Introduction: The relationship between BMI and early renal function recovery after kidney transplantation is important due to the rising global obesity rates. Methods: A retrospective study on 320 patients who received allograft kidney transplantation at Guangxi Medical University Hospital explored the BMI-kidney function relationship using various statistical methods. Mendelian randomization (MR) was also employed to investigate causality. Results: Based on the univariate analysis, multivariate linear regression models, and trend analysis, it was found that there were significant positive correlations between BMI and creatinine, urea, and cystatin C on the 7th day after kidney transplantation (p < 0.05). The sensitivity analysis further confirmed these correlations in different gender stratification, adolescents, and adults. However, the positive correlation with cystatin C was only significant in males. Additionally, after conducting smooth curve fitting analysis and threshold saturation analysis, it was revealed that the negative correlation between early renal function recovery was most significant when BMI was between 22.0 and 25.5 kg/m2, and early postoperative renal function may be optimal when BMI was at 22.2 kg/m2. Finally, the MR analysis confirmed a causal relationship between BMI and renal failure, as indicated by the IVW method (p = 0.003), as well as the weighted median estimator (p = 0.004). Conclusion: This study on kidney transplant patients found that maintaining a BMI within the range of 22.0–25.5 kg/m2, with an optimal BMI of 22.2 kg/m2, improves early renal function recovery. This correlation holds true for different age-groups and genders. Monitoring and controlling BMI in high-risk patients can enhance post-transplantation renal function.
The effects of a high magnetic field on the precipitation behaviour of the primary Al 3 Zr phase are investigated. With and without the field, the primary Al 3 Zr crystals possess three morphologies – small tabular crystals in the deposit layer, long bars and dendritic crystals. The dendritic crystals are probably those surviving from the initial material. The tabular crystals in the deposit layer are those surviving from the heating stage, whereas the long bars are those formed during cooling. With the field, the tabular crystals in the deposit layer and the long bars tend to orient with the 〈110〉 direction parallel to the field direction, but the orientation of the dendritic crystals is less affected. The orientation of the crystals in the deposit layer arises from their magnetocrystalline anisotropy, but that of the long bars and dendritic crystals is disturbed by gravity and the formation of compound twins, respectively. Increased Zr content raises the precipitation amount of the primary Al 3 Zr crystals but weakens the alignment tendency of the tabular ones in the deposit layer. The weakness of the alignment arises from interaction between the crystals.
<p>Figure S8 Phenotype analysis of OT-I cells from B16-OVA tumor and EZH2 knockout provided a similar phenotype of OT-I cells as tazemetostat inhibition but impaired survival upon restimulation.</p>
The dominant white phenotype in pigs is thought to be mainly due to a structural mutation in the KIT gene, a splice mutation (G > A) at the first base in intron 17 which leads to the deletion of exon 17 in the mature KIT mRNA. However, this theory has not yet been validated by functional studies. Here, we created two mouse models, KIT D17/+ to mimic the splice mutation, and KIT Dup/+ to partially mimic the duplication mutation of KIT gene in dominant white pigs using CRISPR/Cas9 technology. We found that the splice mutation homozygote is lethal and the heterozygous mice have a piebald coat. Increased expression of KIT in KIT Dup/+mice did not confer the patched phenotype and had no obvious impact on coat color. Interestingly, the combination of these two mutations reduced the phosphorylation of PI3K and MAPK pathway associated proteins, which may be related to the impaired migration of melanoblasts observed during embryonic development that eventually leads to the dominant white phenotype.
Abstract Protein O‐GlcNAcylation is a ubiquitous posttranslational modification occurring both in animals and plants. While thousands of O‐GlcNAcylated proteins have been identified in animals, the plant O‐GlcNAcylated proteome remains poorly studied. Herein we report the development of a chemoproteomic strategy for profiling of O‐GlcNAcylated proteins in Arabidopsis based on the metabolic glycan labeling (MGL) method. We first demonstrated that both N ‐azidoacetylglucosamine (GlcNAz) and N ‐azidoacetylgalactosamine (GalNAz) can metabolically label O‐GlcNAc with azides in Arabidopsis seedlings. Arabidopsis UDP‐galactose 4‐epimerases were found to interconvert UDP‐GalNAz and UDP‐GlcNAz, supporting the existence of a GalNAc metabolism pathway. By tagging the azide‐incorporated O‐GlcNAc with alkyne‐biotin via click chemistry, the O‐GlcNAcylated proteins were enriched and analyzed by mass spectrometry. We identified 645 candidate O‐GlcNAcylated proteins in Arabidopsis seedlings, of which 592 were newly identified. The identified O‐GlcNAcylated proteins were enriched in various plant‐specific processes such as hormone responses. By co‐expression of a selected list of the identified proteins with SECRET AGENT, the Arabidopsis O‐GlcNAc transferase, we validated that the MGL‐identified proteins were O‐GlcNAc‐modified. Our work establishes a powerful tool for profiling plant O‐GlcNAylation and provides an invaluable resource for investigating the functional role of O‐GlcNAc in Arabidopsis .
Abstract Dominant white phenotype in pigs is considered to be caused by two structural mutations in KIT gene, including a 450-kb duplication encompassing the entire KIT gene, and a splice mutation (G > A) at the first base in intron 17, which leads to the deletion of exon 17 in mature KIT mRNA, and the production of KIT protein lacking a critical catalytic domain of kinase. However, this speculation has not yet been validated by functional studies. Here, by using CRISPR/Cas9 technology, we created two mouse models mimicing the structural mutations of KIT gene in dominant white pigs, including the splice mutation mouse model KIT D17/+ with exon 17 of one allele of KIT gene deleted, and duplication mutation mouse model KIT Dup/+ with one allele of KIT gene coding sequence (CDS) duplicated. We found that each mutation individually can not cause dominant white phenotype. Splice mutation homozygote is lethal and heterozygous mice present piebald coat. Inconsistent with previous speculation, we found KIT gene duplication mutation did not confer the patched phenotype, and had no obvious impact on coat color. Interestingly, combination of these two mutations lead to dominant white phenotype. Further molecular analysis revealed that combination of these two structural mutations could inhibit the kinase activity of the KIT protein, thus reduce the phosphorylation level of PI3K and MAPK pathway associated proteins, which may be related to the observed impaired migration of melanoblasts during embryonic development, and eventually lead to dominant white phenotype. Our study provides a further insight into the underlying genetic mechanisms of porcine dominant white coat colour. Author summary KIT plays a critical role in control of coat colour in mammals. Two mutation coexistence in KIT are considered to be the cause of the Dominant white phenotype in pigs. One mutation is a 450-kb large duplication encompassing the entire KIT gene, another mutation is a splice mutation causing the skipping of KIT exon 17. The mechanism of these two mutations of KIT on coat color formation has not yet been validated. In this study, by using genome edited mouse models, we found each structural mutation individual does not lead dominant white phenotype, but combination of these two mutations could lead to a nearly complete white coat colour similar to pig dominant white phenotype, possibly due to the inhibition of the kinase activity of the KIT protein, thus its signalling function on PI3K and MAPK pathways, leading to impaired migration of melanoblasts during embryonic development, and eventually lead to dominant white phenotype. Our study provides a further insight into the underlying genetic mechanisms of porcine dominant white coat colour.
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