Individuals departing non-breeding areas early achieve earlier breeding and higher breeding success.

Conditions experienced by an individual during migration have the potential to shape migratory tactic and in turn fitness. For large birds, environmental conditions encountered during migration have been linked with survival and subsequent reproductive output, but this is less known for smaller birds, hindering our understanding of mechanisms driving population change. By combining breeding and tracking data from 62 pied flycatchers (Ficedula hypoleuca) representing two breeding populations collected over 2016-2020, we determine how variation in migration phenology and tactic among individuals affects subsequent breeding. Departure date from West African non-breeding areas to European breeding grounds was highly variable among individuals and had a strong influence on migration tactic. Early departing individuals had longer spring migrations which included longer staging duration yet arrived at breeding sites and initiated breeding earlier than later departing individuals. Individuals with longer duration spring migrations and early arrival at breeding sites had larger clutches, and for males higher fledging success. We suggest that for pied flycatchers, individual carry-over effects may act through departure phenology from West Africa, and the associated spring migration duration, to influence reproduction. While our results confirm that departure date from non-breeding areas can be associated with breeding success in migratory passerines, we identify spring staging duration as a key component of this process.

Interspecific plant interaction structures the microbiomes of poplar-soil interface to alter nutrient cycling and utilization.

Terrestrial plants can influence the growth and health of adjacent plants through interspecific interaction. Here, the mechanisms of interspecific plant interaction on microbial function and nutrient utilization in the plant-soil interface (non-rhizosphere soil, rhizosphere soil, and root) were studied by soybean- and potato-poplar intercropping. First, metagenomics showed that soybean- and potato-poplar intercropping influenced the composition and co-occurrence networks of microbial communities in different ecological niches, with higher stability of the microbial community in soybean intercropping. Second, the gene abundance related to carbon metabolism, nitrogen cycling, phosphorus cycling, and sulfur cycling was increased at the poplar-soil interface in soybean intercropping. Moreover, soybean intercropping increased soil nutrient content and enzymatic activity. It showed higher metabolic potential in nutrient metabolism and transportation. Third, functional microorganisms that influenced nutrient cycling and transportation in different intercropping have been identified, namely Acidobacteria, Sphingomonas, Gemmatimonadaceae, Alphaproteobacteria, and Bradyrhizobium. Therefore, intercropping can construct microbial communities to alter metabolic functions and improve nutrient cycling and absorption. Interspecific plant interactions to influence the microbiome were revealed, opening up a new way for the precise regulation of plant microbiome.IMPORTANCEPoplar has the characteristics of wide distribution, strong adaptability, and fast growth, which is an ideal tree species for timber forest. In this study, metagenomics and elemental analysis were used to comprehensively reveal the effects of interspecific plant interactions on microbial communities and functions in different ecological niches. It can provide a theoretical basis for the development and application of the precise management model in poplar.

Association of health-risk behaviors with perceived academic performance among middle and high school students: A cross-sectional study in Shanghai, China.

Adolescence is a susceptible period to establish health-risk behaviors, which may have an impact on academic performance. The aim of this study was to investigate the association between health-risk behaviors (HRBs) and perceived academic performance (PAP) of adolescents in Shanghai, China. The data of the present study included three-round Shanghai Youth Health-risk Behavior Survey (SYHBS). This cross-sectional survey investigated multiple HRBs of students involved in dietary behaviors, physical activity and sedentary behaviors, intentional and unintentional injury behaviors, and substance abuse behaviors, as well as PAP by using self-reported questionnaire. Using a multistage random sampling method, 40,593 middle and high school students aged 12 to 18 years were involved. Only participants with complete data on HRBs information, academic performance and covariates were included. A total of 35,740 participants were involved in analysis. We used ordinal logistic regression to analyze the association between each HRB and PAP adjusting for sociodemographic, family environment and duration of extracurricular study. The results showed that students who did not eat breakfast or drink milk everyday were more likely to have a lower PAP, with a decreased odds of 0.89 (95%CI: 0.86-0.93, P<0.001) and 0.82 (95%CI: 0.79-0.85, P<0.001), respectively. The similar association was also found in students who did exercise ≥60 minutes for less than 5 days/week, spend time on watch TV beyond 3 hours/day and other sedentary behaviors. Most intentional and unintentional injuries, and ever smoked were associated with a lower PAP. Our finding suggests that multiple HRBs negatively associated with PAP of adolescents. It needs to raise public health concerns with HRBs in adolescents, and to develop and implement comprehensive interventions on HRBs.

