Henri Temianka Correspondence; (mombaerts)

This collection contains material pertaining to the life, career, and activities of Henri Temianka, violin virtuoso, conductor, music teacher, and author. Materials include correspondence, concert programs and flyers, music scores, photographs, and books.https://digitalcommons.chapman.edu/temianka_correspondence/4101/thumbnail.jp

A Contextual Model for Axonal Sorting into Glomeruli in the Mouse Olfactory System

AbstractNo models fully account for how odorant receptors (ORs) function in the guidance of axons of olfactory sensory neurons (OSNs) to glomeruli in the olfactory bulb. Here, we use gene targeting in mice to demonstrate that the OR amino acid sequence imparts OSN axons with an identity that allows them to coalesce into glomeruli. Replacements between the coding regions of the M71 and M72 OR genes reroute axons to their respective glomeruli. A series of M71-M72 hybrid ORs uncover a spectrum of glomerular phenotypes, leading to the concept that the identity of OSN axons is revealed depending on what other axons are present. Naturally occurring amino acid polymorphisms in other ORs also produce distinct axonal identities. These critical amino acid residues are distributed throughout the protein and reside predominantly within transmembrane domains. We propose a contextual model for axon guidance in which ORs mediate homotypic interactions between like axons

The beta 2-adrenergic receptor as a surrogate odorant receptor in mouse olfactory sensory neurons

In the mouse, mature olfactory sensory neurons (OSNs) express one allele of one of the similar to 1200 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express the same OR coalesce into homogeneous glomeruli at conserved positions in the olfactory bulb. ORs are involved in OR gene choice and OSN axonal wiring, but the mechanisms remain poorly understood. One approach is to substitute an OR genetically with another GPCR, and to determine in which aspects this GPCR can serve as a surrogate OR under experimental conditions. Here, we characterize a novel gene-targeted mouse strain in which the mouse beta 2-adrenergic receptor (beta 2AR) is coexpressed with tauGFP in OSNs that choose the OR locus M71 for expression (beta 2AR -> M71-GFP). By crossing these mice with beta 2AR -> M71-lacZ gene-targeted mice, we find that differentially tagged beta 2AR -> M71 alleles are expressed monoallelically. The OR coding sequence is thus not required for monoallelic expression - the expression of one of the two alleles of a given OR gene in an OSN. We detect strong (beta 2AR immunoreactivity in dendritic cilia of (beta 2AR -> M71-GFP OSNs. These OSNs respond to the beta 2AR agonist isoproterenol in a dose-dependent manner. Axons of beta 2AR -> M71-GFP OSNs coalesce into homogeneous glomeruli, and beta 2AR immunoreactivity is detectable within these glomeruli. We do not find evidence for expression of endogenous beta 2AR in OSNs of wild-type mice, also not in M71-expressing OSNs, and we do not observe overt differences in the olfactory system of beta 2AR and beta 1AR knockout mice. Our findings corroborate the experimental value of the beta 2AR as a surrogate OR, including for the study of the mechanisms of monoallelic expression. (C) 2013 Elsevier Inc All rights reserved

Dynamical Modeling Techniques for Biological Time Series Data

The present thesis is articulated over two main topics which have in common the modeling of the dynamical properties of complex biological systems from large-scale time-series data. On one hand, this thesis analyzes the inverse problem of reconstructing Gene Regulatory Networks (GRN) from gene expression data. This first topic seeks to reverse-engineer the transcriptional regulatory mechanisms involved in few biological systems of interest, vital to understand the specificities of their different responses. In the light of recent mathematical developments, a novel, flexible and interpretable modeling strategy is proposed to reconstruct the dynamical dependencies between genes from short-time series data. In addition, experimental trade-offs and optimal modeling strategies are investigated for given data availability. Consistent literature on these topics was previously surprisingly lacking. The proposed methodology is applied to the study of circadian rhythms, which consists in complex GRN driving most of daily biological activity across many species. On the other hand, this manuscript covers the characterization of dynamically differentiable brain states in Zebrafish in the context of epilepsy and epileptogenesis. Zebrafish larvae represent a valuable animal model for the study of epilepsy due to both their genetic and dynamical resemblance with humans. The fundamental premise of this research is the early apparition of subtle functional changes preceding the clinical symptoms of seizures. More generally, this idea, based on bifurcation theory, can be described by a progressive loss of resilience of the brain and ultimately, its transition from a healthy state to another characterizing the disease. First, the morphological signatures of seizures generated by distinct pathological mechanisms are investigated. For this purpose, a range of mathematical biomarkers that characterizes relevant dynamical aspects of the neurophysiological signals are considered. Such mathematical markers are later used to address the subtle manifestations of early epileptogenic activity. Finally, the feasibility of a probabilistic prediction model that indicates the susceptibility of seizure emergence over time is investigated. The existence of alternative stable system states and their sudden and dramatic changes have notably been observed in a wide range of complex systems such as in ecosystems, climate or financial markets

