Telomerase is present in over 90% of tumour tissues and immortalized cells and is tightly regulated in most normal somatic cells. This suggests the existence of regulatory mechanisms repressing telomerase in normal cells that somehow have become inactive during cancer development. In this project, I used genetic complementation in the form of microcell-mediated monochromosome transfer (MMCT) to search for chromosomes that repress telomerase activity in a prostate cancer cell line, PC-3. Microcell hybrids generated by introducing normal human chromosome 11 strongly inhibited telomerase. Telomerase is regulated primarily at the level of hTERT transcription, its catalytic subunit. Consequently, endogenous hTERT mRNA levels were measured by quantitative RT-PCR in microcell hybrids generated by transferring normal human chromosomes into a PC-3 sub-clone (PC- 3/hTERT) ectopically expressing hTERT cDNA to prevent senescence. Only hybrids constructed with transferred chromosome 11 showed strong transcriptional repression of hTERT. Next, hybrids were constructed by the MMCT transfer of chromosome 11 fragments (X-ray-induced). FISH analysis of clones with completely silenced endogenous hTERT transcription revealed in all cases a discrete chromosome 11 fragment with both the p-arm and q-arm material. A randomly selected hTERT-repressed clone was treated with ganciclovir to select against the HyTK marker and reverse the phenotype. hTERT expression in majority of GCV-resistant clones returned to levels comparable to the parent PC-3/hTERT cells. Collectively, these results provide strong functional evidence for the presence of a powerful telomerase repressor sequence on the fragment. Transfer of one repressive fragment back into mouse A9 cells was then carried out to facilitate fine-structure mapping of its sequence content. High density STS mapping of the fragment in each of the clones revealed a considerable DNA content heterogeneity across the panel. These content maps, together with a further round of MMCT to confirm hTERTrepressive activity, enabled me to identify three candidate regions on the q-arm of chromosome 11 where the repressor sequence may be located: the first region lies between map positions 64.70Mb to 65.42Mb and the other two regions each flank a single positive STS marker at 69.71Mb and 127.32Mb. KAT5, a histone modifying gene has been identified as a potential candidate for repressing hTERT.

La migration des cellules souches / progénitrices neurales (CSPN) dans le cerveau adulte est cruciale pour la réparation cérébrale. Reeline (Rln) est une protéine de la matrice extracellulaire, régulant le positionnement des neurones pendant la croticogénèse. Nous révélons un rôle nouveau de Rln chez l'adulte. In vitro, Rln est chémocinétique mais pas chémoattractante. In vivo, Rln induit le détachement et la dispersion des CSNP de la zone sousventriculaire (SVZ) hors du courant rostral de migration (RMS) où elles sont sinon confinées. Rln potentialise le recrutement spontané des CSPN vers les lésions démyélinisantes où un tiers deviennent oligodendrocytaires. L'expression endogène de Rln est stimulée après lésion. Les animaux sans voie de signalisation Rln ont un recrutement réduit des CSPN vers les lésions.Ces résultats révèlent que Rln est un arbitre clef de la migration post-lésionnelle des CSPN et que permettre au CSPN de sortir du RMS est une stratégie thérapeutique prometteuse. / Neural stem/ progenitor cell (NSPC) migration in the adult brain is crucial for brain repair. Reelin (Rln) is an extracellular matrix protein regulating neuron positioning during coricogenesis. We reveal new roles of Rln in adult NSPC migration. In vitro, Rln promotes detachment, is chemokinetic but not chemoattractant. After Rln ectopic overexpression in the healthly brain, subventricular zone (SVZ) NSPC detach from the rostal migratory stream (RMS) in which they are normally restricted, and disperse in adjacent fiber tracts. Rln over-expression potentiates spontaneous cell recruitment to demyelinated lesion and one third of the NSPC recruited adopt an oligodendrocytic phenotype. Rln expression is spontaneously upregulated after lesion, and disruption of its signaling pathway results in reduced NSPC recruitment toward lesion. Our study reveals that Rln is a key player of post-lesional NSPC migration and that allowing NSPC to escape from RMS is a promising therapeutic approach

