Molecular chaperones assist de novo protein folding and facilitate the refolding of stress‐denatured proteins. The molecular chaperone concept was coined nearly 35 years ago, and since then, tremendous strides have been made in understanding how these factors support protein folding. Here, we focus on how various chaperone proteins were first identified to play roles in protein folding. Examples are used to illustrate traditional routes of chaperone discovery and point out their advantages and limitations. Recent advances, including (...) the development of folding biosensors and promising methods for the stabilization of proteins in vivo, provide new routes for chaperone discovery. (shrink)

The discovery of “molecular chaperones” has dramatically changed our concept of cellular protein folding. Rather than folding spontaneously, most newly synthesized polypeptide chains seem to acquire their native conformation in a reaction mediated by these versatile helper proteins. Understanding the structure and function of molecular chaperones is likely to yield useful applications for medicine and biotechnology in the future.

In this paper I use a case study—the discovery of the chaperon function exerted by proteins in the various steps of the hereditary process—to re-discuss the question whether the nucleic acids are the sole repositories of relevant information as assumed in the information theory of heredity. The evidence I here present of a crucial role for molecular chaperones in the folding of nascent proteins, as well as in DNA duplication, RNA folding and gene control, suggests that the family of (...) proteins acting as molecular chaperones provides information that is complementary to that stored in the nucleic acids, and equally important. A re-evaluation of the role of proteins in the hereditary process is in order away from the gene-centric approach of the information theory of heredity, to which neo-Darwinian evolutionists adhere. (shrink)

There are two facets to the central dogma proposed by Francis Crick in 1957. One concerns the relation between the sequence of nucleotides and the sequence of amino acids, the second is devoted to the relation between the sequence of amino acids and the native three-dimensional structure of proteins. 'Folding is simply a function of the order of the amino acids,' i.e. no information is required for the proper folding of a protein other than the information contained in its sequence. (...) This protein side of the central dogma was elaborated in a scientific context in which the characteristics and functions of proteins, and the mechanisms of protein folding, were seen very differently. This context, which made the folding problem a simple one, supported the bold proposition of Francis Crick. The protein side of the central dogma was not challenged by the discovery of prions if one adopts the definition of information given by Francis Crick. It might have been challenged by the discovery that regulatory enzymes exist in different conformations, and the evidence for the existence of chaperones assisting protein folding. But it was not, and folding remains what it was for Francis Crick, 'simply a function of the order of amino acids'. But the meaning of 'function' has dramatically changed. It is no longer the result of simple physicochemical laws, but that of a long evolutionary process which has optimized protein folding. Molecular mechanistic explanations have to be allied with evolutionary explanations, in a way characteristic of present biology. (shrink)

Peptidylprolyl‐isomerases (PPIases) comprise of the protein families of FK506 binding proteins (FKBPs), cyclophilins, and parvulins. Their common feature is their ability to expedite the transition of peptidylprolyl bonds between the cis and the trans conformation. Thus, it seemed highly plausible that PPIase enzymatic activity is crucial for protein folding. However, this has been difficult to prove over the decades since their discovery. In parallel, more and more studies have discovered scaffolding functions of PPIases. This essay discusses the hypothesis that (...) PPIase enzymatic activity might be the consequence of binding to peptidylprolyl protein motifs. The main focus of this paper is the large immunophilins FKBP51 and FKBP52, but other PPIases such as cyclophilin A and Pin1 are also described. From the hypothesis, it follows that the PPIase activity of these proteins might be less relevant, if at all, than the organization of protein complexes through versatile protein binding. Also see the video abstract here https://youtu.be/A33la0dx5LE. (shrink)

Dès que Le Deuxième sexe de Simone de Beauvoir paraît en France en 1949, il est pris dans la division intellectuelle de la guerre froide. Mais est-ce le cas dans le reste de l’Europe à mesure que les traductions du livre paraissent? Une comparaison des réceptions et traductions du livre au cours de la guerre froide manque. Elle est pourtant rendue possible grâce à trois récents tournants historiographiques : la guerre froide au prisme du genre, l’étude des circulations transnationales du (...) Deuxième sexe et la traductologie féministe. (shrink)

L'histoire des femmes depuis la Seconde Guerre mondiale est bien plus développée en Italie qu'en France. Le dernier ouvrage d'Anna Rossi-Doria nous en fournit une preuve supplémentaire. S'appuyant sur ses recherches personnelles, mais aussi sur une solide bibliographie, l'auteure s'interroge sur les multiples facettes du droit de vote féminin. Le décret qui institue le droit de vote féminin présente bien des similarités avec l'ordonnance française. Comme en France, celui-ci ne résulte...

