Kavya Annu

BMN 349, a small molecule inhibitor of Z alpha-1 antitrypsin polymerization, increases secretion and reduces intrahepatic inclusions in a mouse model of disease

Britta Handyside, Heather Wenzel, Donald MacKenzie, Catherine Chang et autres

BACKGROUND AND AIMS: Alpha-1 antitrypsin (AAT), encoded by the SERPINA1 gene, is primarily synthesized in the liver and secreted into the blood. The SERPINA1 Z allele encodes Z-AAT (Glu342Lys), a variant that self-associates into polymers that are retained in hepatocytes and trigger …

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Design and Optimization of 1H-1,2,3-Triazole-4-carboxamides as Novel, Potent, and Selective Inverse Agonists and Antagonists of PXR

Yongtao Li, Wenwei Lin, Sergio C. Chai, Jing Wu et autres

The pregnane X receptor (PXR) is a key regulator of drug metabolism. Many drugs bind to and activate PXR, causing adverse drug responses. This suggests that PXR inhibitors have therapeutic value, but potent PXR inhibitors have so far been lacking. Herein, we …

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Molecular basis of crosstalk in nuclear receptors: heterodimerization between PXR and CAR and the implication in gene regulation

Monicah N Bwayi, Efren Garcia-Maldonado, Sergio C. Chai, Boer Xie et autres

The 48 human nuclear receptors (NRs) form a superfamily of transcription factors that regulate major physiological and pathological processes. Emerging evidence suggests that NR crosstalk can fundamentally change our understanding of NR biology, but detailed molecular mechanisms of crosstalk are lacking. Here, …

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Vitamin D levels do not cause vitamin-drug interactions with dexamethasone or dasatinib in mice

Kavya Annu, Kazuto Yasuda, William Caufield, Burgess B. Freeman et autres

Vitamin D3 (VD3) induces intestinal CYP3A that metabolizes orally administered anti-leukemic chemotherapeutic substrates dexamethasone (DEX) and dasatinib potentially causing a vitamin-drug interaction. To determine the impact of VD3 status on systemic exposure and efficacy of these chemotherapeutic agents, we used VD3 sufficient …

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Accurate genomic variant detection in single cells with primary template-directed amplification

Veronica Gonzalez-Pena, Sivaraman Natarajan, Yuntao Xia, David Klein et autres

Improvements in whole genome amplification (WGA) would enable new types of basic and applied biomedical research, including studies of intratissue genetic diversity that require more accurate single-cell genotyping. Here, we present primary template-directed amplification (PTA), an isothermal WGA method that reproducibly captures …

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Accurate Genomic Variant Detection in Single Cells with Primary Template-Directed Amplification

Veronica D. Gonzalez, Sivaraman Natarajan, Yuntao Xia, David Klein et autres

Abstract Improvements in whole genome amplification (WGA) would enable new types of basic and applied biomedical research, including studies of intratissue genetic diversity that require more accurate single-cell genotyping. Here we present primary template-directed amplification (PTA), a new isothermal WGA method that …

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Vitamin D Levels Affect Survival in a BCR-ABL Acute Lymphoblastic Leukemia Mouse Model but Do Not Cause Vitamin-Drug Interactions

Kavya Annu

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an …

Role of Vitamins A and D in BCR-ABL Arf−/− Acute Lymphoblastic Leukemia

Kavya Annu, Cynthia Cline, Kazuto Yasuda, Samit Ganguly et autres

Abstract The effects of vitamin A and/or vitamin D deficiency were studied in an Arf−/− BCR-ABL acute lymphoblastic leukemia murine model. Vitamin D sufficient mice died earlier (p = 0.003) compared to vitamin D deficient (VDD) mice. Vitamin A deficient (VAD) mice …

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P15 - Vitamin D deficiency alters CYP3A gene expression and pharmacokinetics of dexamethasone

Kavya Annu, Jean Cai, Burgess B. Freeman, Erin G. Schuetz

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TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics

Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing et autres

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Role of NKCC2A in Nervous system Activity

Kavya Annu, James B. Lucot, Teresa L. Garrett, Mauricio DiFulvio et autres

The NKCC2A channel is a splice variant of the Na + K + 2Cl ‐ co‐transporter 2 (Slc12a1), which is abundantly expressed in macula densa and apical membrane of the tubular cells in the kidney but has not been reported in nervous …

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The Role of NKCC2A on the Nervous System Activity

Kavya Annu

The NKCC2A is a splice variant of the Na+K+2Cl- co-transporter 2 (Slc12a1), which is abundantly expressed in macula densa and in the apical membrane of the tubular cells in the kidney. Most of our knowledge regarding NKCC2 function is limited to the …

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