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Stuart Firestein

Blythe D Shepard, Lydie Cheval, Zita Peterlin, Stuart Firestein, Hermann Koepsell, Alain Doucet, Jennifer L Pluznick
Olfactory receptors (ORs) are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Here we describe a novel role for one of these ORs, Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels...
October 14, 2016: Scientific Reports
Erwan Poivet, Zita Peterlin, Narmin Tahirova, Lu Xu, Clara Altomare, Anne Paria, Dong-Jing Zou, Stuart Firestein
Associating an odorant's chemical structure with its percept is a long-standing challenge. One hindrance may come from the adoption of the organic chemistry scheme of molecular description and classification. Chemists classify molecules according to characteristics that are useful in synthesis or isolation, but which may be of little importance to a biological sensory system. Accordingly, we look to medicinal chemistry, which emphasizes biological function over chemical form, in an attempt to discern which among the many molecular features are most important for odour discrimination...
2016: Nature Communications
Hans Clevers, Stuart Firestein, Leonie Ringrose, Rene Bernards, K Heran Darwin, Russell E Vance
No abstract text is available yet for this article.
November 5, 2015: Cell
Jessica H Brann, Deandrea P Ellis, Benson S Ku, Eleonora F Spinazzi, Stuart Firestein
While the capacity of the olfactory epithelium (OE) to generate sensory neurons continues into middle age in mice, it is presumed that this regenerative potential is present throughout all developmental stages. However, little experimental evidence exists to support the idea that this regenerative capacity remains in late adulthood, and questions about the functionality of neurons born at these late stages remain unanswered. Here, we extend our previous work in the VNO to investigate basal rates of proliferation in the OE, as well as after olfactory bulbectomy (OBX), a commonly used surgical lesion...
2015: Frontiers in Neuroscience
Chien-Fu F Chen, Dong-Jing Zou, Clara G Altomare, Lu Xu, Charles A Greer, Stuart J Firestein
The piriform cortex (PCX) is the largest component of the olfactory cortex and is hypothesized to be the locus of odor object formation. The distributed odorant representation found in PCX contrasts sharply with the topographical representation seen in other primary sensory cortices, making it difficult to test this view. Recent work in PCX has focused on functional characteristics of these distributed afferent and association fiber systems. However, information regarding the efferent projections of PCX and how those may be involved in odor representation and object recognition has been largely ignored...
November 25, 2014: Proceedings of the National Academy of Sciences of the United States of America
Yadi Li, Zita Peterlin, Jianghai Ho, Tali Yarnitzky, Min Ting Liu, Merav Fichman, Masha Y Niv, Hiroaki Matsunami, Stuart Firestein, Kevin Ryan
The mammalian odorant receptors (ORs) form a chemical-detecting interface between the atmosphere and the nervous system. This large gene family is composed of hundreds of membrane proteins predicted to form as many unique small molecule binding niches within their G-protein coupled receptor (GPCR) framework, but very little is known about the molecular recognition strategies they use to bind and discriminate between small molecule odorants. Using rationally designed synthetic analogs of a typical aliphatic aldehyde, we report evidence that among the ORs showing specificity for the aldehyde functional group, a significant percentage detect the aldehyde through its ability to react with water to form a 1,1-geminal (gem)-diol...
November 21, 2014: ACS Chemical Biology
Jessica H Brann, Stuart J Firestein
Neurogenesis continues well beyond embryonic and early postnatal ages in three areas of the nervous system. The subgranular zone supplies new neurons to the dentate gyrus of the hippocampus. The subventricular zone supplies new interneurons to the olfactory bulb, and the olfactory neuroepithelia generate new excitatory sensory neurons that send their axons to the olfactory bulb. The latter two areas are of particular interest as they contribute new neurons to both ends of a first-level circuit governing olfactory perception...
2014: Frontiers in Neuroscience
Zita Peterlin, Stuart Firestein, Matthew E Rogers
The odorant receptors (ORs) provide our main gateway to sensing the world of volatile chemicals. This involves a complex encoding process in which multiple ORs, each of which detects its own set of odorants, work as an ensemble to produce a distributed activation code that is presumably unique to each odorant. One marked challenge to decoding the olfactory code is OR deorphanization, the identification of a set of activating odorants for a particular receptor. Here, we survey various methods used to try to express defined ORs of interest...
May 2014: Journal of General Physiology
Arie S Mobley, Alex K Bryant, Marion B Richard, Jessica H Brann, Stuart J Firestein, Charles A Greer
Throughout life the subventricular zone (SVZ) is a source of new olfactory bulb (OB) interneurons. From the SVZ, neuroblasts migrate tangentially through the rostral migratory stream (RMS), a restricted route approximately 5 mm long in mice, reaching the OB within 10-14 days. Within the OB, neuroblasts migrate radially to the granule and glomerular layers where they differentiate into granule and periglomerular (PG) cells and integrate into existing synaptic circuits. SVZ neurogenesis decreases with age, and might be a factor in age-related olfactory deficits...
July 2013: Neurobiology of Aging
Jennifer L Pluznick, Ryan J Protzko, Haykanush Gevorgyan, Zita Peterlin, Arnold Sipos, Jinah Han, Isabelle Brunet, La-Xiang Wan, Federico Rey, Tong Wang, Stuart J Firestein, Masashi Yanagisawa, Jeffrey I Gordon, Anne Eichmann, Janos Peti-Peterdi, Michael J Caplan
Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels...
March 12, 2013: Proceedings of the National Academy of Sciences of the United States of America
Stuart Firestein
No abstract text is available yet for this article.
