In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis.

Single-nucleotide polymorphisms in the ELANE (Elastase, Neutrophil Expressed) gene are associated with severe congenital neutropenia, while the ELANE gene provides instructions for making a protein called neutrophil elastase. We identified disease susceptibility single-nucleotide polymorphisms (SNPs) in the ELANE gene using several computational tools. We used cutting-edge computational techniques to investigate the effects of ELANE mutations on the sequence and structure of the protein. Our study suggested that eight nsSNPs (rs28931611, rs57246956, rs137854448, rs193141883, rs201723157, rs201139487, rs137854451, and rs200384291) are the most deleterious in ELANE gene and disturb protein structure and function. The mutants F218L, R34W, G203S, R193W, and T175M have not yet been identified in patients suffering from SCN and cyclic hematopoiesis, while C71Y, P139R, C151Y, G214R, and G203C reported in our study are already associated with both of the disorders. These mutations are shown to destabilize structure and disrupt ELANE protein activation, splicing, and folding and might diminish trypsin-like serine protease efficiency. Prediction of posttranslation modifications highlighted the significance of deleterious nsSNPs because some of nsSNPs affect potential phosphorylation sites. Gene-gene interactions showed the relation of ELANE with other genes depicting its importance in numerous pathways and coexpressions. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking. This research sheds light on how ELANE failure upon mutation results in disease progression, including congenital neutropenia, and validation of these novel predicted nsSNPs is required through the wet lab.

Impacts of Colored Light-Emitting Diode Illumination on the Reproductive Performance and Bioactive Constituents and the Molecular Mechanism of Hypothalamus Gland in Zi-geese.

Goose is a seasonal breeding animal. Its reproduction is regulated by hypothalamus-pituitary-gonad axis and also affected by environmental factors such as light and location. Zi-goose is characterized with long egg-laying period and high egg-laying potential and belongs to the long-day type of seasonal breeding. In this study, the regulation mechanism of different lighting on reproductive performance of Zi-goose by using metabonomics analysis technology. In addition, 1,481 differential metabolites were screened out totally. 583 differential metabolites were identification in hypothalamus of Zi-goose. 196 differential metabolites were identification in pituitary of Zi-goose. 692 differential metabolites were identification in ovary of Zi-goose. Under red light condition for 12 h, expression of 433 differential metabolites were down-regulated and expression of 150 differential metabolites were up regulated in hypothalamus of Zi-goose, expression of 125 differential metabolites were down-regulated and expression of 71 differential metabolites were up-regulated in pituitary of Zi-goose, expression of 355 differential metabolites were down-regulated and expression of 337 differential metabolites were up-regulated in ovary of Zi-goose. 33 differential metabolites were closely associated with 1,264 transcripts and 400 homologous genes of related enzymes in hypothalamus of Zi-goose. 15 differential metabolites were closely associated with 163 transcripts and 47 homologous genes of related enzymes in pituitary of Zi-goose. 55 differential metabolites were closely associated with 1,255 transcripts and 360 homologous genes of related enzymes in ovary of Zi-goose. It was confirmed that four metabolic pathways were closely related to light regulation of reproductive performance of Zi-goose, namely GnRH signaling pathway, prolactin signaling pathway, thyroid hormone synthesis and ovarian steroidogenesis. Typical differential metabolites of arachidonic acid, glucose-6-phosphate, progesterone, glutathione, oxidized glutathione, testosterone, deoxyepiandrosterone and their related protein genes would play an important role in light regulation of reproductive performance of Zi-goose.

Predicting the Most Deleterious Missense Nonsynonymous Single-Nucleotide Polymorphisms of Hennekam Syndrome-Causing CCBE1 Gene, In Silico Analysis.