Systemic regulation of nodule structure and assimilated carbon distribution by nitrate in soybean.

Background: The nitrate regulates soybean nodulation and nitrogen fixation systemically, mainly in inhibiting nodule growth and reducing nodule nitrogenase activity, but the reason for its inhibition is still inconclusive. Methods: The systemic effect of nitrate on nodule structure, function, and carbon distribution in soybean (Glycine max (L.) Merr.) was studied in a dual-root growth system, with both sides inoculated with rhizobia and only one side subjected to nitrate treatment for four days. The non-nodulating side was genetically devoid of the ability to form nodules. Nutrient solutions with nitrogen concentrations of 0, 100, and 200 mg L-1 were applied as KNO3 to the non-nodulating side, while the nodulating side received a nitrogen-free nutrient solution. Carbon partitioning in roots and nodules was monitored using 13C-labelled CO2. Other nodule responses were measured via the estimation of the nitrogenase activity and the microscopic observation of nodule ultrastructure. Results: Elevated concentrations of nitrate applied on the non-nodulating side caused a decrease in the number of bacteroids, fusion of symbiosomes, enlargement of the peribacteroid spaces, and onset of degradation of poly-ß-hydroxybutyrate granules, which is a form of carbon storage in bacteroids. These microscopic observations were associated with a strong decrease in the nitrogenase activity of nodules. Furthermore, our data demonstrate that the assimilated carbon is more likely to be allocated to the non-nodulating roots, as follows from the competition for carbon between the symbiotic and non-symbiotic sides of the dual-root system. Conclusion: We propose that there is no carbon competition between roots and nodules when they are indirectly supplied with nitrate, and that the reduction of carbon fluxes to nodules and roots on the nodulating side is the mechanism by which the plant systemically suppresses nodulation under nitrogen-replete conditions.

Systematic analysis of microbiota in pregnant Chinese women and its association with miscarriage.

Background: Miscarriage is the most common adverse pregnancy outcome and more than 50% of its incidence remains unexplained. Earlier studies have suggested that maternal microbiota might be associated with miscarriage, but the association is insufficiently understood. Methods: We used 16S ribosomal RNA (rRNA) amplicon sequencing and metagenomic sequencing technology to characterize the bacterial composition of three sites including the rectum, vagina, and cervix of a case group of 63 pregnant women who had miscarried compared to a control group of 24 pregnant women who underwent voluntary elective abortion. Results: The alpha-diversity from the rectum and cervix was significantly decreased in the case group relative to the control group. However, we did not find significant differences in microbial diversity of vaginal samples between the two groups. Lactobacillus was the most predominant genus in the cervix and vaginal samples. Gestational age at the time of surgery was positively associated with the rectum microbiota diversity, with an effect size of 10% (P=0.004). Host factors including gestational age and red blood count (RBC) were associated with the rectal microbiota diversity. Conclusions: We detected a significantly lower rectal microbiota diversity and a pro-inflammatory tendency in the miscarriage group. This is the first study to investigate the association of microbiota from samples collected from three sites and miscarriage. Further studies are warranted to explore further the role of microbiota in miscarriage.

Multi-omics analysis of the regulatory effects of low-phosphorus stress on phosphorus transport in soybean roots.

