ABSTRACT
Identifying efficient and accurate optimization algorithms is a long-desired goal for the scientific community. At present, a combination of evolutionary and deep-learning methods is widely used for optimization. In this paper, we demonstrate three cases involving different physics and conclude that no matter how accurate a deep-learning model is for a single, specific problem, a simple combination of evolutionary and deep-learning methods cannot achieve the desired optimization because of the intrinsic nature of the evolutionary method. We begin by using a physics-supervised deep-learning optimization algorithm (PSDLO) to supervise the results from the deep-learning model. We then intervene in the evolutionary process to eventually achieve simultaneous accuracy and efficiency. PSDLO is successfully demonstrated using both sufficient and insufficient datasets. PSDLO offers a perspective for solving optimization problems and can tackle complex science and engineering problems having many features. This approach to optimization algorithms holds tremendous potential for application in real-world engineering domains.
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Human Na+ taurocholate co-transporting protein (hNTCP) is a key bile salt transporter to maintain enterohepatic circulation and is responsible for the recognition of hepatitis B and D viruses. Despite landmark cryoelectron microscopy studies revealing open-pore and inward-facing states of hNTCP stabilized by antibodies, the transport mechanism remains largely unknown. To address this knowledge gap, we used molecular dynamics and enhanced sampling metadynamics simulations to elucidate the intrinsic mechanism of hNTCP-mediated taurocholate acid (TCA) transport driven by Na+ binding. We uncovered three TCA-binding modes, including one that closely matched the limited cryoelectron microscopy density observed in the open-pore hNTCP. We also captured several key hNTCP conformations in the substrate transport cycle, particularly including an outward-facing, substrate-bound state. Furthermore, we provided thermodynamic evidence supporting that changes in the Na+-binding state drive the TCA transport by exploiting the amphiphilic nature of the substrate and modulating the protein environment, thereby enabling the TCA molecule to flip through. Understanding these mechanistic details of Na+-driven bile acid transport may aid in the development of hNTCP-targeted therapies for liver diseases.
Subject(s)
Molecular Dynamics Simulation , Organic Anion Transporters, Sodium-Dependent , Sodium , Symporters , Taurocholic Acid , Symporters/metabolism , Symporters/chemistry , Organic Anion Transporters, Sodium-Dependent/metabolism , Organic Anion Transporters, Sodium-Dependent/chemistry , Humans , Sodium/metabolism , Taurocholic Acid/metabolism , Biological Transport , Bile Acids and Salts/metabolism , ThermodynamicsABSTRACT
BACKGROUND: Natural proteins occupy a small portion of the protein sequence space, whereas artificial proteins can explore a wider range of possibilities within the sequence space. However, specific requirements may not be met when generating sequences blindly. Research indicates that small proteins have notable advantages, including high stability, accurate resolution prediction, and facile specificity modification. RESULTS: This study involves the construction of a neural network model named TopoProGenerator(TPGen) using a transformer decoder. The model is trained with sequences consisting of a maximum of 65 amino acids. The training process of TopoProGenerator incorporates reinforcement learning and adversarial learning, for fine-tuning. Additionally, it encompasses a stability predictive model trained with a dataset comprising over 200,000 sequences. The results demonstrate that TopoProGenerator is capable of designing stable small protein sequences with specified topology structures. CONCLUSION: TPGen has the ability to generate protein sequences that fold into the specified topology, and the pretraining and fine-tuning methods proposed in this study can serve as a framework for designing various types of proteins.
