcohol dependence (AD) is not well understood, particularly the effects of oral microbiota on the intestinal microbiota. The current study aimed to explore the association between oral and gut microbiota in AD to clarify whether oral microbiota could ectopically colonize into the gut. Methods: 16S rRNA sequence libraries were used to compare oral and gut microbial profiles in persons with AD and healthy controls (HC). Source Tracker and NetShift were used to identify bacteria responsible for ectopic colonization and indicate the driver function of ectopic colonization bacteria. Results: The α-diversity of oral microbiota and intestinal microbiota was significantly decreased in persons with AD (all p < 0.05). Principal coordinate analysis indicated greater similarity between oral and gut microbiota in persons with AD than that in HC, and oral-gut overlaps in microbiota were found for 9 genera in persons with AD relative to only 3 genera in HC. The contribution ratio of oral microbiota to intestinal microbiota composition in AD is 5.26% based on Source Tracker，and the AD with ectopic colonization showed the daily maximum standard drinks, red blood cell counts, hemoglobin content, and PACS scores decreasing (all p < 0.05). Discussion: Results highlight the connection between oral-gut microbiota in AD and suggest novel potential mechanistic possibilities.

PmAGAMOUS recruits polycomb protein PmLHP1 to regulate single-pistil morphogenesis in Japanese apricot.

Japanese apricot (Prunus mume Sieb. et Zucc.) is a traditional fruit tree with a long history. Multiple pistils (MP) lead to the formation of multiple fruits, decreasing fruit quality and yield. In this study, the morphology of flowers was observed at 4 stages of pistil development: undifferentiated stage (S1), predifferentiation stage (S2), differentiation stage (S3), and late differentiation stage (S4). In S2 and S3, the expression of PmWUSCHEL (PmWUS) in the MP cultivar was significantly higher than that in the single-pistil (SP) cultivar, and the gene expression of its inhibitor, PmAGAMOUS (PmAG), also showed the same trend, indicating that other regulators participate in the regulation of PmWUS during this period. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) showed that PmAG could bind to the promoter and the locus of PmWUS, and H3K27me3 repressive marks were also detected at these sites. The SP cultivar exhibited an elevated level of DNA methylation in the promoter region of PmWUS, which partially overlapped with the region of histone methylation. This suggests that the regulation of PmWUS involves both transcription factors and epigenetic modifications. Also, the gene expression of Japanese apricot LIKE HETEROCHROMATIN PROTEIN (PmLHP1), an epigenetic regulator, in MP was significantly lower than that in SP in S2 to 3, contrary to the trend in expression of PmWUS. Our results showed that PmAG recruited sufficient PmLHP1 to maintain the level of H3K27me3 on PmWUS during the S2 of pistil development. This recruitment of PmLHP1 by PmAG inhibits the expression of PmWUS at the precise time, leading to the formation of 1 normal pistil primordium.

Genome-Wide Identification of the KNOX Gene Family in Japanese Apricot (Prunus mume Sieb. et Zucc.) and Functional Characterization of PmKNAT2 Genes.

The Knotted1-like Homeobox gene is crucial for plant morphological development and growth. Physicochemical characteristics, phylogenetic relationships, chromosomal localization, cis-acting elements, and tissue-specific expression patterns of the 11 PmKNOX genes found in the Japanese apricot genome in this study were examined. Proteins of 11 PmKNOX were soluble proteins with isoelectric points between 4.29 and 6.53, molecular masses between 15.732 and 44.011 kDa, and amino acid counts between 140 and 430. The identified PmKNOX gene family was split into three subfamilies by jointly constructing the phylogenetic tree of KNOX proteins in Japanese apricot and Arabidopsis thaliana. Combined outcomes of the analyzed conserved motifs and gene structures of the 11 PmKNOX genes from the same subfamily displayed comparable gene structure and motif patterns. The 11 PmKNOX members were distributed across six chromosomes, while two sets of PmKNOX genes were found to be collinear. Analysis of the 2000 bp promoter upstream of the coding region of the PmKNOX gene revealed that most PmKNOX genes might be involved in the physiological metabolism, growth and development processes of plants. The PmKNOX gene expression profile revealed that these genes were expressed at varying levels in different tissues, and most of them were linked to the meristems of leaf and flower buds, suggesting that PmKNOX may be involved in plants' apical meristems. In Arabidopsis thaliana, functional validation of PmKNAT2a and PmKNAT2b revealed that these two genes might be involved in regulating leaf and stem development. In addition to laying the groundwork for future research on the function of these genes, understanding the evolutionary relationships between members of the PmKNOX gene family provides opportunities for future breeding in Japanese apricots.

