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Imprinting, characterized by unequal expression of the offspring's genes in a parent-of-origin dependent manner, has been functionally implicated in brain development and in psychiatric disorders. In this study, unambiguous distortion in paternal but not maternal transmission of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 (T/G) clearly indicated the presence of parent-of-origin effect (POE) in the GABAA receptor β2 subunit gene (GABRB2). ‘Flipping’ of allelic mRNA expression in heterozygotes of SNP rs2229944 (C/T) and the observed two-tiered distribution of mRNA expression levels in heterozygotes of the disease-associated SNP rs1816071 (G/A) furnished important support for the occurrence of imprinting at GABRB2. Imprinting in effect introduced heterozygotes from different parents-of-origin endowed with dissimilar mRNA expression capabilities. The deficit of upper-tiered expressions accounted for the lowered mRNA expression levels in the schizophrenic heterozygotes. This pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, allele-specific methylation was observed at the disease-associated SNPs rs6556547 and rs1816071. These findings raised the possibility that CpG methylation status of these sites could have an impact on the expression of GABRB2 and the risk of schizophrenia. Furthermore, the occurrence of imprinting and allele-specific methylation in the schizophrenia candidate gene GABRB2 was compatible with the epigenetic hypothesis for schizophrenia pathophysiology, thereby calling for the need to explore the role of epigenetic factors in mediating susceptibility to schizophrenia.
Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
GABRB2, the gene for β2 subunit of the gamma-aminobutyric acid type A (GABAA) receptor, is known to display two splicing isoforms in the brain, namely β2L containing Exon 10 and β2S devoid of Exon 10. Previously, the expressions of these isoforms were correlated with both schizophrenia and various sequence polymorphisms of the gene. in the present study, a series of deletions made on Intron 9 of a minigene construct affected the expression of Exon 10, and generated additional splicing variations suggesting the existence of additional splicing variants of β2subunit. A search among brain cDNAs uncovered the two novel short forms: β2S1which is devoid of Exons 10 and 11 and bears an extended Exon 9, and β2S2 which is devoid of Exon 10 and bears a shortened Exon 11.Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics, 30 bipolar disorder and 31 controls of US population, showed that the level of β2S2 was significantly decreased in bipolar disorder, and marginally decreased in schizophrenia, while β2S1 was marginally increased in both of these psychotic disorders. Significant genotypic effects of rs1816071, rs1816072 and rs187269 on β2S2 level were observed in male schizophrenic and bipolar patients. These findings pointed to the neighborhood of Exon 10 as an alternate-splicing hot-spot, and underlined the relevance of β2 subunit isoforms to the etiology of psychotic disorders.
The purpose of this paper is to focus directly on the phase shift. For one thing, we ask whether a New Keynesian sticky-price model economy can account for both countercyclical prices and procyclical inflation. We present findings in which the price level is countercyclical and the inflation rate is procyclical. We proceed to use the model economy as an identification mechanism. What set of individual shocks are necessary to account for the phase shift? That set contains the price markup shock. Next, we ask what set of shocks are sufficient to account for the phase shift. This set contains three elements: the price markup and wage markup shocks along with the government spending shock. The results are important as a building block. We infer that price stickiness is an important model feature; without price stickiness, we are in the real business cycle economies that Cooley and Hansen studied. But, it raises further questions. For instance, is price stickiness of the Calvo form—the one used here—necessary to explain the phase shift?
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Predicting mental workload of pilots can provide cockpit designers with useful information to reduce the possibility of pilot error and cost of training, improve the safety and performance of systems, and increase operator satisfaction. We present a theoretical model of mental workload, using information theory, based on review investigations of how effectively task complexity, visual performance, and pilot experience predict mental workload. The validity of the model was confirmed based on data collected from pilot taxiing experiments. Experiments were performed on taxiing tasks in four different scenarios. Results showed that predicted values from the proposed mental workload model were highly correlated to actual mental workload ratings from the experiments. The findings indicate that the proposed mental workload model appears to be effective in the prediction of pilots’ mental workload over time.