Subject(s)
Amino Acids , Electric Power Supplies , Amino Acid Sequence , Language , LearningABSTRACT
BACKGROUND: Respiratory diseases are a major health burden, and educational inequalities may influence disease prevalence. We aim to evaluate the causal link between educational attainment and respiratory disease, and to determine the mediating influence of several known modifiable risk factors. METHODS: We conducted a two-step, two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) and single nucleotide polymorphisms (SNPs) as instrumental variables for educational attainment and respiratory diseases. Additionally, we performed a multivariable MR analysis to estimate the direct causal effect of each exposure variable included in the analysis on the outcome, conditional on the other exposure variables included in the model. The mediating roles of body mass index (BMI), physical activity, and smoking were also assessed. FINDINGS: MR analyses provide evidence of genetically predicted educational attainment on the risk of FEV1 (ß = 0.10, 95% CI 0.06, 0.14), FVC (ß = 0.12, 95% CI 0.07, 0.16), FEV1/FVC (ß = - 0.005, 95% CI - 0.05, 0.04), lung cancer (OR = 0.54, 95% CI 0.45, 0.65) and asthma (OR = 0.86, 95% CI 0.78, 0.94). Multivariable MR dicated the effect of educational attainment on FEV1 (ß = 0.10, 95% CI 0.04, 0.16), FVC (ß = 0.07, 95% CI 0.01, 0.12), FEV1/FVC (ß = 0.07, 95% CI 0.01, 0.01), lung cancer (OR = 0.55, 95% CI 0.42, 0.71) and asthma (OR = 0.88, 95% CI 0.78, 0.99) persisted after adjusting BMI and cigarettes per day. Of the 23 potential risk factors, BMI, smoking may partially mediate the relationship between education and lung disease. CONCLUSION: High levels of educational attainment have a potential causal protective effect on respiratory diseases. Reducing smoking and adiposity may be a target for the prevention of respiratory diseases attributable to low educational attainment.
Subject(s)
Asthma , Lung Neoplasms , Respiration Disorders , Respiratory Tract Diseases , Humans , Genome-Wide Association Study , Mendelian Randomization Analysis , Educational Status , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Asthma/diagnosis , Asthma/epidemiology , Asthma/geneticsABSTRACT
BACKGROUND: Metals have been linked to a diverse spectrum of age-related diseases; however, the effects of metal exposure on health span remains largely unknown. This cohort study aims to determine the association between plasma metal and health span in elder adults aged ≥ 90 years. METHODS: The plasma concentrations of seven metals were measured at baseline in 300 elder adults. The end of the health span (EHS) was identified as the occurrence of one of eight major morbidities or mortality events. We used Cox regression to assess hazard ratios (HR). The combined effects of multiple metal mixtures were estimated using grouped-weighted quantile sum (GWQS), quantile g-computation (Q-gcomp), and Bayesian kernel machine regression (BKMR) methods. RESULTS: The estimated HR for EHS with an inter-quartile range (IQR) increment for selenium (Se) was 0.826 (95% confidence interval [CI]: 0.737-0.926); magnesium (Mg), 0.806 (95% CI: 0.691-0.941); iron (Fe), 0.756 (95% CI: 0.623-0.917), and copper (Cu), 0.856 (95% CI: 0.750-0.976). The P for trend of Se, Mg, and Fe were all < 0.05. In the mixture analyses, Q-gcomp showed a negative correlation with EHS (P = 0.904), with the sum of the negative coefficients being -0.211. CONCLUSION: Higher plasma Se, Mg, and Fe reduced the risk of premature end of health span, suggesting that essential metal elements played a role in health maintenance in elder adults.
Subject(s)
Metals , Humans , Female , Male , Aged, 80 and over , Prospective Studies , Metals/blood , Cohort Studies , Longevity/physiology , Longevity/drug effects , Environmental Exposure/adverse effects , Selenium/bloodABSTRACT
OBJECTIVES: To examine the correlation between healthy lifestyle patterns, their change trajectories, and the risk of multimorbidity in adults. METHODS: Based on two representative national cohorts, the English Longitudinal Study of Aging (ELSA) and the Health and Retirement Study (HRS) including adults aged 50 years and over. We employed Cox regression, lifestyle change trajectories, and restricted mean survival times to explore the relationship between lifestyle (assessed by SCORE2, LE'8, and HLS scores) and multimorbidity. We also conducted mediation analysis to investigate the underlying mechanisms. RESULTS: A healthy lifestyle (higher LE'8, higher HLS, or lower SCORE2) can reduce the risk of multimorbidity. 2-10% lower multimorbidity risk per one-point increase in LE'8 and HLS. The hazard ratio of multimorbidity for improvements in unhealthy lifestyles or deterioration in healthy lifestyles compared to always healthy lifestyles ranged from 1.598 to 5.602. Besides, for LE'8 and HLS, participants with higher scores had a slower decrease in survival probability in ELSA. Triglyceride, C-reaction protein, fibrinogen, and cystatin C partly mediate the association between lifestyle and multimorbidity. CONCLUSIONS: Keeping a healthy lifestyle over time can help reduce the risk of multimorbidity.
