On receiver-based teleosemantic theories of representation, the chemical states of the circadian clocks in animal, plant and cyanobacterial cells constitute signals of future states of affairs, often the rising and setting of the sun. This signalling is much more rigid than sophisticated representational systems like human language, but it is not simple on all dimensions. In most organisms the clock regulates many different circadian rhythms. The process of entrainment ensures that the mapping between chemical states of the (...) clock and the daily light-dark cycle is adjusted to deal with seasonal changes. In regulating anticipatory behaviour, the states of the clock look forward both to the time the behaviour is supposed to happen and the later time when the anticipated circumstances are supposed to arise. The case of the circadian clock shows that purely indicative signals can arise in very basic biological systems and brings into sharp relief the trade-offs involved in characterizing representational systems. On receiver-based teleosemantic theories, future-directed signals are not restricted to complex multicellular organisms but are ubiquitous in the biological world. (shrink)

Daylight is the primary cue used by circadian clocks to entrain to the day/night cycle so as to synchronize physiological processes with periodic environmental changes induced by Earth rotation.However, the temporal daylight pattern is not the same every day due to erratic weather fluctuations or regular seasonal changes. Then, how do circadian clocks operate properly in varying weather and seasons? In this paper, we discuss the strategy unveiled by recent studies of the circadian clock of (...) Ostreococcus tauri, the smallest free‐living eukaryotic organism. It combines mechanisms controlling light inputs and clock sensitivity, shaping both the dynamics of the core circadian oscillator and its forcing by light so as to ensure stable and precise synchronization in all weather and seasons.Editor's suggested further reading in BioEssays: Another place, another timer: Marine species and the rhythms of life Abstract. (shrink)

A circadian clock, with physiological characteristics similar to those of eukaryotes, functions in the photosynthetic prokaryote, cyanobacteria. The molecular mechanism of this clock has been efficiently dissected using a luciferase reporter gene that reports the status of the clock. A circadian clock gene cluster, kaiABC, has been cloned via rhythm mutants of cyanobacterium, Synechococcus, and many clock mutations mapped to the three kai genes. Although kai genes do not share any homology with clock genes so far identified in (...) eukaryotes, analysis of their expression suggests that a negative feedback control of kaiC expression by KaiC generates the circadian oscillation and that KaiA functions as a positive factor to sustain this oscillation. BioEssays 22:10–15, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

A paradigm shift in the human chronotoxicity of xenobiotics would study two‐sided desynchronized phenomena of interfacial interactions between cyclic or periodic environmental insults and the endogenous response and recovery profile. These systems‐based networks are under the influence of well‐synchronized biological clocks and their metabolic regulators. This perspective argues in favor of addressing the concept of synchronization in studies involving critical life windows of susceptibility, or circadian rhythms, or 24‐hour (periodic) diurnal rhythms and answering whether these disruptions in synchronization (...) would affect response and recovery or disease phenotypes associated with environmental insults, e.g., xenobiotics. Synchronization or synchrony is defined as the totality of elements that appear during the same time period within a system, including the network of interactions between the system's elements. Desynchronized interfaces during critical life windows or in time‐repeated exposure events would likely lead to initiating a cascade of adverse health effects associated with differentiated disease phenotypes. (shrink)

Daily rhythms are a ubiquitous feature of living systems. Generally, these rhythms are not just passive consequences of cyclic fluctuations in the environment, but instead originate within the organism. In mammals, including humans, the master pacemaker controlling 24‐hour rhythms is localized in the suprachiasmatic nuclei of the hypothalamus. This circadian clock is responsible for the temporal organization of a wide variety of functions, ranging from sleep and food intake, to physiological measures such as body temperature, heart rate and hormone (...) release. The retinal circadian clock was the first extra‐SCN circadian oscillator to be discovered in mammals and several studies have now demonstrated that many of the physiological, cellular and molecular rhythms that are present within the retina are under the control of a retinal circadian clock, or more likely a network of hierarchically organized circadian clocks that are present within this tissue. BioEssays 30:624–633, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Integration of knowledge concerning circadian rhythms, metabolic networks, and sleep‐wake cycles is imperative for unraveling the mysteries of biological cycles and their underlying mechanisms. During the last decade, enormous progress in circadian biology research has provided a plethora of new insights into the molecular architecture of circadian clocks. However, the recent identification of autonomous redox oscillations in cells has expanded our view of the clockwork beyond conventional transcription/translation feedback loop models, which have been dominant since the (...) first circadian period mutants were identified in fruit fly. Consequently, non‐transcriptional timekeeping mechanisms have been proposed, and the antioxidant peroxiredoxin proteins have been identified as conserved markers for 24‐hour rhythms. Here, we review recent advances in our understanding of interdependencies amongst circadian rhythms, sleep homeostasis, redox cycles, and other cellular metabolic networks. We speculate that systems‐level investigations implementing integrated multi‐omics approaches could provide novel mechanistic insights into the connectivity between daily cycles and metabolic systems. -/- . (shrink)