Disrupted diurnal oscillations of the gut microbiota in patients with alcohol dependence.

Background: Patients with alcohol dependence (AD) can exhibit gut dysbacteria. Dysbacteria may co-occur with disruptions of circadian rhythmicity of the gut flora, which can aggravate AD. Herein, this study aimed to investigate diurnal oscillations of the gut microbiota in AD patients. Methods: Thirty-two patients with AD, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 20 healthy subjects were enrolled in this study. Demographic and clinical data were collected by self-report questionnaires. Fecal samples at 7:00 AM, 11:00 AM, 3:00 PM, and 7:00 PM were collected from each subject. 16S rDNA sequencing was conducted. Wilcoxon and Kruskal-Wallis tests were performed to characterize alterations and oscillations of the gut microbiota. Results: We found that ß-diversity of the gut microbiota in AD patients oscillated diurnally compared with healthy subjects (p = 0.01). Additionally, 0.66% of operational taxonomic units oscillated diurnally in AD patients versus 1.68% in healthy subjects. At different taxonomic levels, bacterial abundance oscillated diurnally in both groups, such as Pseudomonas and Prevotella pallens (all p < 0.05). ß-diversity of the gut microbiota in AD patients with high daily alcohol consumption, high-level cravings, short AD durations, and mild withdrawal symptoms oscillated diurnally compared with other AD patients (all p < 0.05). Conclusion: The gut microbiota in AD patients exhibits disruptions of diurnal oscillation, which may provide novel insights into mechanisms of AD and the development of therapeutic strategies.

[Identifying Depressive Disorder With Sleep Electroencephalogram Data: A Study Based on Deep Learning].

Objective: To explore the effectiveness of using deep learning network combined Vision Transformer (ViT) and Transformer to identify patients with depressive disorder on the basis of their sleep electroencephalogram (EEG) signals. Methods: The sleep EEG signals of 28 patients with depressive disorder and 37 normal controls were preprocessed. Then, the signals were converted into image format and the feature information on frequency domain and spatial domain was retained. After that, the images were transmitted to the ViT-Transformer coding network for deep learning of the EEG signal characteristics of the rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep in patients with depressive disorder and those in normal controls, respectively, and to identify patients with depressive disorder. Results: Based on the ViT-Transformer network, after examining different EEG frequencies, we found that the combination of delta, theta, and beta waves produced better results in identifying depressive disorder. Among the different EEG frequencies, EEG signal features of delta-theta-beta combination waves in REM sleep achieved 92.8% accuracy and 93.8% precision for identifying depression, with the recall rate of patients with depression being 84.7%, and the F0.5 value being 0.917±0.074. When using the delta-theta-beta combination EEG signal features in NREM sleep to identify depressive disorder, the accuracy was 91.7%, the precision was 90.8%, the recall rate was 85.2%, and the F0.5 value was 0.914±0.062. In addition, through visualization of the sleep EEG of different sleep stages for the whole night, it was found that classification errors usually occurred during transition to a different sleep stage. Conclusion: Using the deep learning ViT-Transformer network, we found that the EEG signal features in REM sleep based on delta-theta-beta combination waves showed better effect in identifying depressive disorder.

Diurnal changes of the oral microbiome in patients with alcohol dependence.

Background: Saliva secretion and oral microbiota change in rhythm with our biological clock. Dysbiosis of the oral microbiome and alcohol consumption have a two-way interactive impact, but little is known about whether the oral microbiome undergoes diurnal changes in composition and function during the daytime in patients with alcohol dependence (AD). Methods: The impact of alcohol consumption on the diurnal salivary microbiome was examined in a case-control study of 32 AD patients and 21 healthy control (HC) subjects. We tested the changes in microbial composition and individual taxon abundance by 16S rRNA gene sequencing. Results: The present study is the first report showing that alcohol consumption enhanced the richness of the salivary microbiome and lowered the evenness. The composition of the oral microbiota changed significantly in alcohol-dependent patients. Additionally, certain genera were enriched in the AD group, including Actinomyces, Leptotrichia, Sphaerochaeta and Cyanobacteria, all of which have pathogenic effects on the host. There is a correlation between liver enzymes and oral microbiota. KEGG function analysis also showed obvious alterations during the daytime. Conclusion: Alcohol drinking influences diurnal changes in the oral microbiota, leading to flora disturbance and related functional impairment. In particular, the diurnal changes of the oral microbiota may open avenues for potential interventions that can relieve the detrimental consequences of AD.