Subject(s)
Healthy Lifestyle , Multimorbidity , Humans , Middle Aged , Female , Male , Prospective Studies , Aged , Longitudinal Studies , England/epidemiologyABSTRACT
A variety of organometallic supramolecular architectures have been constructed over the past decades and their properties were also explored via different strategies. However, the synthesis of metalla-Russian doll is still a fascinating challenge. Herein, a series of new coordination supramolecular complexes, including a metalla-Russian doll, metalla[2]catenanes, and metallarectangles, were synthesized by using meticulously selected Cp*Rh (Cp* = η5-C5Me5) building units (E1, E2, and E3) and three rigid anthracylpyridine ligands (L1, L2, and L3) via a self-assembly strategy. While the combination of the short ligand L1 and E1 or E2 generated two metallarectangles, the longer ligand L2 containing an alkynyl group resulted in two new [2]catenanes, most likely due to which the strong electron-donating effect of alkynyl groups causes self-accumulation. Interestingly, an unusual Russian doll assembly was obtained through the reaction of L3 and E3 based on sextuple π···π stacking interactions. Furthermore, the dynamic structural conversion between [2]catenanes and the corresponding metallarectangles could be observed through concentration-, solvent-, and guest-induced effects. The [2]catenane complexes 4b displayed efficient photothermal conversion efficiency in solution (20.2%), in comparison with other organometallic macrocycles. We believe that π···π stacking interactions generate active nonradiative pathways and promote radiative photodeactivation pathways. This study proves the versatility of half-sandwich building units, not only to build complicated supramolecular topologies but also in effective functional materials for various appealing applications.
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OBJECTIVE: To investigate the predictive value of three-dimensional ultrasound assessment of endometrial receptivity in PGD/PGS transplantation patients on pregnancy outcome. METHODS: 280 patients undergoing PGD/PGS transplantation were enrolled and divided into group A and group B according to the patients' pregnancy outcomes. The general conditions, endometrial receptivity indexes of the two groups were compared. Multifactorial logistic regression analysis was used to determine the factors influencing pregnancy outcome in PGD/PGS transplant patients. ROC curves were plotted to analyze the predictive value of 3D ultrasound parameters on pregnancy outcome. The results of the study were validated with patients who underwent FET transplantation, and the patients in the validation group were treated with the same 3D ultrasound examination method and treatment plan as the observation group. RESULTS: The differences in basic situations between two groups were not statistically significant (P > 0.05). The percentage of endometrial thickness, endometrial blood flow, and endometrial blood flow classification type II + II were higher in group A than in group B (P < 0.05). Multifactorial logistic regression analysis showed that endometrial thickness, endometrial blood flow and endometrial blood flow classification were influencing factors of pregnancy outcome in PGD/PGS patients. The sensitivity of predicting pregnancy outcome based on the results of transcatheter 3D ultrasound was 91.18%, the specificity was 82.35%, and the accuracy was 90.00%, which has a high predictive value. CONCLUSION: 3D ultrasound can predict pregnancy outcome by assessing the endometrial receptivity of PGD/PGS transplantation, in which endometrial thickness and endometrial blood flow have a good predictive value.