Based on genetic and biochemical advances on the molecular mechanism of circadian rhythms, a computational model for the mammalian circadian clock is used to examine the dynamical bases of circadian‐clock‐related physiological disorders in humans. Entrainment by the light–dark cycle with a phase advance or a phase delay is associated with the Familial advanced sleep phase syndrome (FASPS) or the Delayed sleep phase syndrome (DSPS), respectively. Lack of entrainment corresponding to the occurrence of quasiperiodic oscillations with or without (...) phase jump can be associated with the non‐24 h sleep–wake syndrome. In the close vicinity of the entrainment domain, the model uncovers the possibility of infradian oscillations of very long period. Perturbation in the form of chronic jet lag, as used in mice, prevents entrainment of the circadian clock and results in chaotic or quasiperiodic oscillations. It is important to clarify the conditions for entrainment and for its failure because dysfunctions of the circadian clock may lead to physiological disorders, which pertain not only to the sleep–wake cycle but also to mood and cancer. BioEssays 30:590–600, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Cellular circadian clocks represent ancient anticipatory systems which co‐evolved with the first cells to safeguard their survival. Cyanobacteria represent one of the most ancient cells, having essentially invented photosynthesis together with redox‐based cellular circadian clocks some 2.7 billion years ago. Bioelectricity phenomena, based on redox homeostasis associated electron transfers in membranes and within protein complexes inserted in excitable membranes, play important roles, not only in the cellular circadian clocks and in anesthetics‐sensitive cellular sentience (awareness (...) of environment), but also in the coupling of single cells into tissues and organs of unitary multicellular organisms. This integration of cellular circadian clocks with cellular basis of sentience is an essential feature of the cognitive CBC‐Clock basis of cellular life. (shrink)

This paper distinguishes between causal isolation robustness analysis and independent determination robustness analysis and suggests that the triangulation of the results of different epistemic means or activities serves different functions in them. Circadian clock research is presented as a case of causal isolation robustness analysis: in this field researchers made use of the notion of robustness to isolate the assumed mechanism behind the circadian rhythm. However, in contrast to the earlier philosophical case studies on causal isolation robustness analysis (...) (Weisberg and Reisman in Philos Sci 75:106–131, 2008 ; Kuorikoski et al. in Br J Philos Sci 61:541–567, 2010 ), robustness analysis in the circadian clock research did not remain in the level of mathematical modeling, but it combined it with experimentation on model organisms and a new type of model, a synthetic model. (shrink)

Reciprocal interactions between the host circadian clock and the microbiota are evidenced by recent literature. Interestingly, dysregulation of either the circadian clock or microbiota is associated with common human pathologies such as obesity, type 2 diabetes, or neurological disorders. However, it is unclear to what extent a perturbation of pathways regulated by both the circadian clock and microbiota is involved in the development of these disorders. It is speculated that these perturbations are associated with impaired growth hormone (...) (GH) secretion and sexual development. The GH axis is a broadly neglected pathway and could be the main converging point for the interaction of both circadian clock and microbiota. Here, the links between the circadian clock and microbiota are reviewed. Finally, the effects of chronodisruption and dysbiosis on physiology and pathology are discussed and it is speculated whether a common deregulation of the GH pathway could mediates those effects. (shrink)

Circadian rhythm abnormalities in bipolar disorder have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at (...) three levels: essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies. (shrink)

