We are immersed within an odorous sea of chemical currents that we parse into individual odors with complex structures. Odors have been posited as determined by the structural relation between the molecules that compose the chemical compounds and their interactions with the receptor site. But, naturally occurring smells are parsed from gaseous odor plumes. To give a comprehensive account of the nature of odors the chemosciences must account for these large distributed entities as well. We offer a focused (...) review of what is known about the perception of odor plumes for olfactory navigation and tracking, which we then connect to what is known about the role odorants play as properties of the plume in determining odor identity with respect to odor quality. We end by motivating our central claim that more research needs to be conducted on the role that odorants play within the odor plume in determining odor identity. (shrink)

Molecular vibrations and quantum tunneling may link ligand binding to the function of pharmacological receptors. The well‐established lock‐and‐key model explains a ligand's binding and recognition by a receptor; however, a general mechanism by which receptors translate binding into activation, inactivation, or modulation remains elusive. The Vibration Theory of Olfaction was proposed in the 1930s to explain this subset of receptor‐mediated phenomena by correlating odorant molecular vibrations to smell, but a mechanism was lacking. In the 1990s, inelastic electron tunneling (...) was proposed as a plausible mechanism for translating molecular vibration to odorant physiology. More recently, studies of ligands’ vibrational spectra and the use of deuterated ligand analogs have provided helpful information to study this admittedly controversial hypothesis in metabotropic receptors other than olfactory receptors. In the present work, based in part on published experiments from our laboratory using planarians as an experimental organism, I will present a rationale and possible experimental approach for extending this idea to ligand‐gated ion channels. (shrink)

Any living organism interacts with and responds specifically to environmental molecules by expressing specific olfactory receptors. In this paper, this specificity will be first examined in causal terms with particular emphasis on the mechanisms controlling olfactory gene expression, cell-to-cell interactions and odor-decoding processes. However, this type of explanation does not entirely justify the role olfactory receptors have played during evolution, since they are also expressed ectopically in different organs and/or tissues. Homologous olfactory genes have in fact been found in (...) such diverse cells and/or organs as spermatozoa, testis and kidney where they are assumed to act as chemotactic sensors or renin modulators. To justify their functional diversity, homologous olfactory receptors are assumed to share the same basic role: that of conferring a self-identity to cells or tissues under varying environmental conditions. By adopting this standpoint, the functional attribution as olfactory or chemotactic sensors to these receptors should not be seen either as a cause conditioning receptor gene expression, or as a final effect resulting from genetically predetermined programs, but as a direct consequence of the environmental conditions olfactory receptor genes have explored during evolution. The association of odorant patterns with specific environmental or contextual situations makes their relationship semiotically triadic, due to the emergence of an interpretant capable of perceiving odorants as meaningful signs out of a noisy background. This perspective highlights the importance of odorant-receptor relationships as respect to the properties of the interacting partners. It is our contention that only when taken together can these different explanatory strategies provide a realistic account of how olfactory receptor genes have been structurally and functionally modified during evolution. (shrink)

La Terre est un jardin bordé de nuit. Tels des aveugles nous avançons, mais sûrs de nous, fiers, cruels, consommateurs, assoiffés de profit. Modernes? Que restera-t-il à nos enfants de cette oasis si humaine? Seront-ils seulement là pour contempler nos méfaits? Verront-ils, comme nous, les fleurs, le désert, le ciel aux mille étoiles, la vie menacée, la guerre? Théodore Monod - qui avait seize ans quand les cloches de France sonnèrent la paix en 1918 - nous offre une méditation lucide (...) et pleine d'espoir. Il se bat aujourd'hui comme il l'a toujours fait. Et nous dit : ne mourons pas résignés devant nos ordinateurs. Dans le silence. Dans nos lits. Battons-nous. Cherchons le beau, le vrai. Ayons enfin le courage des larmes. Et révérons la vie. (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