Life-history theory predicts a trade-off between the juvenile growth rate and adult traits related to survival. However, this hypothesized negative correlation is difficult to test robustly because many trade-offs are mild, and environmental variables, such as changes in nutrient availability, can ameliorate the trade-off or make it more pronounced. Thus, it is reasonable to expect that the expression of the trade-off can be condition-dependent. In the present study, we first examined the pre-adult life-history traits of the cotton bollworm, Helicoverpa armigera, collected from northern, central, and southern China at different temperatures. We found that the northern China population has a significantly shorter pre-adult developmental time and higher growth rate than the southern China population as a result of adaptation to the decreased seasonal length. Then, we tested for a trade-off between the juvenile growth rate and adult lifespan in different temperature and nutrient conditions. We found a negative relationship between juvenile growth rate and adult lifespan under starvation or desiccation conditions; however, a continuous supply of sugar can diminish or obviate the apparent negative relationship, in which the adult lifespan did not show a significant difference in most of the comparisons. These results suggested a resource-mediated trade-off may exist between juvenile growth rate and adult lifespan. However, the adult size may have some positive effect on the lifespan under starvation and desiccation conditions, which may affect the expression of trade-off.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
Increasing evidence has demonstrated that the environmental conditions experienced by parents can shape offspring phenotypes. Here, we examined the effects of the photoperiod and temperature experienced by parents on the incidence of diapause in their progeny in the cabbage beetle, Colaphellus bowringi, using three experiments. The first experiment examined parental diapause incidence under different photoperiods at 25°C and the incidence of diapause in progeny from both non-diapausing and diapausing parents under the same rearing conditions. The results revealed that the incidence of diapause among progeny was exactly opposite to that of their parents, i.e., higher parental diapause incidence led to lower progeny diapause incidence, showing a negative relationship in diapause incidence between the parental generation and the progeny generation. The incidence of diapause among progeny produced by diapausing parents was higher than that in progeny produced by non-diapausing parents. The second experiment examined parental diapause incidence at different temperatures under LD 12:12 and the incidence of diapause in progeny from both non-diapausing and diapausing parents under the same rearing conditions. Similarly, the incidence of diapause in progeny was also opposite to that of their parents. However, the incidence of diapause in progeny produced by non-diapausing parents was different from that in progeny produced by diapausing parents. In the third experiment, naturally diapausing adults were maintained at a constant temperature of 9, 28°C or the mean daily summer temperature of 27.84°C under continuous darkness for 3 months of dormancy. After dormancy, the progeny of these post-diapause parents were reared under different photoperiods at 25°C. The results showed that the incidence of diapause among progeny was higher when their parents experienced high temperatures than when they experienced low temperatures. All results demonstrate that the photoperiod and temperature experienced by parents may significantly affect the diapause incidence among progeny.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
The fruit of Ligustrum lucidum (FLL, Nuzhenzi in Chinese) is an important traditional medicine, and have attracted significant research attention because of their various biological activities. However, there are few research reports available on the use of FLL as a feed additive in livestock nutrition, particularly in layers. This study was conducted to determine the effects of supplementation of the diet of laying hens with FLL on laying performance, egg quality and blood metabolites. A total of 360 72-week-old hens were allocated to three dietary treatments (eight replications of 15 hens/treatment group) and were fed either a control diet or a diet supplemented with an inclusion level of 0.25% or 0.50% of FLL powder in the final feed, until 78 weeks of age. Hens were housed in a three-tier cage system. Feed and water were provided ad libitum. Blood samples and eggs were collected at the end of the experiment. The results showed that dietary supplementation with FLL did not affect egg weight, feed conversion ratio, eggshell thickness, albumen height, egg yolk color, eggshell breaking strength or egg shape index. However, FLL supplementation significantly decreased (P<0.001) mortality, cracked-egg rate and blood serum levels of cholesterol, low-density lipoprotein cholesterol, triglycerides and alanine aminotransferase, and increased (P<0.001) blood serum levels of high-density lipoprotein cholesterol. No differences in serum levels of total protein, albumin, glucose, calcium, aspartate aminotransferase or alkaline phosphatase were observed in hens fed FLL compared with the control group. It can be concluded that FLL, at a supplementation level of 0.25% final feed, can be used as an effective feed additive to improve the performance of laying hens during the late laying period.