Subject(s)
Pregnancy Outcome , Preimplantation Diagnosis , Female , Pregnancy , Humans , Embryo Transfer , Ultrasonography , Endometrium/diagnostic imagingABSTRACT
BACKGROUND: Long-term ambient particulate matter (PM) exposure exerts detrimental effects on cardiovascular health. Evidence on the relation of chronically exposed ambient PM10 and PM2.5 with coronary stenosis remains lacking. Our aim was to investigate the association of PM10 and PM2.5 with coronary stenosis in patients undergoing coronary angiography. METHODS: We performed a retrospective cohort study consisting of 7513 individuals who underwent coronary angiography in Fujian Province, China, from January 2019 to December 2021. We calculated a modified Gensini score (GS) to represent the degree of stenosis in coronary arteries by selective coronary angiography. We fitted linear regressions and logistic models to assess the association of PM10 and PM2.5 with coronary stenosis. We employed restricted cubic splines to describe the exposure-response curves. We performed mediation analyses to assess the potential mediators. RESULTS: Long-term ambient PM10 and PM2.5 (prior three years average) exposure was significantly associated with the GS, with a breakpoint concentration of 47.5 µg/m3 and 25.8 µg/m3 for PM10 and PM2.5, respectively, above which we found a linear positive exposure-response relationship of ambient PM with GS. Each 10 µg /m3 increase in PM10 exposure (ß: 4.81, 95 % CI: 0.44-9.19) and PM2.5 exposure [ß: 10.50, 95 % CI: 3.14-17.86] were positively related to the GS. The adjusted odds ratio (OR) for each 10 µg/m3 increment in PM10 exposure on severe coronary stenosis was 1.33 (95 % CI: 1.04-1.76). Correspondingly, the adjusted OR for PM2.5 was 1.87 (95 % CI: 1.24-2.99). The mediation analysis indicated that the effect of PM10 on coronary stenosis may be partially mediated through total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, serum creatinine and blood urea nitrogen, and the effect of PM2.5 may be mediated in part by hemoglobin A1c. CONCLUSION: Our study provides the first evidence that chronic ambient PM10 and PM2.5 exposure was associated with coronary stenosis assessed by GS in patients with suspected coronary artery disease and reveals its potential mediators.
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The effects of variations in the heat treatment process of milk on its quality and flavor are inevitable. This study investigated the effect of direct steam injection and instantaneous ultra-high-temperature (DSI-IUHT, 143 °C, 1-2 s) sterilization on the physicochemical properties, whey protein denaturation (WPD) rate, and volatile compounds (VCs) of milk. The experiment compared raw milk as a control with high-temperature short-time (HTST, 75 °C 15 s and 85 °C 15 s) pasteurization and indirect ultra-high-temperature (IND-UHT, 143 °C, 3-4 s) sterilization. The results showed no significant differences (p > 0.05) in physical stability between milk samples with different heat treatments. The DSI-IUHT and IND-UHT milks presented smaller particle sizes (p < 0.05) and more concentrated distributions than the HTST milk. The apparent viscosity of the DSI-IUHT milk was significantly higher than the other samples (p < 0.05) and is consistent with the microrheological results. The WPD of DSI-IUHT milk was 27.52% lower than that of IND-UHT milk. Solid-phase microextraction (SPME) and solvent-assisted flavor evaporation (SAFE) were combined with the WPD rates to analyze the VCs, which were positively correlated with ketones, acids, and esters and negatively associated with alcohols, heterocycles, sulfur, and aldehydes. The DSI-IUHT samples exhibited a higher similarity to raw and HTST milk than the IND-UHT samples. In summary, DSI-IUHT was more successful in preserving the milk's quality due to its milder sterilization conditions compared to IND-UHT. This study provides excellent reference data for the application of DSI-IUHT treatment in milk processing.
