26 research outputs found
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A novel ZRS variant causes preaxial polydactyly type I by increased sonic hedgehog expression in the developing limb bud.
PurposePreaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown.MethodsA rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model.ResultsA novel g.101779T>A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression.ConclusionOur results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms
Theoretical insight into the roles of cocatalysts in the Ni-NiO/β-Ga2O3 photocatalyst for overall water splitting
The formation and stability of Nin and (NiO)n (n = 1-4) clusters on the β-Ga2O3 surface have been studied by means of first-principles density functional theory calculations. It is found that the optimum interaction of the Nin and (NiO)n clusters with the surface requires different surface sites. This optimizes the formation of interfacial bonds between the atoms from clusters and the coordinatively unsaturated atoms from the surface. The stability of the adsorbed Ni clusters increases with the number of Ni atoms. In a Nin/Ga2O3 system, as the Ga unoccupied states overlap with the unoccupied Ni state, the excited electrons transferred from Ga to Ni participate in the proton reduction reaction. Our calculations show that (NiO)n clusters strongly adsorb on the Ga2O3 surface due to the negative adsorption energies within -1.9 eV to -3.7 eV. For (NiO)n/Ga2O3, occupied states from the (NiO)n cluster may accept the holes from O atoms in the Ga2O3 surface to take part in the photocatalytic water oxidation reaction
Theoretical insight into the roles of cocatalysts in the Ni-NiO/β-Ga2O3 photocatalyst for overall water splitting
The formation and stability of Nin and (NiO)n (n = 1-4) clusters on the β-Ga2O3 surface have been studied by means of first-principles density functional theory calculations. It is found that the optimum interaction of the Nin and (NiO)n clusters with the surface requires different surface sites. This optimizes the formation of interfacial bonds between the atoms from clusters and the coordinatively unsaturated atoms from the surface. The stability of the adsorbed Ni clusters increases with the number of Ni atoms. In a Nin/Ga2O3 system, as the Ga unoccupied states overlap with the unoccupied Ni state, the excited electrons transferred from Ga to Ni participate in the proton reduction reaction. Our calculations show that (NiO)n clusters strongly adsorb on the Ga2O3 surface due to the negative adsorption energies within -1.9 eV to -3.7 eV. For (NiO)n/Ga2O3, occupied states from the (NiO)n cluster may accept the holes from O atoms in the Ga2O3 surface to take part in the photocatalytic water oxidation reaction
Theoretical insight into the roles of cocatalysts in the Ni-NiO/β-Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e photocatalyst for overall water splitting
\u3cp\u3eThe formation and stability of Ni\u3csub\u3en\u3c/sub\u3e and (NiO)\u3csub\u3en\u3c/sub\u3e (n = 1-4) clusters on the β-Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e surface have been studied by means of first-principles density functional theory calculations. It is found that the optimum interaction of the Ni\u3csub\u3en\u3c/sub\u3e and (NiO)\u3csub\u3en\u3c/sub\u3e clusters with the surface requires different surface sites. This optimizes the formation of interfacial bonds between the atoms from clusters and the coordinatively unsaturated atoms from the surface. The stability of the adsorbed Ni clusters increases with the number of Ni atoms. In a Ni\u3csub\u3en\u3c/sub\u3e/Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e system, as the Ga unoccupied states overlap with the unoccupied Ni state, the excited electrons transferred from Ga to Ni participate in the proton reduction reaction. Our calculations show that (NiO)\u3csub\u3en\u3c/sub\u3e clusters strongly adsorb on the Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e surface due to the negative adsorption energies within -1.9 eV to -3.7 eV. For (NiO)\u3csub\u3en\u3c/sub\u3e/Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e, occupied states from the (NiO)\u3csub\u3en\u3c/sub\u3e cluster may accept the holes from O atoms in the Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e surface to take part in the photocatalytic water oxidation reaction.\u3c/p\u3
