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Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
The very high temperature reactor (VHTR) is a development of the high-temperature gas-cooled reactors (HTGRs) and one of the six proposed Generation IV reactor concept candidates. The 10 MW high temperature gas-cooled reactor (HTR-10) is the first pebble-bed gas-cooled test reactor in China. A sampling system for the measurement of carbon-14 (14C) was established in the helium purification system of the HTR-10 primary loop, which could sample 14C from the coolant at three locations. The results showed that activity concentration of 14C in the HTR-10 primary coolant was 1.2(1) × 102 Bq/m3 (STP). The production mechanisms, distribution characteristics, reduction routes, and release types of 14C in HTR-10 were analyzed and discussed. A theoretical model was built to calculate the amount of 14C in the core of HTR-10 and its concentration in the primary coolant. The activation reaction of 13C has been identified to be the dominant 14C source in the core, whereas in the primary coolant, it is the activation of 14N. These results can supplement important information for the source term analysis of 14C in HTR-10 and promote the study of 14C in HTGRs.
Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
The present study evaluates the use of multiple correspondence analysis (MCA), a type of exploratory factor analysis designed to reduce the dimensionality of large categorical data sets, in identifying behaviours associated with measures of overweight/obesity in Vanuatu, a rapidly modernizing Pacific Island country.
Starting with seventy-three true/false questions regarding a variety of behaviours, MCA identified twelve most significantly associated with modernization status and transformed the aggregate binary responses of participants to these twelve questions into a linear scale. Using this scale, individuals were separated into three modernization groups (tertiles) among which measures of body fat were compared and OR for overweight/obesity were computed.
Ni-Vanuatu adults (n 810) aged 20–85 years.
Among individuals in the tertile characterized by positive responses to most of or all the twelve modernization questions, weight and measures of body fat and the likelihood that measures of body fat were above the US 75th percentile were significantly greater compared with individuals in the tertiles characterized by mostly or partly negative responses.
The study indicates that MCA can be used to identify individuals or groups at risk for overweight/obesity, based on answers to simply-put questions. MCA therefore may be useful in areas where obtaining detailed information about modernization status is constrained by time, money or manpower.
Heading date (HD) and flowering date (FD) are critical for yield potential and stability, so understanding their genetic foundation is of great significance in wheat breeding. Three related recombinant inbred line populations with a common female parent were developed to identify quantitative trait loci (QTL) for HD and FD in four environments. In total, 25 putative additive QTL and 20 pairwise epistatic effect QTL were detected in four environments. The additive QTL were distributed across 17 wheat chromosomes. Of these, QHd-1A, QHd-1D, QHd-2B, QHd-3B, QHd-4A, QHd-4B and QHd-6D were major and stable QTL for HD. QFd-1A, QFd-2B, QFd-4A and QFd-4B were major and stable QTL for FD. In addition, an epistatic interaction test showed that epistasis played important roles in controlling wheat HD and FD. Genetic relationships between HD/FD and five yield-related traits (YRTs) were characterized and ten QTL clusters (C1–C10) simultaneously controlling YRTs and HD/FD were identified. The present work laid a genetic foundation for improving yield potential in wheat molecular breeding programmes.
Hepatitis E is an important zoonosis that is prevalent in China. Hepatitis E virus (HEV) is a pathogen that affects humans and animals and endangers public health in China. In this study, the detection of HEV epidemics in swine in Sichuan Province, China, was carried out by nested real-time PCR. A total of 174 stool samples and 160 bile samples from swine in Sichuan Province were examined. In addition, software was used to analyse the biological evolution of HEV. The results showed that within 2 years of swine HEV (SHEV) infection in China, SHEV was first detected in Sichuan Province. HEV was endemic in Sichuan; the positive rate for pig farms was 11.1%, and the total positive sample rate was 10.5%. The age of swine with the highest positive rate (17.9%) was 5–9 weeks. The examined swine species in order of highest to lowest HEV infection rates were Chenghua pig, Large White, Duroc, Pietrain, Landrace and Hampshire. Nucleotide and amino acid sequence analysis showed that the HEV epidemic in swine in Sichuan Province was related to genotype IV, which had the highest homology to HEV in Beijing. Sichuan strains have greater variation than Chinese representative strains, which may indicate the presence of new HEV strains.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Extensive insecticide use has led to the resistance of mosquitoes to these insecticides, posing a major barrier to mosquito control. Previous Solexa high-throughput sequencing of Culex pipiens pallens in the laboratory has revealed that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain. Real-time quantitative PCR revealed that the miR-13664 transcript level was lower in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain increased the susceptibility of these mosquitoes to deltamethrin, whereas inhibition of miR-13664 made the DS strain more resistant to deltamethrin. Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1 expression in the DR strain reduced the resistance of mosquitoes to deltamethrin. Taken together, our results indicate that miR-13664 could regulate deltamethrin resistance by interacting with CpCYP314A1, providing new insights into mosquito resistance mechanisms.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The effects of soluble fiber inclusion in gestation diets with varying fermentation characteristics (fermentation kinetics and short-chain fatty acids (SCFA)-profile) on lactational feed intake of sows and their piglet growth over two parities were investigated using an in vitro–in vivo methodology. After breeding, 90 multiparous Landrace sows were randomized to one of three experimental diets: the control (CON) diet, konjac flour (KF) diet or sugar beet pulp (SBP) diet. All diets had similar levels of net energy, CP, insoluble fiber and NDF, but KF and SBP diets had higher soluble fiber levels than the CON diet. During gestation, the sows were restrictively fed with three different diets, but during lactation, all the sows were similarly fed ad libitum. The three gestation diets were enzymatically hydrolyzed using pepsin and pancreatin, and enzymolyzed residues were used in in vitro fermentation. Gas and SCFA production were monitored during fermentation. After fermentation, enzymolyzed residues of KF or SBP diets resulted in higher final asymptotic gas volume than those of the CON diet. The enzymolyzed residues of KF diet were mainly part of rapidly fermented fractions, whereas those of SBP diet were mainly part of slowly fermented fractions. In addition, the acetic acid, butyric acid and total SCFA concentrations of enzymolyzed residues of KF diet were higher (P<0.01) than the control and SBP diets. In the in vivo studies, on day 90 of gestation, the KF diet sows had higher plasma SCFA concentration (P<0.05) at 4 h after feeding than the CON diet sows. Furthermore, the KF diet sows had lower plasma free fatty acid (FFA) concentration (P<0.01) at 4 h after feeding, and a lower value of homeostasis model assessment (HOMA)-insulin resistance (P<0.05), but a higher value of HOMA-insulin sensitivity (P<0.01). The KF diet sows also consumed more feed during lactation (P<0.01) and weaned significantly heavier pigs (P<0.01) than the CON diet sows. The overall results showed that the high fermentation capacity KF diet contributed to an increased lactational feed intake and improved performance of piglets in the second reproductive cycle.
Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
Athetis lepigone (Möschler) (Lepidoptera: Noctuidae) is a new outbreak pest in China. Consequently, it is unclear whether the emergence and spread of the outbreak of this pest are triggered by rapid in situ population size increases in each outbreak area, or by immigrants from a potential source area in China. In order to explore the outbreak process of this pest through a population genetics approach, we developed ten novel polymorphic expressed sequence tags (EST)-derived microsatellites. These new microsatellites had moderately high levels of polymorphism in the tested population. The number of alleles per locus ranged from 3 to 19, with an average of 8.6, and the expected heterozygosity ranged from 0.269 to 0.783. A preliminary population genetic analysis using these new microsatellites revealed a lack of population genetic structure in natural populations of A. lepigone. The estimates of recent migration rate revealed strong gene flow among populations. In conclusion, our study developed the first set of EST-microsatellite markers and shed a new light on the population genetic structure of this pest in China.
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.
Flour whiteness (FW) is an important factor in assessing flour quality and determining the end product quality. It is an integrated sensory indicator reflecting flour colour and is negatively correlated with protein content. In order to dissect the genetic relationship between FW and its five related traits at the quantitative trait locus (QTL)/gene level, a recombinant inbred line population was evaluated under three environments. Quantitative trait loci for FW were analysed by unconditional and conditional QTL mapping. Four unconditional additive QTLs and 16 conditional additive QTLs were detected across the three environments. Of these QTLs, only one major additive QTL (Qfw1D1-1) was consistently identified using both unconditional and conditional QTL analysis. This QTL was independent of flour colour a* (a function of red-green with a positive a* for redness and negative for greenness) and b* (a green-blue value with positive value for yellowness and negative for blueness) and was only slightly affected by flour protein content. A minor additive QTL (Qfw4A-4) was also detected using these two QTL mapping methods, being independent of flour colour a* and b*. Five unconditional and ten conditional epistatic minor QTLs were detected, from which only one pair (Qfw3A-10/Qfw6B-6) was identified by both unconditional and conditional QTL mapping, also independent of flour colour a* and b*. The major QTL (Qfw1D1-1) identified in the current study for the first time can be used for improving wheat FW in marker-assisted breeding.