This thesis aims at contributing to the existing studies in the dynamic stochastic general equilibrium model, particularly in the new Keynesian models, on three aspects. It consists of three chapters. Chapter 2 is on “Dynamic new Keynesian Life-Cycle Model.” Chapter 3 is on “Re-thinking Price Stability in an Economy with Endogenous Firm Entry: Real Imperfections under Product Variety.” Chapter 4 is on “Growth Expectation.” Abstracts of each Chapter are as follows. In Chapter 2, we first construct a dynamic new Keynesian model that incorporates life-cycle behavior a la Gertler (1999), in order to study whether structural shocks to the economy have asymmetric effects on heterogeneous agents, namely workers and retirees. We also examine whether considerations of life-cycle and demographic structure alter the dynamic properties of the monetary business cycle model, specifically the degree of amplification in impulse responses. According to our simulation results, shocks indeed have asymmetric impacts on different households and the demographic structure does alter the size of responses against shocks by changing the trade-off between substitution and income effects. In Chapter 3, we re-think price stability in an economy with endogenous firm entry under possible distortions. We first demonstrate that endogenous entry causes real imperfections. Reflecting fluctuations in the number of varieties, the gap between the natural and the efficient level of output is no longer constant and variant to shocks. As a result, the central bank faces a trade-off between stabilizing inflation and welfare-relevant output gap. Then, we show that this results in the non-zero optimal rate of inflation. We further check whether welfare can be enhanced by targeting welfare-based inflation instead of cross-sectional average inflation contrary to the previous findings. Simulations even with such distortions as unknown natural interest rate or no fiscal remedy for efficient non-stochastic steady states, however, support cross-sectional average inflation targeting although there may exist some small gains by referring also to welfare-based inflation rates. Incomplete stabilization may enhance welfare in an economy when agents cannot internalize the externality on the love for variety. Chapter 4 is about the difficulty in producing reasonable business cycles for the expectation shock about higher future technology. For a long time, changes in expectations about the future have been thought to be significant sources of economic fluctuations, as argued by Pigou (1926). Although creating such an expectation-driven cycle (the Pigou cycle) in equilibrium business cycle models was considered to be a difficult challenge, as pointed out by Barro and King (1984), recently, several researchers have succeeded in producing the Pigou cycle by balancing the tension between the wealth effect and the substitution effect stemming from the higher expected future productivity. Seminal research by Christiano et al. (2007a) explains the “stock market boom-bust cycles,” characterized by increases in consumption, labor inputs, investment and the stock prices relating to high expected future technology levels, by introducing investment growth adjustment costs, habit formation in consumption, sticky prices and an inflation-targeting central bank. We, however, show that such a cycle is difficult to generate based on “growth expectation,” which reflect expectations of higher productivity growth rates. Thus, Barro and King’s (1984) prediction still applies.

High performance liquid chromatography was used to measure ribonucleoside triphosphates in microbial samples. Anion exchange columns in a radial compression module were used to separate and quantify purine and pyrimidine ribonucleotides. Endogenous ribonucleoside triphosphates were extracted from Escherichia coli and pseudomonas aeruginosa using three different solvents, namely trifluorocetic acid (TFA; 0.5M), trichloroacetic acid (TCA; 6 per cent w/v) and formic acid (1.0M) Extracts were assayed for uridine 5'-triphosphate (ATP), and guanosine 5'-triphosphate (GTP) by using anion exchange radial compression high performance (pressure) liquid chromatography. The three extraction produres were compared for yield of triphosphates. E. coli, the TFA extraction procedure was more sensitive and reliable than TCA and formic acid extraction procedures, but , in P. aeruginosa, the best yields of ATP and GTP were obrained following extraction with TFA. Yields of UTP and CTP increased when extraction was performed in TCA. These data illustrate that different extraction produres produce different measures for different triphosphates, a point often overlooked.