Depuis les années 1980, l’histoire de la médecine a connu un très fort renouvellement de ses approches, de ses objets et de sa mise en récit. L’histoire des femmes, du genre et des sexualités, en plein essor depuis ces mêmes années, a contribué de manière non négligeable à ce renouvellement en s’emparant de sources médicales délaissées par l’histoire de la médecine traditionnelle. En effet, durablement imprégnées par l’héritage positiviste du xixe siècle, l’histoire de la médecine et plus lar...

Durant les années 1950 et plus encore la décennie suivante, les ouvrages sur les questions féminines se multiplient. Cet article s’interroge sur les auteures de ces essais. Se dessine ainsi une génération d’expertes en études sur les femmes. Nées au début du siècle, profondément marquées par l’expérience de la deuxième guerre, ces nouvelles spécialistes sont diplômées des universités. Elles bénéficient de l’essor des médias mais ne parviennent pas toujours à avoir une situation professionnelle stable. Ensemble et s’appuyant sur les réflexions (...) beauvoiriennes, elles construisent un nouveau champ d’études, dont nous sommes les héritières. (shrink)

Yvonne Knibiehler continue son histoire des mères commencée il y a quelques années et arrêtée au seuil des ses propres enfantements, comme elle le rappelle dans l'introduction. L'entreprise n'est pourtant pas aisée. Non pas que le sujet déborderait trop sur l'intime de la chercheuse. L'égo-histoire, qui ne rime décidément pas avec l'histoire tout court, ne dépasse pas les premières pages de l'ouvrage. Mais le sujet est miné, piégé de l'intérieur par une charge idéologique hors du commu...

L'histoire des femmes depuis la Seconde Guerre mondiale est bien plus développée en Italie qu'en France. Le dernier ouvrage d'Anna Rossi-Doria nous en fournit une preuve supplémentaire. S'appuyant sur ses recherches personnelles, mais aussi sur une solide bibliographie, l'auteure s'interroge sur les multiples facettes du droit de vote féminin. Le décret qui institue le droit de vote féminin présente bien des similarités avec l'ordonnance française. Comme en France, celui-ci ne résulte..

Ce gros livre est le fruit d’un travail collectif, réalisé à l’initiative de l’Agence nationale de recherche sur le sida et les hépatites virales (ANRS), par un collectif de treize chercheur-e-s (sociologues, démographes, épidémiologistes, psycho-sociologues, économistes). Un long questionnaire a été élaboré et soumis par téléphone par soixante et un enquêteurs de l’Institut de sondage Ipsos à plus de 12 000 personnes âgées de 18 à 69 ans entre septembre 2005 et mars 2006. Cette enquête dite...

Yvonne Knibiehler continue son histoire des mères commencée il y a quelques années et arrêtée au seuil des ses propres enfantements, comme elle le rappelle dans l'introduction. L'entreprise n'est pourtant pas aisée. Non pas que le sujet déborderait trop sur l'intime de la chercheuse. L'égo-histoire, qui ne rime décidément pas avec l'histoire tout court, ne dépasse pas les premières pages de l'ouvrage. Mais le sujet est miné, piégé de l'intérieur par une charge idéologique hors du commu..

Sans prétendre faire œuvre exhaustive ni même définitive, Mariette Sineau et Evelyne Tardy se livrent à un instructif travail comparatif sur le droit des femmes dans les deux territoires francophones. Malgré toutes leurs différences, ceux-ci se montrent suffisamment proches pour soutenir la comparaison. Tous deux adoptent le code civil napoléonien (en 1866 pour le Québec pourtant cerné par la bien plus progressive common law), tous deux sont également à forte dominante catholique. Le m...

