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Stratospheric airships are lighter-than-air vehicles that work at an altitude of 20km in the lower calm portion of the stratosphere. They can be used as real-time surveillance platforms for environment monitoring and civil communication. Solar energy is the ideal power choice for long-endurance stratospheric airships. Attitude control is important for airships so that they can point at a target for observation or adjust the attitude to improve the output performance of solar panels. Stratospheric airships have a large volume and semi-flexible structure. The typical actuators used are aerodynamic surfaces, vectored thrust and ballonets. However, not all these actuators can work well under special working conditions, such as low density and low speed. In this study, moving-mass control is introduced to stratospheric airships because its control efficiency is independent of airspeed and atmospheric density. A nonlinear feedback controller based on generalised inverse with a nonlinear mapping module is designed to implement moving-mass control. Such a new station keeping scheme with moving masses is proposed for airships with different working situations.
Manure is a primary source of methane (CH4) emissions into the atmosphere. A large proportion of CH4 from manure is emitted during storage, but this varies with storage methods. In this research, we tested whether covering a manure heap with plastic reduces CH4 emission during a short-term composting process. A static chamber method was used to detect the CH4 emission rate and the change of the physicochemical properties of cattle manure which was stored either uncovered (treatment UNCOVERED) or covered with plastic (treatment COVERED) for 30-day periods during the four seasons? The dry matter content of the COVERED treatment was significantly less than the UNCOVERED treatment (P < 0.01), and the C/N ratio of the COVERED treatment significantly greater than the UNCOVERED treatment (P > 0.05) under high temperature. In the UNCOVERED treatment, average daily methane (CH4) emissions were in the order summer > spring > autumn > winter. CH4 emissions were positively correlated with the temperature (R2 = 0.52, P < 0.01). Compared to the UNCOVERED treatment, the daily average CH4 emission rates from COVERED treatment manure were less in the first 19 days of spring, 13 days of summer, 10 days of autumn and 30 days of winter. In summary, covering the manure pile with plastic reduces the evaporation of water during storage; and in winter, long-term covering with plastic film reduces the CH4 emissions during the storage of manure.
Glutamine synthetase (GS) and glutamate synthase (GOGAT) play a central role in plant nitrogen (N) metabolism. In order to study the effect of powdery mildew (Blumeria graminis f. sp. tritici, Bgt) on N metabolism, field experiments were carried out to evaluate GS and GOGAT activity, GS expression and grain protein content (GPC) in susceptible (Xi'nong 979) and resistant (Zhengmai 103) wheat cultivars under three treatments. The three treatments were no inoculation (CK), inoculated once with Bgt (MP) and inoculated nine times with Bgt (HP). For Xi'nong 979, the activities of GS and GOGAT in grains as well as GS activity in flag leaves increased at 10–15 days after anthesis (DAA), and decreased significantly at 15 or 20–30 DAA in HP and MP. However, GS activity in grains decreased from 20 DAA, which was later than that of flag leaves (15 DAA). At the same time, GS expression in grains was up-regulated at early stage, with GS1 at 10 DAA and GS2 at 15 DAA, followed by a continuous down-regulation. This result indicated that GS and GOGAT activity as well as GS expression were inhibited by powdery mildew, indicating that N metabolism in grains was inhibited at 20–30 DAA. The current study also found out that the yield of the susceptible cultivar decreased significantly, while its GPC increased obviously in HP. It was shown that the increase of GPC was not due to the enhancement of N metabolism, but due to the passive increase caused by yield reduction.