Epigenome-wide DNA methylation analysis of whole blood cells derived from patients with GAD and OCD in the Chinese Han population.

Generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) had high comorbidity and affected more than 44 million people around the world leading to a huge burden on health and economy. Here, we conducted an epigenome-wide DNA methylation study employing 93 patients with GAD, 65 patients with OCD, and 302 health controls, to explore epigenetic alterations associated with the onset and differences of GAD and OCD. We identified multiple differentially methylated positions (DMPs) and regions (DMRs): three DMP genes included RIOK3 (cg21515243, p = 8.00 × 10-10), DNASE2 (cg09379601, p = 1.10 × 10-9), and PSMB4 (cg01334186, p = 3.70 × 10-7) and two DMR genes USP6NL (p = 4.50 × 10-4) and CPLX1 (p = 6.95 × 10-4) were associated with the onset of GAD and OCD; three DMPs genes included LDLRAP1 (cg21400344, p = 4.40 × 10-12), ACIN1 (cg23712970, p = 2.98×10-11), and SCRT1 (cg25472897, p = 5.60 × 10-11) and three DMR genes WDR19 (p = 3.39 × 10-3), SYCP1 (p = 6.41 × 10-3), and FAM172A (p = 5.74 × 10-3) were associated with the differences between GAD and OCD. Investigation of epigenetic age and chronological age revealed a different epigenetic development trajectory of GAD and OCD. Conclusively, our findings which yielded robust models may aid in distinguishing patients from healthy controls (AUC = 0.90-0.99) or classifying patients with GAD and OCD (AUC = 0.89-0.99), and may power the precision medicine for them.

Impulsive trait mediates the relationship between white matter integrity of prefrontal-striatal circuits and the severity of dependence in alcoholism.

Background: Alcohol dependence (AD) remains one of the major public health concerns. Impulsivity plays a central role in the transfer from recreational alcohol use to dependence and relapse. White matter dysfunction has been implicated in alcohol addiction behaviors and impulsivity. However, little is known about the role of systematic striatal structural connections underlying the mechanism of impulsive traits in AD. Methods: In our study, we used seed-based classification by probabilistic tractography with five target masks of striatal circuits to explore the differences in white matter integrity (fractional anisotropy, FA) in AD male patients (N = 51) and healthy controls (N = 27). We mainly explored the correlation between FA of the striatal circuits and impulsive traits (Barratt Impulsiveness Scale, BIS-11), and the mediation role of impulsivity in white matter integrity and the severity of alcohol dependence. Results: Compared with healthy controls, AD showed much lower FA in the left and right striatum-supplementary motor area (SMA) and left striatum-amygdala. We also found the decreased FA of right striatum-vlPFC was correlated with higher impulsivity. Besides, the relationship between reduced FA of right striatum-vlPFC and severity of dependence could be mediated by impulsivity. Conclusion: In our study, we found disrupted white matter integrity in systematic striatal circuits in AD and the decreased FA of right striatum-vlPFC was correlated with higher impulsivity in AD. Our main findings provide evidence for reduced white matter integrity of systematic striatal circuits and the underlying mechanisms of impulsivity in male AD individuals.

Bioinformatics Study of Aux/IAA Family Genes and Their Expression in Response to Different Hormones Treatments during Japanese Apricot Fruit Development and Ripening.

Auxin/indole-3-acetic acid (Aux/IAA) is a transcriptional repressor in the auxin signaling pathway that plays a role in several plant growth and development as well as fruit and embryo development. However, it is unclear what role they play in Japanese apricot (Prunus mume) fruit development and maturity. To investigate the role of Aux/IAA genes in fruit texture, development, and maturity, we comprehensively identified and expressed 19 PmIAA genes, and demonstrated their conserved domains and homology across species. The majority of PmIAA genes are highly responsive and expressed in different hormone treatments. PmIAA2, PmIAA5, PmIAA7, PmIAA10, PmIAA13, PmIAA18, and PmIAA19 showed a substantial increase in expression, suggesting that these genes are involved in fruit growth and maturity. During fruit maturation, alteration in the expression of PmIAA genes in response to 1-Methylcyclopropene (1-MCP) treatment revealed an interaction between auxin and ethylene. The current study investigated the response of Aux/IAA development regulators to auxin during fruit ripening, with the goal of better understanding their potential application in functional genomics.

