- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- PI3K/AKT/mTOR signaling in cancer
- Diabetes and associated disorders
- Diabetes Management and Research
- Ubiquitin and proteasome pathways
- Metal-Organic Frameworks: Synthesis and Applications
- American Constitutional Law and Politics
- Pancreatic and Hepatic Oncology Research
- Echinoderm biology and ecology
- Polyamine Metabolism and Applications
- Genomics and Chromatin Dynamics
- Advanced Biosensing Techniques and Applications
- Biochemical and Structural Characterization
- Animal Genetics and Reproduction
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- TGF-β signaling in diseases
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Crystallography and molecular interactions
- Signaling Pathways in Disease
- Advanced Polymer Synthesis and Characterization
- Magnesium Oxide Properties and Applications
United States Army Combat Capabilities Development Command
2021-2025
DEVCOM Army Research Laboratory
2021-2025
California Institute of Technology
2015-2024
University of Pittsburgh
2011-2013
Takara (United States)
2006
Harvard University Press
1998
Massachusetts General Hospital
1995-1998
Harvard University
1995-1998
University of Washington
1995
University of California, San Francisco
1995
The present study identifies the operation of a signal tranduction pathway in mammalian cells that provides checkpoint control, linking amino acid sufficiency to control peptide chain initiation. Withdrawal acids from nutrient medium CHO-IR results rapid deactivation p70 S6 kinase and dephosphorylation eIF-4E BP1, which become unresponsive all agonists. Readdition mixture quickly restores phosphorylation responsiveness BP1 insulin. Increasing ambient twice usually employed increases basal...
The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mitogen-stimulated phosphorylation in situ that is partially inhibited by rapamycin. Previous work has established the protein known as mTOR/RAFT-1/FRAP target through which rapamycin·FKBP12 complex acts to dephosphorylate/deactivate kinase; thus, some mTOR mutants have lost ability bind vitro can protect against rapamycin-induced dephosphorylation/deactivationin situ. We show herein such also dephosphorylation, for both BP1,...
A stepwise ligand exchange strategy is utilized to prepare a series of isoreticular bio-MOF-100 analogues. Specifically, in situ with progressively longer dicarboxylate linkers performed on single crystalline starting materials synthesize products larger mesoporous cavities. The new members this materials, bio-MOFs 101-103, each exhibit permanent mesoporosity and pore sizes ranging from ~2.1-2.9 nm surface areas 2704 4410 m(2)/g. volume for bio-MOF 101 2.83 cc/g. Bio-MOF-102 103 have volumes...
The p70 S6 kinase is activated by diverse stimuli through a multisite phosphorylation directed at three separate domains as follows: cluster of (Ser/Thr) Pro sites in an autoinhibitory segment the noncatalytic carboxyl-terminal tail; Thr-252 activation loop catalytic domain; and Ser-394 Thr-412 immediately to domain. Phosphorylation <i>in vitro</i> enzyme phosphatidylinositol 3-phosphate-dependent kinase-1 or mutation → Glu has each been shown previously engender some kinase, whereas both...
Previous studies have shown that the noncatalytic carboxy-terminal tail of p70 S6 kinase (amino acids 422 to 525) contains an autoinhibitory pseudosubstrate domain is phosphorylated in situ during activation and vitro by mitogen-activated protein kinases. The present study shows a recombinant deleted (p70 delta CT104) nevertheless exhibits basal serum-stimulated 40S activity susceptibility inhibition wortmannin very similar those parent, full-length kinase. Carboxy-terminal deletion reduces...
The p70 S6 kinase is activated by insulin and mitogens through multisite phosphorylation of the enzyme. One set activating phosphorylations occurs in a putative autoinhibitory domain noncatalytic carboxyl-terminal tail. Deletion this tail yields variant (p70 delta CT104) that nevertheless continues to be mitogen regulated. Coexpression with recombinant constitutively active phosphatidylinositol (PI) 3-kinase (EC 2.7.1.137) gives substantial activation both full-length CT104 but not Rsk....