The regulatory effects of uneven phosphorus supplies on phosphorus transport in soybean roots are still unclear. To further analyze the regulatory effects of low-phosphorus stress on phosphorus transport in soybean roots and the effects of uneven phosphorus application on the physiological mechanism of phosphorus transport in soybean roots, dual-root soybean plants were prepared via grafting, and a sand culture experiment was performed. From the unfolded cotyledon stage to the initial flowering stage, one side of each dual-root soybean system was irrigated with a low-phosphorus-concentration solution (phosphorus-application [P+] side), and the other side was irrigated with a phosphorus-free nutrient solution (phosphorus-free [P-] side); this setup allowed the study of the effects of different phosphorus supply levels on the expression of genes and proteins and the accumulation of metabolites in soybean roots on the P- side to clarify the method through which phosphorus transport is regulated in soybean roots and to provide a theoretical basis for improving the use rate of phosphorus fertilizer. The results revealed that the unilateral supply of low-concentration phosphorus promoted the uptake of phosphorus by soybean roots and the transport of phosphorus from the P+ side to the P- side. Compared with the normal concentration of phosphorus supply and the phosphorus-free supply, the low concentration phosphorus supply affected the regulation of the metabolic pathways involved in starch and sucrose metabolism, glycolysis, fructose, and mannose metabolism, etc., thereby affecting soybean root phosphorus transport. The low-phosphorus stress inhibited fructose synthesis and sucrose synthase synthesis in the soybean roots and the synthesis of hexokinase (HK) and fructose kinase, which catalyzes the conversion of fructose to fructose-6-phosphate. Low-phosphorus stress promoted the synthesis of sucrose invertase and the conversion of sucrose into maltose by the activity of starch synthase (StS) and stimulated the synthesis of UDPG pyrophosphorylase (UGP) and phosphoglucose isomerase (GP1), which is involved in the conversion of UDP-glucose to glucose-6-phosphate. The phosphorus transport pathway of soybean roots was then affected, which promoted phosphorus allocation to UTP and glucose-6-phosphate. Additionally, low-phosphorus stress hastened glycolysis in the soybean roots and inhibited the synthesis of malic acid, thereby promoting the transport of phosphorus in the roots. In addition, low-phosphorus stress inhibited the synthesis of fructose, mannose, and mannose-1-phosphate and the synthesis of other enzymes involved in phosphorus transport as well as invertase, thereby inhibiting the transport and synthesis of several organic phosphorus-containing compounds.

Systemic regulation of soybean nodulation and nitrogen fixation by nitrogen via isoflavones.

Nitrogen (N) inhibits soybean (Glycine max L.) nodulation and N2 fixation. Isoflavones secreted by soybean roots can stimulate signal transduction for symbiotic nodules, thus playing a key role in root nodule development and N2 fixation. The relationship between the inhibition of soybean nodulation, N2 fixation and isoflavones by N is still unclear. In this study, dual-root soybean plants were prepared by grafting, and N or isoflavones were supplied to unilateral roots. The number and dry weight of the soybean nodules, nitrogenase activity, isoflavone concentrations and relative changes in the level of expression of nodulation-related genes were measured to study the response relationship between the N systemic regulation the soybean nodule N2 fixation and changes in the concentrations of isoflavones in its roots. The results showed that N supply to one side of the dual-root soybeans systematically affected the N2 fixation of root nodules on both sides, and this effect began in the early stage of nodulation. Moreover, a unilateral supply of N systematically affected the concentrations of daidzein and genistein on both sides of the roots. The concentrations of isoflavones were consistent with the change trend of soybean root nodule and nodulation-related gene expression level. Treatment with unilateral N or isoflavones affected the soybean nodule N2 fixation and its nodulation-related genes, which had the same response to the changes in concentrations of root isoflavones. N regulates soybean nodulation and N2 fixation by systematically affecting the concentrations of isoflavones in the roots.

Integrated Transcriptome and Metabolome Analyses Reveal the Anthocyanin Biosynthesis Pathway in AmRosea1 Overexpression 84K Poplar.

Populus alba × Populus glandulosa (84K poplar) is model material with excellent genetic engineering resource and ornamental value. In our study, AmRosea1 (Antirrhinum majus) was overexpressed in 84K poplar, and the transgenic 84K (AM) poplar with high content of anthocyanin exhibited red pigmentation leaves. The transcriptome analysis between wild type (WT) and AM showed that 170 differentially expressed genes (DEGs) (86 up-regulated and 84 down-regulated) were found, and some DEGs were involved in flavone and flavonol biosynthesis, flavonoid biosynthesis and anthocyanin biosynthesis. The metabolome analysis showed that 13 anthocyanins-related differentially accumulated metabolites (DAMs) were detected in AM. The correlation analysis between DEGs and DAMs were performed, and the results revealed that 18 DEGs, including 11 MYB genes, two BZ1 genes, one FG2 gene, one ANS gene, and three IF7MAT genes, were negatively or positively correlated with 13 DAMs. The phylogenetic analysis demonstrated that there was high homology between AmRosea1 and PagMYB113, and MYB113 co-expressed with BZ1, ANS and DFR directly. Our results elucidated the molecular mechanism of plant color change mediated by anthocyanin biosynthesis pathway, which laid the foundation for the development and utilization of colorful woody plant.

Early childhood sleep trajectories and association with maternal depression: a prospective cohort study.

