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Biomedical subjects

John R Carlson

Publications and source records attributed to John R Carlson.

At least 19 recordsLinked to original sources
PubMed2006

Coding of odors by a receptor repertoire.

We provide a systematic analysis of how odor quality, quantity, and duration are encoded by the odorant receptor repertoire of the Drosophila antenna. We test the receptors with a panel of over 100 odors and find that strong responses are sparse, with response density dependent on chemical class. Individual receptors range along a continuum from narrowly tuned to broadly tuned. Broadly tuned receptors are most sensitive to structurally similar odorants. Strikingly, inhibitory responses are widespread among receptors. The temporal dynamics of the receptor repertoire provide a rich representation of odor quality, quantity, and duration. Receptors with similar odor sensitivity often map to widely dispersed glomeruli in the antennal lobe. We construct a multidimensional "odor space" based on the responses of each individual receptor and find that the positions of odors depend on their chemical class, concentration, and molecular complexity. The space provides a basis for predicting behavioral responses to odors.

Animal Structures↗
PubMed2006

Insect odor and taste receptors.

Insect odor and taste receptors are highly sensitive detectors of food, mates, and oviposition sites. Following the identification of the first insect odor and taste receptors in Drosophila melanogaster, these receptors were identified in a number of other insects, including the malaria vector mosquito Anopheles gambiae; the silk moth, Bombyx mori; and the tobacco budworm, Heliothis virescens. The chemical specificities of many of the D. melanogaster receptors, as well as a few of the A. gambiae and B. mori receptors, have now been determined either by analysis of deletion mutants or by ectopic expression in in vivo or heterologous expression systems. Here we discuss recent advances in our understanding of the molecular and cellular basis of odor and taste coding in insects.

Animals↗
PubMed2005

Chemosensory coding by neurons in the coeloconic sensilla of the Drosophila antenna.

Odor coding is based on the diverse sensitivities and response properties of olfactory receptor neurons (ORNs). In the Drosophila antenna, ORNs are housed in three major morphological types of sensilla. Although investigation of the Drosophila olfactory system has been expanding rapidly, the ORNs in one of these types, the coeloconic sensilla, have been essentially unexplored. We define four functional types of coeloconic sensilla through extracellular physiological recordings. Each type contains at least two neurons, with a total of at least seven distinct ORN classes that vary remarkably in their breadth of tuning. Analysis of 315 odorant-ORN combinations reveals how these neurons sample odor space via both excitation and inhibition. We identify a class of neurons that is narrowly tuned to small amines, and we find humidity detectors that define a cellular basis for hygroreception in Drosophila. The temporal dynamics of responses vary widely, enhancing the potential for complexity in the odor code. Molecular and genetic analysis shows that a broadly tuned ORN, antennal coeloconic 3B (ac3B), requires the odor receptor gene Or35a for its response in vivo. The activity of ac3B is not required for the response of the other ORN within that sensillum, ac3A. The functional analysis presented here, revealing a combination of highly specialized neurons and a broadly tuned ORN, along with the ancient origin of coeloconic sensilla, suggests that the specificities of these ORNs may reflect basic needs of an ancestral insect.

Animals↗
PubMed2005

The molecular basis of odor coding in the Drosophila larva.

We have analyzed the molecular basis of odor coding in the Drosophila larva. A subset of Or genes is found to be expressed in larval olfactory receptor neurons (ORNs). Using an in vivo expression system and electrophysiology, we demonstrate that these genes encode functional odor receptors and determine their response spectra with 27 odors. The receptors vary in their breadth of tuning, exhibit both excitation and inhibition, and show different onset and termination kinetics. An individual receptor appears to transmit signals via a single ORN to a single glomerulus in the larval antennal lobe. We provide a spatial map of odor information in the larval brain and find that ORNs with related functional specificity map to related spatial positions. The results show how one family of receptors underlies odor coding in two markedly different olfactory systems; they also provide a molecular mechanism to explain longstanding observations of larval odor discrimination.