An isoreticular series of cobalt-adeninate bio-MOFs (bio-MOFs-11–14) is reported. The pores bio-MOFs-11–14 are decorated with acetate, propionate, butyrate, and valerate, respectively. nitrogen (N2) carbon dioxide (CO2) adsorption properties these materials studied compared. isosteric heats for CO2 calculated, the : N2 selectivities each material determined. As lengths aliphatic chains decorating in increase, BET surface areas decrease from 1148 m2 g−1 to 17 while predicted ideal adsorbed...
The transplantation of pancreatic endocrine islet cells from cadaveric donors is a promising treatment for type 1 diabetes (T1D), which chronic autoimmune disease that affects approximately nine million people worldwide. However, the demand donor islets outstrips supply. This problem could be solved by differentiating stem and progenitor to cells. many current culture methods used coax differentiate into require Matrigel, matrix composed extracellular (ECM) proteins secreted mouse sarcoma...
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Engineered microbial communities show promise in a wide range of applications, including environmental remediation, microbiome engineering, and synthesis fine chemicals. Here we present methods by which bacterial aggregates can be directed into several distinct architectures inducible surface expression heteroassociative protein domains (SpyTag/SpyCatcher SynZip17/18). Programmed aggregation used to activate quorum-sensing circuit, aggregate size tuned via control the amount associative...
Abstract The Spec gene family of Strongylocentrotus purpuratus is expressed exclusively in aboral ectoderm cells during embryogenesis. To investigate the regulation activity, region around Spec1 transcriptional initiation site was analyzed for sites protein–DNA interaction. One high-affinity bound a factor termed SpFl within 5′ untranslated leader at position +39 to +60. core sequence recognized by SpFl, CACGTG, same as that upstream stimulatory (USF), widely occurring vertebrate...
Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells treating type 1 diabetes. However, it remains unclear whether young (1-week-old) harbors multipotent progenitors capable of differentiating into duct, acinar, and cells. Laminin an extracellular matrix (ECM) protein important β-cells' survival function. We established artificial (aECM) that contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin (designated aECM-lam). Whether...
Abstract Pancreatic ductal progenitor cells have been proposed to contribute adult tissue maintenance and regeneration after injury, but the identity of such remains elusive. Here, from mice, we identify a near homogenous population progenitor-like clusters, with an average 8 per cluster. They are rare subpopulation, about 0.1% total pancreatic cells, can be sorted using fluorescence-activated cell sorter CD133highCD71lowFSCmid-high phenotype. exhibit properties in self-renewal tri-lineage...
Abstract To identify positive or negative factors for HIV-1 infectivity, clones from the U937 promonocytic cell line that express similar levels of CD4 and CXCR4, but differ in susceptibility, were compared. In contrast to permissive clone 10 (plus), nonpermissive 17 (minus) was adherent coverslips coated with chemokines, phagocytic, killed bacteria, expressed human leukocyte elastase (HLE) a granule-like compartment (HLEG) never detected at surface (HLECS). minus clone, plus HLE on HLECS...
Pluripotent stem cells may serve as an alternative source of beta-like for replacement therapy type 1 diabetes; however, the generated in many differentiation protocols are immature. The maturation endogenous beta involves increase insulin expression starting late gestation and a gradual acquisition abilities to sense glucose secrete by week 2 after birth mice; what molecules regulate these processes incompletely known. In this study, we aim identify small that affect immature cells. A...
Previous studies showed that the core promoter of mouse cAMP-dependent protein kinase regulatory subunit type II beta (RII beta) gene was composed two functional elements. One element GC rich and bound Sp1 transcription factor. The second contained a helix-loop-helix (HLH)-motif. Each conferred transcriptional activity when inserted upstream reporter gene, chloramphenicol acetyltransferase transfected into NB2a neuroblastoma cells Chinese hamster ovary (CHO) cells. further characterized by...