STUDY OBJECTIVES: To investigate trajectories of early childhood sleep in the first 3 years and their association with maternal depressive symptoms. METHODS: Data were from 243 Chinese mother-child dyads. Children's sleep duration and night-waking were assessed using the Brief Infant Sleep Questionnaire (BISQ) at 42 days, 3, 6, 9, 12, 18, 24, and 36 months postpartum. The Center for Epidemiological Survey-Depression Scale (CES-D), Edinburgh Postnatal Depression Scale (EPDS), and Profile of Mood States (POMS) were used to assess maternal depressive symptoms at late pregnancy, 42 days, and 36 months postpartum, respectively. Early childhood sleep trajectories were estimated with group-based trajectory models. The association between early childhood sleep trajectories and maternal depressive symptoms was examined with binary and multinomial logistic regression models and linear regression models. RESULTS: Three trajectories of daytime sleep duration ("short", 14.4%; "medium", 60.4%; "long", 25.2%), nighttime sleep duration ("increasing", 17.6%; "stable", 76.3%; "decreasing", 6.1%), and total sleep duration ("short", 21.5%; "medium", 59.9%; "long",18.6%), and two trajectories of night-waking ("resolving", 22.9%; "persistent", 77.1%) were identified. Controlling for confounding factors, maternal depression at 42 days postpartum was associated with higher risks for short daytime sleep duration and persistent night-waking in children. Persistent night-waking in children was associated with increased maternal depressive symptoms at 36 months postpartum. CONCLUSION: Early childhood sleep follows distinct trajectories in the first 3 years of life. The trajectories of short daytime sleep duration and persistent night-waking are associated with maternal depression. The findings indicate tailored interventions should target both unfavorable early childhood sleep trajectories and maternal depression.

Weight spectrum and executive function in adolescents: the moderating role of negative emotions.

BACKGROUND: While recent works suggested that overweight/obesity may impair executive function (EF), the overweight/obesity-EF relationship has not been well studied in adolescents. Furthermore, no research has investigated adolescent EF impairments across the weight spectrum (e.g., underweight or thinness, normal, overweight/obesity), especially those with underweight condition, with the moderating effect of negative emotions in the weight-EF association being limitedly investigated. We aimed to determine whether overall and abdominal weight spectrum associated with EF impairments and to identity whether negative emotions moderate the weight-EF link in adolescents. METHODS: We applied a subsample of the SCHEDULE-A project. Adolescents (11-18 years) were recruited using a multi-stage cluster random sampling approach. We measured the overall and abdominal weight spectrum by body mass index z-score and waist-to-height ratio, respectively. We used the Behavior Rating Inventory of Executive Function (BRIEF) to evaluate adolescent EF in nature setting, and utilized the Depression Anxiety and Stress Scales (DASS-21) to assess three types of negative emotional status (i.e., depression, anxiety, and stress). RESULTS: Of the 1935 adolescents, 963 (49.8%) were male. We observed that abdominal, not overall, overweight was associated with the Global Executive Composite (GEC) impairment (OR = 1.59, 95% CI 1.07-2.35), particularly for inhibit, emotion control, shift, working memory, and monitor domains. Furthermore, depression moderated the abdominal overweight-GEC association (P = 0.032 for interaction term), especially for emotional control, working memory, and initiate dimensions. Moreover, we also found abdominal thinness was associated with the Metacognition Index problem (OR = 1.33, 95% CI 1.04-1.72), particularly for plan and monitor areas. CONCLUSIONS: Both abdominal overweight and thinness were associated with adolescent EF, and depression would be a modifiable target to improve EF in adolescents with abdominal overweight. Future longitudinal studies are needed to investigate the causal relationship between abdominal weight spectrum and EF, as well as the underlying mechanisms among adolescents suffering from depression.

Unravelling the causes and consequences of dispersal syndromes in a wild passerine.