The goal of this thesis is to develop a DSGE model that accounts for the key business cycle properties of the Czech labor market. We used standard New Keynesian framework for monetary policy analysis and incorporated an elaborated labor market setup with equi- librium wage derived via an alternating offer bargaining protocol originally proposed by Rubinstein (1982) and follow the work of Christiano, Eichenbaum and Trabandt (2013) in the following steps. Firstly, we calibrated the closed economy model according to values suited for the Czech economy and found that the model can not only account for higher volatility of the real wage and unemployment, but can also explain the contemporaneous rise of both wages and employment after an expansionary shock in the economy, so called Shimer puzzle (Shimer, 2005a). Secondly, we demonstrated that the alternating offer bar- gaining sharing rule outperforms the Nash sharing rule under assumption of using the hiring costs in our framework (more so while using search costs) and therefore is better suited for use in larger scale models. Thirdly, we concluded that after estimating the labor market parameters using the Czech data, our model disproved the relatively low values linked to the probabilities of unsuccessful bargaining and job destruction. JEL...

Different types of shocks, or the treatment of one of the players in a specific network, may influence not only the future performance of themselves but also affect their network connections. It is crucial to explore the behaviour of the whole network in response to such an event. This paper focuses on the cases of endogenously formed shock. The logic used in the peer effect literature is adopted to develop the dynamic model and accounts for the endogeneity of the shock. The model allows us to predict the endogenous part of the shock and use the remaining unexpected component to estimate the effect of the shock on the changes in the performance of network connections. The identification conditions for effect are derived, and the consistent estimation procedure is proposed. / Series: Department of Economics Working Paper Series

O teste de atenção encoberta descrito por Posner (1980) vem sendo intensamente utilizado em estudos sobre orientação da atenção visuo-espacial em seres humanos. Mais recentemente, esse teste foi adaptado para avaliação da atenção em ratos, com resultados entusiasmantes, pois parece haver uma analogia entre os fenômenos atencionais envolvendo seres humanos e ratos (ROSNER; MITTLEMAN, 1996; WARD; BROWN, 1996; LUCK E VECERA, 2002). A distinção entre orientação exógena (ou \"automática\", na literatura envolvendo humanos) e endógena (ou \"voluntária\", na literatura envolvendo humanos) da atenção, postuladas principalmente com base nas diferenças do curso temporal da resposta ao alvo visual, foram em parte descritas em ratos; esses trabalhos iniciais sugeriam apenas a ocorrência de respostas automáticas em ratos. Porém, Marote e Xavier (2011) mostraram efeito de validade quando pistas preditivas e não-preditivas precediam o alvo em 200, 400 e 800 ms; porém, esse efeito foi maior quando as pistas preditivas precederam o alvo em 800 ms, o que em humanos é tido como efeito da orientação voluntária da atenção. Dado que na maioria dos estudos envolvendo ratos a pista utilizada é periférica, torna-se difícil distinguir claramente entre a ocorrência de efeitos exógenos e efeitos endógenos da orientação da atenção. No presente estudo avaliamos a orientação encoberta da atenção visuo-espacial em ratos empregando pistas simbólicas preditivas, isto é, um tipo de pista que, em seres humanos, restringiria a orientação da atenção apenas ao componente voluntário. Os resultados mostraram que ratos exibem redução do tempo de reação e aumento na percentagem de respostas corretas a um alvo visual precedido por pista simbólica auditiva preditiva válida em relação à pista inválida. Esse efeito manifestou-se quando o intervalo entre a pista e o alvo foi de 100 ou de 700 ms, mas não quando foi de 400 ms. Esses resultados sugerem a existência de dois tipos de fenômenos usualmente atribuídos à orientação da atenção visuo-espacial, o primeiro determinado pelos efeitos do pareamento repetitivo entre a pista e o alvo (que talvez envolva condicionamento clássico), que se manifesta quando o intervalo entre esses estímulos é da ordem de 100 ms, e o segundo determinado pela orientação endógena da atenção, que se manifesta quando o intervalo é igual ou maior que 700 ms. / The covert orienting of attention task described by Posner (1980) has been extensively used for investigating orientation of visuo-spatial attention in humans. There have been attempts to adapt it for rats, with encouraging results; data revealed that attentional phenomena in humans and rats are partially analogous (ROSNER, MITTLEMAN, 1996; WARD, BROWN, 1996; LUCK and VECERA, 2002). The distinction between exogenous (or \"automatic\", in human literature) and endogenous (or \"voluntary\", in human literature) orienting of attention, relying mainly on differences in the time course of the reaction time to the visual target, was partially described for rats; these early studies indicated that rats exhibited only the automated component of orienting. However, Marote and Xavier (2011) showed validity effects when using either predictive or non-predictive cues preceding the target by 200, 400 and 800 ms; however, this validity effect was greater for predictive cues preceding the target by 800 ms, a result that in human studies is taken as evidence of voluntary orienting of attention. Most of rat studies using this task employ peripheral cues, rendering difficult to distinguish exogenous and endogenous effects of orienting of attention. In the present study orienting of visuo-spatial attention was investigated in rats by using symbolic predictive cues, a kind of cue usually considered to engage voluntary attention in humans. The results showed that rats exhibit a reduction of reaction times and an increase in percentage of correct responses to a visual target preceded by a valid symbolic auditory predictive cue as compared to an invalid cue, when the stimulus onset asynchrony was either 100 or 700 ms, but not when it was 400 ms. These figures suggest that the validity effect in rats is underlied by at least two processes, the first determined by repetitive and contingent cue-target pairings (that might involve classical conditioning) that occurs when the cue-target time interval is about 100 ms, and the second determined by endogenous orienting of attention that occurs when the cue-target time interval is about 700 ms.

