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Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
The six LIGO detections of merging black holes (BHs) allowed to infer slow spin values for the two pre-merging BHs. The three cases where the spins of the BHs can be determined in high-mass X-ray binaries (HMXBs) show that those BHs have high spin values. We discuss here scenarios explaining these differences in spin properties in these two classes of object.
It is important to identify molecular candidates involved in morphological and functional changes in the female reproductive system. We have discovered several candidate genes that were significantly altered in chick oviducts by exogenous estrogen and those candidates included dexamethasone (DEX)-induced RAS-related protein 1 (RASD1). RAS-related protein 1, a member of the Ras family of monomeric G proteins, is involved in various cellular processes including cell growth, proliferation and differentiation, as well as a cell-signaling protein regulating hormonal actions. Although the RASD1 gene was first identified as a DEX (a corticosteroid) inducible gene, there is evidence that it is also an estrogen-responsive gene. However, hormone-mediated expression and biological functions of RASD1 in the avian female reproductive system are poorly understood. Therefore, we tested the hypothesis that RASD1 may be involved in the development and remodeling of the chicken reproductive system as an estrogen-responsive gene. Here we demonstrate differential expression of RASD1 gene and candidate microRNAs (miRNAs) targeting chicken RASD1 transcripts in chicken oviducts in response to diesthylstilbestrol (DES, a synthetic non-steroidal estrogen) and the estrogen-mediated molting process. Result of the present study indicated that expression of RASD1 messenger RNA (mRNA) increased in the developing oviducts of chicks treated with DES, particularly in the glandular (GE) and luminal (LE) epithelia of the magnum and the shell gland. Also, during induced molting by zinc feeding, RASD1 expression changed in concert with changes in concentrations of estrogen in blood of laying hens. Our results revealed that expression of RASD1 mRNA decreased as the oviduct regressed and then increased as the oviduct underwent re-growth and recrudescence in hens. Furthermore, RASD1 mRNA was expressed predominantly in GE and LE of the oviduct of laying hens during regeneration of the oviduct after induced molting, but not during the period of regression of the oviduct during molting. In addition, the relative expression of candidate miRNAs (miR-30a-5p, miR-30b-5p, miR-30c-5p and miR-30d) regulating RASD1 transcripts changed in response to estrogen stimulation of chick oviducts. These results indicate that transcription of the RASD1 gene and miRNAs regulating post-transcriptional aspects of expression of RASD1 are modulated by estrogen which is critical for growth, development, remodeling and maintenance of function of the chicken oviduct.
Hepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5′ UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.
Bacillary dysentery continues to be a major health issue in developing countries and ambient temperature is a possible environmental determinant. However, evidence about the risk of bacillary dysentery attributable to ambient temperature under climate change scenarios is scarce. We examined the attributable fraction (AF) of temperature-related bacillary dysentery in urban and rural Hefei, China during 2006–2012 and projected its shifting pattern under climate change scenarios using a distributed lag non-linear model. The risk of bacillary dysentery increased with the temperature rise above a threshold (18·4 °C), and the temperature effects appeared to be acute. The proportion of bacillary dysentery attributable to hot temperatures was 18·74% (95 empirical confidence interval (eCI): 8·36–27·44%). Apparent difference of AF was observed between urban and rural areas, with AF varying from 26·87% (95% eCI 16·21–36·68%) in urban area to −1·90% (95 eCI −25·03 to 16·05%) in rural area. Under the climate change scenarios alone (1–4 °C rise), the AF from extreme hot temperatures (>31·2 °C) would rise greatly accompanied by the relatively stable AF from moderate hot temperatures (18·4–31·2 °C). If climate change proceeds, urban area may be more likely to suffer from rapidly increasing burden of disease from extreme hot temperatures in the absence of effective mitigation and adaptation strategies.
