combining-raman-imaging-multivariate-analysis-to-visualize-lignin

Combining Raman Imaging and Multivariate Analysis to Visualize Lignin, Cellulose, and Hemicellulose in the Plant Cell Wall

The application of Raman imaging to plant biomass is increasing because it can offer spatial and compositional information on aqueous solutions. The ...

in-vitro-reconstitution-actin-cytoskeleton-inside-giant-unilamellar

<em>In Vitro</em> Reconstitution of the Actin Cytoskeleton Inside Giant Unilamellar Vesicles

The actin cytoskeleton, the principal mechanical machinery in the cell, mediates numerous essential physical cellular activities, including cell ...

Beijing Forestry University

Yale University

Multidrug resistance-associated protein 2 (MRP2) excretes conjugated organic anions including bilirubin and bile acids. Malfunction of MRP2 leads to jaundice in patients. Studies in rodents indicate that Radixin plays a critical role in determining Mrp2 canalicular membrane expression. However, it is not known how human hepatic MRP2 expression is regulated in cholestasis.

Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis.

The tumour suppressor complex BRCA1-BARD1 functions in the repair of DNA double-stranded breaks by homologous recombination. During this process, BRCA1-BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumour suppressor complex, BRCA2-PALB2, and the recombinase RAD51. Here, by examining purified wild-type and mutant BRCA1-BARD1, we show that both BRCA1 and BARD1 bind DNA and interact with RAD51, and that BRCA1-BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1-BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. We provide evidence that BRCA1 and BARD1 are indispensable for RAD51 stimulation. Notably, BRCA1-BARD1 mutants with weakened RAD51 interactions show compromised DNA joint formation and impaired mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1-BARD1 in homologous recombination, an attribute of the tumour suppressor complex that could be targeted in cancer therapy.

BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing.

Bile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis.

Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis.

Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis. WGS reveals a SEMA7A homozygous mutation in a female child with elevated levels of serum ALT, AST, and total bile acid (TBA) of unknown etiology. This patient also carried a SLC10A1 allele, but Slc10a1 homozygous mice exhibited normal liver function. Similar to the child, Sema7a homozygous mice displayed elevated levels of serum ALT, AST, and TBA. Remarkably, liver histology and LC-MS/MS analyses exhibited hepatocyte hydropic degeneration and increased liver bile acid (BA) levels in Sema7a homozygous mice. Further mechanistic studies demonstrated that Sema7a mutation reduced the expression of canalicular membrane BA transporters, bile salt export pump (Bsep), and multidrug resistance-associated protein-2 (Mrp2), causing intrahepatic cholestasis in mice. Administration with ursodeoxycholic acid and a dietary supplement glutathione improved liver function in the child. Therefore, Sema7a homozygous mutation causes intrahepatic cholestasis by reducing hepatic Bsep and Mrp2 expression.

A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.

A novel role for interleukin 32 in cholestasis.

Dense assemblies of self-propelling rods (SPRs) may exhibit fascinating collective behaviors and anomalous physical properties that are far away from equilibrium. Using large-scale Brownian dynamics simulations, we investigate the dynamics of disclination defects in 2D fluidized swarming motions of dense dry SPRs (, without hydrodynamic effects) that form notable local positional topological structures that are reminiscent of smectic order. We find the deformations of smectic-like rod layers can create unique polar structures that lead to slow translations and rotations of ±1/2-order defects, which are fundamentally different from the fast streaming defect motions observed in wet active matter. We measure and characterize the statistical properties of topological defects and reveal their connections with the coherent structures. Furthermore, we construct a bottom-up active-liquid-crystal model to analyze the instability of polar lanes, which effectively leads to defect formation between interlocked polar lanes and serves as the origin of the large-scale swarming motions.

ArticleTotal : 2	Year
Publication title Cited by 14	2017
Publication title Cited by 5	2022

Article	Year
Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. Journal of hepatology\| PubMed ID: 26212029	2015
BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing. Nature\| PubMed ID: 28976962	2017
Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology\| PubMed ID: 30063921	2018
A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis. EMBO molecular medicine\| PubMed ID: 34585848	2021
A novel role for interleukin 32 in cholestasis. Clinical and translational medicine\| PubMed ID: 34841712	2021
Understanding topological defects in fluidized dry active nematics. Soft matter\| PubMed ID: 35018951	2022

Sheng Chen

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