O enriquecimento ambiental (EA) é capaz de alterar a percepção a estímulos nociceptivos, bem como de aumentar a resposta analgésica induzida por opioides. Considerando que a dor neuropática é um grave problema de saúde pública e o tratamento para esta condição ainda é insatisfatório e acarreta efeitos adversos severos, os objetivos deste trabalho foram avaliar a interferência do bem-estar animal na sensibilidade dolorosa de ratos frente a diferentes estímulos nociceptivos e investigar possíveis mecanismos envolvidos neste efeito. Os animais foram submetidos à avaliação da ansiedade e da sensibilidade dolorosa, em modelo de neuropática, frente a estímulos nociceptivos mecânicos e térmicos. Foi verificado que um protocolo de EA elaborado e iniciado desde o nascimento foi capaz de reverter totalmente a dor neuropática de animais submetidos à constrição crônica do nervo isquiático (CCI). Este efeito foi completamente abolido quando os animais enriquecidos foram tratados com naloxona, um antagonista opioide não seletivo. Análises de Western Blot não mostraram diferenças na expressão de receptores opioides em regiões relacionadas ao processamento e controle da dor, porém os níveis circulantes de beta-endorfina e met-encefalina aumentaram na presença de dor crônica nos animais enriquecidos. Os níveis séricos de corticosterona também se apresentaram aumentados nos animais com EA, independentemente da neuropatia, mas o tratamento com mifepristona, um antagonista de receptores de glicocorticoides, não alterou a analgesia dos animais operados. Ainda, o EA também reduziu a imunorreatividade para serotonina na medula espinal de animais com CCI. Além do efeito analgésico, o EA também reduziu o marcador de lesão neuronal ATF-3 no gânglio da raiz dorsal e, no local da constrição, reduziu a degeneração neuronal característica do modelo, induzindo ainda, a presença predominantemente de macrófagos do tipo M2. Este trabalho reforça a importância do bem-estar na prevenção do desenvolvimento da dor neuropática e mostra uma abordagem não farmacológica que pode aumentar a resiliência de animais contra estímulos nocivos. / Environmental enrichment (EE) is capable of altering the perception of nociceptive stimuli, as well as increasing the analgesic response induced by opioids. Considering that neuropathic pain is a serious public health problem and the treatment for this condition is still unsatisfactory and induces severe side effects, the aims of this study were to evaluate the interference of animal welfare in the sensitivity to different nociceptive stimuli and to investigate possible mechanisms involved in this effect. Animals were submitted to the evaluation of anxiety and pain sensitivity in a model of neuropathic pain, against mechanical and thermal nociceptive stimuli. It was seen that an elaborated EE starting from birth was able to totally reverse the neuropathic pain of animals submitted to chronic constriction injury of the sciatic nerve (CCI). This effect was completely abolished when enriched animals were treated with naloxone, a nonselective opioid antagonist. Western blot analysis did not show differences in opioid receptor expression in regions related to pain processing and control, however, circulating levels of beta-endorphin and met-enkephalin were increased in the presence of chronic pain in enriched animals. Serum corticosterone levels were also increased in animals with EE regardless of neuropathy, but treatment with mifepristone, a nonselective glucocorticoid receptor antagonist, did not alter the analgesia of operated animals. Moreover, EE reduced serotonin immunoreactivity in the spinal cord of CCI animals. In addition to analgesic effect, EE also reduced the neuronal injury marker ATF-3 at the dorsal root ganglia and, at the site of constriction, decreased the neuronal degeneration characteristic of the model, inducing the presence of M2 macrophages subtype predominantly. This work reinforces the importance of well-being in preventing the development of neuropathic pain and shows a non-pharmacological approach that may increase animal resilience against noxious stimuli.