The analysis of genetic structure and characteristics of the chloroplast genome in different Japanese apricot germplasm populations.

BACKGROUND: Chloroplast (cp) genomes are generally considered to be conservative and play an important role in population diversity analysis in plants, but the characteristics and diversity of the different germplasm populations in Japanese apricot are still not clear. RESULTS: A total of 146 cp genomes from three groups of wild, domesticated, and bred accessions of Japanese apricot were sequenced in this study. The comparative genome analysis revealed that the 146 cp genomes were divided into 41 types, and ranged in size from 157,886 to 158,167 bp with a similar structure and composition to those of the genus Prunus. However, there were still minor differences in the cp genome that were mainly caused by the contraction and expansion of the IR region, and six types of SSR in which mono-nucleotide repeats were the most dominant type of repeats in the cp genome. The genes rpl33 and psbI, and intergenic regions of start-psbA, rps3-rpl22, and ccsA-ndhD, showed the highest nucleotide polymorphism in the whole cp genome. A total of 325 SNPs were detected in the 146 cp genomes, and more than 70% of the SNPs were in region of large single-copy (LSC). The SNPs and haplotypes in the cp genome indicated that the wild group had higher genetic diversity than the domesticated and bred groups. In addition, among wild populations, Southwest China, including Yunnan, Tibet, and Bijie of Guizhou, had the highest genetic diversity. The genetic relationship of Japanese apricot germplasm resources in different regions showed a degree of correlation with their geographical distribution. CONCLUSION: Comparative analysis of chloroplast genomes of 146 Japanese apricot resources was performed to analyze the used to explore the genetic relationship and genetic diversity among Japanese apricot resources with different geographical distributions, providing some reference for the origin and evolution of Japanese apricot.

Mutations in PmUFGT3 contribute to color variation of fruit skin in Japanese apricot (Prunus mume Sieb. et Zucc.).

BACKGROUND: Japanese apricot (Prunus mume Sieb. et Zucc.) is popular for both ornamental and processing value, fruit color affects the processing quality, and red pigmentation is the most obvious phenotype associated with fruit color variation in Japanese apricot, mutations in structural genes in the anthocyanin pathway can disrupt the red pigmentation, while the formation mechanism of the red color trait in Japanese apricot is still unclear.  RESULTS: One SNP marker (PmuSNP_27) located within PmUFGT3 gene coding region was found highly polymorphic among 44 different fruit skin color cultivars and relative to anthocyanin biosynthesis in Japanese apricot. Meantime, critical mutations were identified in two alleles of PmUFGT3 in the green-skinned type is inactivated by seven nonsense mutations in the coding region, which leads to seven amino acid substitution, resulting in an inactive UFGT enzyme. Overexpression of the PmUFGT3 allele from red-skinned Japanese apricot in green-skinned fruit lines resulted in greater anthocyanin accumulation in fruit skin. Expression of same allele in an Arabidopsis T-DNA mutant deficient in anthocyanidin activity the accumulation of anthocyanins. In addition, using site-directed mutagenesis, we created a single-base substitution mutation (G to T) of PmUFGT3 isolated from green-skinned cultivar, which caused an E to D amino acid substitution and restored the function of the inactive allele of PmUFGT3 from a green-skinned individual. CONCLUSION: This study confirms the function of PmUFGT3, and provides insight into the mechanism underlying fruit color determination in Japanese apricot, and possible approaches towards genetic engineering of fruit color.

Exposure to Olfactory Alcohol Cues During Non-rapid Eye Movement Sleep Did Not Decrease Craving in Patients With Alcohol Dependence.

