A single nucleotide variant in HNF-1β is associated with maturity-onset diabetes of the young in a large Chinese family

Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported. Methods: To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations. DNA was extracted from the periphery blood samples of (i) 9 affected members, (ii) 17 unaffected members, and (iii) 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity of DNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants. Results: Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P<0.001) between the affected vs. unaffected members and the affected vs. healthy controls, but not between the unaffected members vs. healthy controls. MODY5-related gene, hepatocyte nuclear factor-1β (HNF-1β) on 17q12 near D17S798 became the candidate gene. A single nucleotide variant (SNV) of C77T in the non-coding area of exon 1 of HNF-1β was found to be related to MODY5. Conclusion: This novel SNV of HNF-1β contributes to the diabetes development in the family through regulating gene expression most likely. The findings help presymptomatic diagnosis, and imply that mutations in the non-coding areas, as well as in the exons, play roles in the etiology of MODY

Full-length transcriptome analysis provides insights into larval shell formation in Mulinia lateralis

Mollusca is the second largest animal phylum and represents one of the most evolutionarily successful animal groups. Mulinia lateralis, a small bivalve, is a promising model organism to facilitate studies of mollusc development. However, because of the lack of published genomic and transcriptomic resources, integrated research on the formation of larval shells in this species, which is a representative developmental process of molluscs and of great importance for larva survival, is hindered. In this study, the blastula, gastrula, trochophore larva, and D-shaped larva of M. lateralis were utilized for generating a comprehensive full-length transcriptome through Pacific BioSciences (PacBio) isoform sequencing (Iso-seq) and Illumina RNA-Seq. A total of 238,919 full-length transcripts with an average length of 3,267 bp and 121,424 annotated genes were obtained. Illumina RNA-Seq data analysis showed that 4,512, 10,637, and 17,829 differentially expressed genes (DEGs) were obtained between the two adjacent developmental stages. Functional annotation and enrichment analysis revealed the specific function of genes in shell biomineralization during different developmental stages. Twelve genes that may be involved in the formation of the larval shell of M. lateralis were identified, including insoluble shell matrix protein-encoding gene 1 (ISMP1), ISMP2, ISMP5, chitin synthase, tyrosinase, chitin-binding protein, collagen and pu14 involved in shell matrix deposition, and carbonic anhydrase, solute carrier family 4 member 8 (slc4a8), EF-hand, and a calmodulin coding gene C-2442 participated in ion transportation. In addition, calcium ion binding function, calcium signaling pathway, and endocrine and other factor-regulated calcium reabsorption pathways were significantly enriched. Weighted gene correlation network analysis (WGCNA) identified two modules related to biomineralization and larval shell formation, and slc4a8 and ring finger protein 41 (rnf41) were key hub genes that may be involved in this process. Moreover, it could be implied that the process of ion transport occurs earlier than the deposition of the shell matrix. This work provided a clear view of the transcriptome for M. lateralis and will be valuable in elucidating the mechanisms of larval shell formation as well as other developmental processes in molluscs

A single nucleotide variant in HNF-1β is associated with maturity-onset diabetes of the young in a large Chinese family

Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported. Methods: To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations. DNA was extracted from the periphery blood samples of (i) 9 affected members, (ii) 17 unaffected members, and (iii) 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity of DNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants. Results: Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P<0.001) between the affected vs. unaffected members and the affected vs. healthy controls, but not between the unaffected members vs. healthy controls. MODY5-related gene, hepatocyte nuclear factor-1β (HNF-1β) on 17q12 near D17S798 became the candidate gene. A single nucleotide variant (SNV) of C77T in the non-coding area of exon 1 of HNF-1β was found to be related to MODY5. Conclusion: This novel SNV of HNF-1β contributes to the diabetes development in the family through regulating gene expression most likely. The findings help presymptomatic diagnosis, and imply that mutations in the non-coding areas, as well as in the exons, play roles in the etiology of MODY

Numerical and Experimental Research on the Effect of Platform Heave Motion on Vortex-Induced Vibration of Deep Sea Top-Tensioned Riser

The prediction and control of vortex-induced vibration (VIV) is one of the key problems for riser design. The effect of platform heave motion on VIV of deep sea top-tensioned riser (TTR) is presented by means of numerical simulation and experiment in this research. First, the heave motion was modeled as a parametric excitation, and the governing equation of VIV of riser considering the parametric excitation was established. Then, the dynamic response of TTR was calculated numerically by the finite difference method based on the Van der Pol wake-oscillator model. Finally, a validation experiment was carried out at the towing tank of Tianjin university. The results show that the VIV response at the bottom of riser is significantly increased due to the platform heave motion, especially in the situation of low current velocity. The larger amplitude and the higher frequency of the platform heave motion with the greater influence are generated on VIV of TTR. In particular, the value of 0.5 times, 1 time, or other multiples of the platform heave frequency will be included in the vibration frequency component of TTR when the platform heave amplitude is large and the frequency is high