La domestication des bétails représente une étape importante dans l'histoire de l'humanité. Le mouton était l'un des premiers animaux à être domestiqués dans le croissant fertile. Ces événements de domestication, probablement initiés au début du Néolithique, ont génétiquement construit les races contemporaines du Moyen-Orient mais aussi du monde entier. L'élevage de moutons, principalement mouton de la race Awassi, représente une activité économique essentielle du Liban ; cependant, jusqu'à présent, il n'existe que très peu de données génétiques sur cette race. De nos jours, les outils moléculaires disponibles nous permettent de définir en détail la diversité génétique des populations de moutons et de retracer leur histoire évolutive. Par conséquent, l'objectif principal de mon projet de thèse était de caractériser génétiquement la race Awassi du Liban. Pour cette étude, 277 échantillons d'ADN génomique prélevés des moutons Awassi du Liban (n = 254) et de la Syrie (n = 23) ont été analysés. Au début, nous avons utilisé cinq rétrovirus endogènes (rétrovirus endogène de moutons de Jaagsiekte-enJSRV) qui sont polymorphiques par insertion dans les génomes du mouton domestique (enJSRV-18, -7, -15, -16 et -22) et ont été précédemment considérés comme très informatifs principalement pour distinguer génétiquement les moutons primitifs des races plus modernes (c.-à-d. le dernier issu de l'épisode migratoire impliquant des moutons avec des traits de production améliorés). En utilisant cette approche, nos résultats montrent une prédominance du type R2 (enjSRV-18 seulement) confirmant que le mouton Awassi du Liban est une race moderne. Comme prévu, le rétrotype R4 (à la fois enJSRV-18 et enJSRV-7), une caractéristique commune des populations de moutons du bassin méditerranéen, se trouve également dans le génome des moutons d'Awassi du Liban et plus accentué dans les troupeaux Syriens. Il est intéressant de noter que les populations de moutons d'Awassi situés dans le nord-est du Liban et ayant ainsi un accès plus restreint à la mer Méditerranée que les autres populations (c'est-à-dire en raison de la chaîne de montagne centrale qui coupe le pays sur deux), présentent une faible fréquence de R4. Bien que l'origine des animaux utilisés pour établir les troupeaux analysés au cours de cette étude soit inconnue, nos résultats fournissent également certaines preuves que le mode d'élevage (ouvert ou fermé) peut influencer les rétrotypes observés et en particulier le R4. De manière surprenante, au cours de cette étude, nous avons également dévoilé la présence de soi-disant "Solo-LTR" (c'est-à-dire généré par une recombinaison homologue) pour un autre enJSRV (enJSRV-6) qui prédomine dans deux troupeaux d'une région particulière du Liban (Nabatieh). Et comme approche complémentaire, deux marqueurs mitochondriaux ont été utilisés, le cytochrome b (Cyt-b) et D-Loop, pour étudier l'origine maternelle de cette race et sa relation phylogénétique au sein de la famille Ovis aries. Dans notre étude, le Cyt-b se révèle plus discriminant que le D-Loop. Des mouton d'Awassi analysé, quatre haplogroupes (HPG) du Moyen-Orient ont été trouvés avec l'analyse du Cyt-b : HPG A, B, C et E, ce dernier étant peu fréquent. De même, l’analyse de la super-séquence, alignement Cyt-b_D-Loop, a permis l’identification de l’HPG D, un HPG extrêmement rare et limité jusqu’à présent aux moutons à queue grasse tel que l’Awassi. Enfin, une expansion passée de la population est observée pour les HPG A, B et C (mais pas pour HPG E) avec les distributions incompatibles et des tests de neutralité négatifs significatifs. Dans l'ensemble, les