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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.
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.
Polarimetric studies of pulsars at low radio frequencies provide important observational insights into the pulsar emission mechanism and beam models, and probe the properties of the magneto-ionic interstellar medium (ISM). Aperture arrays are the main form of next-generation low-frequency telescopes, including the Murchison Widefield Array (MWA). These require a distinctly different approach to data processing (e.g. calibration and beamforming) compared to traditional dish antennas. As the second paper of this series, we present a verification of the MWA’s pulsar polarimetry capability, using two bright southern pulsars, PSRs J0742–2822 and J1752–2806. Our observations simultaneously cover multiple frequencies (76–313 MHz) and were taken at multiple zenith angles (ZA) during a single night for each pulsar. We show that the MWA can be reliably calibrated for ZA ≲45° and frequencies ≲270 MHz. We present the polarimetric profiles for PSRs J0742–2822 and J1752–2806 at frequencies lower than 300 MHz for the first time, along with an analysis of the linear polarisation degree and pulse profile evolution with frequency. For PSR J0742–2822, the measured degree of linear polarisation shows a rapid decrease at low frequencies, in contrast with the generally expected trend, which can be attributed to depolarisation effects from small-scale, turbulent, magneto-ionic ISM components. This effect has not been widely explored for pulsars in general and will be further investigated in future work.
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.
The Murchison Widefield Array, and its recently developed Voltage Capture System, facilitates extending the low-frequency range of pulsar observations at high-time and -frequency resolution in the Southern Hemisphere, providing further information about pulsars and the ISM. We present the results of an initial time-resolved census of known pulsars using the Murchison Widefield Array. To significantly reduce the processing load, we incoherently sum the detected powers from the 128 Murchison Widefield Array tiles, which yields ~10% of the attainable sensitivity of the coherent sum. This preserves the large field-of-view (~450 deg2 at 185 MHz), allowing multiple pulsars to be observed simultaneously. We developed a WIde-field Pulsar Pipeline that processes the data from each observation and automatically folds every known pulsar located within the beam. We have detected 50 pulsars to date, 6 of which are millisecond pulsars. This is consistent with our expectation, given the telescope sensitivity and the sky coverage of the processed data (~17 000 deg2). For 10 pulsars, we present the lowest frequency detections published. For a subset of the pulsars, we present multi-frequency pulse profiles by combining our data with published profiles from other telescopes. Since the Murchison Widefield Array is a low-frequency precursor to the Square Kilometre Array, we use our census results to forecast that a survey using the low-frequency component of the Square Kilometre Array Phase 1 can potentially detect around 9 400 pulsars.
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.
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.
Historically, alloy development with better radiation performance has been focused on traditional alloys with one or two principal element(s) and minor alloying elements, where enhanced radiation resistance depends on microstructural or nanoscale features to mitigate displacement damage. In sharp contrast to traditional alloys, recent advances of single-phase concentrated solid solution alloys (SP-CSAs) have opened up new frontiers in materials research. In these alloys, a random arrangement of multiple elemental species on a crystalline lattice results in disordered local chemical environments and unique site-to-site lattice distortions. Based on closely integrated computational and experimental studies using a novel set of SP-CSAs in a face-centered cubic structure, we have explicitly demonstrated that increasing chemical disorder can lead to a substantial reduction in electron mean free paths, as well as electrical and thermal conductivity, which results in slower heat dissipation in SP-CSAs. The chemical disorder also has a significant impact on defect evolution under ion irradiation. Considerable improvement in radiation resistance is observed with increasing chemical disorder at electronic and atomic levels. The insights into defect dynamics may provide a basis for understanding elemental effects on evolution of radiation damage in irradiated materials and may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.
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.
The Asian corn borer, Ostrinia furnacalis enters diapause as fully grown larvae. Owing to geographical variation in photoperiodic control of diapause, the subtropical strain from Hefei city (HF) enters diapause in response to short daylengths, whereas the tropical strain from Ledong county (LD) exhibits almost no diapause under the same conditions. The two strains were used in crosses to study the inheritance of diapause. The HF strain showed a typical long-day response with a critical daylength of approximately14.97 h at 22 °C, 14.60 h at 25 °C and 13.68 h at 28 °C. The LD strain showed weak photoperiodic responses at 22 and 25 °C; and the F1 progeny also showed a long-day response with significantly shorter critical daylength compared with the HF strain. However, the LD × HF (F × M) crosses had significantly longer critical daylengths than HF × LD crosses, indicating a sexual bias in the inheritance of diapause induction, with the male parent having more influence on the F1 progeny. The critical daylength in a backcross to HF was significantly longer than a backcross to LD. Whether the inheritance of diapause fits an additive hypothesis or not depended on photoperiod, with results from different photoperiods showing additive inheritance or incomplete dominance of either diapause or non-diapause. Unlike diapause induction, the duration of diapause for reciprocal crosses was equally influenced by each parent, suggesting that diapause incidence and maintenance are controlled by separate systems in O. furnacalis.
