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Cesium lead iodide perovskite (CsPbI3) with excellent optical and electrical properties have attracted numerous academic attentions. Specifically, the black cubic phase CsPbI3 with a direct band gap of 1.74 eV has been most appropriate materials for various optoelectronic applications, especially for photovoltaic (PV), Light-Emitting Diodes (LED) and photodetector applications1. However, the preferred cubic phase of bulk CsPbI3 (α-CsPbI3) is usually only stable at high temperatures and it will undergo an immediate phase transformation to orthorhombic phase (δ-CsPbI3) after fabrication at room temperature. In this work, we have discovered a convenient CVD method to investigate the growth behavior of the cubic α-CsPbI3 film on the porous alumina substrate. The lead iodide and cesium iodide were used as the precursors for the deposition of CsPbI3. The porous alumina with high surface area and large pore volume was used as growth substrate. It was shown that the porous alumina promoted the growth of CsPbI3 film by absorbing the precursor and increasing the nucleation density. The prepared CsPbI3 film emitted strong and stable red light under ultraviolet light excitation at room temperature and ambient atmosphere. The lead iodide was absorbed on the surface of the porous alumina firstly then reacted with cesiumiodide to form the CsPbI3. The successful preparation of the CsPbI3 by the direct CVD method paves the way for its large scale growth and application in optoelectronic devices.
A stable reference gene is a key prerequisite for accurate assessment of gene expression. At present, the real-time reverse transcriptase quantitative polymerase chain reaction has been widely used in the analysis of gene expression in a variety of organisms. Neoseiulus barkeri Hughes (Acari: Phytoseiidae) is a major predator of mites on many important economically crops. Until now, however, there are no reports evaluating the stability of reference genes in this species. In view of this, we used GeNorm, NormFinder, BestKeeper, and RefFinder software tools to evaluate the expression stability of 11 candidate reference genes in developmental stages and under various abiotic stresses. According to our results, β-ACT and Hsp40 were the top two stable reference genes in developmental stages. The Hsp60 and Hsp90 were the most stable reference genes in various acaricides stress. For alterations in temperature, Hsp40 and α-TUB were the most suitable reference genes. About UV stress, EF1α and α-TUB were the best choice, and for the different prey stress, β-ACT and α-TUB were best suited. In normal conditions, the β-ACT and α-TUB were the two of the highest stable reference genes to respond to all kinds of stresses. The current study provided a valuable foundation for the further analysis of gene expression in N. barkeri.
Over the recent years, potential associations between Toxoplasma gondii (T. gondii) infection and cancer risk have attracted a lot of attention. Nevertheless, the association between T. gondii infection and oral cancer remains relatively unexplored. We performed a case–control study of 861 oral cancer patients and 861 control subjects from eastern China with the aim to detect antibodies to T. gondii by enzyme-linked immunosorbent assay (ELISA) in these patients. The results showed that oral cancer patients (21.72%, 187/861) had a significantly higher seroprevalence than control subjects (8.25%, 71/861) (P < 0.001). Among them, 144 (16.72%) oral cancer patients and 71 (8.25%) control subjects were positive for IgG antibodies to T. gondii, while 54 (6.27%) oral cancer patients and 9 (1.05%) controls were positive for IgM antibodies to T. gondii. In addition, multiple logistic analysis showed that T. gondii infection in oral cancer patients was associated with blood transfusion history, keeping cats at home, and oyster consumption. To our knowledge, this is the first study that provided a serological evidence of an association between T. gondii infection and oral cancer patients. However, further studies are necessary to elucidate the role of T. gondii in oral cancer patients.