résultats obtenus au cours de cette étude fournissent une caractérisation génétique complète ainsi que quelques idées sur la structure phylogéographique des populations de moutons de la race Awassi au Liban. / Livestock domestication represents a milestone in the history of mankind. Sheep was one of the first animals to be domesticated in the Fertile Crescent. These domestication events, probably initiated in the early Neolithic, have genetically built the contemporary races of the Middle East but also of the whole world. Sheep farming, mainly sheep of Awassi breed, represents an essential economic activity of Lebanon; however, so far, only very few genetic data exist on this breed. Nowadays, the molecular tools available allow us to define in details the genetic diversity of sheep populations and to trace their evolutionary history. Hence, the main objective of my PhD project was to genetically characterize the Awassi breed of Lebanon. For this study, 277 genomic DNA samples collected from Awassi sheep of Lebanon (n=254) and Syria (n=23) were analyzed. Initially, we used five endogenous retroviruses (endogenous Jaagsiekte sheep retrovirus-enJSRV) that are insertionally polymorphic within the genomes of domestic sheep (enJSRV-18, -7, -15, -16 and -22) and have been previously shown to be very informative mainly to genetically distinguish between primitive sheep from more modern breeds (i.e. the latter originating from the migratory episode involving sheep with improved production traits). Using this approach, our results show a predominance of the R2 retrotype (enJSRV-18 only) confirming that the Awassi sheep of Lebanon is a modern breed. As expected, the R4 retrotype (both enJSRV-18 and enJSRV-7), a common feature of the sheep populations present within the Mediterranean area, is also found in the Awassi sheep of Lebanon and to more extend in those of Syria. Interesting, the populations of Awassi sheep located in the northeast of Lebanon and thus having a more restricted access to the Mediterranean Sea than the other populations (i.e. due to the central mountain chain cutting the country in two) present R4 weaklier. Even though the origin of the animals used to establish the herds analyzed during this study is unknown, our results also provide some evidences that the mode of rearing (open or closed) may influence the observed retrotypes and in particular R4. Surprisingly, during this study, we also unveiled the presence of so-called “Solo-LTR” (i.e. generated by homologous recombination) for another enJSRV (enJSRV-6) that are predominant in two herds of a particular region of Lebanon (Nabatieh). As a complementary approach, two mitochondrial markers were used, the cytochrome b (Cyt-b) and D-Loop, to investigate the maternal origin of this breed and its phylogenetic relationship within the Ovis aries family. In our study, the Cyt-b turns out to be more discriminative than the D-Loop. From the Awassi sheep analyzed, four haplogroups (HPGs) of the Middle-East were found with Cyt-b analysis: HPG A, B, C and E, the latter being the least frequent. Also, the super-sequence analysis, Cyt-b_D-Loop alignment, allowed the identification of HPG D, an extremely rare HPG, limited till now to fat-tailed sheep such as Awassi. Finally, a past population expansion is observed for the HPG A, B and C (but not for HPG E) with mismatch distributions and significant negative neutrality tests. Overall, the results obtained during this study provide a comprehensive genetic characterization as well as some insights into the phylogeographic structure of the sheep populations of the Awassi breed in Lebanon.