Evidence accumulates that dispersal is correlated with individual behavioural phenotype (dispersal syndrome). The evolutionary causes and consequences of such covariation depend on the degree of plasticity versus inheritance of the traits, which requires challenging experiments to implement in mobile organisms. Here, we combine a forced dispersal experiment, natural colonization and longitudinal data to establish if dispersal and aggression levels are integrated and to test their adaptive nature in pied flycatchers (Ficedula hypoleuca). We found that (forced) dispersers behaved more aggressively in their first breeding year after dispersal and decreased their aggression in following years. Strength of dispersal syndrome and direction of fecundity selection on aggression in newly colonized areas varied between years. We propose that the net benefits of aggression for dispersers increase under harsh conditions (e.g. low food abundance). This hypothesis now warrants further testing. Overall, this study provides unprecedented experimental evidence that dispersal syndromes can be remodelled via adaptive plasticity depending on the individuals' local breeding experience and/or year-specific ecological conditions. It highlights the importance of individual behavioural variation in population dynamics.

Morphological and Comparative Transcriptome Analysis of Three Species of Five-Needle Pines: Insights Into Phenotypic Evolution and Phylogeny.

Pinus koraiensis, Pinus sibirica, and Pinus pumila are the major five-needle pines in northeast China, with substantial economic and ecological values. The phenotypic variation, environmental adaptability and evolutionary relationships of these three five-needle pines remain largely undecided. It is therefore important to study their genetic differentiation and evolutionary history. To obtain more genetic information, the needle transcriptomes of the three five-needle pines were sequenced and assembled. To explore the relationship of sequence information and adaptation to a high mountain environment, data on needle morphological traits [needle length (NL), needle width (NW), needle thickness (NT), and fascicle width (FW)] and 19 climatic variables describing the patterns and intensity of temperature and precipitation at six natural populations were recorded. Geographic coordinates of altitude, latitude, and longitude were also obtained. The needle morphological data was combined with transcriptome information, location, and climate data, for a comparative analysis of the three five-needle pines. We found significant differences for needle traits among the populations of the three five-needle pine species. Transcriptome analysis showed that the phenotypic variation and environmental adaptation of the needles of P. koraiensis, P. sibirica, and P. pumila were related to photosynthesis, respiration, and metabolites. Analysis of orthologs from 11 Pinus species indicated a closer genetic relationship between P. koraiensis and P. sibirica compared to P. pumila. Our study lays a foundation for genetic improvement of these five-needle pines and provides insights into the adaptation and evolution of Pinus species.

A case report of congenital idiopathic hypogonadotropic hypogonadism caused by novel mutation of GNRHR gene.

RATIONALE: This study aimed to investigate the genetic mutation characteristics of congenital idiopathic hypogonadotropic hypogonadism (IHH) through the clinical features and genetic analysis of 2 patients with IHH in 1 pedigree. PATIENT CONCERNS: A 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development. DIAGNOSES: Combined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH. INTERVENTIONS: Whole exome and Sanger sequencing were performed to validate the mutation in family members. OUTCOMES: A novel homozygous missense mutation c.521A > G (p.Q174R) in the GNRHR gene was identified in the 2 affected sisters. Familial segregation showed that the homozygous variant was inherited from their parents respectively and the eldest sister was the carrier without correlative symptom. LESSONS: We reported a novel GNRHR mutation in a pedigree with congenital idiopathic hypogonadotropic hypogonadism. Glutamine at amino acid position 174 was highly conserved among various species. The molecular structure of GNRHR protein showed that p.Q174R mutation brought in a new stable hydrogen bond between position 174 and 215, may impede conformational mobility of the TMD4 and TMD5. It suggests that the missense mutation c.521A > G related to congenital idiopathic hypogonadotropic hypogonadism was probably a causative factor for both sisters. Through high-throughput sequencing and experimental verification, we had basically determined the patient's pathogenic mutation and inheritance, which could better guide doctors for treatment.

Engineering application and study on polyurethane-corrugated steel plate insulation lining of existing railway tunnel in seasonal frozen area.

In order to solve the problem of freezing damage treatment and anti-freezing design for railway tunnels in operation in the seasonal frozen area, this paper proposes a polyurethane-corrugated steel plate insulation lining, and studies its thermal insulation effect, relying on a freezing damage treatment project of an existing passenger-dedicated tunnel for on-site application. In this paper, the insulation lining is applied to the actual project and the insulation effect is verified by the field monitoring. The temperature test section was set in the anti-freezing design section. The polyurethane-corrugated steel plate insulation lining proposed in this paper is mainly composed of corrugated steel plate, polyurethane insulation layer and waterproof layer. The polyurethane-corrugated steel insulation lining is applied by using self-made rail flat battery car, door-type scaffolding, arch slide and other construction equipments. The on-site temperature test shows that the insulation effect is obvious. The polyurethane-corrugated steel plate insulation lining has the advantages of fast construction speed, good thermal insulation effect, preventing concrete from peeling off blocks, easy removal and replacement. According to the field temperature test, under the natural temperature outside the tunnel from -18°C to -22°C in winter of 2018-2020, the temperature of the interface between surrounding rock and lining of the tunnel monitoring sections are all above 0°C so that the freezing damage is eliminated from the root. Research results can provide a theoretical basis for the anti-freezing projects of tunnels in seasonal frozen area.