Most organisms display oscillations of approximately 24 hours in their physiology. In higher organisms, these circadian oscillations in biochemical and physiological processes ultimately control complex behavioral rhythms that allow an organism to thrive in its natural habitat. Daily and seasonal light cycles are mainly responsible for keeping the circadian system properly aligned with the environment. The molecular mechanisms responsible for the control of the circadian clock have been explored in a number of systems. Interestingly, the circadian (...) oscillations that are responsive to environmental stimuli are present very early during development. This review focuses on the advantages of using the zebrafish to study the development of the vertebrate circadian system and light‐dependent signaling to the clock. BioEssays 24:419–426, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Positing representations and operations on them as a way of explaining behavior was one of the major innovations of the cognitive revolution. Neuroscience and biology more generally also employ representations in explaining how organisms function and coordinate their behavior with the world around them. In discussions of the nature of representation, theorists commonly differentiate between the vehicles of representation and their content—what they denote. Many contentious debates in cognitive science, such as those pitting neural network models against symbol processing accounts, (...) have focused on the types of vehicles proposed for mental representation and whether they have the appropriate structure to succeed in bearing their contents. Philosophers, in contrast, have focused their debates on content and the particular way in which vehicles might bear content—that is, the process of representing rather than the format of representations. I will offer a novel answer to the question of how it is that a representation has content by focusing on the architecture of representation. My proposal is that representations occur in a particular type of mechanism—one in which a control system regulates a plant—and that we can gain traction on cognitive systems of representation by considering how this works in physical systems more generally. (shrink)

A vast network of cellular circadian clocks regulates 24‐hour rhythms of behavior and physiology in mammals. Complex environments are characterized by multiple, and often conflicting time signals demanding flexible mechanisms of adaptation of endogenous rhythms to external time. Traditionally this process of circadian entrainment has been conceptualized in a hierarchical scheme with a light‐reset master pacemaker residing in the hypothalamus that subsequently aligns subordinate peripheral clocks with each other and with external time. Here we review new (...) experiments using conditional mouse genetics suggesting that resetting of the circadian system occurs in a more “federated” and tissue‐specific fashion, which allows for increased noise resistance and plasticity of circadian timekeeping under natural conditions. (shrink)

The plant maintains a 24‐h circadian cycle that controls the sequential activation of many physiological and developmental functions. There is empirical evidence suggesting that two types of circadian rhythms exist. Some plant rhythms appear to be set by the light transition at dawn, and are calibrated to circadian (zeitgeber) time, which is measured from sunrise. Other rhythms are set by both dawn and dusk, and are calibrated to solar time that is measured from mid‐day. Rhythms on (...) class='Hi'>circadian timing shift seasonally in tandem with the timing of dawn that occurs earlier in summer and later in winter. On the other hand, rhythms set to solar time are maintained independently of the season, the timing of noon being constant year‐round. Various rhythms that run in‐phase and out‐of‐phase with one another seasonally may provide a means to time and induce seasonal events such as flowering. (shrink)

In mammals, a network of cellular circadian clocks organizes physiology and behavior along the 24‐h day cycle. The traditional hierarchical model of circadian clock organization with a central pacemaker and peripheral slave oscillators has recently been challenged by studies combining tissue‐specific mouse mutants with transcriptome analyses. First, a surprisingly small number of tissue rhythms are lost when only local clocks are ablated and, second, transcriptional circadian rhythms appear to be regulated by a complex mix of (...) local and systemic factors. As reviewed here, these findings suggest a more integrated model of clock network interaction with the central pacemaker as the main source of behavioral and systemic–physiological rhythms and peripheral clocks controlling some local rhythms while at the same time acting as gatekeepers that temporally adjust cellular responses to external stimuli. (shrink)

The circadian clock is a cell autonomous oscillator that controls many aspects of physiology through generating rhythmic gene expression in a time of day dependent manner. In addition, in endothermic mammals body temperature cycles contribute to rhythmic gene expression. These body temperature‐controlled rhythms are hard to distinguish from classic circadian rhythms if analyzed in vivo in endothermic organisms. However, they do not fulfill all criteria of being circadian if analyzed in cell culture or in conditions where body (...) temperature of an endothermic organism can be manipulated. Here we review and compare these characteristics, discuss the core clock independent mechanism of temperature‐controlled alternative splicing and highlight the requirement of double‐checking rhythms that appear circadian within an endothermic organism in a system that allows temperature manipulation. (shrink)