Animals↗
PubMed2005

Coexpression of two functional odor receptors in one neuron.

One of the most fundamental tenets in the field of olfaction is that each olfactory receptor neuron (ORN) expresses a single odorant receptor. However, the one receptor-one neuron principle is difficult to establish rigorously. Here we construct a receptor-to-neuron map for an entire olfactory organ in Drosophila and find that two receptor genes are coexpressed in one class of ORN. Both receptors are functional in an in vivo expression system, they are only 16% identical in amino acid sequence, and the genes that encode them are unlinked. Most importantly, their coexpression has been conserved for >45 million years. Expression of multiple odor receptors in a cell provides an additional degree of freedom for odor coding.

Animals↗
PubMed2005

Symptom-focused management for African American women with Type 2 diabetes: a pilot study.

The purpose of this pilot study was to test the effectiveness of an in-home, nurse-delivered, symptom-focused teaching/counseling intervention with older rural African American women who have type 2 diabetes. Forty-one participants were randomly assigned to either the intervention or the comparison group. Participants in the intervention showed statistically significant improvement in their medication, diet, home glucose monitoring self-care practices, perceptions of quality of life, and distress from symptoms. Both groups evidenced improvement of HbA(1c) levels. The intervention group achieved greater improvement, but the difference was not statistically significant. Participant satisfaction was high. Further studies should look into the cost of the intervention, as compared with that of usual care, and its long-term effects.

Adult↗
PubMed2005

Insect chemoreception.

Insect chemoreception is mediated by a large and diverse superfamily of seven-transmembrane domain receptors. These receptors were first identified in Drosophila, but have since been found in other insects, including mosquitoes and moths. Expression and functional analysis of these receptors have been used to identify receptor ligands and to map receptors to functional classes of neurons. Many receptors detect general odorants or tastants, whereas some detect pheromones. The non-canonical receptor Or83b, which is highly conserved across insect orders, dimerizes with odorant and pheromone receptors and is required for efficient localization of these proteins to dendrites of sensory neurons. These studies provide a foundation for understanding the molecular and cellular basis of olfactory and gustatory coding.

Animals↗
PubMed2005

Self-monitoring and pelvic floor muscle exercises to treat urinary incontinence.

Urinary incontinence (UI) is a common chronic condition among women. Treatment of UI can involve behavioral techniques, pharmacological strategies, or surgical intervention. Clinically, treatment strategies should start with the simplest and least invasive measures. To overcome the deficiencies in previous research and provide definitive information for clinical practice, a randomized clinical trial is currently underway. This clinical trial uses a pretest-posttest design to first determine the effectiveness of self-monitoring techniques before subjects are randomized into one of two treatment groups or an attentional control group with a 1-year followup. The study design, sampling plan, and interventions used in an ongoing clinical trial to assess the effectiveness of self-monitoring and efficacy of biofeedback to treat UI in women are described. Innovative techniques to assess adherence to the pelvic muscle exercise protocol are addressed.

Adult↗
PubMed2004

Olfactory receptor neuron axon targeting: intrinsic transcriptional control and hierarchical interactions.

From insects to mammals, olfactory receptor neurons (ORNs) expressing a common olfactory receptor target their axons to specific glomeruli with high precision. Here we show in Drosophila that the POU transcription factor Acj6 controls the axon targeting specificity of a subset of ORN classes, as defined by the olfactory receptors that they express. Of these classes, some require Acj6 cell-autonomously, whereas others require Acj6 cell-nonautonomously. Mosaic analyses show that cooperative targeting occurs between axon terminals of the same ORN classes and that there are hierarchical interactions among different ORN classes. We propose that the precision of ORN axon targeting derives from both intrinsic transcriptional control and extensive axon-axon interactions.

Animals↗
PubMed2004

The molecular basis of odor coding in the Drosophila antenna.