A constituição de estudo acerca da ritmicidade biológica do indivíduo, e sua expressão social no mundo contemporâneo foi objetivo desta dissertação, ela integra as Ciências Humanas com as Ciências Biológicas. Estuda-se a construção cultural da virtude relacionada ao trabalho intenso e extenuante, faz-se isso analisando inicialmente o processo histórico na transição do feudalismo para o capitalismo mercantil até o capitalismo contemporâneo. No decorrer desta construção histórica, observa-se a inversão de valores voltados ao trabalho, que de castigo torna-se virtude. Essa transformação está associada a conflitos e revoluções de ordem religiosa e econômica. A relação trabalho-tempo se transforma de um modo de produção tradicional, no feudalismo, no qual o tempo do trabalho é o tempo da terra, é o tempo do plantar e do colher, é o tempo da natureza para uma relação trabalho-tempo ditada por salários, pelo sincronismo das máquinas, pela doutrinação religiosa, pelo controle dos horários e pela coação da lei. Essa relação trabalho-tempo que emerge no capitalismo mercantil reverbera nos dias atuais através do fenômeno ideológico moldado nos últimos quatro séculos por meio de mecanismos semelhantes, econômicos, religiosos e legais. De forma que contemporaneamente, de forma geral, se entende que quanto mais tempo se dedica ao trabalho, quanto mais cedo se acorda para trabalhar mais virtuoso é o indivíduo. Por lado quanto mais tarde se acorda para trabalhar e quanto mais se invade a noite para o lazer mais vagabundo. No entanto de uma área da Biologia surgida nos meados do século XX; a Cronobiologia, emerge o conhecimento sobre o tempo biológico que surge então como elemento adicional para se pensar o tempo e o trabalho. O tempo na cronobiologia é a integração entre o tempo dos organismos e o tempo da natureza, do dia e da noite, é o dia interior ajustado ao dia exterior. É, portanto individual, é genético e ontogênico. Os horários sociais nos quais se exerce as rotinas de trabalho nem sempre estão em harmonia com o tempo biológico o que leva parte da população a uma espécie de desarranjo temporal ou a pratica de horários não triviais como acordar nas primeiras horas da tarde, por exemplo. Imposições temporais como o horário de verão, horário de aula para alunos, turnos de trabalhos invertidos, não levam em consideração resultados de estudos de grande parte da literatura na área de cronobiologia, e resultam em consequências para a saúde da população. Assim concluímos que estigmatizar quem pratica horários incomuns ou estabelecer uma rigidez de horários nos quais se deve exercer atividades como trabalho ou dormir são construções ideológicas historicamente determinadas, as quais o saber cronobiológico descontrói, pois a compreensão do tempo biológico resulta em entender sua adaptabilidade no contexto dos horários sociais. Além disso, entende se que são necessárias Políticas Públicas relacionadas a intervenções nos horários de trabalho e educação do quotidiano que levem em consideração estes novos conhecimentos surgidos no final do século XX que terão papel preventivo em doenças contemporâneas como câncer e doenças psiquiátricas / The study of individual biological rhythmicity and its social expression in the contemporary world was objective of this dissertation, which integrates Human and Biological sciences. We have studied the cultural construction of virtue related to intense and hard work. We analyzed initially the historical process of the transition from feudalism to the mercantile capitalism and to contemporary capitalism. During this process there were an inversion of values; the work from punishment becomes virtue. This transformation is associated with conflicts and revolutions of religious and economic order. The relationship \"work-time\" changes from a traditionalist production method, in feudalism, in which working time is the time of the land, is the time of planting and harvest, is the time of nature, to a temporal relationship dictated by wages, the timing of machines, by religious indoctrination, by schedule control and enforcement of the law. This working time relationship that emerges in mercantile capitalism reverberates today through an ideological phenomenon in the last four centuries, through similar, economic, religious and legal mechanisms. Contemporaneously, in general, it is understood that the more time is devoted to work, the sooner one agrees to work more virtuous he is. On the other side who wakes up to work at noon and breaks the night for leisure is a vagabond . However an area of Biology that emerged in the mid-twentieth century, the Chronobiology, brings knowledge about the biological timing as an additional element to think about the time and work. Time in chronobiology is the integration between the time of nature day and night, and time of body , is the day inside adjusted to the day outside. It is, therefore, individual, it is genetic and ontogenetic. Social schedules and work routines are not always in harmony with the biological timing what leads people either to a kind of temporal misalignment or to practice nontrivial temporal schedules like waking up in the afternoon, for example. Time impositions for daylight saving time, class time for students, inverted shifts to workers, do not take into account the results of most studies of chronobiology literature and result in consequences for the health of the population. Thus, we can conclude that stigmatize those who practice unusual times or set a rigid schedule to carrying out activities such as work or to sleep are ideological constructions historically determined, which the knowledge in Chronobiology deconstructs since it can interpreted that the understanding of biological timing allows to understand its adaptability to social context. We also considered that public policies related to interventions in working hours and education that take into account this new knowledge that emerged in the late twentieth century in Biology will have a role in preventive medicine in contemporary diseases such as cancer and psychiatric disorders