In 1991, Linda Buck and Richard Axel identified the multigene family expressing odor receptors. Their discovery transformed research on olfaction overnight, and Buck and Axel were awarded the 2004 Nobel Prize in Physiology or Medicine. Behind this success lies another, less visible study about the methodological ingenuity of Buck. This hidden tale holds the key to answering a fundamental question in discovery analysis: What makes specific discovery tools fit their tasks? Why do some strategies turn out to be more (...) fruitful than others? The fit of a method with an experimental system often establishes the success of a discovery. However, the underlying reasoning of discovery is hard to codify. These difficulties point toward an element of discovery analysis routinely sidelined as a mere biographical element in the philosophical analysis of science: the individual discoverer’s role. I argue that the individual researcher is not a replaceable epistemic element in discovery analysis. This article draws on contemporary oral history, including interviews with Buck and other actors key to developments in late 1980s olfaction. (shrink)

Current research on the origin of DNA and RNA, viruses, and mobile genetic elements prompts a re-evaluation of the origin and nature of genetic material as the driving force behind evolutionary novelty. While scholars used to think that novel features resulted from random genetic mutations of an individual’s specific genome, today we recognize the important role that acquired viruses and mobile genetic elements have played in introducing evolutionary novelty within the genomes of species. Viral infections and subviral RNAs can enter (...) the host genome and persist as genetic regulatory networks. Persistent viral infections are also important to understand the split between great apes and humans. Nearly all mammals and nonhuman primates rely on olfaction, i.e., chemoreception as the basis of the sense of smell for social recognition, group membership, and the coordination of organized social life. Humans, however, evolved other means to establish social bonding, because several infection waves by endogenous retroviruses caused a loss of odor receptors in human ancestors. The human independence from olfaction for social recognition was in turn one driver of the rather abrupt human transition to dependence on visual information, gesture production, and facial recognition that are at the roots of language-based communication. (shrink)

Herein, I discuss the enduring mystery of the receptor layout in the vertebrate olfactory system. Since the awarding of the 2004 Nobel Prize to Axel and Buck for their discovery of the gene family that encodes olfactory receptors, our field has enjoyed a golden era. Despite this Renaissance, an answer to one of the most fundamental questions for any sensory system—what is the anatomical logic of its receptor array?—eludes us, still, for olfaction! Indeed, the only widely debated hypothesis, (...) finding its origins in the musing of another Nobel laureate Sir Edgar Adrian, has it that the vertebrate nose organizes its receptors according to the “sorptive” properties of their ligands. This idea, known as the “sorption” or “chromatography” hypothesis, enjoys considerable support despite being controversial. Here, I review the history of the hypothesis—its rises and falls—and discuss the latest data and future prospects for this perennial idea whose history I liken to the mythical Phoenix. (shrink)

Animals use their chemosensory systems to detect and discriminate among chemical cues in the environment. Remarkable progress has recently been made in our knowledge of the molecular and cellular basis of chemosensory perception in insects, based largely on studies in Drosophila. This progress has been possible due to the identification of gene families for olfactory and gustatory receptors, the use of electro‐physiological recording techniques on sensory neurons, the multitude of genetic manipulations that are available in this species, and insights from (...) several insect model systems. Recent studies show that the superfamily of chemoreceptor proteins represent the essential elements in chemosensory coding, endowing chemosensory neurons with their abilities to respond to specific sets of odorants, tastants or pheromones. Investigating how insects detect chemicals in their environment can show us how receptor protein structures relate to ligand binding, how nervous systems process complex information, and how chemosensory systems and genes evolve. BioEssays 28:23–34, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