The morphological and ecological diversity of lemurs and lorisiformes once rivaled that of the rest of the primate order. Here, we assemble a dataset of 3D models representing the second mandibular molars of a wide range of extant and fossil strepsirrhines encompassing this diversity. We use these models to distill quantitative descriptors of tooth form and then analyze these data using new analytical methods. We employ a recently developed dental topography metric (ariaDNE), which is less sensitive to details of random error in 3D model quality than previously used metrics (e.g., DNE); Bayesian multinomial modeling with metrics designed to measure overfitting risk; and a tooth segmentation algorithm that allows the shapes of disaggregated tooth surface features to be quantified using dental topography metrics. This approach is successful at reclassifying extant strepsirrhine primates to known dietary ecology and indicates that the averaging of morphological information across the tooth surface does not interfere with the ability of dental topography metrics to predict dietary adaptation. When the most informative combination of dental topography metrics is applied to extinct species, many subfossil lemurs and the most basal fossil strepsirrhines are predicted to have been primarily frugivorous or gummivorous. This supports an ecological contraction among the extant lemurs and the importance of frugivory in the origins of crown Strepsirrhini, potentially to avoid competition with more insectivorous and folivorous members of Paleogene Afro-Arabian primate faunas.
ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.
ABSTRACT IMPACT: Understanding dietary patterns and nutrient intakes of the aging population may help address concerns and dietary guidelines regarding their nutritional needs. OBJECTIVES/GOALS: The objective of this study is to test the hypothesis that a healthy dietary pattern in the oldest old (aged 80 years and older) is related to greater compliance with dietary recommendations and better nutrient intake profiles. METHODS/STUDY POPULATION: We conducted a cross-sectional study of 122 participants aged 82 to 97 years old from the Geisinger Rural Aging Study (GRAS) cohort in rural Pennsylvania (n = 56 men and 66 women). The main outcome measures of the investigation were the daily nutrient intakes and food group intakes evaluated from the average of three 24-hour dietary recalls. The dietary patterns were determined by cluster analysis from 28 food groups. Diet quality and adherence to the Dietary Guidelines for Americans was assessed by the Healthy Eating Index (HEI)-2015 and the Dietary Screening Tool (DST). Recommended intakes were determined by the Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs). RESULTS/ANTICIPATED RESULTS: Less than 50% of participants met the dietary recommended intakes for vitamins D, E, K, B6, dietary fiber, zinc, potassium, and calcium. The more-nutrient-dense cluster was characterized by higher intakes of fruits and vegetables. The less-nutrient-dense cluster was characterized by higher intakes of foods including desserts and sweets. After adjusting for age, sex, and energy intake, participants in the more-nutrient-dense dietary pattern had a higher intake of vitamins A, D, K, C, fiber, and potassium (p < 0.05 for all). After adjusting for age and sex, participants in the more-nutrient-dense pattern had better diet quality assessed by the (HEI)-2015 (p < 0.001) and DST (p = 0.006). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among the oldest old, many participants were found to have nutrient intakes lower than the recommended levels for fundamental nutrients suggesting that dietary guidance in addition to a dietary pattern more aligned with dietary guidelines may be beneficial for supporting healthy aging.
Research on flight emissions at airports is very important for environmental policymaking. This study analysed the trend of aircraft air pollutant emissions at mainland China airports from 1990 to 2017, mainly focusing on standard landing and take-off (LTO) cycles. Total flight movements increased 29-fold from 1990 to 2017 at Chinese airports. Over the same period, the emissions of NOx, SOx, CO, hydrocarbons (HC), and particulate matter (PM) increased 46, 27, 12, 5, and 4 times, respectively. Emissions at the 216 public airports showed a growth trend. It was estimated that in 2017, Chinese airports emitted 12,875 kilotons of CO2, 59 kilotons of NOx, 3 kilotons of SOx, 38 kilotons of CO, 5 kilotons of HC, and 0.4 kilotons of PM. The largest 30 airports produced 68.2% of the total emissions. Emissions from B737-800, A320, A321, B737-700, A330-300, and A319 aircraft accounted for more than 75% of aircraft LTO emissions at Chinese airports in 2017. Results show that average emissions per passenger have decreased for CO2, CO, HC, SOx, PM, and NOx from 1990 to 2017.
