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Bruce Blumberg

Publications and source records attributed to Bruce Blumberg.

23 records · Page 2Linked to original sources
PubMed2003

Active repression by unliganded retinoid receptors in development: less is sometimes more.

The retinoid receptors have major roles throughout development, even in the absence of ligand. Here, we summarize an emerging theme whereby gene repression, mediated by unliganded retinoid receptors, can dictate cell fate. In addition to activating transcription, retinoid receptors actively repress gene transcription by recruiting cofactors that promote chromatin compaction. Two developmental processes for which gene silencing by the retinoid receptors is essential are head formation in Xenopus and skeletal development in the mouse. Inappropriate repression, by oncogenic retinoic acid (RA)**Abbreviations used in this paper: APL, acute promyelocytic leukemia; dnRARalpha, dominant-negative version of the RARalpha; E, embryonic age; HDAC, histone deacetylase; LCoR, ligand-dependent corepressor; NCoR, nuclear receptor corepressor; RA, retinoic acid; RAR, RA receptor; RARE, RXR homodimer bound to bipartite response element; RXR, retinoid X receptor; TSA, trichostatin A; CYP26, cytochrome p450, 26; TR, thyroid hormone receptor. receptor (RAR) fusion proteins, blocks myeloid differentiation leading to a rare form of leukemia. Our current understanding of the developmental role of retinoid repression and future perspectives in this field are discussed.

Animals↗
PubMed2003

Overlapping gene structure of human VLCAD and DLG4.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a major enzyme catalysing the first step in mitochondrial beta-oxidation of long-chain fatty acids. During analysis of the VLCAD promoter, we discovered that another gene, discs-large-related 4 (DLG4), overlaps VLCAD and is transcribed in the opposite direction. DLG4 encodes postsynaptic density-95 (PSD95) protein, which plays critical roles in the formation and maintenance of synaptic junctions. The transcription start site of the VLCAD gene was determined by primer extension analysis and the overlapping structure of VLCAD and DLG4 was clarified. VLCAD and DLG4 are arranged in a head-to-head orientation on chromosome 17p13, and share a 245 bp overlapping region that contains part of DLG4 exon 1 and the entire exon 1 of VLCAD including 62 bp of protein coding sequence. Despite the overlap of their 5' ends, DLG4 and VLCAD exhibit peak mRNA expression in different tissues, suggesting that they are independently regulated at the transcriptional level. Interestingly, VLCAD and DLG4 genes do not overlap in the mouse or Drosophila genomes.

5' Flanking Region↗
PubMed2002

Benzoate X receptors alpha and beta are pharmacologically distinct and do not function as xenobiotic receptors.

The Xenopus benzoate nuclear hormone receptors, BXRalpha and BXRbeta, share 82% identity within their ligand-binding domains and are classified as members of the NR1I2 subfamily that includes the mammalian steroid and xenobiotic receptor, SXR/PXR. Although alkyl benzoates have been identified as endogenous ligands, the exact role of the benzoate receptors in amphibian physiology has not been established. In this report, we show that BXRalpha and BXRbeta are pharmacologically distinct from each other: BXRalpha is more promiscuous than BXRbeta with respect to both ligand specificity and co-activator recruitment. BXRalpha can be transactivated by a number of benzoate derivatives including 4-amino-butylbenzoate (4-ABB), 4-hydroxy-butylbenzoate (4-HBB), 3-hydroxy ethyl benzoate (3-HEB), and benzyl benzoate, but only 4-HBB acts as an agonist for both receptors. Furthermore, BXRalpha-specific agonists such as 4-ABB, chlorpyrifos, and trifluralin act as antagonists on BXRbeta. BXRs are widely distributed in adult tissues but do not show any enrichment in liver and intestine, major sites of SXR/PXR expression that are critical in xenobiotic metabolism. Neither BXR shows the broad specificity toward steroids or xenobiotics exhibited by SXR/PXR. Therefore, we conclude that the BXRs are pharmacologically distinct from each other and unlikely to serve as xenobiotic sensors.

Animals↗
PubMedDate not supplied

Learning from and about others: towards using imitation to bootstrap the social understanding of others by robots.

We want to build robots capable of rich social interactions with humans, including natural communication and cooperation. This work explores how imitation as a social learning and teaching process may be applied to building socially intelligent robots, and summarizes our progress toward building a robot capable of learning how to imitate facial expressions from simple imitative games played with a human, using biologically inspired mechanisms. It is possible for the robot to bootstrap from this imitative ability to infer the affective reaction of the human with whom it interacts and then use this affective assessment to guide its subsequent behavior. Our approach is heavily influenced by the ways human infants learn to communicate with their caregivers and come to understand the actions and expressive behavior of others in intentional and motivational terms. Specifically, our approach is guided by the hypothesis that imitative interactions between infant and caregiver, starting with facial mimicry, are a significant stepping-stone to developing appropriate social behavior, to predicting others' actions, and ultimately to understanding people as social beings.

Comprehension↗