Subject(s)
Hot Temperature , Milk , Animals , Milk/chemistry , Steam , Temperature , Sterilization , Whey Proteins/analysisABSTRACT
Since coronavirus disease 2019 (COVID-19) was first reported on December 2019 in Wuhan, it fast spread to the rest of China, which has turned into a global public health problem later and generated global stock markets to violently shake. We inspect the causal relationships between economic development (ED) and environmental quality (EQ) during the period from January 2019 to May 2020 with the structural break for China and investigate the causal linkages between ED and EQ in subgroup of before and after the outbreak of COVID-19 with a semi-parametric model. The empirical tests show that smoothing structural transforms matter for the linkages of causality between ED and EQ, especially after COVID-19 infection. While the Toda-Yamamoto causality analysis supports unidirectional causality between ED and EQ before the outbreak of COVID-19, under structural shifts by the causality supplies of bidirectional casual linkages after the outbreak of COVID-19. Our results further clarified the proof that the economic activity gives rise to the environmental pollution and energy utilization mainly via the shock of COVID-19 in China. The emphasis on nonlinear causality between economic development and environmental quality may be an opportunity for China's economic recovery under considering the factor of COVID-19 infection.
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Lung cancer is a very aggressive cancer characterized with molecular heterogeneities in different subtypes, including lung adenocarcinoma and lung squamous cell carcinoma. However, few related molecular signatures have been established for the treatment of lung cancer subtypes. Polo-like kinase (PLK) family is a crucial regulator during cell division. Aberrant genetic and epigenetic alteration of PLK members plays a controversial role among different cancers. In this study, we performed an analysis of transcriptional and protein expression to identify overexpressed PLK1/4 and under-expressed PLK2/3 in lung cancer subtypes. We then analysed biological function of PLKs and related genes. Besides, we estimated a correlation of PLKs with patient's genders and TP53 mutation in lung cancer. Higher PLK1/4 expression was significantly associated with male patient and TP53 mutant status, separately. Moreover, we carried out a methylation profile analysis including methylation level, DNA methyltransferases correlation and survival analysis of global methylation. Global methylation survival analysis showed that prognostic value of PLK1/2/4 methylation remained the same significant trend between two lung cancer subtypes, whereas prognostic value of PLK3 methylation lacked consistency. Taken together, these results provided instructive insights into a comprehensive evaluation for advanced therapeutic strategy based on epigenetic evidences.
Subject(s)
Adenocarcinoma of Lung/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cell Cycle Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Tumor Suppressor Proteins/genetics , Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/pathology , DNA Methylation/genetics , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Prognosis , Tumor Suppressor Protein p53/genetics , Polo-Like Kinase 1ABSTRACT
OBJECTIVE: To establish a nicotine intravenous self-administration rat model, and to examine, with this model, the effects of two flavoring additives, menthol and cineole, on nicotine dependence. METHODS: Thirty male Sprague-Dawley (SD) rats were included in the study. After jugular venous catheterization was performed, fixed concentration of nicotine was administered in order to train the rats and establish the rat model of intravenous self-administration groups, receiving intraperitoneal injection of menthol, cineole, and dimethyl sulfoxide (DMSO), the vehicle that was used for the control group. The rats were tested with different fixed-ratio (FR) schedules, including FR1 schedule, in which the rat received one nicotine infusion for every active nose poke, FR2 schedule, in which the rat received one nicotine infusion for every two active nose pokes, and FR5 schedule, in which the rat received one nicotine infusion for every five active nose pokes. The number of active and inactive poke responses and the number of nicotine infusion were documented accordingly. RESULTS: After 10 days of training in nicotine self-administration, the 30 rats demonstrated significant increase in the number of active poke responses and the number of nicotine infusion, which were maintained at a stable and relatively high level. The number of active poke responses was significantly higher that of inactive poke responses ( P< 0.001). The rat model of intravenous nicotine self-administration was successfully established. In the testing phase, under the FR2 schedule, the menthol group showed a reduced number of active poke responses ( P=0.020). Under the FR5 schedule, the groups showed obvious interaction between time and the number of active poke responses ( P<0.011), with the menthol group showing reduced number of active poke responses on day three ( P=0.011) and the cineole group showing rising number of active poke responses on day three ( P=0.003). The DMSO control group did not show any significant change. CONCLUSIONS: Menthol and cineole are shown to have an effect on nicotine dependence. When there is relative difficulty involved in obtaining nicotine, menthol suppresses nicotine dependence, whereas cineole enhances nicotine dependence.