We have undertaken a functional analysis of the odorant receptor repertoire in the Drosophila antenna. Each receptor was expressed in a mutant olfactory receptor neuron (ORN) used as a "decoder," and the odor response spectrum conferred by the receptor was determined in vivo by electrophysiological recordings. The spectra of these receptors were then matched to those of defined ORNs to establish a receptor-to-neuron map. In addition to the odor response spectrum, the receptors dictate the signaling mode, i.e., excitation or inhibition, and the response dynamics of the neuron. An individual receptor can mediate both excitatory and inhibitory responses to different odorants in the same cell, suggesting a model of odorant receptor transduction. Receptors vary widely in their breadth of tuning, and odorants vary widely in the number of receptors they activate. Together, these properties provide a molecular basis for odor coding by the receptor repertoire of an olfactory organ.

Action Potentials↗
PubMed2004

Olfaction: mosquito receptor for human-sweat odorant.

Female Anopheles mosquitoes, the world's most important vector of Plasmodium falciparum malaria, locate their human hosts primarily through olfactory cues, but the molecular mechanisms that underlie this recognition are a mystery. Here we show that the Anopheles gambiae protein AgOr1, a female-specific member of a family of putative odorant receptors, responds to a component of human sweat. Compounds designed to activate or block receptors of this type could function as attractants for trapping mosquitoes or as insect repellents in helping to control Anopheles and other insect pests.

Animals↗
PubMed2004

The odor coding system of Drosophila.

Our understanding of the molecular and cellular organization of the Drosophila melanogaster olfactory system has increased dramatically in recent years. A large family of approximately 60 odorant receptors has been identified, and many of these receptors have been functionally characterized. The odor responses of olfactory receptor neurons have been characterized, and much has been learned about how odors are represented in olfactory centers in the brain. The circuitry of the olfactory system has been studied in detail, and the developmental mechanisms that specify the wiring and functional diversity of olfactory neurons are becoming increasingly well understood. Thus, functional, anatomical and developmental studies are rapidly being integrated to form a unified picture of odor coding in this model olfactory system.

Animals↗
PubMed2003

Molecular evolution of the insect chemoreceptor gene superfamily in Drosophila melanogaster.

The insect chemoreceptor superfamily in Drosophila melanogaster is predicted to consist of 62 odorant receptor (Or) and 68 gustatory receptor (Gr) proteins, encoded by families of 60 Or and 60 Gr genes through alternative splicing. We include two previously undescribed Or genes and two previously undescribed Gr genes; two previously predicted Or genes are shown to be alternative splice forms. Three polymorphic pseudogenes and one highly defective pseudogene are recognized. Phylogenetic analysis reveals deep branches connecting multiple highly divergent clades within the Gr family, and the Or family appears to be a single highly expanded lineage within the superfamily. The genes are spread throughout the Drosophila genome, with some relatively recently diverged genes still clustered in the genome. The Gr5a gene on the X chromosome, which encodes a receptor for the sugar trehalose, has transposed from one such tandem cluster of six genes at cytological location 64, as has Gr61a, and all eight of these receptors might bind sugars. Analysis of intron evolution suggests that the common ancestor consisted of a long N-terminal exon encoding transmembrane domains 1-5 followed by three exons encoding transmembrane domains 6-7. As many as 57 additional introns have been acquired idiosyncratically during the evolution of the superfamily, whereas the ancestral introns and some of the older idiosyncratic introns have been lost at least 48 times independently. Altogether, these patterns of molecular evolution suggest that this is an ancient superfamily of chemoreceptors, probably dating back at least to the origin of the arthropods.

Alternative Splicing↗
PubMed2003

Targeted mutation of a Drosophila odor receptor defines receptor requirement in a novel class of sensillum.