β-Selection: Abundance of TCRβ–/γδ– CD44–CD25– (DN4) cells in the foetal thymus

Expression of TCRβ and pre-TCR signalling are essential for differentiation of CD4–CD8– double negative (DN) thymocytes to the CD4+CD8+ double-positive (DP) stage. Thymocyte development in adult Rag1, Rag2 or TCRβδ-deficient mice is arrested at the DN3 stage leading to the assumption that pre-TCR signalling and β-selection occur at, and are obligatory for, the transition from DN3 to DN4. We show that the majority of DN3 and DN4 cells that differentiate during early embryogenesis in wild-type mice do not express intracellular (ic) TCRβ/γδ. These foetal icTCRβ−/γδ− DN4 cells were T lineage as determined by expression of Thy1 and icCD3 and TCRβ DJ rearrangement. In addition, in the foetal Rag1–/– thymus, a normal percentage of DN4 cells were present. In wild-type mice after hydrocortisone-induced synchronisation of differentiation, the majority of DN4 cells that first emerged did not express icTCRβ/γδ, showing that adult thymocytes can also differentiate to the DN4 stage independently of pre-TCR signalling. Pre-TCR signalling induced expansion in the DN4 population, but lack of TCRβ/γδ expression did not immediately induce apoptosis. Our data demonstrate in vivo differentiation from DN3 to DN4 cell in the absence of TCRβ/γδ expression in the foetal thymus, and after hydrocortisone treatment of adult mice

Structure and Emergence of Specific Olfactory Glomeruli in the Mouse

Olfactory sensory neurons (OSNs) expressing a given odorant receptor (OR) gene project their axons to a few specific glomeruli that reside at recognizable locations in the olfactory bulb. Connecting ∼1000 populations of OSNs to the ∼1800 glomeruli of the mouse bulb poses a formidable wiring problem. Additional progress in understanding the mechanisms of neuronal connectivity is dependent on knowing how these axonal pathways are organized and how they form during development. Here we have applied a genetic approach to this problem. We have constructed by gene targeting novel strains of mice in which either all OSNs or those that express a specific OR gene, M72 or M71, also produce green fluorescent protein (GFP) or a fusion of tau with GFP. We visualized OSNs and their axons in whole mounts with two-photon laser scanning microscopy. The main conclusion we draw from the three-dimensional reconstructions is the high degree of morphological variability of mature glomeruli receiving axonal input from OR-expressing OSNs and of the pathways taken by the axons to those glomeruli. We also observe that axons of OR-expressing OSNs do not innervate nearby glomeruli in mature mice. Postnatally, a tangle of axons from M72-expressing OSNs occupies a large surface area of the bulb and coalesces abruptly into a protoglomerulus at a reproducible stage of development. These results differ in several aspects from those reported for the development of glomeruli receiving input from OSNs expressing the P2 OR, suggesting the need for a more systematic examination of OR-specific glomeruli

In vivo layer visualization of rat olfactory bulb by a swept source optical coherence tomography and its confirmation through electrocoagulation and anatomy

Here, we report in vivo 3-D visualization of the layered organization of a rat olfactory bulb (OB) by a swept source optical coherence tomography (SS-OCT). The SS-OCT operates at a wavelength of 1334 nm with respective theoretical depth and lateral resolutions of 6.7 μm and 15.4 μm in air and hence it is possible to get a 3D structural map of OB in vivo at the micron level resolution with millimeter-scale imaging depth. Up until now, with methods such as MRI, confocal microscopy, OB depth structure in vivo had not been clearly visualized as these do not satisfy the criterion of simultaneously providing micron-scale spatial resolution and imaging up to a few millimeter in depth. In order to confirm the OB’s layered organization revealed by SS-OCT, we introduced the technique of electrocoagulation to make landmarks across the layered structure. To our knowledge this is such a first study that combines electrocoagulation and OCT in vivo of rat OB. Our results confirmed the layered organization of OB, and moreover the layers were clearly identified by electrocoagulation landmarks both in the OCT structural and anatomical slice images. We expect such a combined study is beneficial for both OCT and neuroscience fields

The Influence of Prior Hyperthyroidism on Euthyroid Graves’ Ophthalmopathy

Background. To investigate the influence of previous exposure to elevated thyroid hormones in euthyroid Graves’ ophthalmopathy. Design. Retrospective, observational case series in university setting Median follow-up of 1 year with ranges of 0,8–7,6 years. Study performance of 10 years. Participants. We reviewed the clinical records of 731 Graves’ ophthalmopathy patients. There were 88 (12%) patients with onset of Graves’ ophthalmopathy during euthyroidism: 37 (5%) patients had ophthalmopathy without known history of thyroid dysfunction (group A) and 51 patients (6%) had onset of ophthalmopathy 6 months or more euthyroid after completion of antithyroid therapy (group B). Main Outcome Measures. Graves’ ophthalmopathy was graded using the EUGOGO severity criteria. Unilaterality was investigated. TSH receptor antibody and thyroid peroxidase antibody were measured as markers of Graves’ disease. Results. Group A had more often a normal ocular motility (46%) and less proptosis (14±4 mm) compared to group B (22%, 16±4 mm) (P=0.032 and 0.028, resp.). TSH receptor antibody was more frequently elevated in group B (94%) than in group A (17%) (P<0.001). Conclusion. Patients with euthyroid Graves’ ophthalmopathy present more often with ocular muscle restriction and proptosis when previously exposed to elevated thyroid hormones