A disruption database characterizing the current quench of disruptions with ITER-like tungsten divertor has been developed on EAST. It provides a large number of plasma parameters describing the predisruptive plasma, current quench time, eddy current, and mitigation by massive impurity injection, which shows that the current quench time strongly depends on magnetic energy and post-disruption electron temperature. Further, the energy balance and magnetic energy dissipation during the current quench phase has been well analysed. Magnetic energy is also demonstrated to be dissipated mainly by ohmic reheating and inductive coupling, and both of the two channels have great effects on current quench time. Also, massive gas injection is an efficient method to speed up the current quench and increase the fraction of impurity radiation.
We examined whether breakfast frequency was associated with chronic inflammatory, as assessed by high-sensitivity C-reactive protein (CRP) concentration.
Kailuan community, China.
Included were 70 092 Chinese adults without CVD and cancer in 2014 with CRP concentrations <10 mg/l, when breakfast frequency was assessed via a questionnaire, and plasma CRP concentration was measured.
Breakfast frequency was associated with CRP concentration (P-trend < 0·001). The adjusted mean CRP was 1·33 mg/l (95 % CI 1·23, 1·44) for the ‘no breakfast’ group and 1·07 mg/l (95 % CI 1·0, 1·14) for the ‘breakfast everyday’ group (P-difference < 0·001), adjusting for age, sex, diet quality, total energy, obesity, education, occupation, marital status, smoking, alcohol consumption, blood pressure, sleep parameters, fasting blood glucose and lipid profiles. Consistently, the adjusted OR for CRP ≥ 1·0 mg/l and CRP ≥ 3·0 mg/l were 1·86 (95 % CI 1·73, 2·00) and 1·27 (95 % CI 1·15, 1·40), respectively, when comparing these two breakfast consumption groups (P-trend < 0·001 for both). The associations were more pronounced among older adults, relative to those who were younger (P-interaction < 0·001). Significant association between breakfast skipping and elevated CRP concentration was observed in those with poor diet quality, but not those with good diet quality.
Habitually skipping breakfast is associated with elevated concentrations of CRP. Future prospective studies including repeated assessment of inflammatory biomarkers and a collection of detailed information on type and amount of breakfast foods are warranted.
Damage to the corticospinal tract (CST) from stroke leads to motor deficits. The damage can be quantified as the amount of overlap between the stroke lesion and CST (CST Injury). Previous literature has shown that the degree of motor deficits post-stroke is related to the amount of CST Injury. These studies delineate the stroke lesion from structural T1-weighted magnetic resonance imaging (MRI) scans, often acquired for research. In Canada, computed tomography (CT) is the most common imaging modality used in routine acute stroke care. In this proof-of-principle study, we determine whether CST Injury, using lesions delineated from CT scans, significantly explains the variability in motor impairment in individuals with stroke.
Thirty-seven participants with stroke were included in this study. These individuals had a CT scan within the acute stage (7 days) of their stroke and underwent motor assessments. Brain images from CT scans were registered to MRI space. We performed a stepwise regression analysis to determine the contribution of CST injury and demographic variables in explaining motor impairment variability.
Using clinically available CT scans, we found modest evidence that CST Injury explains variability in motor impairment (R2adj = 0.12, p = 0.02). None of the participant demographic variables entered the model.
We show for the first time a relationship between CST Injury and motor impairment using CT scans. Further work is required to evaluate the utility of data derived from clinical CT scans as a biomarker of stroke motor recovery.
Porphyromonas gingivalis has been linked to the development and progression of oesophageal squamous cell carcinoma (ESCC), and is considered to be a high-risk factor for ESCC. Currently, the commonly used methods for P. gingivalis detection are culture or DNA extraction-based, which are either time and labour intensive especially for high-throughput applications. We aimed to establish and evaluate a rapid and sensitive direct quantitative polymerase chain reaction (qPCR) protocol for the detection of P. gingivalis without DNA extraction which is suitable for large-scale epidemiological studies. Paired gingival swab samples from 192 subjects undergoing general medical examinations were analysed using two direct and one extraction-based qPCR assays for P. gingivalis. Tris-EDTA buffer-based direct qPCR (TE-direct qPCR), lysis-based direct qPCR (lysis-direct qPCR) and DNA extraction-based qPCR (kit-qPCR) were used, respectively, in 192, 132 and 60 of these samples for quantification of P. gingivalis. The sensitivity and specificity of TE-direct qPCR was 95.24% and 100% compared with lysis-direct qPCR, which was 100% and 97.30% when compared with kit-qPCR; TE-direct qPCR had an almost perfect agreement with lysis-direct qPCR (κ = 0.954) and kit-qPCR (κ = 0.965). Moreover, the assay time used for TE-direct qPCR was 1.5 h. In conclusion, the TE-direct qPCR assay is a simple and efficient method for the quantification of oral P. gingivalis and showed high sensitivity and specificity compared with routine qPCR.
