A combination of genome-wide association study and selection signature analysis dissects the genetic architecture underlying bone traits in chickens

The bones of chicken play an important role in supporting and protecting the body. The growth and development of bones have a substantial influence on the health and production performance in chickens. However, genetic architecture underlying chicken bone traits is not well understood. The objectives of this study are to dissect the genetic basis of bone traits in chickens and to identify valuable genes and genetic markers for chicken breeding. We performed a combination of genome-wide association study (GWAS) and selection signature analysis (fixation index values and nucleotide diversity ratios) in an F₂ crossbred experimental population with different genetic backgrounds (broiler × layer) to identify candidate genes and significant variants related to femur, shank, keel length, chest width, metatarsal claw weight, metatarsal length, and metatarsal circumference. A total of 545 individuals were genotyped based on the whole genome re-sequencing method (26 F₀ individuals were re-sequenced at 10 × coverage; 519 F₂ individuals were re-sequenced at 3 × coverage). A total of 2 028 112 single-nucleotide polymorphisms (SNPs) remained to carry out analysis after quality control and imputation. The integration of GWAS and selection signature analysis indicated that all significant SNPs responsible for bone traits were mainly localized on chicken chromosomes 1, 4, and 27. Finally, we identified 21 positional candidate genes that might regulate chicken bone growth and development, including LRCH1, RB1, FNDC3A, MLNR, CAB39L, FOXO1, LHFP, TRPC4, POSTN, SMAD9, RBPJ, PPARGC1A, SLIT2, NCAPG, NKX3-2, CPZ, SPOP, NGFR, SOST, ZNF652, and HOXB3. Additionally, an array of uncharacterized genes was identified. The findings provide an in-depth understanding of the genetic architecture of chicken bone traits and offer a molecular basis for applying genomics in practical chicken breeding.     

Energy and Carbon Management Systems

This article examines an important class of information system that serves as the foundation for corporate energy and greenhouse gas (GHG) accounting: energy and carbon management systems (ECMS). Investors, regulators, customers, and employees increasingly demand that organizations provide information about their organizational energy use and GHG emissions. However, there is little transparency about how organizations use ECMS to meet such demands. To shed light on ECMS implementation and application, we collected extensive qualitative interview data from two service‐sector organizations: one that uses a spreadsheet‐based ECMS and another that implemented an ECMS provided by a third‐party vendor. Our analysis of collected data revealed numerous challenges in the areas of business processes, managerial capabilities, data capture and integration, and data quality. Though our study is built on only two organizations and requires confirmation in large‐sample surveys, we provide several recommendations for organizations regarding ECMS. We also provide suggestions for future studies to build on our tentative results.     

Synthesis,docking study and relaxant effect of 2-alkyl and 2-naphthylchromones on rat aorta and guinea-pig trachea through phosphodiesterase inhibition

Chromone (4), which form the base structure of various flavonoids isolated as natural products, is capable of relaxing smooth muscle. This is relevant to the treatment of high blood pressure, asthma and chronic obstructive pulmonary disease. The former disorder involves the contraction of vascular smooth muscle (VSM), and the latter two bronchoconstriction of airway smooth muscle (ASM). One of the principal mechanisms by which flavonoids relax muscle tissue is the inhibition of phosphodiesterases (PDEs), present in both VSM and ASM. Therefore, a study was designed to analyze the structure–activity relationship of chromone derivatives in vaso- and bronchorelaxation through the inhibition of PDE. Docking studies showed that these chromones bind at the catalytic site of PDEs. Consequently, we synthesized analogs of chromones substituted at position C-2 with alkyl and naphthyl groups. These compounds were synthesized from 2-hydroxyacetophenone and acyl chlorides in the presence of DBU and pyridine, modifying the methodology reported for the synthesis of 3-acylchromones by changing the reaction temperature from 80 to 30 °C and using methylene chloride as solvent, yielding the corresponding phenolic esters 10a–10h. These compounds were cyclized with an equivalent of DBU, pyridine as solvent, and heated at reflux temperature, yielding the chromones 11a–11h. Evaluation of the vasorelaxant effect of 4, 11a–11h on rat aorta demonstrated that potency decreases with branched alkyl groups. Whereas the EC₅₀ of compound 11d (substituted by an n-hexyl group) was 8.64 ± 0.39 μM, that of 11f (substituted by an isobutyl group) was 14.58 ± 0.64 μM. Contrarily, the effectiveness of the compound is directly proportional to the length of the alkyl chain, as evidenced by the increase in maximal effect of compound 11c versus 11d (66% versus 100%) and 11e versus 11f (60% versus 96%). With an aromatic group like naphthyl as the C-2 substituent, the effectiveness was only 43%. All compounds tested on guinea pig trachea showed less than 55% effectiveness. Compounds 4, 11a–11h were evaluated as PDE inhibitors in vitro, with 11d showing the greatest effect (73%), corroborating the importance of a long alkyl chain, which inhibits the decomposition of cGMP. Docking studies showed that the compound 11d was selective for the inhibition of PDE-5.     