Subject(s)
Menthol , Tobacco Use Disorder , Animals , Conditioning, Operant , Eucalyptol , Male , Rats , Rats, Sprague-Dawley , Reinforcement, Psychology , NicotianaABSTRACT
BACKGROUND: To illuminate the mechanisms underlying the high-altitude tolerance of Tibetan pig spermatozoa, proteomes of spermatozoa from Tibetan pigs raised in high and low altitudes were compared using a tandem mass tag (TMT)-labeled quantitative proteomics approach. RESULTS: A total of 77 differentially expressed proteins (DEPs) were identified. Gene Ontology (GO) analysis revealed DEPs that were predominantly associated with the actin cytoskeleton, the tricarboxylic acid (TCA) cycle, and adenosine triphosphate (ATP) metabolism, and were from 12 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Three subnetworks were significantly enriched and 10 centric proteins were identified by protein-protein interaction (PPI) network analysis. Relative expression levels of the proteins (ATP5H, CYCS, MYH9 and FN1) were confirmed using Western blotting. CONCLUSIONS: Our study is the first to use a tandem mass tag (TMT) approach to analyze Tibetan pig spermatozoa, and provides a foundation to understand the mechanisms underlying the reproductive adaptations of Tibetan pigs to high-altitude environments.
Subject(s)
Altitude , Proteomics , Spermatozoa/metabolism , Swine , Adaptation, Physiological/genetics , Animals , Male , Molecular Sequence Annotation , Protein Interaction MappingABSTRACT
Following publication of the original article [1], the authors reported an error in one of the authors' names. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.
ABSTRACT
Cross-regional redeployment (or relocation) of government officials has a significant effect on the local economic development and environmental protection. Based on the panel data of 31 provinces (municipalities) in China from 2001 to 2016 and the environmental pollution index obtained by Entropy method, the dynamic panel regression model was applied to verify the relationship between the officials' cross-regional redeployment and environmental pollution. The results show that environmental pollution was positively correlated with officials' relocation and their tenure after the redeployment. As the officials' tenure increases to the critical value, the positive correlation between the official's tenure and environmental pollution would change. By measuring this threshold, we find that the average critical value for China was 5.14 years, which were the same as the average tenure of Chinese officials. Moreover, the result also illustrates the difference between central eastern China and western China, with the average threshold being 4.01 years and 5.89 years, respectively. In addition, the impact of officials' cross-regional redeployment on the environment would also be affected by the initial condition of the region. According to the result, the environmental governance within the central eastern regions was better than that in the western region. In the last part of this paper, we proposed measures and suggestions, such as changing the incentive policies of officials, perfecting the local policies and the cultivate and exchange system of cadres, as well as strengthen the power of social supervision, for the sake of facilitating the healthy and green development of the regional economy.
Subject(s)
Conservation of Natural Resources , Environmental Policy , China , Cities , Environmental PollutionABSTRACT
A simple and efficient femtosecond nonlinear polarization evolution (NPE) mode-locked laser is presented. Different from conventional NPE fiber lasers, the polarization beam splitter (PBS) is three-dimensionally manipulated to achieve polarization control and state selection in our NPE laser. The polarizer, half-wave plate, and quarter-wave plate from conventional NPE fiber lasers are replaced by this PBS. Thus, the configuration and the system gain of our proposed laser are simply and efficiently improved. As a result, transfer efficiency of 24.17% is experimentally demonstrated. In addition, measured self-started pulses with average power of 49 mW and center wavelength of 1584 nm are generated with single-pulse energy of 1.51 nJ.