Increased EEG coherence in long-distance and short-distance connectivity in children with autism spectrum disorders.

INTRODUCTION: Autism spectrum disorder (ASD) is a complex and prevalent neurodevelopmental disorder characterized by deficits in social communication and social interaction as well as repetitive behaviors. Alterations in function connectivity are widely recognized in recent electroencephalogram (EEG) studies. However, most studies have not reached consistent conclusions, which could be due to the developmental nature and the heterogeneity of ASD. METHODS: Here, EEG coherence analysis was used in a cohort of children with ASD (n = 13) and matched typically developing controls (TD, n = 15) to examine the functional connectivity characteristics in long-distance and short-distance electrode pairs. Subsequently, we explore the association between the connectivity strength of coherence and symptom severity in children with ASD. RESULTS: Compared with TD group, individuals with ASD showed increased coherence in short-distance electrode pairs in the right temporal-parietal region (delta, alpha, beta bands), left temporal-parietal region (all frequency bands), occipital region (theta, alpha, beta bands), right central-parietal region (delta, alpha, beta bands), and the prefrontal region (only beta band). In the long-distance coherence analysis, the ASD group showed increased coherence in bilateral frontal region, temporal region, parietal region, and frontal-occipital region in alpha and beta bands. The strength of such connections was associated with symptom severity. DISCUSSION: Our study indicates that abnormal connectivity patterns in neuroelectrophysiology may be of critical importance to acknowledge the underlying brain mechanism.

Assessment of Binocular Imbalance with an Augmented Virtual Reality Platform in a Normal Population.

We examined and analyzed binocular imbalance in a group of randomly selected normal subjects with corrected visual acuity of 0.8 or more in both eyes without ocular diseases, by using augmented virtual reality system. This study will quantify the correlation between binocular imbalance in these normal subjects and various spatial frequencies and temporal frequencies in the integrated binocular stimulation mode. A retrospective study was carried out and data from 97 patients (51 males and 46 females) who were diagnosed with no eye diseases, and with corrected binocular visual acuity of 0.8 or more, were collected. Their binocular visual function, Hirschberg test refraction status, and binocular imbalance were assessed using the quantified visual perception stimulation mode in an augmented virtual reality platform. When normal subjects (with corrected binocular vision of 0.8 or more without ocular diseases) were assessed using the integrated binocular stimulation mode with different temporal and spatial frequencies, a gradual reduction of binocular imbalance could be observed when spatial frequencies were increased. When contrast balance was adjusted, binocular imbalance was more prevalent in the horizontal state compared with the vertical state. This was seen when patients were stimulated by different temporal frequencies in the virtual reality testing mode. 17.53% and 29.90% of participants reached complete binocular fusion under low temporal frequency stimulation and high temporal frequency stimulation, respectively, while binocular imbalance was found in 65.9% and 62.89% of participants who were stimulated, respectively, by low temporal frequency and high temporal frequency. In addition, 16.5% and 7.21% experienced severe binocular imbalance under low temporal and high temporal frequency stimulation, respectively. The integrated binocular stimulation mode under low temporal frequency was more sensitive in detecting binocular imbalance. The status of binocular balance in normal subjects was not the same when stimulated by the augmented virtual reality platform, as many showed varying degrees of binocular imbalance. The results from our clinical study demonstrate that integrated binocular stimulation with different spatial and temporal frequencies enables a more sensitive detection of binocular imbalance, making it a powerful new tool for the diagnosis and analysis of clinical binocular abnormalities. In addition, since more than half of the normal subjects (without eye diseases who has corrected vision of 0.8 or more) exhibited binocular imbalance in our study, we believe that this brief binocular imbalance is likely a transient physiological phenomenon, which is not pathological to visual acuity and function, and should only be seen as pathological when binocular imbalance is prolonged, causing functional deficits such as reading impairment.