April 2012: Scientific American
Josef Lazar, Alexey Bondar, Stepan Timr, Stuart J Firestein
Membrane proteins are a large, diverse group of proteins, serving a multitude of cellular functions. They are difficult to study because of their requirement of a lipid membrane for function. Here we show that two-photon polarization microscopy can take advantage of the cell membrane requirement to yield insights into membrane protein structure and function, in living cells and organisms. The technique allows sensitive imaging of G-protein activation, changes in intracellular calcium concentration and other processes, and is not limited to membrane proteins...
August 2011: Nature Methods
Florencia Marcucci, Elizabeth Maier-Balough, Dong-Jing Zou, Stuart Firestein
Neural connections in the adult nervous system are established with a high degree of precision. Several examples throughout the nervous system indicate that this precision is achieved by first establishing an initial exuberant immature pattern of connectivity that is then sculpted into the adult pattern via pruning. This often emerges as an activity-dependent process. In the olfactory system, sensory axons from neurons expressing the same odorant receptor project with high precision to specific glomerular structures in the olfactory bulb...
December 15, 2011: Journal of Comparative Neurology
Xiaohong Zhang, Florencia Marcucci, Stuart Firestein
We performed comprehensive data mining to explore the vomeronasal receptor (V1R and V2R) repertoires in mouse and rat using the mm5 and rn3 genome, respectively. This bioinformatic analysis was followed by investigation of gene expression using a custom designed high-density oligonucleotide array containing all of these receptors and other selected genes of interest. This array enabled us to detect the specific expression of V1R and V2Rs which were previously identified solely based on computational prediction from gene sequence data, thereby establishing that these genes are indeed part of the vomeronasal system, especially the V2Rs...
2010: Frontiers in Neuroscience
Jessica H Brann, Stuart Firestein
During normal and diseased aging, it is thought the capacity for tissue regeneration and repair in neuronal tissues diminishes. In the peripheral olfactory system, stem cell reservoirs permit regeneration of olfactory and vomeronasal sensory neurons, a unique capacity among neurons. Following injury, a large number of new neurons can be regenerated in a young animal. However, it is unknown whether this capacity for renewal exists in aged proliferative populations. Here, we report that neuronal replacement-associated proliferation continues in the vomeronasal organ of aged (18-24 months) mice...
November 17, 2010: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Alexandra M Miller, Lydia R Maurer, Dong-Jing Zou, Stuart Firestein, Charles A Greer
Olfactory sensory neuron (OSN) axons exit the olfactory epithelium (OE) and extend toward the olfactory bulb (OB) where they coalesce into glomeruli. Each OSN expresses only 1 of approximately 1,200 odor receptors (ORs). OSNs expressing the same OR are distributed in restricted zones of the OE. However, within a zone, the OSNs expressing a specific OR are not contiguous - distribution appears stochastic. Upon reaching the OB the OSN axons expressing the same OR reproducibly coalesce into two to three glomeruli...
2010: Neural Development
Diego J Rodriguez-Gil, Helen B Treloar, Xiaohong Zhang, Alexandra M Miller, Aimee Two, Carrie Iwema, Stuart J Firestein, Charles A Greer
As odorant receptors (ORs) are thought to be critical determinants of olfactory sensory neuron (OSN) axon targeting and organization, we examined the spatiotemporal onset of mice ORs expression from the differentiation of OSNs in the olfactory placode to an aging olfactory epithelium. ORs were first detected in the placode at embryonic day 9 (E9), at the onset of OSN differentiation but before axon extension. By E13, 22 of 23 ORs were expressed. Onset of individual OR expression was diverse; levels and patterns of expression were unique for each OR...
July 28, 2010: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Michael D Kurland, Michael B Newcomer, Zita Peterlin, Kevin Ryan, Stuart Firestein, Victor S Batista
The discrimination of n-alkyl-saturated aldehydes during the early stage of odorant recognition by the rat I7 olfactory receptor (OR-I7) is investigated. The concentrations of odorants necessary for 50% activation (or inhibition) of the OR-I7 are measured by calcium imaging recordings of dissociated rat olfactory sensory neurons, expressing the recombinant OR-I7 from an adenoviral vector. These are correlated with the corresponding binding free energies computed for a homology structural model of the OR-I7 built from the crystal structure of bovine visual rhodopsin at 2...
August 3, 2010: Biochemistry
Matthew T Valley, Tanner R Mullen, Lucy C Schultz, Botir T Sagdullaev, Stuart Firestein
Adult neurogenesis replenishes olfactory bulb (OB) interneurons throughout the life of most mammals, yet during this constant flux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the sub-ventricular zone (SVZ). Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs) born after the lesion, and a gradual decrease in the population of GCs born before the lesion...
2009: Frontiers in Neuroscience
Angela Corcelli, Simona Lobasso, Patrizia Lopalco, Michele Dibattista, Ricardo Araneda, Zita Peterlin, Stuart Firestein
The response of olfactory sensory neurons to TNT and RDX as well as to some volatile organic compounds present in the vapors of antipersonnel landmines has been studied both in the pig and in the rat. GC/MS analyses of different plastic components of six different kinds of landmines were performed in order to identify the components of the "perfume" of mines. Studies on rat olfactory mucosa were carried out with electro-olfactogram and calcium imaging techniques, while changes in the cyclic adenosine monophosphate (cAMP) levels following exposure to odorants and explosives were used as a criterion to evaluate the interaction of TNT and RDX with olfactory receptors in a preparation of isolated pig olfactory cilia...
March 15, 2010: Journal of Hazardous Materials
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