Hand-foot-mouth disease (HFMD) is a frequently occurring epidemic and has been an important cause of childhood mortality in China. Given the disease's significant impact nationwide, the epidemiological characteristics and spatio-temporal clusters in Fuyang from 2008 to 2013 were analysed in this study. The disease exhibits strong seasonality with a rising incidence. Of the reported HFMD cases, 63·7% were male and 95·2% were preschool children living at home. The onset of HFMD is age-dependent and exhibits a 12-month periodicity, with 12-, 24- and 36-month-old children being the most frequently affected groups. Across the first 60 months of life, children born in April [relative risk (RR) 8·18], May (RR 9·79) and June (RR 8·21) exhibited an elevated infection risk of HFMD relative to January-born children; the relative risk compared with the reference (January-born) group was highest for children aged 24 months born in May (RR 34·85). Of laboratory-confirmed cases, enterovirus 71 (EV71), coxsackie A16 (Cox A16) and other enteroviruses accounted for 60·1%, 7·1% and 32·8%, respectively. Spatio-temporal analysis identified one most likely cluster and several secondary clusters each year. The centre of the most likely cluster was found in different regions in Fuyang. Implications of our findings for current and future public health interventions are discussed.
Green leaf volatiles (GLVs) have been reported to play an important role in the host-locating behavior of several folivores that feed on angiosperms. However, next to nothing is known about how the green leafhopper, Empoasca vitis, chooses suitable host plants and whether it detects differing emission levels of GLV components among genetically different tea varieties. Here we found that the constitutive transcript level of the tea hydroperoxide lyase (HPL) gene CsiHPL1, and the amounts of (Z)-3-hexenyl acetate and of total GLV components are significantly higher in tea varieties that are susceptible to E. vitis (Enbiao (EB) and Banzhuyuan (BZY)) than in varieties that are resistant to E. vitis (Changxingzisun (CX) and Juyan (JY)). Moreover, the results of a Y-tube olfactometer bioassay and an oviposition preference assay suggest that (Z)-3-hexenyl acetate and (Z)-3-hexenol offer host and oviposition cues for E. vitis female adults. Taken together, the two GLV components, (Z)-3-hexenol and especially (Z)-3-hexenyl acetate, provide a plausible mechanism by which tea green leafhoppers distinguish among resistant and susceptible varieties. Future research should be carried out to obtain the threshold of the above indices and then assess their reasonableness. The development of practical detection indices would greatly improve our ability to screen and develop tea varieties that are resistant to E. vitis.
Concentrations of organic carbon, carbon isotopes (13C and 14C), atmospheric 10Be in soil, and in situ 10Be in bedrock and weathering rock were determined in a study of a profile of a grassland slope at the Heshan Hilly Land Interdisciplinary Experimental Station, Chinese Academy of Sciences, in Guangdong Province, China. A good linear relationship between depth and the 14C apparent age of the organic carbon demonstrates that the rock weathering process and the accumulation process of organic matter in the slope are relatively stable. Both 14C and 10Be results show that about 34% of soil in the grassland slope has been eroded during the past 3800 yr. The 10Be results for interstitial soil from weathered rocks show that the 90-cm-thick weathering rock layer above the bedrock has evolved over a period of 1.36 Myr. The concentrations of in situ 10Be in the weathered rock and bedrock are 10.7 × 104 atoms/g and 8.31 × 104 atoms/g, respectively. The weathering rate of the bedrock, equivalent to the soil production rate, was estimated at 8.8 × 10-4 cm/yr, and the exposure ages of the weathered rock and the bedrock were 72 kyr and 230 kyr, respectively.
While radiocarbon is widely applied in dating ancient samples, recent studies reveal that 14C concentrations in modern samples can also yield precise ages due to the atmospheric testing of thermonuclear devices between 1950 and 1963. 14C concentrations in both enamel and organic matter of 13 teeth from 2 areas in China were examined to evaluate and improve this method of forensic investigation. Choosing enamel near the cervix of the tooth can reduce the error caused by the difference between the sample formation time and whole enamel formation time because tooth enamel formations take a long time to complete. A proper regional data set will be helpful to get an accurate result when calculating the age of the sample (T1) by the CALIBomb program. By subtracting the enamel formation time (t), the birth date of an individual (T2) can be confirmed by enamel F14C from 2 teeth formed at different ages. Calculated enamel formation dates by 14C concentration are basically consistent with corresponding actual values, with a mean error of 1.9 yr for all results and 0.2 yr for the samples formed after AD 1960. This method is more effective for dating samples completed after AD 1960. We also found that 14C concentrations in organic matter of tooth roots are much lower than atmospheric concentrations in root formation years, suggesting that the organic material keeps turning over even after tooth formation is complete. This might be a potential tool for identification of death age to extract a proper component for 14C dating. We also observed that δ13C values between hydroxyapatite and organic matter indicate that isotopic fractionation during the biomineralization is 8–9%‰ more positive in mineral fractions than in organic matter.