In vertebrates, individual olfactory neurons are thought to express a single odorant receptor (Or) gene, but it is not clear that all odor-evoked activity in each neuron is exclusively dependent on an individual odorant receptor. In Drosophila, little is known about what receptors impart odor sensitivity to particular olfactory neurons. Here, we demonstrate the use of gene targeting to produce a null mutant of the putative odorant receptor Or43b and find that the mutant is defective for odor-evoked activity in ab8A neurons, a single functional class of olfactory neurons in Drosophila. ab8A neurons lacking Or43b are still present in the mutants and display spontaneous activity but are insensitive to odor stimulation. Therefore, Or43b is required for odor responsiveness in these olfactory neurons in vivo. Or83b, a receptor expressed in a large fraction of olfactory neurons including Or43b neurons, does not confer odor responsiveness in the absence of Or43b. Olfactory behavior elicited by odorants that activate the ab8A neurons is indistinguishable between Or43b mutants and controls, demonstrating a surprising degree of functional redundancy among the limited odor receptor repertoire in this species. These studies demonstrate that a reverse genetic approach can be used to correlate specific olfactory receptors with odor specificity of functional classes of olfactory neurons.

Animals↗
PubMed2003

Drosophila Gr5a encodes a taste receptor tuned to trehalose.

Recent studies have suggested that Drosophila taste receptors are encoded by a family of G protein-coupled receptor genes comprising at least 56 members. One of these genes, Gr5a, has been shown by genetic analysis to be required by the fly for behavioral and sensory responses to a sugar, trehalose. Here, we show that Gr5a is expressed in neurons of taste sensilla located on the labellum and legs. Expression is observed in most if not all labellar sensilla and suggests that many taste neurons express more than one receptor. We demonstrate by heterologous expression in a Drosophila S2 cell line that Gr5a encodes a receptor tuned to trehalose. This is the first functional expression of an invertebrate taste receptor.

Animals↗
PubMed2003

Integrating the molecular and cellular basis of odor coding in the Drosophila antenna.

We investigate how the molecular and cellular maps of the Drosophila olfactory system are integrated. A correspondence is established between individual odor receptors, neurons, and odors. We describe the expression of the Or22a and Or22b receptor genes, show localization to dendritic membranes, and find sexual dimorphism. Or22a maps to the ab3A neuron, which responds to ethyl butyrate. Analysis of a deletion mutant lacking Or22a, along with transgenic rescue experiments, confirms the mapping and demonstrates that an Or gene is required for olfactory function in vivo. Ectopic expression of Or47a in a mutant cell identifies the neuron from which it derives and its odor ligands. Ectopic expression in a wild-type cell shows that two receptors can function in a single cell. The ab3A neuron does not depend on normal odor receptor gene expression to navigate to its target in the CNS.

Amino Acid Sequence↗
PubMed2003

Preterm infants' behavioural indicators of oxygen decline during bottle feeding.

BACKGROUND: During the time when preterm infants' oral feeding skills are developing they often experience physiological instability and need assistance from caregivers to maintain adequate oxygenation. Assisting infants to maintain optimal oxygenation during oral feeding requires an understanding of how they express and aim to self-regulate their oxygen status. AIM: The purpose of this study was to identify potential behavioural indicators of declining oxygenation during preterm infant early bottle-feeding. METHOD: The design was explorative. Data were collected from a secondary analysis of 20 videotapes of preterm infant bottle feedings which included concurrent oxygen saturation data. In this analysis infant behaviours and quality of breathing were coded and compared across three periods: high oxygen saturation, immediately preceding an oxygen desaturation event, and during an oxygen desaturation event. FINDINGS: Infants gave limited behavioural indicators of declining oxygenation. Immediately prior to a desaturation event, they had an increase in eye flutter and were typically sucking and apnoeic. During a desaturation event, they typically relaxed their arms/hands and stopped sucking. CONCLUSIONS: Reliance on preterm infant behavioural cues will be insufficient for detection of oxygen desaturation during oral feeding. Attention to changes in breath sounds and to the pattern of sucking are potentially important intervention strategies for the prevention of and appropriate response to oxygen decline during feeding. Sucking pauses may be a time when preterm infants aim to regulate their breathing pattern and thereby increase oxygenation. Interventions that focus on detection and minimization of apnoea during feeding, and which aim to protect infant sucking pauses, may reduce the number and severity of desaturation events preterm infants experience during bottle feeding.

Bottle Feeding↗