In spite of advances in medicine and public health, malaria and other mosquito‐borne diseases are on the rise worldwide. Although vaccines, genetically modified mosquitoes and safer insecticides are under development, herein we examine a promising new approach to malaria control through better repellents. Current repellents, usually based on DEET, inhibit host finding by impeding insect olfaction, but have significant drawbacks. We discuss how comparative genomics, using data from the Anopheles genome project, allows the rapid identification of members of three protein (...) classes critical to insect olfaction: odorant‐binding proteins, G‐protein‐coupled receptors, and odorant‐degrading enzymes. A rational design approach similar to that used by the pharmaceutical industry for drug development can then be applied to the development of products that interfere with mosquito olfaction. Such products have the potential to provide more complete, safer and longer lasting protection than conventional repellents, preventing disease transmission by interrupting the parasite life cycle. BioEssays 25:1011–1020, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Chemotaxis and thermotaxis in Caenorhabditis elegans are based on the chemical senses (smell and taste) and the thermal sense, respectively, which are important for the life of the animal. Laser ablation experiments have allowed identification of sensory neurons and some interneurons required for these senses. Many mutants that exhibit various abnormalies have been isolated and analyzed. These studies have predicted novel signaling pathways whose components include a putative odorant specific transmembrane receptor (ODR‐10) and a cyclic nucleotide‐gated channel (TAX‐4/TAX‐2) functioning (...) in taste and thermosensation as well as in smell. The emerging picture of the mechanisms of sensory transduction in C. elegans seems to be basically similar to what is known of visual and olfactory sensory transduction in vertebrates. Thus, molecular and cellular analyses of chemotaxis and thermotaxis in C. elegans have proved useful and will continue to provide significant implications for the molecular basis of sensory systems in higher animals. (shrink)

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set (...) has allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

It is arguably the case that olfactory system contains two senses that share the same type of stimuli, sensory transduction mechanism, and processing centers. Yet, orthonasal and retronasal olfaction differ in their types of perceptible objects as individuated by their sensory qualities. What will be explored in this paper is how the account of orthonasal smell developed in the Molecular Structure Theory of smell can be expanded for retronasal olfaction (Young, 2016, 2019a-b, 2020). By considering the object of olfactory perception (...) to be the molecular structure of chemical compounds composing odor plumes, Molecular Structure Theory provides a means for determining an odor’s olfactory quality, how odors can be identified and individuated, and how we perceive smellscapes. Surveying the differences between orthonasal and retronasal olfaction provides the basis for the central argument of the paper that the perceptible objects we refer to as smells and individuated on the basis of their olfactory qualities are only relative to orthonasal olfaction. Retronasal olfaction it is speculatively concluded might play an essential role in our perception of flavorful objects. (shrink)

Olfaction represents odors, if it represents anything at all. Does olfaction also represent ordinary objects like cheese, fish and coffee-beans? Many think so. This paper argues that it does not. Instead, we should affirm an austere account of the intentional objects of olfaction: olfactory experience is about odors, not objects. Visuocentric thinking about olfaction has tempted some philosophers to say otherwise.

O texto parte de um diagnóstico fenomenológico: o de que toda emergência pandêmica (como a da covid, por exemplo) é o sintoma fatídico de um estado de crise motivado nas entranhas mesmas ontológicas da racionalidade tal qual toma forma em nossa cultura no Ocidente. A tarefa do pensamento não consiste em destruir a razão, mas salvaguardá-la ante o perigo, sempre iminente, do irracionalismo. Assim, toda forma de obscurantismo emerge como uma figura decadente tendo como pano de fundo sintomático a crise (...) da própria razão; crise essa instalada pela distinção de princípio entre cultura e natureza tão bem prefigurada por Marx e aprofundada por Merleau-Ponty. O texto examina esse ponto nevrálgico e termina realçando o caráter essencial e, portanto, inalienavelmente político desse fenômeno. (shrink)

Scientists have shown that many non‐human animals such as ants, dogs, or rats are very good at using smells to find their way through their environments. But are humans also capable of navigating through their environment based on olfactory cues? There is not much research on this topic, a gap that the present research seeks to bridge. We here provide one of the first empirical studies investigating the possibility of using olfactory cues as landmarks in human wayfinding. Forty subjects participated (...) in a piloting study to determine the olfactory material for the main experiment. Then, 24 subjects completed a wayfinding experiment with 12 odors as orientation cues. Our results are astonishing: Participants were rather good at what we call “odor‐based wayfinding.” This indicates that the ability of humans to use olfactory cues for navigation is often underestimated. We discuss two different cognitive explanations and rule out the idea that our results are just an instance of sequential learning. Rather, we argue that humans can enrich their cognitive map of the environment with olfactory landmarks and may use them for wayfinding. (shrink)