It is not clear why cancer cells choose to disrupt their circadian clock rhythms, and whether such disruption governs a selective fitness and a survival advantage. In this review, I focus on understanding the impacts of clock gene disruption on a simpler model, such as the unicellular cyanobacterium, in order to explain how cancer cells may alter the circadian rhythm to reprogram their metabolism based on their needs and status. It appears to be that the activation of the (...) oxidative pentose phosphate pathway (OPPP) and production of NADPH, the preferred molecule for detoxification of reactive oxygen species, is a critical process for night survival in unicellular organisms. The circadian clock acts as a gatekeeper that controls how the organism will utilize its sugar, shifting sugar influx between glycolysis and OPPP. The circadian clock can thus act as a gatekeeper between an anabolic, proliferative mode and a homeostatic, survival mode. (shrink)

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse. Considerable progress has been made in identifying some of the molecular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PER and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker neurons, the (...) PER and TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feature which permits a compelling molecular description of both behavioural light entrainment and phase responses to light pulses. The regulation of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue‐specific regulation. Evolution appears to have modified the way in which the two genes are utilised to generate circadian phenotypes. More recently, the cloning of mouse clock genes, including putative per homologues, opens up exciting possibilities for mammalian molecular chronobiology. (shrink)

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse. Considerable progress has been made in identifying some of the molecular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PER and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker neurons, the (...) PER and TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feature which permits a compelling molecular description of both behavioural light entrainment and phase responses to light pulses. The regulation of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue‐specific regulation. Evolution appears to have modified the way in which the two genes are utilised to generate circadian phenotypes. More recently, the cloning of mouse clock genes, including putative per homologues, opens up exciting possibilities for mammalian molecular chronobiology. (shrink)

Circalunar clocks, which allow organisms to time reproduction to lunar phase, have been experimentally proven but are still not understood at the molecular level. Currently, a new generation of researchers with new tools is setting out to fill this gap. Our essay provides an overview of classic experiments on circalunar clocks. From the unpublished work of the late D. Neumann we also present a novel phase response curve for a circalunar clock. These experiments highlight avenues for molecular work (...) and call for rigor in setting up and analyzing the logistically complex experiments on circalunar clocks. Re‐evaluating classic experiments, we propose that (1) circalunar clocks in different organisms will have divergent mechanisms and physiological bases, (2) they may have properties very different from the well‐studied circadian clocks and (3) they may have close mechanistic and molecular relations to seasonal rhythms and diapause. (shrink)

Coordinated daily rhythms are evident in most aspects of our physiology, driven by internal timing systems known as circadian clocks. Our understanding of how biological clocks are built and function has grown exponentially over the past 20 years. With this has come an appreciation that disruption of the clock contributes to the pathophysiology of numerous diseases, from metabolic disease to neurological disorders to cancer. However, it remains to be determined whether it is the disruption of our rhythmic (...) physiology per se (loss of timing itself), or altered functioning of individual clock components that drive pathology. Here, we review the importance of circadian rhythms in terms of how we (and other organisms) relate to the external environment, but also in relation to how internal physiological processes are coordinated and synchronized. These issues are of increasing importance as many aspects of modern life put us in conflict with our internal clockwork. (shrink)

Ultradian rhythms are those that cycle many times in a day and are therefore measured in hours, minutes, seconds or even fractions of a second. In yeasts and protists, a temperature‐compensated clock with a period of about an hour (30–90 minutes) provides the time base upon which all central processes are synchronized. A 40‐minute clock in yeast times metabolic, respiratory and transcriptional processes, and controls cell division cycle progression. This system has at its core a redox cycle involving NAD(P)H and (...) dithiol–disulfide interconversions. It provides an archetype for biological time keeping on longer time scales (e.g. the daily cycles driven by circadian clocks) and underpins these rhythms, which cannot be understood in isolation. Ultradian rhythms are the foundation upon which the coherent functioning of the organism depends. BioEssays 29:465–473, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Circadian rhythms in the sleep/wake cycle, along with a range of physiological measures, are severely disrupted in individuals with major depressive disorder (MDD). Moreover, several central circadian genes have been implicated as potential genetic factors underlying the illness through candidate gene studies and some genome wide association studies. However, investigations into the molecular underpinnings of circadian disturbances in the human brain have been quite challenging. In their recent publication, Li and colleagues have used a novel approach to (...) determine the rhythmic patterns of circadian gene expression in several regions of the human brain, and how these patterns are disrupted in MDD. Their findings demonstrate that in healthy subjects, several brain regions outside the suprachiasmatic nucleus (the master clock) exhibit diurnal gene expression patterns that are disrupted in the brains of MDD subjects. These findings will provide the foundation for future studies of gene‐specific drug targets, and biomarkers for the disease. (shrink)