As a consequence of geographical variation in diapause mechanism in the cabbage beetle, Colaphellus bowringi, the southern strains enter diapause as an adult in response to long photoperiod, whereas the northern strains enter diapause in response to temperature. In the present study, we examined the inheritance of diapause by crossing a southern Xiushui strain (XS) with a most-northern Harbin strain (HB). The southern XS strain showed a clear short-day response for the induction of diapause, whereas the most-northern strain entered diapause regardless of photoperiod. Interestingly, the XS×HB progeny showed a short-day response, but the HB×XS progeny had no photoperiodic response, indicating that photoperiodic induction of diapause is influenced by maternal genotype. The incidence of diapause of F1 progeny was intermediate between their parents under short daylengths of 12 and 13 h. However, there was a sexual asymmetry, with the female parent exerting a greater effect on diapause incidence than the male parent, indicating a sex linkage in the inheritance of diapause induction. The χ2 test in C. bowringi revealed that the inheritance of diapause does not fit an additive hypothesis and also that the capacity for diapause is transmitted genetically (or possibly epigenetically) in a manner of incomplete dominance. These results suggest that a number of genetic factors are associated with differences in diapause capability in this beetle.
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.
A single specimen of a new species of the synziphosurine Kasibelinurus Pickett, 1993 is described from the Lower Devonian (Lochkovian) Xiaxishancun Formation of Yunnan Province, China. The new species, K. yueya sp. nov., extends the geographic extent of the family Kasibelinuridae from the Australian palaeocontinent to the South China palaeocontinent, and the stratigraphic range back some 50 Ma from Late to Early Devonian.
This study examined whether participation in a variety of lifestyle activities was comparable to frequent participation in cognitively challenging activities in mitigating impairments in cognitive abilities susceptible to aging in healthy, community-dwelling older women. Frequencies of participation in various lifestyle activities on the Lifestyle Activities Questionnaire (LAQ) were divided according to high (e.g., reading), moderate (e.g., discussing politics), and low (e.g., watching television) cognitive demand. We also considered the utility of participation in a variety of lifestyle activities regardless of cognitive challenge. Immediate and delayed verbal recall, psychomotor speed, and executive function were each measured at baseline and at five successive exams, spanning a 9.5-year interval. Greater variety of participation in activities, regardless of cognitive challenge, was associated with an 8 to 11% reduction in the risk of impairment in verbal memory and global cognitive outcomes. Participation in a variety of lifestyle activities was more predictive than frequency or level of cognitive challenge for significant reductions in risk of incident impairment on measures sensitive to cognitive aging and risk for dementia. Our findings offer new perspectives in promoting a diverse repertoire of activities to mitigate age-related cognitive declines. (JINS, 2012, 18, 286–294)
Under field conditions, the cabbage butterfly, Pieris melete, displays a pupal summer diapause in response to relatively low daily temperatures and gradually increasing day-length during spring and a pupal winter diapause in response to the progressively shorter day-length. To determine whether photoperiod is ‘more’ important than temperature in the determination of summer and winter diapause, or vice versa, the effects of naturally changing day-length and temperature on the initiation of summer and winter diapause were systematically investigated under field conditions for five successive years. Field results showed that the incidence of summer diapause significantly declined with the naturally increasing temperature in spring and summer generations. Path coefficient analysis showed that the effect of temperature was much greater than photoperiod in the determination of summer diapause. In autumn, the incidence of diapause was extremely low when larvae developed under gradually shortening day-length and high temperatures. The incidence of winter diapause increased to 60–90% or higher with gradually shortening day-length combined with temperatures between 20.0°C and 22.0°C. Decreasing day-length played a more important role in the determination of winter diapause induction than temperature. The eco-adaptive significance of changing day-length and temperature in the determination of summer and winter diapause was discussed.
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.