Vetulicolians are a group of exclusively Cambrian animals characterized by an anterior section with lateral pouches and a posterior section that appears segmented. The precise phylogenetic affinity of vetulicolians is debated because there is a lack of consensus regarding the interpretation of their anatomical features. Their disparate morphology might even cause one to question whether this is a monophyletic taxon. In total, there are 15 species grouped into three families included in vetulicolians. Here we focus on new specimens of Yuyuanozoon magnificissimi Chen, Feng, and Zhu in Chen et al., 2003, a species that was first described from only a single specimen from the Chengjiang Biota (Cambrian Series 2, Stage 3, Eoredlichia-Wutingaspis trilobite Biozone), Yunnan Province, China. The species is notable in being exceptionally large (up to 20 cm long). Morphological observations on the new specimens clarify the nature of the wide circular opening at the presumed anterior end of the animal and the cowl-shaped lateral openings within this anterior section. Taphonomic observations identify wrinkles in the anterior section and twists in the posterior segmented section. In particular, the shape of the anterior opening of Yuyuanozoon magnificissimi suggests significant differences from other vetulicolians. Taxonomic reappraisal of Y. magnificissimi indicates that it belongs within the family Didazoonidae, as that is presently defined.
As one of the major components of the Himalayan–Tibetan Orogeny, the Lhasa terrane plays a key role in understanding the origin and evolution of this giant orogenic belt and the opening and closure of the Tethys oceans. The eclogite-bearing Sumdo Complex in the central Lhasa terrane was recognized as the main suture of the Palaeo-Tethys Ocean between the north and south Lhasa sub-terranes. Despite the eclogite having been studied for a long time, no attempts have been applied to studying the country rocks, causing confusion in understanding the relationship between the eclogite and the adjacent schist. Petrological investigations and phase equilibrium calculations on the garnet-bearing mica schist of the Sumdo Complex have been performed to constrain its metamorphic evolution. The P–T conditions for three metamorphic stages are constrained as P1 (480–500°C, 2.6–2.7 GPa), P2 (580–600°C, 1.3–1.4 GPa) and R (530°C, 0.9 GPa), which represent the prograde, temperature peak and retrograde stages. Two possible P–T paths were constructed, which experienced isothermal decompression (PT1) or heating with a decompression process (PT2), corresponding to the growth and extinction of garnet porphyroblasts in the matrix. The LA-MC-ICP-MS U–Pb dating method yielded a metamorphic age of 229.7±3.5 Ma, which was interpreted as the age of amphibolite-facies metamorphism at c. 600°C, 1.2–1.4 GPa during the closure of the Palaeo-Tethys Ocean, resulting in the aggregation of the north and south Lhasa sub-terranes. The close relationship between the eclogite and garnet-bearing mica schist, and their similar P–T–t paths indicate an in situ tectonic evolution rather than tectonic juxtaposition during exhumation.
The prevalence of overweight and obesity is growing rapidly in many countries. Socioeconomic inequalities might be important for this increase. The aim of this study was to determine associations of body mass index (BMI), overweight and obesity with educational level and marital status in Chinese twins. Participants were adult twins recruited through the Chinese National Twin Registry (CNTR), aged 18 to 79 years, and the sample comprised 10,448 same-sex twin pairs. Current height, weight, educational attainment, and marital status were self-reported. Regression analyses and structural equation models were conducted to evaluate BMI, overweight, and obesity associated with educational level and marital status in both sexes. At an individual level, both educational level and marital status were associated with higher BMI and higher risk of being overweight and obesity in men, while in women the effects of educational level on BMI were in the opposite direction. In within-Monozygotic (MZ) twin-pair analyses, the effects of educational level on BMI disappeared in females. Bivariate structural equation models showed that genetic factors and shared environmental confounded the relationship between education and BMI in females, whereas marital status was associated with BMI on account of significant positive unique environmental correlation apart in both sexes. The present data suggested that marital status and BMI were associated, independent of familiar factors, for both sexes of this study population, while common genetic and shared environmental factors contributed to education-associated disparities in BMI in females.