Background and Objectives: Cue exposure therapy (CET) has been used to reduce alcohol use, but the effect of CET during sleep on alcohol dependence (AD) is unclear. The present study examined the effect of repeated exposure to an olfactory stimulus during non-rapid eye movement (NREM) sleep on cue reactivity and craving in patients with AD. Methods: Thirty-five patients with AD were enrolled according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). All the subjects were randomly assigned to the experimental or control group. The experimental group was exposed to alcohol odor for 10 min during NREM sleep. The other group (controls) was exposed to water [control stimulus (CtrS)] for 10 min during NREM sleep. Demographic, alcohol-related, and clinical characteristics were collected at baseline. A cue-reactivity test was conducted before and after exposure to evaluate the effect of memory manipulation on acute response to an alcohol stimulus. Results: There were no significant time × group interactions according to the visual analog scale (VAS) score of craving intensity, skin conductance response (SCR), systolic blood pressure (SBP), and diastolic blood pressure (DBP; all p > 0.05). Two-way ANOVA showed significant main effects of time on SCR [F (1,33) = 4.453, p = 0.043], SBP [F (1,33) = 14.532, p = 0.001], DBP [F (1,33) = 8.327, p = 0.007], Craving-VAS [F (1,33) = 1.997, p = 0.167] in two groups. Conclusion: Exposure to olfactory alcohol cues during NREM sleep had no significant effect on alcohol craving in subjects with AD during hospitalization.

Novel insights into the dissemination route of Japanese apricot (Prunus mume Sieb. et Zucc.) based on genomics.

Japanese apricot (Prunus mume) is an attractive fruit tree originating from China, and its cultivation history dates back 7000 years. In this study, we investigated the genetic diversity, population structure, and genetic relationship of Japanese apricots in different regions of China and Japan. The analyses of the genetic variation between wild and cultivated populations improved our understanding of the general mechanisms of domestication and improvement. A total of 146 accessions of Japanese apricot from different geographic locations were sequenced. The genetic diversity of wild and domesticated accessions (3.60 × 10-3 and 3.51 × 10-3 , respectively) from China was high, and the effect of artificial selection pressure on domesticated accessions was small; however, the genetic diversity of artificially bred accessions decreased significantly (2.68 × 10-3 ) compared to domesticated accessions, which had an obvious improvement bottleneck effect. The chloroplast genome results showed that 41 haplotypes were detected, and Japanese apricots from the Yunnan region had the most haplotypes and the highest genetic diversity. The results revealed the dissemination route of Japanese apricot, not only along the Yangtze River basin system (from southwest China to Hunan, Jiangxi, and Anhui, and finally to the Jiangsu, Zhejiang, and Shanghai areas). Additionally, we discovered a second route for Japanese apricot dispersion, which was mostly in the Pearl River basin system, from southwest China to Libo of Guizhou and then to the Guangdong, Fujian, and Taiwan areas. This also showed that Japanese-bred accessions originated from Zhejiang, China. In addition, selective sweep analysis showed that most of the high-impact single nucleotide polymorphisms were identified in genes related to glucose metabolism, aromatic compound metabolism, flowering time, dormancy, and resistance to abiotic stress during the domestication and improvement of Japanese apricot.

Identification of novel risk loci with shared effects on alcoholism, heroin, and methamphetamine dependence.

Different substance dependences have common effects on reward pathway and molecular adaptations, however little is known regarding their shared genetic factors. We aimed to identify the risk genetic variants that are shared for substance dependence (SD). First, promising genome-wide significant loci were identified from 3296 patients (521 alcoholic/1026 heroin/1749 methamphetamine) vs 2859 healthy controls and independently replicated using 1954 patients vs 1904 controls. Second, the functional effects of promising variants on gene expression, addiction characteristics, brain structure (gray and white matter), and addiction behaviors in addiction animal models (chronic administration and self-administration) were assessed. In addition, we assessed the genetic correlation among the three SDs using LD score regression. We identified and replicated three novel loci that were associated with the common risk of heroin, methamphetamine addiction, and alcoholism: ANKS1B rs2133896 (Pmeta = 3.60 × 10-9), AGBL4 rs147247472 (Pmeta = 3.40 × 10-12), and CTNNA2 rs10196867 (Pmeta = 4.73 × 10-9). Rs2133896 in ANKS1B was associated with ANKS1B gene expression and had effects on gray matter of the left calcarine and white matter of the right superior longitudinal fasciculus in heroin dependence. Overexpression of anks1b gene in the ventral tegmental area decreased addiction vulnerability for heroin and methamphetamine in self-administration rat models. Our findings could shed light on the root cause for substance dependence and will be helpful for the development of cost-effective prevention strategies for general addiction disorders.

Association between blooming time and climatic adaptation in Prunus mume.