Exceptionnel, l'itinéraire politique de Marcelle Devaud, l'est assurément. Sénatrice dès 1946 puis députée (de 1958 à 1962), maire de Colombes (1959-1965), membre de Conseil Economique et Social (1962-1979), représentante de la France à la commission de la femme aux Nations-Unies (1975-1983), elle cumule tous ces mandats avec de nombreuses responsabilités dans les associations féminines, dont plusieurs fondées par elle-même. Quand on sait qu'elle est par ailleurs mère de 6 enfants, on...

Cet ouvrage reprend sous forme remaniée les actes du colloque « Germaine Poinso-Chapuis, témoin de son temps » organisé à Marseille par l'association Les Femmes et la Ville (20-22 novembre 1997). Il répare heureusement l'oubli injuste d'une figure majeure de l'histoire de l'après-guerre. Moins connue que les femmes sous-secrétaires d'État du Front populaire alors qu'elle est la première femme ministre de plein exercice, moins populaire que Simone Veil alors qu'elle a été députée pendan...

Pour celles et ceux qui ne connaîtraient pas ou peu, ou mal Marie-France Brive, ce livre offre l'occasion de multiples rencontres émouvantes avec l'une des figures majeures de l'histoire des femmes en France. Car, comme son titre ne l'indique pas, cet ouvrage collectif est un hommage posthume. Ironie de l'histoire, le nom de celle qui affirmait : « il y a une construction de l'oubli des femmes en histoire » (p. 333) se trouve ainsi effacé de la couverture du livre (...) qui lui est consacré.... (shrink)

L'ouvrage de William Guéraiche s'inscrit dans un renouvellement notable de l'historiographie de ces quelques dernières années. L'après-Deuxième Guerre mondiale, les années cinquante se voient revisitées de multiples façons par les travaux de Noël Burch et Geneviève Sellier, Luc Capdevila, Fabrice Virgili et moi-même. Le découpage chronologique de l'étude ne suit pas les coupures majeures de l'histoire politique française; ni 1958 ni 1968 ne fondent de ruptures, par exemple. La superpos...

Sans prétendre faire œuvre exhaustive ni même définitive, Mariette Sineau et Evelyne Tardy se livrent à un instructif travail comparatif sur le droit des femmes dans les deux territoires francophones. Malgré toutes leurs différences, ceux-ci se montrent suffisamment proches pour soutenir la comparaison. Tous deux adoptent le code civil napoléonien (en 1866 pour le Québec pourtant cerné par la bien plus progressive common law), tous deux sont également à forte dominante catholique. Le m..

Exceptionnel, l'itinéraire politique de Marcelle Devaud, l'est assurément. Sénatrice dès 1946 puis députée (de 1958 à 1962), maire de Colombes (1959-1965), membre de Conseil Economique et Social (1962-1979), représentante de la France à la commission de la femme aux Nations-Unies (1975-1983), elle cumule tous ces mandats avec de nombreuses responsabilités dans les associations féminines, dont plusieurs fondées par elle-même. Quand on sait qu'elle est par ailleurs mère de 6 enfants, on ..

This book compiles and reviews the most prominent linguistic theories into a single source that serves as an essential reference for future solutions to one of the most important challenges of our age.

Histone variants are specialized histones which replace their canonical counterparts in specific nucleosomes. Together with histone post‐translational modifications and DNA methylation, they contribute to the epigenome. Histone variants are incorporated at specific locations by the concerted action of histone chaperones and ATP‐dependent chromatin remodelers. Recent studies have shown that the histone chaperone FACT plays key roles in preventing pervasive incorporation of two histone variants: H2A.Z and CenH3/CENP‐A. In addition, Spt6, another histone chaperone, was also shown to be important (...) for appropriate H2A.Z localization. FACT and Spt6 are both associated with elongating RNA polymerase II. Based on these two examples, we propose that the establishment and maintenance of histone variant genomic distributions depend on a transcription‐coupled epigenome editing (or surveillance) function of histone chaperones. (shrink)