Neoseiulus barkeri (HUGHES) is the natural enemy of spider mites, whiteflies and thrips. Screening for chemically-resistant predatory mites is a practical way to balance the contradiction between the pesticide using and biological control. In this study, the number of eggs laid by fenpropathrin-susceptible and resistant strains of N. barkeri was compared. Additionally, we cloned three N. barkeri vitellogenin (Vg) genes and used quantitative real-time polymerase chain reaction to quantify Vg expression in susceptible and resistant strains. The total number of eggs significantly increased in the fenpropathrin-resistant strain. The full-length cDNA cloning of three N. barkeri Vg genes (NbVg1, NbVg2 and NbVg3) revealed that the open reading frames of NbVg1, NbVg2 and NbVg3 were 5571, 5532 and 4728 bp, encoding 1856, 1843 and 1575 amino acids, respectively. The three N. barkeri Vg possessed the Vitellogenin-N domain (or lipoprotein N-terminal domain (LPD_N)), von Willebrand factor type D domain (VWD) and the domain with unknown function 1943 (DUF1943). The NbVg1 and NbVg2 expression levels were significantly higher in the resistant strain than in the susceptible strain, while the NbVg3 expression level was lower in the resistant strain. Thus, we speculate that the increased number of eggs laid by the fenpropathrin-resistant strain of N. barkeri may be a consequence of changes in Vg gene expression.
The role of the protozoan parasite Toxoplasma gondii in the pathogenesis of liver disease has recently gained much interest. The aim of this study was to determine the prevalence and risk factors associated with T. gondii infection in patients with liver disease from three cities in Shandong and Henan provinces, China. A case–control study was conducted from December 2014 to November 2015 and included 1142 patients with liver disease and 1142 healthy controls. Serum samples were collected from all individuals and were examined with enzyme-linked immunosorbent assay for the presence of anti-T. gondii IgG and IgM antibodies. Information on the demographics, clinical, and lifestyle characteristics of the participants was collected from the medical records and by the use of a questionnaire. The prevalence of anti-T. gondii IgG was 19·7% in patients with liver disease compared with 12·17% in the controls. Only 13 patients had anti-T. gondii IgM antibodies compared with 12 control individuals (1·14% vs. 1·05%, respectively). The highest seroprevalence was detected in patients with liver cancer (22·13%), followed by hepatitis patients (20·86%), liver cirrhosis patients (20·42%), and steatosis patients (20%). Multivariate logistic regression analysis indicated that consumption of raw meat (odds ratio (OR) = 1·32; 95% confidence interval (CI) 1·01–1·71; P = 0·03) and source of drinking water from wells (OR = 1·56; 95% CI 1·08–2·27; P = 0·01) were independent risk factors for T. gondii infection in liver disease patients. These findings indicate that T. gondii infection is more likely to be present in patients with liver disease. Therefore, efforts should be directed toward health education of populations at high risk of T. gondii infection and measures should be taken to protect vulnerable patients with liver disease.
Obesity is associated with blood pressure (BP), but the associations between different obesity indicators and BP have not reached agreement. Besides, both obesity and BP are influenced by genetic and environmental factors. Whether they share the same genetic or environmental etiology has not been fully understood. We therefore analyzed the relationship between different obesity indicators and BP components as well as the genetic and environmental contributions to these relationships in a Chinese adult twin sample. Twins aged 18–79 years (n = 941) were included in this study. Body mass index (BMI) was used as the index of general obesity, whereas waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) were used as the indicators of central obesity. BP components included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Linear regression models and bivariate structural equation models were used to examine the relation of various obesity indicators with BP components, and genetic or environmental influences on these associations, respectively. A strong association of BP components with BMI—and a somewhat weaker association with WC, WHtR, and WHR—was found in both sexes, independent of familial factors. Of these phenotypic correlations between obesity indicators and BP components, 60–76% were attributed to genetic factors, whereas 24–40% were attributed to unique environmental factors. General obesity was most strongly associated with high BP in Chinese adult twins. There were common genetic backgrounds for obesity and BP, and unique environmental factors also played a role.