Characteristics and exploration targets of Chang 7 shale oil in Triassic Yanchang Formation, Ordos Basin, NW China

The geological characteristics and enrichment laws of the shale oil in the third submember of the seventh member of Triassic Yanchang Formation (Chang 73) in the Ordos Basin were analyzed by using the information of core observations, experiments and logging, and then the exploration potential and orientation of the Chang 73 shale oil were discussed. The research findings are obtained in three aspects. First, two types of shale oil, i.e. migratory-retained and retained, are recognized in Chang 73. The former is slightly better than the latter in quality. The migratory-retained shale oil reservoir is featured with the frequent interbedding and overlapping of silty–sandy laminae caused by sandy debris flow and low-density turbidity current and semi-deep–deep lacustrine organic-rich shale laminae. The retained shale oil reservoir is composed of black shale with frequent occurrence of bedding and micro-laminae. Second, high-quality source rocks provide a large quantity of hydrocarbon-rich high-quality fluids with high potential energy. The source-reservoir pressure difference provides power for oil accumulation in thin interbeds of organic-poor sandstones with good seepage conditions and in felsic lamina, tuffaceous lamina and bedding fractures in shales. Hydrocarbon generation-induced fractures, bedding fractures and microfractures provide high-speed pathways for oil micro-migration. Frequent sandstone interlayers and felsic laminae provide a good space for large-scale hydrocarbon accumulation, and also effectively improve the hydrocarbon movability. Third, sand-rich areas around the depression are the main targets for exploring migratory-retained shale oil. Mature deep depression areas are the main targets for exploring retained oil with medium to high maturity. Theoretical research and field application of in-situ conversion in low-mature deep depression areas are the main technical orientations for exploring retained shale oil with low to medium maturity

Identification and Expressional Analysis of Putative PRDI-BF1 and RIZ Homology Domain-Containing Transcription Factors in <i>Mulinia lateralis</i>

Mollusca represents one of the ancient bilaterian groups with high morphological diversity, while the formation mechanisms of the precursors of all germ cells, primordial germ cells (PGCs), have not yet been clarified in mollusks. PRDI-BF1 and RIZ homology domain-containing proteins (PRDMs) are a group of transcriptional repressors, and PRDM1 (also known as BLIMP1) and PRDM14 have been reported to be essential for the formation of PGCs. In the present study, we performed a genome-wide retrieval in Mulinia lateralis and identified 11 putative PRDMs, all of which possessed an N-terminal PR domain. Expressional profiles revealed that all these prdm genes showed specifically high expression levels in the given stages, implying that all PRDMs played important roles during early development stages. Specifically, Ml-prdm1 was highly expressed at the gastrula stage, the key period when PGCs arise, and was specifically localized in the cytoplasm of two or three cells of blastula, gastrula, or trochophore larvae, matching the typical characteristics of PGCs. These results suggested that Ml-prdm1-positive cells may be PGCs and that Ml-prdm1 could be a candidate marker for tracing the formation of PGCs in M. lateralis. In addition, the expression profiles of Ml-prdm14 hinted that it may not be associated with PGCs of M. lateralis. The present study provides insights into the evolution of the PRDM family in mollusks and offers a better understanding of the formation of PGCs in mollusks

Quality of Life and Influencing Factors in Henan Rural People Living with HIV/AIDS

Background HIV/AIDS is an issue that seriously endangers public health. With the implementation of social support policies for people living with HIV/AIDS, although the mortality of them has decreased significantly, their survival is still a big concern. Objective To understand the quality of life and influencing factors in people living with HIV/AIDS in Henan rural areas. Methods By use of cluster sampling, we selected the persons living with HIV/AIDS treated by highly active antiretroviral therapy (HAART) who were managed by the local center for disease control and prevention in a rural area of Henan from June 3 to June 12, 2020. We collected their general data and laboratory test findings, and assessed their quality of life using the Chinese version of the WHOQOL-HIV BREF. We used multiple linear regression to identify the associated factors of quality of life. Results A total of 415 cases attended the questionnaire survey, and 400 of them (96.39%) who effectively completed the questionnaire were finally included for analysis. All the respondents were Han people, most of them were diagnosed over eight years, males, and aged over 50 years, and had a spouse, no stable income, low education level and CD4+ T lymphocytes greater than 500/&#x03BC;l with transmission mainly through blood, and over eight years of continuous HAART. The total score of quality of life of the respondents differed by sex, age, education level, marital status, income status, route of getting HIV infection, time of HIV diagnosis, and continuous treatment duration of HAART (P&lt;0.05) . Multiple linear regression analysis indicated that age (&#x03B2;&apos;=-0.152) , marital status (&#x03B2;&apos;=0.171) , income status (&#x03B2;&apos;=-0.138) , and route of getting HIV infection (&#x03B2;&apos;=0.104) were associated with the quality of life (P&lt;0.05) . Conclusion Special attention should be given to the quality of life of people living with HIV/AIDS infected by blood contact with an age of over 50 years, no spouse, and no stable income