Comparative Transcriptome Analysis Reveals the Effect of Lignin on Storage Roots Formation in Two Sweetpotato (<i>Ipomoea batatas</i> (L.) Lam.) Cultivars
Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important crops with high storage roots yield. The formation and expansion rate of storage root (SR) plays a crucial role in the production of sweet potato. Lignin affects the SR formation; however, the molecular mechanisms of lignin in SR development have been lacking. To reveal the problem, we performed transcriptome sequencing of SR harvested at 32, 46, and 67 days after planting (DAP) to analyze two sweet potato lines, Jishu25 and Jishu29, in which SR expansion of Jishu29 was early and had a higher yield. A total of 52,137 transcripts and 21,148 unigenes were obtained after corrected with Hiseq2500 sequencing. Through the comparative analysis, 9577 unigenes were found to be differently expressed in the different stages in two cultivars. In addition, phenotypic analysis of two cultivars, combined with analysis of GO, KEGG, and WGCNA showed the regulation of lignin synthesis and related transcription factors play a crucial role in the early expansion of SR. The four key genes swbp1, swpa7, IbERF061, and IbERF109 were proved as potential candidates for regulating lignin synthesis and SR expansion in sweet potato. The data from this study provides new insights into the molecular mechanisms underlying the impact of lignin synthesis on the formation and expansion of SR in sweet potatoes and proposes several candidate genes that may affect sweet potato yield
Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells
The type III transforming growth factor-β (TGF-β) receptor (TβRIII), a coreceptor of the TGF-β superfamily, is known to bind TGF-βs and regulate TGF-β signaling. However, the regulatory roles of TβRIII in TGF-β-induced mesenchymal stem cell (MSC) chondrogenesis have not been explored. The present study examined the effect of TβRIII RNA interference (RNAi) on TGF-β3-induced human MSC (hMSC) chondrogenesis and possible signal mechanisms. A lentiviral expression vector containing TβRIII small interfering RNA (siRNA) (SiTβRIII) or a control siRNA (SiNC) gene was constructed and infected into hMSCs. The cells were cultured in chondrogenic medium containing TGF-β3 or control medium. TβRIII RNAi significantly enhanced TGF-β3-induced chondrogenic differentiation of hMSCs, the ratio of type II (TβRII) to type I (TβRI) TGF-β receptors, and phosphorylation levels of Smad2/3 as compared with cells infected with SiNC. An inhibitor of the TGF-β signal, SB431542, not only inhibited TβRIII RNAi-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also inhibited the effects of TβRIII RNAi on TGF-β3-induced chondrogenic differentiation. These results demonstrate that TβRIII RNAi enhances TGF-β3-induced chondrogenic differentiation in hMSCs by activating TGF-β/Smad2/3 signaling. The finding points to the possibility of modifying MSCs by TβRIII knockdown as a potent future strategy for cell-based cartilage tissue engineering
A Three-Dimensional Tetraphenylethylene-Based Fluorescence Covalent Organic Framework for Molecular Recognition
The development of
highly-sensitive recognition of hazardous chemicals, such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs), is of
significant importance because of their widespread social concerns related to
environment and human health. Here, we
report a three-dimensional (3D) covalent organic framework (COF, termed
JUC-555) bearing tetraphenylethylene (TPE) side chains as an
aggregation-induced emission (AIE) fluorescence probe for sensitive
molecular recognition. Due to the rotational restriction of TPE rotors in highly
interpenetrated framework after inclusion of dimethylformamide (DMF), JUC-555 shows impressive AIE-based strong fluorescence. Meanwhile, owing to the large pore size (11.4 Å) and suitable intermolecular distance of aligned TPE
(7.2 Å) in JUC-555, the obtained
material demonstrates an
excellent performance in the molecular recognition of
hazardous chemicals, e.g., nitroaromatic explosives, PAHs, and even thiophene
compounds, via a fluorescent quenching mechanism. The quenching constant (KSV) is two orders of magnitude better than
those of other fluorescence-based porous materials reported to date. This
research thus opens 3D functionalized COFs as a promising identification tool
for environmentally hazardous substances.</p