Prunus mume Sieb. et Zucc. is an important fruit crop of the subtropical region, originating in China. It blooms earlier than other deciduous fruit trees, but different regions have different blooming periods. The time of anthesis is related to the dormancy period, and a certain amount of chilling promotes bud break and blooming. To identify the relationship between blooming time and the climatic adaptation of P. mume cultivars in China, the nuclear and chloroplast genomes of 19 cultivars from the main cultivation areas of P. mume in China were resequenced. The average depth of coverage was 34X-76X, and a total of 388,134 single nucleotide polymorphisms were located within the coding regions of the gene (CDs). Additionally, the 19 cultivar accessions were divided into three groups based on their blooming time: early, mid, and late. Associated with the blooming time groups, 21 selective sweep regions were identified, which could provide evidence supporting the possible model of P. mume domestication originating due to natural selection. Furthermore, we identified a flowering gene, FRIGIDA-LIKE 3 (FRL3), seems to affect the blooming time and the climatic adaptation of P. mume cultivars. This study is a major step toward understanding the climatic adaptation of P. mume cultivars in China.

Comparative analysis of the complete chloroplast genome among Prunus mume, P. armeniaca, and P. salicina.

Prunus mume Sieb. et Zucc., P. armeniaca L., and P. salicina L. are economically important fruit trees in temperate regions. These species are taxonomically perplexing because of shared interspecific morphological traits and variation, which are mainly attributed to hybridization. The chloroplast is cytoplasmically inherited and often used for evolutionary studies. We sequenced the complete chloroplast genomes of P. mume, P. armeniaca, and P. salicina using Illumina sequencing followed by de novo assembly. The three chloroplast genomes exhibit a typical quadripartite structure with conserved genome arrangement, structure, and moderate divergence. The lengths of the genomes are 157,815, 157,797, and 157,916 bp, respectively. The length of the large single-copy region (LSC) region is 86,113, 86,283, and 86,122 bp, and the length of the SSC region is 18,916, 18,734, and 19,028 bp; the IR region is 26,393, 26,390, and 26,383 bp, respectively. Each of the three chloroplast genomes encodes 133 genes, including 94 protein-coding, 31 tRNA, and eight rRNA genes. Differential gene analysis for the three species revealed that trnY-ATA is a unique gene in P. armeniaca; in contrast, the gene trnI-TAT is only present in P. mume and P. salicina, though the position of the gene in these chloroplast genomes differs. Further comparative analysis of the complete chloroplast genome sequences revealed that the ORF genes and the sequences of linked regions rps16 and atpA, atpH and atpI, trnc-GCA and psbD, ycf3 and atpB, and rpL32 and ndhD are significantly different and may be used as molecular markers in taxonomic studies. Phylogenetic evolution analysis of the three species suggests that P. mume has a closer genetic relationship to P. armeniaca than to P. salicina.

Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.

Alcohol-related behaviors are moderately heritable and have ethnic-specific characteristics. At present, genetic studies for alcohol dependence (AD) in Chinese populations are underrepresented. We are the first to conduct a genome-wide association study (GWAS) for AD using 533 male alcoholics and 2848 controls of Han Chinese ethnicity and replicate our findings in 146 male alcoholics and 200 male controls. We then assessed genetic effects on AD characteristics (drinking volume/age onset/Michigan Alcoholism Screening Test (MAST)/Barratt Impulsiveness Scale (BIS-11)), and compared the polygenic risk of AD in Han Chinese with other populations (Thai, European American and African American). We found and validated two significant loci, one located in 4q23, with lead SNP rs2075633*ADH1B (Pdiscovery = 6.64 × 10-16) and functional SNP rs1229984*ADH1B (Pdiscovery = 3.93 × 10-13); and the other located in 12q24.12-12q24.13, with lead SNP rs11066001*BRAP (Pdiscovery = 1.63 × 10-9) and functional SNP rs671*ALDH2 (Pdiscovery = 3.44 × 10-9). ADH1B rs1229984 was associated with MAST, BIS_total score and average drinking volume. Polygenic risk scores from the Thai AD and European American AD GWAS were significantly associated with AD in Han Chinese, which were entirely due to the top two loci, however there was no significant prediction from African Americans. This is the first case-control AD GWAS in Han Chinese. Our findings demonstrate that these variants, which were highly linked with ALDH2 rs671 and ADH1B rs1229984, were significant modulators for AD in our Han Chinese cohort. A larger replication cohort is still needed to validate our findings.