Mental illness and well‐being: an affect regulation perspective

Mental health crucially depends upon affective states such as emotions, stress responses, impulses and moods. These states shape how we think, feel and behave. Often, they support adaptive functioning. At other times, however, they can become detrimental to mental health via maladaptive affect generation processes and/or maladaptive affect regulation processes. Here, we present an integrative framework for considering the role of affect generation and regulation in mental illness and well‐being. Our model views affect generation as an iterative cycle of attending to, appraising and responding to situations. It views affect regulation as an iterative series of decisions aimed at altering affect generation. Affect regulation decisions include identifying what, if anything, should be changed about affect, selecting where to intervene in the affect generation cycle, choosing how to implement this intervention, and monitoring the regulation attempt to decide whether to maintain, switch or stop it. Difficulties with these decisions, often arising from biased inputs to them, can contribute to manifestations of mental illness such as clinical symptoms, syndromes and disorders. The model has a number of implications for clinical assessment and treatment. Specifically, it offers a common set of concepts for characterizing different affective states; it highlights interactions between affect generation and affect regulation; it identifies assessment and treatment targets among the component processes of affect regulation; and it is applicable to prevention and treatment of mental illness as well as to promotion and restoration of psychological well‐being.     

Paroxysmal and cognitive phenotypes in Prrt2 mutant mice

Mutations in proline‐rich transmembrane protein 2 (PRRT2) cause a range of episodic disorders that include paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy. Mutations are generally loss of function and include the c649dupC frameshifting mutation that is present in around 80% of affected individuals. To investigate how Prrt2 loss of function mutations causes disease, we performed a phenotypic investigation of a transgenic Prrt2 knockout (Prrt2 KO) mouse. We observed spontaneous paroxysmal episodes with behavioural features of both seizure and movement disorders, as well as unexplained deaths in KO and HET animals. KO mice showed spatial learning deficits in the Morris water maze, as well as gait abnormalities in the quantitative Digigait analysis; both of which may be representative of the more severe phenotypes experienced by homozygous patients. These findings extend the described phenotypes of Prrt2 mutant mice, further confirming their utility for in vivo investigation of the role of Prrt2 mutations in episodic diseases.     

Combined brain‐derived neurotrophic factor with extinction training alleviate impaired fear extinction in an animal model of post‐traumatic stress disorder

Impaired fear memory extinction (Ext) is one of the hallmark symptoms of post‐traumatic stress disorder (PTSD). However, since the precise mechanism of impaired Ext remains unknown, effective interventions have not yet been established. Recently, hippocampal‐prefrontal brain‐derived neurotrophic factor (BDNF) activity was shown to be crucial for Ext in naïve rats. We therefore examined whether decreased hippocampal‐prefrontal BDNF activity is also involved in the Ext of rats subjected to a single prolonged stress (SPS) as a model of PTSD. BDNF levels were measured by enzyme‐linked immunosorbent assay (ELISA), and phosphorylation of TrkB was measured by immunohistochemistry in the hippocampus and medial prefrontal cortex (mPFC) of SPS rats. We also examined whether BDNF infusion into the ventral mPFC or hippocampus alleviated the impaired Ext of SPS rats in the contextual fear conditioning paradigm. SPS significantly decreased the levels of BDNF in both the hippocampus and mPFC and TrkB phosphorylation in the ventral mPFC. Infusion of BDNF 24 hours after conditioning in the infralimbic cortex (ILC), but not the prelimbic cortex (PLC) nor hippocampus, alleviated the impairment of Ext. Since amelioration of impaired Ext by BDNF infusion did not occur without extinction training, it seems the two interventions must occur consecutively to alleviate impaired Ext. Additionally, BDNF infusion markedly increased TrkB phosphorylation in the ILC of SPS rats. These findings suggest that decreased BDNF signal transduction might be involved in the impaired Ext of SPS rats, and that activation of the BDNF‐TrkB signal might be a novel therapeutic strategy for the impaired Ext by stress.     

Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

Prostaglandin E2 (PGE2) is an endogenous lipid molecule involved in normal brain development. Cyclooxygenase‐2 (COX2) is the main regulator of PGE2 synthesis. Emerging clinical and molecular research provides compelling evidence that abnormal COX2/PGE2 signaling is associated with autism spectrum disorder (ASD). We previously found that COX2 knockout mice had dysregulated expression of many ASD genes belonging to important biological pathways for neurodevelopment. The present study is the first to show the connection between irregular COX2/PGE2 signaling and autism‐related behaviors in male and female COX2‐deficient knockin, (COX)‐2^?, mice at young (4‐6 weeks) or adult (8‐11 weeks) ages. Autism‐related behaviors were prominent in male (COX)‐2^? mice for most behavioral tests. In the open field test, (COX)‐2^? mice traveled more than controls and adult male (COX)‐2^? mice spent less time in the center indicating elevated hyperactive and anxiety‐linked behaviors. (COX)‐2^? mice also buried more marbles, with males burying more than females, suggesting increased anxiety and repetitive behaviors. Young male (COX)‐2^? mice fell more frequently in the inverted screen test revealing motor deficits. The three‐chamber sociability test found that adult female (COX)‐2^? mice spent less time in the novel mouse chamber indicative of social abnormalities. In addition, male (COX)‐2^? mice showed altered expression of several autism‐linked genes: Wnt2, Glo1, Grm5 and Mmp9. Overall, our findings offer new insight into the involvement of disrupted COX2/PGE2 signaling in ASD pathology with age‐related differences and greater impact on males. We propose that (COX)‐2^? mice might serve as a novel model system to study specific types of autism.     

