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Biomedical subjects

S L Sullivan

Publications and source records attributed to S L Sullivan.

11 recordsLinked to original sources

Target-independent pattern specification in the olfactory epithelium.

In mammals, odors are detected by approximately 1000 different types of odorant receptors (ORs), each expressed by a fraction of neurons in the olfactory epithelium. Neurons expressing a given OR are confined to one of four spatial zones but are distributed randomly throughout that zone. In the olfactory bulb, the axons of neurons expressing different ORs synapse at different sites, giving rise to a highly organized and stereotyped information map. An important issue is whether the epithelial and bulbar maps evolve independently or are linked, for example, by retrograde influences of the bulb on the epithelium. Here we examined the onset of expression and patterning of genes encoding ORs and sensory transduction molecules during mouse embryogenesis and in mice lacking olfactory bulbs. Our results argue for an independent development of epithelial and bulbar maps and an early functional development that may be pertinent to pattern development in the olfactory bulb.

Animals

Spatial patterning and information coding in the olfactory system.

The ability of mammals to discriminate thousands of structurally diverse odorants appears to derive from the existence of a multigene family that encodes approximately 1000 different odorant receptors. Recent studies have used this family to explore how the olfactory system organizes sensory information. These studies reveal striking patterns of organization suggesting that incoming sensory information is first broadly organized in the nose and is then transformed in the olfactory bulb into a stereotyped and highly organized spatial map.

Animals

Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb.

In the mammalian olfactory system, information from approximately 1000 different odorant receptor types is organized in the nose into four spatial zones. Each zone is a mosaic of randomly distributed neurons expressing different receptor types. In these studies, we have obtained evidence that information highly distributed in the nose is transformed in the olfactory bulb of the brain into a highly organized spatial map. We find that specific odorant receptor gene probes hybridize in situ to small, and distinct, subsets of olfactory bulb glomeruli. The spatial and numerical characteristics of the patterns of hybridization that we observe with different receptor probes indicate that, in the olfactory bulb, olfactory information undergoes a remarkable organization into a fine, and perhaps stereotyped, spatial map. In our view, this map is in essence an epitope map, whose approximately 1000 distinct components are used in a multitude of different combinations to discriminate a vast array of different odors.

Animals

A molecular dissection of spatial patterning in the olfactory system.

The identification and cloning of genes encoding odorant receptors has provided molecular probes with which to examine the molecular mechanisms and organizational strategies underlying olfactory information processing. Recent studies using odorant receptor genes have revealed unexpected patterns of expression that provide new insights into how information may be organized in the nose and in the axonal projection from the nose to the brain.

Amino Acid Sequence

Odorant receptor diversity and patterned gene expression in the mammalian olfactory epithelium.

The mammalian olfactory system is capable of discriminating a vast array of structurally diverse odors. We have identified a novel multigene family whose unusual size and diversity suggest that odor discrimination may rely heavily on the existence of many hundreds of different types of odorant receptors which are differentially expressed by olfactory sensory neurons in the nasal cavity. We have found that the members of this family are segregated in their expression into a series of distinct, and highly specified, zones within the olfactory epithelium. Our experiments suggest that the odorant receptor expression zones may provide for an initial organization of sensory information in the nasal cavity which is maintained in the transmission of this information to the olfactory bulb of the brain.

Amino Acid Sequence

A zonal organization of odorant receptor gene expression in the olfactory epithelium.

The mechanisms by which mammals discriminate a vast array of diverse odors are poorly understood. To gain insight into the organizational strategies underlying this discriminatory capacity, we have examined the spatial distribution of odorant receptor RNAs in the mouse olfactory epithelium. We have observed topographically distinct patterns of receptor RNAs suggesting that the nasal cavity is divided into a series of expression zones. The zones exhibit bilateral symmetry in the two nasal cavities and are organized along the dorsal-ventral and medial-lateral axes. Within each zone, a neuron may select a gene for expression from a zonal gene set via a stochastic mechanism. The observed zonal patterning may serve as an initial organizing step in olfactory sensory information coding.

Amino Acid Sequence

Requirement for E. coli NusG protein in factor-dependent transcription termination.

The 21 kd NusG protein is essential for E. coli viability. Cells depleted for NusG were defective for factor-dependent transcription termination. Rho-induced polarity in the gal operon and the Rho-dependent lambda tR1 and lambda tL1 terminators were suppressed in NusG-deficient cells. NusG depletion inactivated the phage HK022 Nun termination factor. In contrast, the factor-independent lambda tl terminator was fully active in NusG-depleted cells and could be suppressed by phage lambda N function.

Bacterial Proteins

Effect of Escherichia coli nusG function on lambda N-mediated transcription antitermination.

The Escherichia coli Nus factors act in conjunction with the bacteriophage lambda N protein to suppress transcription termination on the lambda chromosome. NusA binds both N and RNA polymerase and may also interact with other Nus factors. To search for additional components of the N antitermination system, we isolated host revertants that restored N activity in nusA1 mutants. One revertant, nusG4, was mapped to the rif region of the E. coli chromosome and shown to represent a point mutation near the 3' end of the nusG gene. The nusG4 mutation also suppressed nusE71 but not nusASal, nusB5, nusC60 (rpoB60), or nusD026 (rho026). However, nusG+ expressed from a multicopy plasmid suppressed nusD026 and related rho mutants for both lambda and phage T4 growth. These results suggest that NusG may act as a component of the N antitermination complex. In addition, the data imply a role for NusG in Rho-dependent termination.

Bacterial Proteins

Sequence and transcriptional pattern of the essential Escherichia coli secE-nusG operon.

Two genes, secE and nusG, situated between the tufB and ribosomal protein rplKAJL operons in the rif region at 90 min on the Escherichia coli chromosome, have been sequenced and characterized. The secE gene encodes a 127-amino-acid-long polypeptide, which is an integral membrane protein essential for protein export (P. J. Schatz, P. D. Riggs, A. Jacq, M. J. Fath, and J. Beckwith, Genes Dev. 3:1035-1044, 1989). The nusG gene encodes a 181-amino-acid-long polypeptide and is involved in transcription antitermination. The protein product of nusG is essential for bacterial viability. The secE-nusG genes are cotranscribed, with transcripts initiated at the PEG promoter and terminated at the Rho-independent terminator in the region of the rplK promoter. The majority of transcripts are processed at a number of sites in the 5' untranslated leader region by RNase III and are possibly also processed by a second unidentified nuclease. The role of transcript processing in the regulation of secE and nusG has not yet been established. The juxtaposition and coregulation of a protein export factor and a transcriptional factor raise questions concerning a functional connection between the two processes.

Amino Acid Sequence

Cephalosporin-induced interstitial pneumonitis.

This report describes a patient who developed dyspnea and bilateral pulmonary infiltrates following exposure to cephradine. The role of cephradine was substantiated by rechallenge.

Cephalosporins