Supercapacitor has received intense interest due to its high-charge/discharge rate and high-power density. C/Fe2O3 layer with different C/Fe ratios were synthesized by a solution-based approach for supercapacitor application. The influence of synthesis conditions on their electrochemical performances was investigated. Cobalt was added into C/Fe2O3 and significant improved its performance. The optimal C/Fe2O3 sample gives a high specific capacitance of 85.3 F/g and the addition of Co3O4 further increase the capacitance of obtained C/Fe2O3/Co3O4 to 144.4 F/g at 5 A/g. This work demonstrates an efficient supercapacitor application of low-cost metal oxides and facile solution-based synthesis approach.
We investigate theoretically the field-free orientation of CO molecules induced by a single-cycle THz laser pulse train. It is shown that the molecular orientation can be obviously enhanced by applying the pulse train. The laser intensity and pulse number have some effects on the molecular orientation. The high degree of field-free molecular orientation |⟨cosθ⟩|max=0.9246 is obtained at temperature T=0 K. The variations of the maximum orientation degree with the experimentally available pulse number and peak intensity are given. Temperature T has a considerable influence on the field-free molecular orientation. The maximal field-free molecular orientation at T=0, 10, 20 and 30 K for N=14 and E0=1.8 MV/cm are |⟨cosθ⟩|max=0.9188, 0.7338, 0.6055 and 0.5154 in order, and the corresponding effective duration times of molecular orientation are Δt=0.759, 0.432, 0.297 and 0.117 ps.
With an influx of successful genome-wide association studies to identify genetic variations associated with complex diseases, an unprecedented wealth of knowledge has been accumulated for SNP–phenotype associations (McCarthy et al., 2008; Witte 2010; Manolio 2013). However, many SNP–disease associations do not lend themselves to molecular interpretations, because many of the identified loci are located outside of the coding regions. Even when a gene can be inferred to be causal, there is often a significant gap towards the understanding of the underlying molecular mechanisms (Schadt et al., 2005; McCarthy et al., 2008). Genome-wide eQTL mapping has been one effective approach to bridge this gap (Mackay et al., 2009). In eQTL studies, gene expression levels measured by high-throughput technologies, such as microarrays and RNA-Seq, are treated as quantitative traits. Marker genotypes are also collected from the same set of individuals, and statistical analyses are performed to detect associations between markers and expression traits. By simultaneously capturing many regulatory interactions, eQTLs offer valuable insights on the genetic architecture of expression regulation (Rockman and Kruglyak 2006). The ultimate goal of eQTL studies is to elucidate how genetic variations affect phenotypes by using gene expression levels as intermediate molecular phenotypes (Nica and Dermitzakis 2008). In this chapter, we provide an overview of the eQTL analysis workflow (Figure 14.1), introduce publicly available tools for analysis, and further discuss challenges and issues.
Genome-wide eQTL mapping considers high-density SNP genotype data and gene expression data from the same individuals in a segregating population. Both require appropriate pre-processing as described below for subsequent analysis.
Three quality control (QC) criteria are often used in the pre-processing of the genotype data. (1) Missing rate: individuals with a large proportion of missing SNP genotypes (e.g., 10%) should be excluded because the DNA samples of those individuals may be of poor quality. SNPs with a large missing rate (e.g., 5%) should also be filtered out. (2) Hardy–Weinberg Equilibrium (HWE): statistically significant deviations from HWE often result from genotyping errors. Therefore, SNPs that fail an exact HWE test (e.g., a P-value less than 0.001) should be filtered out. The criterion does not apply to haploid organisms, such as yeast. (3) Minor allele frequency (MAF): SNPs with low MAF (e.g., 0.05) are sometimes filtered out because of the insufficient statistical power for studies with a relatively small sample size and potentially higher genotype calling error.