Progress in solving the structure of insulin bound to its receptor has been slow and stepwise, but a milestone has now been reached with a refined structure of a complex of insulin with a “microreceptor” that contains the primary binding site. The insulin receptor is a dimeric allosteric enzyme that belongs to the family of receptor tyrosine kinases. The insulin binding process is complex and exhibits negative cooperativity. Biochemical evidence suggested that insulin, through two distinct binding sites, (...) crosslinks two receptor sites located on each α subunit. The structure of the unliganded receptor ectodomain showed a symmetrical folded‐over conformation with an antiparallel disposition. Further work resolved the detailed structure of receptor site 1, both without and with insulin. Recently, a missing piece in the puzzle was added: the C‐terminal portion of insulin's B‐chain known to be critical for binding and negative cooperativity. Here I discuss these findings and their implications. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite (...) of the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

Odor and color are strongly associated. Numerous studies demonstrate consistent odor‐color associations, as well as effects of color on odor perception and language. Yet, we know little about how these associations arise. Here, we test whether language is a possible mediator of odor‐color associations, specifically whether odor‐color associations are mediated by implicit odor naming. In two experiments, we used an interference paradigm to prevent the verbalization of odors during an odor‐color matching task. If (...) participants generate color associations subsequent to labeling an odor, interfering with verbalization during the task should affect the ability to make color associations. In Experiment 1, contrary to our hypothesis, verbal interference did not affect odor‐color matches. However, since performance accuracy on the verbal interference task was high, it is possible our task did not sufficiently disrupt verbal processing. In Experiment 2, we, therefore, used an active verbal interference task, and still found no difference across interference conditions. Odor naming accuracy, odor familiarity, and odor pleasantness, however, did predict odor‐color matches. This suggests that although color associations are related to semantic factors, they are not generated by recruiting odor labels in the moment. Overall, our results do not provide evidence that language plays an online role in odor‐color associations, instead, they are consistent with the claim that language may have shaped associations during development. (shrink)

Estrogen receptor α (ERα) is a ligand‐dependent transcription factor that regulates the expression of estrogen‐responsive genes. Approximately 70% of patients with breast cancer are ERα positive. Estrogen stimulates cancer cell proliferation and contributes to tumor progression. Endocrine therapies, which suppress the ERα signaling pathway, significantly improve the prognosis of patients with breast cancer. However, the development of de novo or acquired endocrine therapy resistance remains a barrier to breast cancer treatment. Therefore, understanding the regulatory mechanisms of ERα is essential (...) to overcome the resistance to treatment. This review focuses on the regulation of ERα expression, including copy number variation, epigenetic regulation, transcriptional regulation, and stability, as well as functions from the point of view post‐translational modifications. (shrink)

This article explores how historians of emotions and historians of the senses can collaborate to write a history of emotional experience that takes seriously the corporeality of emotions. It invest...

The evolutionist theories of Bachofen on the priority of matriarchy are today no more than one of the most unusual pieces of the historical museum of anthropology. The wealth and diversity of historical and literary sources therein are juxtaposed with the construction of a conjectural chronology organizing the relationship between the sexes in a progressive mode and in accordance with an immanent finality. But it is also necessary to distinguish, on the one hand, Bachofen's historicism as an expression of the (...) evolutionist tendencies of that time, based on natural sciences and the results of Darwin's work, and, on the other, interest in the inter-sexual relationship within the social institution. For the invention of successive stages in order to propose a social history of sexuality is based as much on evolutionism as on constitutive psychic representations of the individual. By projecting these representations into a pseudo-historical period and by ordering them, at each level, in terms of the two parameters of domination / subjection and collectivity / individuality, Bachofen assigned semantics to history and an evolutionary sense to transformations in marriage and the family. And by conferring historical validity on the myths of Antiquity, he set forth an implicit denial both of the work of the imagination (not to say sub-conscious, which would be an anachronism for this pre-Freudian period) as well as of ideological ruses in the political field. Bachovian evolutionism thus developed a new myth out of the ancient myths, false witnesses of the past but authentic representatives of the ahistorical present of the psyche, endowing with scientific color the image of humanity progressing from dominance of the mother and collectivism to the triumph of the father and individualism. The idea of “matriarchy” (Mutterrecht) in Bachofen is indeed to be taken in the sense of “maternal dominance” (as the German expression better suggests), and not that of political power of women. (shrink)