This survey examines the geometrically nonlinear bending of a doubly clamped nanobeam that is subjected to combined actions of actuator voltage, prestress, and intermolecular force, with the pull-in instability as the primary objective. A nonlocal Euler-Bernoulli beam model, which takes the small scale effect into account, is developed making use of the principle of virtual displacement on the basis of Eringen's nonlocal theory in conjunction with von Kármán assumption. Due to complexity of the resulting equations, a shooting technique is established through taking the applied voltage as an unknown and the central deflection as a control parameter. This treatment has the capability of tackling the nonlinearities from both the large deformation and electrostatic force as well as the intermolecular force and enables the size dependent deflection response to an applied voltage of the nanobeam to be obtained conveniently. Validation is conducted in numerical examples through direct comparisons with existing solutions to confirm the proposed method. Parametric studies are undertaken addressing the impacts of the nonlocal effect, intermolecular force, residual stress, and geometry of the beam on the pull-in behaviors.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Lodging can be an important factor in limiting yield and quality of summer foxtail millet [Setaria italica (L.) P. Beauv.]. Although lodging resistance varies among different genotypes, direct selection for lodging resistance is difficult because of its sporadic occurrence in the field and inconsistency between years. A 2-year-field study was conducted with 35 summer foxtail millet cultivars or advanced breeding lines to determine the association between lodging resistance and culm morphology, anatomy and chemical composition. Path analyses indicated that stem-breaking strength had the most important effect on the lodging coefficient. The breaking strength of stem was associated with specific morphological properties of the culm, such as greater culm diameter and most importantly culm wall thickness. Width of sclerenchyma tissue, and the number and sheath width of the large vascular bundles were the major anatomical properties that influenced stem-breaking strength. The cellulose and lignin compositions of the culm had different effects on stem-breaking strength. Cultivars with smaller lodging coefficients contained higher levels of cellulose, but lower levels of lignin than the cultivars that were more prone to lodging. The findings from the present study provide useful information on lodging-associated traits in the culm that can be used as indicators for the improvement of lodging resistance in foxtail millet.
The enteric pathogens causing diarrhoea impair children's health severely. This study retrospectively analysed 1577 pathogens isolated from inpatients and outpatients in six hospitals located in Northern (Inner Mongolia), Northeastern (Hebei), Eastern (Shanghai and Jiangsu), Southern (Hainan) and Central (Hubei) China between 2008 and 2013. Of the 1577 enteric pathogens, Salmonella presented with the highest frequency (36·0%), followed by diarrhoeagenic Escherichia coli (23·7%), Staphylococcus aureus (15·0%), Shigella (13·1%), and Aeromonas (4·6%). The predominant pathogens varied in different regions of China, with Salmonella most prevalent in Shanghai and Hainan, diarrhoeagenic E. coli most prevalent in Inner Mongolia, Jiangsu and Hubei, and Shigella most prevalent in Hebei. Enteric pathogens were more frequently isolated in males (56·9%) than in females (43·1%). The highest proportion of all enteric pathogens was found in infants (67·6%) with a peak in summer and autumn (68·5%). Antimicrobial susceptibility assay demonstrated that Shigella was more resistant to ampicillin, ceftriaxone and sulfamethoxazole than Salmonella. Of the top two serotypes in Salmonella, Typhimurium was more resistant to ciprofloxacin, sulfamethoxazole and chloramphenicol than Enteritidis (P < 0·001). Meanwhile, the resistance rates of Shigella flexneri against ampicillin/sulbactam, ciprofloxacin, and chloramphenicol were significantly higher than those of Shigella sonnei (P < 0·001). Multidrug resistance was apparent in 58·2% of Shigella and 45·9% of Salmonella, and this phenomenon was more pronounced in S. flexneri.
Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally?
Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus.
Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n = 27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct.
MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.
The symptoms of major depression (MD) are clinically diverse. Do they form coherent factors that might clarify the underlying nature of this important psychiatric syndrome?
Symptoms at lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years with recurrent DSM-IV MD. Exploratory factor analysis (EFA) and confirmatoryfactor analysis (CFA) were performed in Mplus in random split-half samples.
The preliminary EFA results were consistently supported by the findings from CFA. Analyses of the nine DSM-IV MD symptomatic A criteria revealed two factors loading on: (i) general depressive symptoms; and (ii) guilt/suicidal ideation. Examining 14 disaggregated DSM-IV criteria revealed three factors reflecting: (i) weight/appetite disturbance; (ii) general depressive symptoms; and (iii) sleep disturbance. Using all symptoms (n = 27), we identified five factors that reflected: (i) weight/appetite symptoms; (ii) general retarded depressive symptoms; (iii) atypical vegetative symptoms; (iv) suicidality/hopelessness; and (v) symptoms of agitation and anxiety.
MD is a clinically complex syndrome with several underlying correlated symptom dimensions. In addition to a general depressive symptom factor, a complete picture must include factors reflecting typical/atypical vegetative symptoms, cognitive symptoms (hopelessness/suicidal ideation), and an agitated symptom factor characterized by anxiety, guilt, helplessness and irritability. Prior cross-cultural studies, factor analyses of MD in Western populations and empirical findings in this sample showing risk factor profiles similar to those seen in Western populations suggest that our results are likely to be broadly representative of the human depressive syndrome.