After the completion of the Human Genome Project (Lander et al., 2001; Venter et al., 2001) and initiation of the International HapMap Project (Sachidanandam et al., 2001), genome-wide association studies (GWAS) were designed to survey the role of common genetic variations in complex human diseases. It was expected that GWAS would have the advantage of not relying on prior knowledge of biological pathways compared with “candidate gene” studies (Tabor et al., 2002; Wang et al., 2005), because it assays a dense set of single-nucleotide polymorphisms (SNPs) across the whole genome. This advantage allows GWAS to overcome the bias of “candidate gene” studies due to incomplete prior knowledge. It was also expected that GWAS would have higher power and finer resolution to identify genetic variants of modest effects compared to family-based linkage studies (Risch & Merikangas, 1996).
The success of identifying genes for age-related macular degeneration (AMD) under the GWAS paradigm (Klein et al., 2005) convinced the genetics community on the efficiency and feasibility of the GWAS approach to identify unknown disease-associated variants. This study used a commercial genotyping array and assayed about 100,000 SNPs throughout the human genome. It identified the association of complement factor H (CFH) with AMD. The success of finding a common risk allele with an odds ratio (OR) of 4.6 in a small sample set of 96 cases and 50 controls has generated considerable excitement in the genetics community. The p-value of the strongest SNP association surpassed the genome-wide significance threshold after the Bonferroni correction. More importantly, this finding was replicated in the following-up studies (Donoso et al., 2010). Undoubtedly, this encouraging finding raised the confidence among researchers to detect genetic variants that underlie various complex diseases through GWAS. In 2007, the Wellcome Trust Case Control Consortium (WTCCC) published the results of seven GWAS, including Bipolar Disorder, Coronary Artery Disease, Crohn's Disease, Hypertension, Rheumatoid Arthritis, Type 1 Diabetes, and Type 2 Diabetes (The Wellcome Trust Case Control Consortium, 2007). The WTCCC study is considered the starting point of large-scale GWAS (Visscher et al., 2012). Since then, an increasing number of GWAS have been conducted and over 10,000 loci have been reported to be significantly associated with at least one complex trait (see the web resource of GWAS catalog (Hindorff et al., 2009), http://www.genome.gov/gwastudies/).
Identification of individuals within pairs of monozygotic (MZ) twins remains unresolved using common forensic DNA typing technology. For some criminal cases involving MZ twins as suspects, the twins had to be released due to inability to identify which of the pair was the perpetrator. In this study, we performed a genome-wide scan on whole blood-derived DNA from four pairs of healthy phenotypically concordant MZ twins using the methylated DNA immunoprecipitation sequencing technology to identify candidate DNA methylation markers with capacity to distinguish MZ twins within a pair. We identified 38 differential methylation regions showing within-pair methylation differences in all four MZ pairs. These are all located in CpG islands, 17 of which are promoter-associated, 17 are intergenic islands, and four are intragenic islands. Genes associated with these markers are related with cell proliferation, differentiation, and growth and development, including zinc finger proteins, PRRX2, RBBP9, or are involved in G-protein signaling, such as the regulator of G-protein signaling 16. Further validation studies on additional MZ twins are now required to evaluate the broader utility of these 38 markers for forensic use.
Vertical Integrative Analysis (Methods Specialized to Particular Data Types)
Cong Li, Yale University, New Haven, CT,
Can Yang, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China,
Greg Hather, Takeda Pharmaceuticals International Co., Cambridge, MA,
Ray Liu, Takeda Pharmaceuticals International Co., Cambridge, MA,
Hongyu Zhao, Yale University, New Haven, CT
Traditional drug discovery practices usually adopt the “one drug – one target” approach, which ignore the fact the disease occurrence is usually the result of an extremely complex combination of molecular events. Pathway-based approaches address this limitation by considering biological pathways as potential drug targets. A first step of pathwaybased drug discovery is to identify associations between drug candidates and biological pathways. This has been made possible by the availability of high-dimensional transcriptional and drug sensitivity profile data. In this chapter, we describe two statistical methods, “iFad” and “iPad”, which perform drug-pathway association analysis by integrating these two types high-dimensional data. We also demonstrate their utilities by applying them to the NCI-60 data set.