Hennekam lymphangiectasia-lymphedema syndrome has been linked to single-nucleotide polymorphisms in the CCBE1 (collagen and calcium-binding EGF domains 1) gene. Several bioinformatics methods were used to find the most dangerous nsSNPs that could affect CCBE1 structure and function. Using state-of-the-art in silico tools, this study examined the most pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) that disrupt the CCBE1 protein and extracellular matrix remodeling and migration. Our results indicate that seven nsSNPs, rs115982879, rs149792489, rs374941368, rs121908254, rs149531418, rs121908251, and rs372499913, are deleterious in the CCBE1 gene, four (G330E, C102S, C174R, and G107D) of which are the highly deleterious, two of them (G330E and G107D) have never been seen reported in the context of Hennekam syndrome. Twelve missense SNPs, rs199902030, rs267605221, rs37517418, rs80008675, rs116596858, rs116675104, rs121908252, rs147974432, rs147681552, rs192224843, rs139059968, and rs148498685, are found to revert into stop codons. Structural homology-based methods and sequence homology-based tools revealed that 8.8% of the nsSNPs are pathogenic. SIFT, PolyPhen2, M-CAP, CADD, FATHMM-MKL, DANN, PANTHER, Mutation Taster, LRT, and SNAP2 had a significant score for identifying deleterious nsSNPs. The importance of rs374941368 and rs200149541 in the prediction of post-translation changes was highlighted because it impacts a possible phosphorylation site. Gene-gene interactions revealed CCBE1's association with other genes, showing its role in a number of pathways and coexpressions. The top 16 deleterious nsSNPs found in this research should be investigated further in the future while researching diseases caused CCBE1 gene specifically HS. The FT web server predicted amino acid residues involved in the ligand-binding site of the CCBE1 protein, and two of the substitutions (R167W and T153N) were found to be involved. These highly deleterious nsSNPs can be used as marker pathogenic variants in the mutational diagnosis of the HS syndrome, and this research also offers potential insights that will aid in the development of precision medicines. CCBE1 proteins from Hennekam syndrome patients should be tested in animal models for this purpose.

Self-assembly and chemical processing of block copolymers: a roadmap towards a diverse array of block copolymer nanostructures.

Block copolymers can yield a diverse array of nanostructures. Their assembly structures are influenced by their inherent structures, and the wide variety of structures that can be prepared especially becomes apparent when one considers the number of routes available to prepare block copolymer assemblies. Some examples include self-assembly, directed assembly, coupling, as well as hierarchical assembly, which can yield assemblies having even higher structural order. These assembly routes can also be complemented by processing techniques such as selective crosslinking and etching, the former technique leading to permanent structures, the latter towards sculpted and the combination of the two towards permanent sculpted structures. The combination of these pathways provides extremely versatile routes towards an exciting variety of architectures. This review will attempt to highlight destinations reached by LIU Guojun and coworkers following these pathways.

Microarray analysis of differentially expressed microRNAs in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common disease characterized by chronic inflammation of the nasal mucosa, but we have not fully understood the mechanism responsible for the development of AR. MicroRNAs (miRNAs) are short endogenous noncoding RNAs regulating protein translation through a mechanism known as RNA interference. To understand the molecular mechanisms of miRNA involved in the pathogenesis of AR, expressed miRNAs in AR were investigated through genomewide microarray analysis. METHODS: Mammalian miRNA microarrays containing whole human mature and precursor miRNA sequences were used for analyzing eight samples of nasal mucosa of AR and eight samples of nonallergic patients. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of some different expressed miRNAs was used to confirm the array results. RESULTS: The miRNA microarray chip analysis identified 421 miRNAs differentially expressed in the nasal mucosa of AR, and a total of 9 miRNAs were identified in the AR group with twofold change compared with control samples (p < 0.05). These included up-regulated miRNAs, hsa-hsa-miR-7, and hsa-miRPlus-E1194, and down-regulated miRNAs, hsa-miR-498, hsa-miR-187, hsa-miR-874, hsa-miR-143, hsa-miR-886-3p, hsa-miR-224, and hsa-miR-767-5p. RT-PCR results also confirmed that part of differentially expressed miRNAs as hsa-miR-224, hsa-miR-187, and hsa-miR-143 were down-regulated in AR. CONCLUSION: The report indicated that many miRNA expressions were altered in AR and differentially expressed miRNAs appear to be involved in the development of AR. The study of miRNAs may lead to a better understanding about the roles of identified miRNAs in the pathogenesis of AR; this would be considered in future therapeutic strategies.