The present study compared the miRNA expression profiles of five Toxoplasma gondii strains, namely RH (Type I, ToxoDB10), TgXD (Type I, ToxoDB10), PRU (Type II, ToxoDB1), QHO (Type II, ToxoDB1) and TgC7 (ToxoDB9), by Solexa deep sequencing, bioinformatics analysis and real-time quantitative PCR. A total of 7, 15, 10, 12 and 10 miRNAs were found from RH, TgXD, PRU, QHO and TgC7 strains, respectively. Thirteen miRNAs were shared by three genotypes, with only one miRNA shared by all of the 5 strains and others shared by 2 or more strains. A large number of targets ranging from 1 to 185 were identified for commonly shared miRNAs and strain-specific miRNAs with complete or nearly complete complementarity. Functional prediction showed that these targets were mostly focused on catalytic activity (191 targets) and binding activity (183 targets). Nonetheless, the majority of targets and most of the miRNAs are related to the virulence or invasion proteins of different strains of T. gondii, including ROP and MIC, as well as some other proteins, such as AMA1, GRA and RHO. The present study characterized comparatively the miRNA profiles of 3 different genotypes of T. gondii, identified genotype-shared miRNAs and strain-specific miRNAs.
The pathogenesis of angiostrongyliasis, resulting from Angiostrongylus cantonensis invasion of the human central nervous system, remains elusive. Anthelmintics are usually used to kill worms, although dead worms in the brain may cause severe inflammation which will lead to central nervous system damage. Therefore, combination therapy with anthelmintics and anti-inflammatory drugs in the treatment of human angiostrongyliasis needs further study. To evaluate the efficacy of albendazole combined with a marine fungal extract (m2-9) in A. cantonensis infection, BALB/c mice infected by the third-stage larvae of A. cantonensis were divided into three groups: mice treated with albendazole or m2-9 alone or in combination from day 5 post-inoculation (PI). Several efficacy parameters were recorded, including weight change, worm recovery, neurological function, behavioural analysis, eosinophil and leucocyte counts. The results showed that combination therapy increased body weight, reduced worm burden, improved learning ability, memory and action, decreased neurological dysfunction and leucocyte response in these mice. The combination of albendazole and m2-9 treatment significantly decreased leucocyte response and increased the frequency of rearing, compared to infected mice treated with either drug alone. Therefore, m2-9 is a natural product with potentially significant therapeutic value for angiostrongyliasis and is worthy of further study.
A harmonic rejection mirror (HRM) can apply pure spectrum for X-ray Absorption Spectrum (XAFS) experiment. The HRM mechanism includes a mirror holding system, a horizontal switch system and a three-point adjustment system. We analyse and calculate the design of the mechanism. Finally, we evaluate the HRM capability based on the rocking curve obtained in a test.
Tight binaries discovered in young nearby associations are ideal targets to provide dynamical mass measurments through orbital monitoring. Coupled with estimated temperatures, surface gravities and luminosities, direct mass measurments provide benchmarks for evolutionary models of low-mass stars (M ≤ 0.5 M๏) and brown dwarfs (M ≤ 0.078 M๏) at young ages (Age ≤ 100 Myrs).
TWA22 AB is likely to be a member of the nearby TW Hydrae association (Age ~ 8 Myr). It was resolved in a tigh binary with a projected separation of a few AU. In this paper we present preliminary results on the companion orbital monitoring and on the spectral characterisation of the system.
The epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (type 1 IGF receptor or IGF1R) have played an important role in the growth and apoptosis of cancer. The RNA interference (RNAi) technique can suppress gene expression, but the effects of dual silencing of EGFR and type 1 IGF receptor have not been well understood.
pU6-EGFR-shRNA-1, pU6-EGFR-shRNA-2, pU6-IGF1R-shRNA-1 and pU6-IGF-1R-shRNA-2 plasimd vectors were transfected to the nasopharyngeal cancer cells. Seven groups were selected for the study. The protein and downstream protein expression were assessed by Western blot. Apoptosis was determined via flow cytometry. Meanwhile, chemosensitivity of nasopharyngeal cancer cell lines transfeced to chemotherapeutic drugs were carried out by MTT.
In dual silencing of EGFR and IGF-1R, the protein expression much more was decreased than single silencing of EGFR or IGF-1R, but the cell apoptosis much more is increased than single silencing EGFR or IGF-1R. Dual silencing of EGFR and IGF-1R enhanced chemosensitivity to anticancer drugs, compared with single silencing of EGFR or IGF-1R.
Dual silencing of EGFR and IGF-1R are capable of suppressing EGFR and IGF-1R expression of the nasopharyngeal cancer cell and can promote apoptosis and increase the cell sensitivity of anticancer drug. The dual silencing of genes RNAi technique is significantly better than a single gene.