Fluid motion has two well-known fundamental processes: the vector transverse process characterized by vorticity, and the scalar longitudinal process consisting of a sound mode and an entropy mode, characterized by dilatation and thermodynamic variables. The existing theories for the sound mode involve the multi-variable issue and its associated difficulty of source identification. In this paper, we define the source of sound inside the fluid by the objective causality inherent in dynamic equations relevant to a longitudinal process, which naturally favours the material time-rate operator
rather than the local time-rate operator
, and describes the sound mode by inhomogeneous advective wave equations. The sources of sound physical production inside the fluid are then examined at two levels. For the conventional formulation in terms of thermodynamic variables at the first level, we show that the universal kinematic source can be condensed to a scalar invariant of the surface deformation tensor. Further, in the formulation in terms of dilatation at the second level, we find that the sound mode in viscous and heat-conducting flow has sources from rich nonlinear couplings of vorticity, entropy and surface deformation, which cannot be disclosed at the first level. Preliminary numerical demonstration of the theoretical findings is made for two typical compressible flows, i.e. the interaction of two corotating Gaussian vortices and the unsteady type IV shock/shock interaction. The results obtained in this study provide a new theoretical basis for, and physical insight into, understanding various nonlinear longitudinal processes and the interactions therein.
To assess the impact of lisdexamfetamine dimesylate (LDX; Vyvanse®, Shire US Inc.), which is the first long-acting prodrug stimulant indicated for treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults in the United States, on performance and quality of life (QOL) in adults with ADHD.
Subjects (n=142; aged 18 to 55 years) with ADHD entered a 4-week open-label dose-optimisation phase, then a 2-week, double-blind crossover phase. The primary efficacy measure was the average postdose total score on the Permanent Product Measure of Performance (PERMP) math test given predose and 2, 4, 8, 10, 12, and 14 hours postdose. The Adult ADHD Impact Module (AIM-A) was self-administered during the dose-optimisation phase. Safety was assessed by monitoring adverse events (AEs).
In the intention-to-treat population (n=105), postdose average PERMP least squares mean (SE) scores were higher (P< .0001) for LDX (312.9 [8.59]) vs placebo (289.5 [8.59]) and at every postdose time point ≥14 hours (P≤.0017 for each). Mean change from baseline scores on AIM-A subscales (n=127) showed improvement (P< .001) with LDX in 6 measured QOL domains (living with ADHD; general wellbeing; work, home, and school performance and daily functioning; relationships and communication; interference with life; and concern caused by symptoms). Treatment-emergent AEs (≥10%) in the dose-optimisation phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), and insomnia (18.3%).
LDX improved QOL and performance (up to 14 hours) and demonstrated a safety profile consistent with long-acting stimulant use.
Supported by funding from Shire Development Inc., Wayne, PA, US.
There are strong links between circadian disturbance and some of the most characteristic symptoms of clinical major depressive disorder (MDD). However there are no published studies of changes in expression of clock genes or of other neuropeptides related to circadian-rhythm regulation, which may influence recurrent susceptibility after treatment with antidepressant in MDD.
Blood samples were collected from twelve healthy controls and twelve male major depressive patients pre- and post- treated with escitalopram for eight weeks at 4-hour intervals for 24 hours. Outcome measures were the relative expression of mRNA of clock genes (hPERIOD1, hPERIOD2, hPERIOD3, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta) and the levels of serum melatonin, Vasoactive Intestinal Peptide (VIP), cortisol, Adrenocorticotropic Hormone (ACTH), Insulin-like Growth Factor-1(IGF-1) and growth hormone (GH) in twelve healthy controls and twelve pre- and post- treated MDD patients.