Fibrillar protein aggregates are the pathological hallmark of a group of age‐dependent neurodegenerative conditions, including Alzheimer's and Parkinson's disease. Aggregates of the microtubule‐associated protein Tau are observed in Alzheimer's disease and primary tauopathies. Tau pathology propagates from cell to cell in a prion‐like process that is likely subject to modulation by extracellular chaperones such as Clusterin. We recently reported that Clusterin delayed Tau fibril formation but enhanced the activity of Tau oligomers to seed aggregation of endogenous Tau in a cellular (...) model. In contrast, Clusterin inhibited the propagation of α‐Synuclein aggregates associated with Parkinson's disease. These findings raise the possibility of a mechanistic link between Clusterin upregulation observed in Alzheimer's disease and the progression of Tau pathology. Here we review the diverse functions of Clusterin in the pathogenesis of neurodegenerative diseases, focusing on evidence that Clusterin may act either as a suppressor or enhancer of pathology. (shrink)

The book is a comprehensive introduction to the work of the Estonian-German biologist Jakob von Uexküll. After a first introductory chapter by Morten Tønnessen and a second chapter on Uexküll's life and philosophical background, it contains four chapters devoted to the analysis of his main works; they are followed by a vast eighth chapter which deals with the influence Uexküll had on other philosophers and scientists, and by a conclusions focused on the possibility of updating Uexküll's work. The monograph combines (...) a careful reconstruction of the historical context in which the Uexküllian concepts emerged (the debate between mechanism and vitalism, contemporary scientific studies) and a thorough analysis of the philosophical contents of the Uexküllian views. As far as the key issue is concerned, Uexküll's notion of Umwelt refers to the perceptive and operative world which surrounds animal species; it is a subjective species-specific construction which provides living organisms with great security and behaviour stability. Moreover, the relationship that the animal carries out with its environment proves to be a complex system of semiotic interactions: its behaviour is not a set of mechanical reactions, but the result of a spontaneous attribution of meaning to the outside world, whose environmental elements are actively interpreted by the subject. The environment of animal species becomes a field of meaning, an exceedingly complex subjective elaboration; this can lessen the distance between animals and men, crediting both with the cognitive ability to grasp meanings and to use signs. (shrink)

Le mot sexologie, la science de la sexualité, apparaît en France au début des années 1910. Il marque, de la part de ceux qui en usent, la volonté à la fois de lutter pour l’égalité des droits en matière de pratiques sexuelles et de rompre avec le savoir médical sur la sexualité. Dans son livre Les origines de la sexologie, 1850-1900, Sylvie Chaperon explore ce champ nouveau de l’histoire et se propose de démêler les fils qui, en ce domaine, enchevêtrent (...) si fortement savoir, pouvoir et représe... (shrink)

We highlight a recent study exploring the hand‐off of UV damage to several key nucleotide excision repair (NER) proteins in the cascade: UV‐DDB, XPC and TFIIH. The delicate dance of DNA repair proteins is choreographed by the dynamic hand‐off of DNA damage from one recognition complex to another damage verification protein or set of proteins. These DNA transactions on chromatin are strictly chaperoned by post‐translational modifications (PTM). This new study examines the role that ubiquitylation and subsequent DDB2 degradation has during (...) this process. In total, this study suggests an intricate cellular timer mechanism that under normal conditions DDB2 helps recruit and ubiquitylate XPC, stabilizing XPC at damaged sites. If DDB2 persists at damaged sites too long, it is turned over by auto‐ubiquitylation and removed from DNA by the action of VCP/p97 for degradation in the 26S proteosome. (shrink)

Self‐renewal and differentiation of stem cells are tightly regulated processes subject to intrinsic and extrinsic signals. Molecular chaperones and co‐chaperones, especially heat shock proteins (Hsp), are ubiquitous molecules involved in the modulation of protein conformational and complexation states. The function of Hsp, which are typically associated with stress response and tolerance, is well characterized in differentiated cells, while their role in stem cells remains unclear. It appears that embryonic stem cells exhibit increased stress tolerance and concomitant high levels of (...) class='Hi'>chaperone expression. This review critically evaluates stem cell research from a molecular chaperone perspective. Furthermore, we propose a model of chaperone‐modulated self‐renewal in mouse embryonic stem cells. (shrink)

Meier shows how the structure of Greek communal life gave individuals a civic role and discusses a crucial reform that institutionalized the idea of equality ...