Modeling population dynamics in a microbial consortium under control of a synthetic pheromone‐mediated communication system

Microbial consortia can be used to catalyze complex biotransformations. Tools to control the behavior of these consortia in a technical environment are currently lacking. In the present study, a synthetic biology approach was used to build a model consortium of two Saccharomyces cerevisiae strains where growth and expression of the fluorescent marker protein EGFP by the receiver strain is controlled by the concentration of α‐factor pheromone, which is produced by the emitter strain. We have developed a quantitative experimental and theoretical framework to describe population dynamics in the model consortium. We measured biomass growth and metabolite production in controlled bioreactor experiments, and used flow cytometry to monitor changes of the subpopulations and protein expression under different cultivation conditions. This dataset was used to parameterize a segregated mathematical model, which took into account fundamental growth processes, pheromone‐induced growth arrest and EGFP production, as well as pheromone desensitization after extended exposure. The model was able to predict the growth dynamics of single‐strain cultures and the consortium quantitatively and provides a basis for using this approach in actual biotransformations.     

GPA: A Microbial Genetic Polymorphisms Assignments Tool in Metagenomic Analysis by Bayesian Estimation

Identifying antimicrobial resistant(AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing(NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations(CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments(GPA). Simulation results showed that GPA has reduced the false discovery rate(FDR) and mean absolute error(MAE) in CNV and single nucleotide variant(SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://github.com/IID-DTH/GPA-package.     

引进马铃薯种质资源抗旱性评价

马铃薯属于干旱敏感型作物,当前生产上的马铃薯品种多数不耐旱,中国马铃薯抗旱育种进程又受到遗传背景狭窄的制约。引进外来种质资源,拓宽我国马铃薯遗传背景,加快选育抗旱品种是马铃薯应对干旱的关键策略。2016年和2017年,在常规滴灌和雨养条件下,利用增广设计方法,以生产上常用的5个马铃薯品种为对照,对来自国际马铃薯中心的315份高代品系和中国已有的3个品种进行抗旱性评价。通过AMMI模型和GGE模型分析基因型、环境及二者互作对产量的影响,并结合抗旱指数筛选抗旱性稳定且产量高的材料。从整体上看,在雨养条件下,两年马铃薯平均产量差异较小,但是变异系数较大,常规滴灌条件下正好相反。马铃薯产量受基因型、环境及其交互作用的显著影响,其变异平方和分别占总处理平方和的43.39%、39.36%和17.26%;C93和YS902两年的抗旱指数均高于对照品种,稳产性好,C48虽然抗旱指数相对较低,但是高产和稳产性高于所有材料。筛选出来的材料不仅可以作为抗旱育种亲本,还可以通过进一步研究其抗旱机制,为抗旱育种提供理论支持。     

入侵害虫菊方翅网蝽在中国的潜在分布预测

菊方翅网蝽Corythucha marmorata(Uhler,1878)是我国新近发现的外来入侵害虫,研究明确菊方翅网蝽在我国的潜在分布范围对其监测预警及科学防控具有重要意义。本研究根据菊方翅网蝽的地理分布数据及相关环境变量,运用Maxent生态位模型与ArcGIS预测了菊方翅网蝽在中国的潜在地理分布范围。预测结果表明:菊方翅网蝽在我国的适生区主要分布于100°～125°E,20°～40°N的亚热带、暖温带区域,其中高适生区主要集中在长江中下游地区,包括浙江、江苏、湖南、上海大部分地区、安徽南部、湖北南部、江西西部及南部、贵州东部、福建东部、广西北部、山东中部、河南南部以及重庆、台湾局部;此外,极端气温、平均气温、最干月份降雨量对菊方翅网蝽的潜在分布影响较大。菊方翅网蝽已在我国成功入侵并迅速蔓延成灾,应在疫区边缘地带加强监测,并采取措施防止其进一步扩散。     

Genome sequencing and CRISPR/Cas9 gene editing of an early flowering Mini‐Citrus (Fortunella hindsii)

Hongkong kumquat (Fortunella hindsii) is a wild citrus species characterized by dwarf plant height and early flowering. Here, we identified the monoembryonic F. hindsii (designated as ‘Mini‐Citrus’) for the first time and constructed its selfing lines. This germplasm constitutes an ideal model for the genetic and functional genomics studies of citrus, which have been severely hindered by the long juvenility and inherent apomixes of citrus. F. hindsii showed a very short juvenile period (~8 months) and stable monoembryonic phenotype under cultivation. We report the first de novo assembled 373.6 Mb genome sequences (Contig‐N50 2.2 Mb and Scaffold‐N50 5.2 Mb) for F. hindsii. In total, 32 257 protein‐coding genes were annotated, 96.9% of which had homologues in other eight Citrinae species. The phylogenomic analysis revealed a close relationship of F. hindsii with cultivated citrus varieties, especially with mandarin. Furthermore, the CRISPR/Cas9 system was demonstrated to be an efficient strategy to generate target mutagenesis on F. hindsii. The modifications of target genes in the CRISPR‐modified F. hindsii were predominantly 1‐bp insertions or small deletions. This genetic transformation system based on F. hindsii could shorten the whole process from explant to T₁ mutant to about 15 months. Overall, due to its short juvenility, monoembryony, close genetic background to cultivated citrus and applicability of CRISPR, F. hindsii shows unprecedented potentials to be used as a model species for citrus research.