Compared with healthy controls, MDD patients showed disruptions in diurnal rhythms of expression of hPERIOD1, hPERIOD2, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta, along with disruptions in diurnal rhythms of release of melatonin, VIP, cortisol, ACTH, IGF-1, and GH. Several of these disruptions (hPER1, hCRY1, melatonin, VIP, cortisol, ACTH, and IGF-1) persisted after eight weeks escitalopram treatment, as did elevation of 24-hour levels of VIP and decreases in 24-hour levels of cortisol and ACTH.
These persisted neurobiological changes may play a role in MDD symptoms that are thought to contribute to recurrence vulnerability and in maintenance therapy for a long term.
Developing empirically sound measures for social cognition is a key step in improving the factors that contribute to deficits in social functioning in schizophrenia. Investigating the psychometric properties and acceptability of social cognitive instruments may contribute to identification of a reliable and valid instrument for schizophrenia patients.
To investigate the psychometric properties and acceptability of a dynamic social cognition scale (DSCB) compared to three common social cognition instruments in schizophrenia.
41 patients with schizophrenia were evaluated to assess acceptability, internal consistency and validity of five social cognition measures: DSCB, Emotion Recognition-40 (ER-40), Facial Emotion Identification Task (FEIT), Tone Matching Task and MSCEIT. Multiple linear regressions were conducted to identify variables which perform well as social cognition determinants.
The DSCB and FEIT showed good acceptability, evidenced by shorter administration time, completion and patient preference for the DSCB. Good levels of internal consistency were found for the DSCB (α = 0.851), ER-40 (α = 0.803), and FEIT (α = 0.782). Confirmatory Factor Analysis indicated sufficient to good model fit. The DSCB and the ER-40 demonstrated a good model fit. The correlations for the DSCB were significant for the ER-40 (r = 0.512) and FEIT (r = 0.500).
Findings suggest that DSCB is the preferred instrument to evaluate social cognition, due to its dynamic nature and short administration time. Further research is needed to develop and improve these measurements. Additionally, the DSCB, FEIT and ER-40 show adequate to good reliability and validity.
The PANSS is utilized in clinical trials for assessment of psychopathology. In order to determine the status of a patient, comparisons within a general population are necessary. If several groups of patients are to be compared, gender, age, co-morbid diagnoses, and other factors affecting clinical status are not identically distributed.
1) Phase 1: To establish the initial psychometric properties of the PANSS-Ru. 2) Phase 2: To establish normed-reference data for the PANSS-Ru.
Phase 1: 40 patients with schizophrenia and other psychotic disorders. Phase 2: 375 individuals (n = 250 patients; n = 125 controls). Responses were assessed for internal consistency, stability, reliability, discriminative validity, and construct validity. Fifth percentile norms are presented as step functions. Data were compared to US norms.
40 subjects enrolled for Phase 1. Alpha coefficient of 0.88 verified good internal consistency. Test-retest comparisons verified time stability (r = 0.67 to 0.92). Correlation between subscale and the total scores ranged from 0.76 to 0.86, compared to > 0.83 for US norm studies. Internal consistencies were α > 0.745. Mean subscale/ total score were equivalent to US population norms within 13%. However, there was a difference of > 5 norm-based points for mean general psychopathology subscale. Norms had a sensitivity of 85% and specificity of 89%.
Preliminary results show that different dimensions of symptom presentations in the Russian population may help to improve symptom-specific treatments, and will also provide comparison data for a Russian population. Further normative studies are warranted in other populations.
Deficits in social functioning, including communication, work, social skills, and community functioning, are a defining feature of schizophrenia. Functional outcomes of schizophrenia are affected by several factors such as social cognition, neurocognition, psychopathology, and clinical outcomes. The multifaceted association among these factors and functional outcome continues to be unclear. Given the significant role of functional outcomes in schizophrenia, there has been increasing importance in factors that may underlie these outcomes. If the characteristics of these factors can be defined, interventions may be developed to improve them, which, in turn, will have a parallel impact on long term functioning and outcome. The current study examines whether social cognition, neurocognition and clinical symptoms have a relationship on functional outcomes in patients with schizophrenia.