ABSTRACT
Although more than 200 genes are known to be related to neural tube defects (NTDs), the exact molecular basis is still unclear. Evaluating the contribution of copy number variation (CNV) might be a priority because CNV involves changes in the copy number of large segments of DNA, leading to phenotypic traits and disease susceptibility. Recent studies have documented that the polarity protein partitioning defective 3 homolog (Pard3) plays an essential role in the process of neural tube closure. The aim of this study was to assess the role of PARD3 CNVs in the etiology of human NTDs. Relative quantitative PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to quantitative measurement of CNVs in 25 PARD3 exons in 202 NTD cases and 231 controls from a region of China with a high prevalence of NTDs. The results showed that microduplications ranging from 3 to 4 were evident in coding Exon 21 and Exon 25 in both case and control groups. A novel heterozygous microdeletion spanning 444 bp of Exon 14 was identified in two cases of anencephaly and is absent from all controls analyzed. Expression analyses indicated that this heterozygotic microdeletion showed no tissue specificity and led to defective expression of PARD3. Our study provides further evidence implicating PARD3 in the etiology of NTDs.
Subject(s)
Cell Cycle Proteins/genetics , DNA Copy Number Variations/genetics , Genetic Predisposition to Disease/genetics , Membrane Proteins/genetics , Neural Tube Defects/genetics , Adaptor Proteins, Signal Transducing , Adult , Cell Cycle Proteins/metabolism , Female , Humans , Male , Membrane Proteins/metabolism , Middle Aged , Real-Time Polymerase Chain Reaction/methodsABSTRACT
Large gradient high magnetic field (LG-HMF) is a powerful tool to study the effects of altered gravity on organisms. In our study, a platform for the long-term culture of aquatic organisms was designed based on a special superconducting magnet with an LG-HMF, which can provide three apparent gravity levels (µ g, 1 g, and 2 g), along with a control condition on the ground. Planarians, Dugesia japonica, were head-amputated and cultured for 5 days in a platform for head reconstruction. After planarian head regeneration, all samples were taken out from the superconducting magnet for a behavioral test under geomagnetic field and normal gravity conditions. To analyze differences among the four groups, four aspects of the planarians were considered, including head regeneration rate, phototaxis response, locomotor velocity, and righting behavior. Data showed that there was no significant difference in the planarian head regeneration rate under simulated altered gravity. According to statistical analysis of the behavioral test, all of the groups had normal functioning of the phototaxis response, while the planarians that underwent head reconstruction under the microgravity environment had significantly slower locomotor velocity and spent more time in righting behavior. Furthermore, histological staining and immunohistochemistry results helped us reveal that the locomotor system of planarians was affected by the simulated microgravity environment. We further demonstrated that the circular muscle of the planarians was weakened (hematoxylin and eosin staining), and the epithelial cilia of the planarians were reduced (anti-acetylated tubulin staining) under the simulated microgravity environment. Bioelectromagnetics. 2018;39:428-440. © 2018 Wiley Periodicals, Inc.
Subject(s)
Magnetic Fields , Planarians/physiology , Regeneration , Animals , Aquatic Organisms , Gravitation , Immunohistochemistry , Movement , Phototaxis , Planarians/anatomy & histology , Time FactorsABSTRACT
The Paired Assistance to Disaster Affected Areas (PADAA) programme is a mutual aid initiative with Chinese characteristics, which speeded up the process of restoring and reconstructing regions affected by the Wenchuan earthquake on 12 May 2008. The PADAA is an efficient instrument for catastrophe recovery, yet it remains a mysterious mechanism to many members of disaster management communities. This paper aims to lift the veil on it by assessing its origins and evolution. It draws on the multi-level moderated competition model to explain how the PADAA functions within the Chinese administrative system. The country's top-down political system allows the central authority to mandate provincial and local governments from more economically developed regions to assist devastated areas with post-disaster reconstruction. The practices of local accountability complement vertical control by giving leaders from donor regions strong incentives to accomplish assigned reconstruction tasks, resulting in intense competition between them.