FADS1-FADS2 and ELOVL2 gene polymorphisms in susceptibility to autism spectrum disorders in Chinese children.

BACKGROUD: Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders with a genetic basis. The role of long-chain polyunsaturated fatty acids (LC-PUFAs) and the occurrence of autism has been the focus of many recent studies. The present study investigates whether genetic variants of the fatty acid desaturase (FADS) 1/2 and elongation of very long-chain fatty acids protein (ELOVL) 2 genes, which are involved in LC-PUFA metabolism, are associated with ASD risk. METHODS: A cohort of 243 ASD patients and 243 unrelated healthy controls were enrolled in this case control study. Sixteen tag single nucleotide polymorphisms from the FADS1-2 and ELOVL2 genes were genotyped using the Sequenom Mass Array. RESULTS: There were significant differences in allelic distribution of FADS2 rs526126 (OR = 0.55, 95% CI = 0.42-0.72, pFDR < 0.05) between autistic children and controls. FADS2 rs526126 and ELOVL2 rs10498676 were associated with decreased ASD risk in recessive model (OR = 0.07, 95% CI = 0.02-0.22, pFDR < 0.01; OR = 0.56, 95% CI = 0.35-0.89, pFDR = 0.042), while ELOVL2 rs17606561, rs3756963, and rs9468304 were associated with increased ASD risk in overdominant model (OR = 1.63, 95% CI = 1.12-2.36, pFDR = 0.036; OR = 1.64, 95% CI = 1.14-2.37, pFDR = 0.039; OR = 1.75, 95% CI = 1.22-2.50, pFDR = 0.017). The A/A genotype of rs10498676 was correlated with a decline in the Autism Diagnostic Interview-Revised communication (verbal and nonverbal) domain. CONCLUSIONS: These findings provide evidence of an association between FADS2 and ELOVL2 polymorphisms and ASD susceptibility in Chinese children.

Analysis of estrogen receptor ß gene methylation in autistic males in a Chinese Han population.

Autism spectrum disorder (ASD) is a neurodevelopment disorder with abnormalities of social interaction, communication and repetitive behaviors. The higher prevalence of ASD in men implies a potential relationship between sex hormones and ASD etiology. The ESR2 gene encodes estrogen receptor beta (ESR2) and plays an important role during brain development. A relationship between ESR2 and ASD has been suggested by studies on single nucleotide polymorphisms and mRNA and protein expression levels in ASD patients. Here, we explored the possible epigenetic regulation of the ESR2 gene in autism. We collected genomic DNA from the peripheral blood of Chinese Han males with autism and age-matched normal males and measured DNA methylation of CpG islands in the ESR2 gene, which consisted of 41 CpG sites among the proximal promoter region and an untranslated exon, by bisulfite sequencing. We also investigated a relationship between DNA methylation and phenotypic features of autism, as assessed by the Children Autism Rating Scale. We found little overall difference in the DNA methylation of the ESR2 5'-flanking region in individuals with autism compared with normal individuals. However, detailed analyses revealed that eight specific CpG sites were hypermethylated in autistic individuals and that four specific CpG sites were positively associated with the severity of autistic symptoms. Our study indicates that the epigenetic dysregulation of ESR2 may govern the development of autism.

Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism.

AIMS: To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism. MAIN METHODS: As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated. KEY FINDINGS: FTY720 (1mg/kg) administration to VPA-exposed rats (1) improved social behavior, spatial learning and memory impairment; (2) resulted in a reduction in neuronal loss and apoptosis of pyramidal cells in hippocampal CA1 regions; (3) inhibited activation of microglial cells, in turn lowering the level of pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-6 in the hippocampus; (4) changed Malondialdehyde (MDA) levels, Glutathione (GSH) levels, superoxide dismutase (SOD) activity and Glutathione Peroxidase (GSH-Px) activity in the hippocampus; (6) inhibited the elevated Bax and caspase-3 protein levels and enhanced the relative expression level of Bcl-2 in the hippocampus; and (7) increased phospho-Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phospho-cAMP-response element binding protein (p-CREB) and Brain Derived Neurotrophic Factor (BDNF) protein expression in the hippocampus. SIGNIFICANCE: FTY720 rescues social deficit, spatial learning and memory impairment in VPA-exposed rats. FTY720 exerts both a direct protection for neurons and an indirect modulation of inflammation-mediated neuron loss as a possible mechanism of neuroprotection.