37 patients with DSM-IV schizophrenia were assessed for: Neurocognition; MCCB-MATRICS, Clinical Symptoms: PANSS, Social Cognition: MSCEIT, Emotion Recognition-40 (ER-40), Dynamic Social Cognition Battery (DSCB: Emotion Identification - Facial, Verbal and Non Verbal), Functional Outcomes: University of San Diego Performance Based Assessment (USCD-UPSA), Social Skills: Personal and Social Performance Scale (PSP). Structural Equation Modeling (SEM) employed with maximum likelihood estimation for test effects.
The overall model fit was χ2=39.6, P<0.14. Fit indexes: Cmin/df=1.25, NFI=0.96, Tucker-Lewis index (Bentler and Bonnet nonformed fit index)=0.97, RMSEA=0.044. Regression weights of the latent variable 'Marder Negative Factor' were significant and high (β=0.91) and a substantial amount of variance could be explained by negative symptoms, indicating that the negative factor is a reliable measure of the latent variable. In addition, the regression weights of the latent variable social cognition to the 3 indicators were moderate and significant (Emotion Recognition DSCB: β=0.77, ER-40: β=0.46, and Nonverbal Emotion Identification, β=0.44). Like social cognition, the latent variable functional assessment explained a substantial amount of variance in the latent variables of working memory (45%). Impact of social cognition on negative symptoms (β=0.91) was greater than the direct impact of social functioning (β=0.78) and functional assessments (β=0.63).
This study suggests that 49% of negative symptoms could be explained by impaired social cognition and that 49% of social functioning skills could be explained by social cognition. Our findings suggest that social cognition may be an essential target to improve functional outcomes. These findings provide evidence that may help develop novel interventions.
Muscle fiber characteristics comprise a set of complex traits that influence the meat quality and lean meat production of livestock. However, the genetic and biological mechanisms regulating muscle fiber characteristics are largely unknown in pigs. Based on a genome-wide association study (GWAS) performed on 421 Large White × Min pig F2 individuals presenting well-characterized phenotypes, this work aimed to detect genome variations and candidate genes for five muscle fiber characteristics: percentage of type I fibers (FIB1P), percentage of type IIA fibers (FIB2AP), percentage of type IIB fibers (FIB2BP), diameter of muscle fibers (DIAMF) and number of muscle fibers per unit area (NUMMF). The GWAS used the Illumina Porcine SNP60K genotypic data, which were analyzed by a mixed model. Seven and 10 single nucleotide polymorphisms (SNPs) were significantly associated with DIAMF and NUMMF, respectively (P < 1.10E-06); no SNP was significantly associated with FIB1P, FIB2AP or FIB2B. For DIAMF, the significant SNPs on chromosome 4 were located in the previously reported quantitative trait loci (QTL) interval. Because the significant SNPs on chromosome 6 were not mapped in the previously reported QTL interval, a putative novel QTL was suggested for this locus. None of the previously reported QTL intervals on chromosomes 6 and 14 harbored significant SNPs for NUMMF; thus, new potential QTLs on these two chromosomes are suggested in the present work. The most significant SNPs associated with DIAMF (ALGA0025682) and NUMMF (MARC0046984) explained 12.02% and 11.59% of the phenotypic variation of these traits, respectively. In addition, both SNPs were validated as associated with DIAMF and NUMMF in Beijing Black pigs (P < 0.01). Some candidate genes or non-coding RNAs, such as solute carrier family 44 member 5 and miR-124a-1 for DIAMF, and coiled-coil serine rich protein 2 for NUMMF, were identified based on their close location to the significant SNPs. This study revealed some genome-wide association variants for muscle fiber characteristics, and it provides valuable information to discover the genetic mechanisms controlling these traits in pigs.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.