Novel thiobarbiturates as potent urease inhibitors with potential antibacterial activity: Design,synthesis, radiolabeling and biodistribution study

Urease enzyme is a virulence factor that helps in colonization and maintenance of highly pathogenic bacteria in human. Hence, the inhibition of urease enzymes is well-established to be a promising approach for preventing deleterious effects of ureolytic bacterial infections. In this work, novel thiobarbiturate derivatives were synthesized and evaluated for their urease inhibitory activity. All tested compounds effectively inhibited the activity of urease enzyme. Compounds 1, 2a, 2b, 4 and 9 displayed remarkable anti-urease activity (IC₅₀ = 8.21–16.95 μM) superior to that of thiourea reference standard (IC₅₀ = 20.04 μM). Moreover, compounds 3a, 3g, 5 and 8 were equipotent to thiourea. Among the tested compounds, morpholine derivative 4 (IC₅₀ = 8.21 µM) was the most potent one, showing 2.5 folds the activity of thiourea. In addition, the antibacterial activity of the synthesized compounds was estimated against both standard strains and clinical isolates of urease producing bacteria. Compound 4 explored the highest potency exceeding that of cephalexin reference drug. Moreover, biodistribution study using radiolabeling approach revealed a remarked uptake of ^99mTc-compound 4 into infection induced in mice. Furthermore, a molecular docking analysis revealed proper orientation of title compounds into the urease active site rationalizing their potent anti-urease activity.     

Using the tools of genetic epidemiology to understand sex differences in neuropsychiatric disorders

Many neuropsychiatric disorders exhibit differences in prevalence, age of onset, symptoms or course of illness between males and females. For the most part, the origins of these differences are not well understood. In this article, we provide an overview of sex differences in psychiatric disorders including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), anxiety, depression, alcohol and substance abuse, schizophrenia, eating disorders and risk of suicide. We discuss both genetic and nongenetic mechanisms that have been hypothesized to underlie these differences, including ascertainment bias, environmental stressors, X‐ or Y‐linked risk loci, and differential liability thresholds in males and females. We then review the use of twin, family and genome‐wide association approaches to study potential genetic mechanisms of sex differences and the extent to which these designs have been employed in studies of psychiatric disorders. We describe the utility of genetic epidemiologic study designs, including classical twin and family studies, large‐scale studies of population registries, derived recurrence risks, and molecular genetic analyses of genome‐wide variation that may enhance our understanding sex differences in neuropsychiatric disorders.     

Association between METTL3 gene polymorphisms and neuroblastoma susceptibility: A nine‐centre case‐control study

Neuroblastoma ranks as the most commonly seen and deadly solid tumour in infancy. The aberrant activity of m⁶A‐RNA methyltransferase METTL3 is involved in human cancers. Therefore, functional genetic variants in the METTL3 gene may contribute to neuroblastoma risk. In the current nine‐centre case‐control study, we aimed to analyse the association between the METTL3 gene single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We genotyped four METTL3 gene SNPs (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G, and rs1263801 G>C) in 968 neuroblastoma patients and 1814 controls in China. We found significant associations between these SNPs and neuroblastoma risk in neither single‐locus nor combined analyses. Interestingly, in the stratified analysis, we observed a significant risk association with rs1061027 AA in subgroups of children ≤ 18 months of age (adjusted OR = 1.87, 95% CI = 1.03‐3.41, P = .040) and females (adjusted OR = 1.86, 95% CI = 1.07‐3.24, P = .028). Overall, we identified a significant association between METTL3 gene rs1061027 C>A polymorphism and neuroblastoma risk in children ≤18 months of age and females. Our findings provide novel insights into the genetic determinants of neuroblastoma.     

Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma(28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total Ig E level(P \ 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However,removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever(DHF) rather than dengue fever(DF). In comparison with DF, DHF was associated with Ig E positivity. Furthermore, specific-Ig E level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.     

Genomic atlases of introgression and differentiation reveal breeding footprints in Chinese cultivated rice

The long history of cultivation and breeding has left a variety of footprints in the genomes of Asian cultivated rice (Oryza sativa L.). In this study, we focus on two types of genomic footprints, introgression and differentiation, in a population of more than 1200 Chinese rice accessions. We found that a Xian/indica and a temperate Geng/japonica accession respectively contained an average of 19.3-Mb and 6.8-Mb alien introgressed chromosomal segments, of which many contained functional sequence variants, quantitative trait loci, or genes controlling flowering, grain, and resistance traits. Notably, we found most introgressions, including the known heterotic loci Hd3a and TAC1, were distributed differentially between the female and male parents of three-line indica hybrid rice, indicating their potential contribution to heterosis. We also found many differentiated regions between subgroups within a subpopulation contained agronomically important loci, such as DTH7, Hd1 for heading date, and qCT7 for cold tolerance, providing new candidates for studying local adaptation or heterosis. Tracing these footprints allows us to better understand the genetic exchange or differentiation underlying agronomic traits in modern Chinese rice cultivars. These findings also provide potential targets for rice genetic research and breeding.     

Molecular identification of selected bees from the Indian Himalaya: A preliminary effort

DNA barcoding has largely been tested for a wide range of taxa and evidenced as a reliable and rapid molecular tool for species-level identification. The present study lends to generate 156 DNA barcodes, of which 141 belonged to 30 morphologically identified bees from the Indian Himalayan Regions (IHRs). The generated barcode data along with 84 sequences of global database distinctly discriminated all the studied species with sufficient genetic distances and cohesive monophyletic clustering in Bayesian analysis (BA) phylogeny. The species delimitation methods, Automatic Barcode Gap Discovery (ABGD), Bayesian Poisson-Tree-Processes (bPTP), and General Mixed Yule-coalescent (GMYC) yielded 68, 70, and 71 molecular operational taxonomic units (MOTUs) respectively. The present DNA barcode-based examination detected the possible cryptic diversity in two Apis species (A. cerana and A. dorsata), Bombus hypnorum, Lepidotrigona arcifera, and Ceratina sutepensis. The present study also evidenced the species complexes within Bombus albopleuralis and Bombus trifasciatus in the IHRs. The species delimitation methods also detected an additional seven putative species from the IHRs, which were identified up to the genus level. In conclusion, this preliminary effort helps to develop a reliable barcode database of bees from the Indian IHRs to facilitate the future systematics study. These molecular data can be utilized to evaluate the population structures and assist to formulate the effective plans for bee conservation.     

Body site‐specific genetic effects influence naevus count distribution in women

Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an increased number of naevi on the lower limbs compared to men (p = 8.5 × 10^?5), showing that a high naevus count on this site persists from childhood throughout life. Then, using data from 3,232 twins, we observed, in women, the lowest naevus count heritability on the trunk (26%), and the highest on the lower limbs (69%). Finally, we showed that, in 2,864 women, six genomic loci previously associated with both naevus count and melanoma risk (IRF4, DOCK8, MTAP, 9q31.2, KITLG and PLA2G6) have an effect on naevus count that is body site‐specific, but whose effect sizes are predominantly stronger on the lower limbs. Sex‐specific genetic influence on naevus count at different sites may explain differences in site‐specific melanoma incidence as well as prognosis between sexes.