Foxtail millet (Setaria italica (L.) P. Beauv.) is a naturally stress-tolerant plant, a major reserve crop and a model for panicoid grasses. The recent completion of the S. italica genome facilitates identification and characterization of WRKY transcription factor family proteins that are important regulators of major plant processes, including growth, development and stress response. The present study identified 103 WRKY transcription factor-encoding genes in the S. italica genome. The genes were named SiWRKY1–SiWRKY103 according to their order on the chromosomes. A comprehensive expression analysis of SiWRKY genes among four different tissues was performed using publicly available RNA sequencing data. Eighty-four SiWRKY genes were more highly expressed in root tissue than in other tissues and nine genes were only expressed in roots. Additionally, real-time quantitative polymerase chain reaction was performed to comprehensively analyse the expression of all SiWRKY genes in response to dehydration. Results indicated that most SiWRKY genes (over 0.8) were up-regulated by drought stress. In conclusion, genome-wide identification and expression profiling of SiWRKY genes provided a set of candidates for cloning and functional analyses in plants’ response to drought stress.
Recent studies indicate that intestinal oxidative stress and microbiota imbalance is involved in weaning-induced intestinal dysfunction in piglets. We have investigated the effect of feeding a carvacrol–thymol blend supplemented diet on intestinal redox status, selected microbial populations and the intestinal barrier in weaning piglets. The piglets (weaned at 21 days of age) were randomly allocated to two groups with six pens per treatment and 10 piglets per pen. At weaning day (21 days of age), six piglets were sacrificed before weaning to serve as the preweaning group. The weaned group was fed with a basal diet, while the weaned-CB group was fed with the basal diet supplemented with 100 mg/kg carvacrol–thymol (1 : 1) blend for 14 days. On day 7 post-weaning, six piglets from each group were sacrificed to determine intestinal redox status, selected microbial populations, messenger RNA (mRNA) transcript levels of proinflammatory cytokines and biomarkers of intestinal barrier function. Weaning resulted in intestinal oxidative stress, indicated by the increased concentration of reactive oxygen species and thiobarbituric acid-reactive substances present in the intestine. Weaning also reduced the population of Lactobacillus genus and increased the populations of Enterococcus genus and Escherichia coli in the jejunum, and increased mRNA levels of tumor necrosis factor α (TNF-α), interleukin 1β and interleukin 6 (IL-6). In addition, decreased mRNA levels of zonula occludens and occludin in the jejunal mucosa and increased plasma diamine oxidase concentrations indicated that weaning induced dysfunction of the intestinal barrier. On day 7 post-weaning, supplementation with the carvacrol–thymol blend restored weaning-induced intestinal oxidative stress. Compared with the weaned group, the weaned-CB group had an increased population of Lactobacillus genus but reduced populations of Enterococcus genus and E. coli in the jejunum and decreased mRNA levels of TNF-α. The results indicated that weaning induced intestinal oxidative stress and dysfunction of the intestinal barrier. Dietary supplementation with 100 mg/kg carvacrol–thymol (1 : 1) decreased the intestinal oxidative stress and influenced selected microbial populations without changing the biomarkers of intestinal barrier in weaning piglets.