In this paper I will give a systematic account of Husserl's notion of the natural attitude in the development from its first presentation in Ideas I (1913) until Husserl's last years. The problem of the natural attitude has to be dealt with on two levels. On the thematic level, it is constituted by the correlation of attitude and horizon, both stemming from Husserl's theory of intentionality. On the methodic level, the natural attitude is constituted by three factors: naturalness, naivety and (...) normality. I shall conclude by sketching out a possible motivation for leaving the natural attitude and thus for entering the sphere of phenomenology. (shrink)

The great biologist Louis Pasteur suppressed 'awkward' data because it didn't support the case he was making. John Snow, the 'first epidemiologist' was doing nothing others had not done before. Gregor Mendel, the supposed 'founder of genetics' never grasped the fundamental principles of 'Mendelian' genetics. Joseph Lister's famously clean hospital wards were actually notorious dirty. And Einstein's general relativity was only 'confirmed' in 1919 because an eminent British scientist cooked his figures. These are just some of the revelations explored in (...) this book. Drawing on current history of science scholarship, Fabulous Science shows that many of our greatest heroes of science were less than honest about their experimental data and not above using friends in high places to help get their ideas accepted. It also reveals that the alleged revolutionaries of the history of science were often nothing of the sort. Prodigiously able they may have been, but the epithet of the 'man before his time' usually obscures vital contributions made their unsung contemporaries and the intrinsic merits of ideas they overturned. These distortions of the historical record mostly arise from our tendency to read the present back into the past. But in many cases, scientists owe their immortality to a combination of astonishing effrontery and their skills as self-promoters. (shrink)

Background: Medical chaperones (MC) are underutilised. The influence of Islamic culture on the use of MC is not known. Aim: To examine physicians’ use and perception of MC in Islamic culture. Setting: A major tertiary care hospital in Saudi Arabia. Methods: 315 self-administered questionnaires were distributed to attendees of grand rounds of 13 departments. Results: 186 (59%) questionnaires were completed. 64.5% of the respondents were 30–49 years old, 75.8% were men and 31.2% were in training; 79% had a clinic load (...) of under 50 patients per week and 47.8% had postgraduate training (PGT) in an Islamic country. MC were reported to be infrequently (⩽25% of the time) used by 44.1% (69.2% female vs 39% male physicians, p = 0.001; 58.6% in training vs 36.8% attending, p = 0.007; 52.1% PGT in Islamic vs 35.6% in western countries, p = 0.027), offered by 52.7% (78.9% female vs 46.8% male physicians, p<0.001) and requested by 79% of patients. MC were reported to be commonly (>75% of the time) used, offered by physicians and requested by patients by 38.2%, 29% and 7.5% of respondents, respectively. The most frequently cited reasons for not using MC were privacy/confidentiality (36.6%) and understaffing (30.5%). Equal numbers of respondents perceived MC use as a protection for physicians or patients (67.7% and 65.6%, respectively). Conclusions: MC are underutilised even in Islamic culture, especially among female physicians. Training in western countries is favourably associated with MC use. Underutilisation appears to be related to privacy/confidentiality, understaffing and failure of patients to request a MC. (shrink)

By modern standards Bacon's writings are striking in their range and diversity, and they are too often considered a separate specialist concerns in isolation from each other. Dr Jardine finds a unifying principle in Bacon's preoccupation with 'method', the evaluation and organisation of information as a procedure of investigation or of presentation. She shows how such an interpretation makes consistent sense of the whole corpus of Bacon's writings: how the familiar but misunderstood inductive method for natural science relations to the (...) more information strategies of argument in his historical, ethical, political and literary work. There is a substantial and valuable study of the intellectual Renaissance background from which Bacon emerged and against which he reacted. Through a series of details comparisons and contrasts we are led to appreciate the true originality and ingenuity of Bacon's own views and also to discount the more superficial resemblances between them and later developments in the philosophy of science. (shrink)