Drug discovery is the process of identifying new candidate medications for diseases of interest. The common practice adopted by the pharmaceutical industry is to design maximally selective drug molecules to act on individual drug targets , which is usually referred to as the “one drug – one target” approach. This paradigm has indeed enjoyed some successes . Yet, the last 15 years have witnessed a significant increase in the attrition rate of new candidate drugs due to their low efficacy and serious side effects [17, 29]. One fundamental reason for the decline in the productivity of the pharmaceutical industry may lie in the core philosophy of the “one drug – one target” approach . Specifically, this philosophy ignores the fact that disease occurrence is usually the result of an extremely complex combination of molecular events  among certain sets of functionally related genes, usually referred to as “pathways”. Targeting an individual drug target may not provide sufficient interference to the whole disease-related pathway and therefore usually results in unsatisfactory efficacy. Moreover, it fails to consider the mechanism of a candidate drug at a systems level, making it extremely difficult to evaluate drug safety and toxicity in the early developmental stages . Due to these limitations of the “one drug – one target” approach, a new concept of drug discovery – polypharmacology  – is emerging as a promising alternative for drug developments. Instead of targeting individual drug targets, polypharmacology seeks to design or find candidate drugs that interfere multiple molecular targets. For example, pathway-based drug discovery, which pursues candidate drugs that interfere the activity of a whole biological pathway, has become increasingly appealing.
This study examined the genetic and environmental effects on variances in weight, height, and body mass index (BMI) under 18 years in a population-based sample from China. We selected 6,644 monozygotic and 5,969 dizygotic twin pairs from the Chinese National Twin Registry (CNTR) aged under 18 years (n = 12,613). Classic twin analyses with sex limitation were used to estimate the genetic and environmental components of weight, height, and BMI in six age groups. Sex-limitation of genetic and shared environmental effects was observed, especially when puberty begins. Heritability for weight, height, and BMI was low at 0–2 years old (less than 20% for both sexes) but increased over time, accounting for half or more of the variance in the 15–17 year age group for boys. For girls, heritabilities for weight, height and BMI was maintained at approximately 30% after puberty. Common environmental effects on all body measures were high for girls (59–87%) and presented a small peak during puberty. Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in the pre-adolescent period and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. Further studies about puberty-related genes and social environment are needed to clarify the mechanism of sex differences.
The current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk.
The PubMed and EMBASE databases were searched. A dose–response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values.
The meta-analysis included seventeen studies.
A total of 10 601 patients.
The non-linear dose–response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0·001). Every 4·5 μg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose–response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187).
Our meta-analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only.
Alpha-lipoic acid (ALA) is known to be a natural antioxidant. The aim of the present study was to evaluate the cryoprotective effect of ALA on the motility of boar spermatozoa and its antioxidant effect on boar spermatozoa during freezing–thawing. Different concentrations (2.0, 4.0, 6.0, 8.0 or 10.0 mg/ml) of ALA were added to the extender used to freeze boar semen, and the effects on the quality and endogenous antioxidant enzyme activities of frozen–thawed spermatozoa were assessed. The results indicated that the addition of ALA to the extender resulted in a higher percentage of motile spermatozoa post-thaw (P < 0.05). The activities of superoxide dismutase, lactate dehydrogenase, glutamic-oxaloacetic transaminase and catalase improved after adding ALA to the extender (P < 0.05). Artificial insemination results showed that pregnancy rate and litter size were significantly higher at 6.0 mg/ml in the ALA group than in the control group (P < 0.05). In conclusion, ALA conferred a cryoprotective capacity to the extender used for boar semen during the process of freezing–thawing, and the optimal concentration of ALA for the frozen extender was 6.0 mg/ml.