Both growth and immune capacity are important traits in animal breeding. The animal quantitative trait loci (QTL) database is a valuable resource and can be used for interpreting the genetic mechanisms that underlie growth and immune traits. However, QTL intervals often involve too many candidate genes to find the true causal genes. Therefore, the aim of this study was to provide an effective annotation pipeline that can make full use of the information of Gene Ontology terms annotation, linkage gene blocks and pathways to further identify pleiotropic genes and gene sets in the overlapping intervals of growth-related and immunity-related QTLs. In total, 55 non-redundant QTL overlapping intervals were identified, 1893 growth-related genes and 713 immunity-related genes were further classified into overlapping intervals and 405 pleiotropic genes shared by the two gene sets were determined. In addition, 19 pleiotropic gene linkage blocks and 67 pathways related to immunity and growth traits were discovered. A total of 343 growth-related genes and 144 immunity-related genes involved in pleiotropic pathways were also identified, respectively. We also sequenced and genotyped 284 individuals from Chinese Meishan pigs and European pigs and mapped the single nucleotide polymorphisms (SNPs) to the pleiotropic genes and gene sets that we identified. A total of 971 high-confidence SNPs were mapped to the pleiotropic genes and gene sets that we identified, and among them 743 SNPs were statistically significant in allele frequency between Meishan and European pigs. This study explores the relationship between growth and immunity traits from the view of QTL overlapping intervals and can be generalized to explore the relationships between other traits.
While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).
Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾50% MADRS score reduction) was the primary outcome.
By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01–0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02–0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days–2 weeks; effect size (ES) = 1.08–1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.
Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.
We derive zphot for sources in the entire (~0.4 deg2) H-HDF-N field with the EAzY code, based on PSF-matched broad-band (U band to IRAC 4.5 μm) photometry. Our catalog consists of a total of 131,678 sources. We find σNMAD = 0.029 for non-X-ray sources. We also classify each object as a star or galaxy through SED fitting. Furthermore, we match our catalog with the 2 Ms CDF-N main X-ray catalog. For the 462 matched non-stellar X-ray sources, we improve their zphot quality (σNMAD = 0.035) by adding three additional AGN templates. We make our photometry and zphot catalog publicly available.
A suspected dengue fever outbreak occurred in 2010 at a solitary construction site in Shenzhen city, China. To investigate this epidemic, we used serological, molecular biological, and bioinformatics techniques. Of nine serum samples from suspected patients, we detected seven positive for dengue virus (DENV) antibodies, eight for DENV-1 RNA, and three containing live viruses. The isolated virus, SZ1029 strain, was sequenced and confirmed as DENV-1, showing the highest E-gene homology to D1/Malaysia/36000/05 and SG(EHI)DED142808 strains recently reported in Southeast Asia. Further phylogenetic tree analysis confirmed their close relationship. At the epidemic site, we also detected 14 asymptomatic co-workers (out of 291) positive for DENV antibody, and DENV-1-positive mosquitoes. Thus, we concluded that DENV-1 caused the first local dengue fever outbreak in Shenzhen. Because no imported case was identified, the molecular fingerprints of the SZ1029 strain suggest this outbreak may be due to vertical transmission imported from Southeast Asia.
For improving the performance of a miniature loudspeaker, engineers have been pursuing a goal of lowering its first damped frequency to have a broad and smooth region of its sound-pressure-level response. This article applies the approach of electro-mechano-acoustical analogy to study the first damped frequency of a miniature loudspeaker used for cellular phones. Using the analogy approach, the authors derive an explicit formulation for the sound-pressure-level of a typical miniature loudspeaker of dynamic type. The veracity of the derived formulation is verified by comparing with the experimental result recorded by B and K apparatus. The derived formulation is further simplified by neglecting factors that are either irrelevant or insignificant for the first damped frequency. Through basic algebraic and calculus operations, this article also presents an explicit form of the first damped frequency. This work has laid the platform for engineers to tailor the design in pursuit of improving the performance of miniature loudspeakers.