Thanks to genetic and biochemical advances on the molecular mechanism of circadian rhythms in Drosophila, theoretical models closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism. Modeling is based on the autoregulatory negative feedback exerted by a complex between PER and TIM proteins on the expression of per and tim genes. The model predicts the occurrence of sustained circadian oscillations in continuous darkness. When incorporating light‐induced TIM degradation, (...) the model accounts for damping of oscillations in constant light, entrainment of the rhythm by light‐dark cycles of varying period or photoperiod, and phase shifting by light pulses. The model further provides a molecular dynamical explanation for the permanent or transient suppression of circadian rhythmicity triggered in a variety of organisms by a critical pulse of light. Finally, the model shows that to produce a robust rhythm the various clock genes must be expressed at the appropriate levels since sustained oscillations only occur in a precise range of parameter values. BioEssays 22:84–93, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

The glowing light of cinema, which continues to claim supremacy as a collective site for evolving senses of time, has fundamentally changed since its inception, from exclusively projected light to primarily emitted light. Digital, rather than analog projectors, dominate in personal rather than public spheres. The physiological and behavioral effects of those technologies manipulate our biological clocks, creating an entanglement of time-sensing. Similarly, the art of cinema now relies far more upon energy-intensive materials and methods, from equipment to image (...) manufacturing and data flow. This essay takes the twelve-hour clock as a slanted optic to address those profound shifts, choosing a handful of moving-image artists to feature, including Deborah Stratman, Nikolaus Geyrhalter, and Mikael Kristersson, who are attempting to find alternative temporal modes of depicting the hyperobjectiveness of eternity, ecocrises, dystopias, and deep time on screen. (shrink)

In many domains of biology, explanation takes the form of characterizing the mechanism responsible for a particular phenomenon in a specific biological system. How are such explanations generalized? One important strategy assumes conservation of mechanisms through evolutionary descent. But conservation is seldom complete. In the case discussed, the central mechanism for circadian rhythms in animals was first identified in Drosophila and then extended to mammals. Scientists' working assumption that the clock mechanisms would be conserved both yielded important generalizations and (...) served as a heuristic for discovery, especially when significant differences between the insect and mammalian mechanism were identified. †To contact the author, please write to: Department of Philosophy and Interdisciplinary Programs in Science Studies and Cognitive Science, 0119, University of California, San Diego, La Jolla, CA 92093‐0119; e‐mail: [email protected]. (shrink)

Circadian rhythms are responsible for 24‐hour oscillations in diverse biological processes. While the central genes governing circadian pacemaker rhythmicity have largely been identified, clock‐controlled output molecules responsible for regulating rhythmic behaviors remain largely unknown. Two recent reports from McDonald and Rosbash1 and Claridge‐Chang et al.2 address this issue. By identifying a large number of genes whose mRNA levels show circadian oscillations, the reports provide important new information on the biology of circadian rhythm. In addition, the reports (...) illustrate both the power and limitations of microarray‐based methods for profiling mRNA expression on a genomic scale. BioEssays 24:494–498, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

A wide range of biological processes, in all eukaryotes and in some prokaryotes, are controlled by rhythms with a period close to 24 hours. The circadian oscillator, which is responsible for generating these rhythms, is controlled by light signals that maintain its synchrony with the environmental day/night cycle. Higher plants exhibit many circadian rhythms, including rhythms in the transcription of specific genes. Molecular tools derived from such clock‐controlled genes have led to the identification of several circadian rhythm (...) mutants in the genetic model, Arabidopsis thaliana. The extensive understanding of photoperception in this species will make it a powerful system with which to investigate the light regulation of circadian rhythms. We compare Arabidopsis rhythms to the results from other systems, and discuss these data with respect to the current phototransduction models. (shrink)

The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme‐responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid (...) metabolism is rhythmically expressed independently of the sleep‐wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian‐ and sleep‐dependent molecules. (shrink)

Previous research has reported that ethical values of business students are lower than those of their peers in other majors. The purpose of this study was to investigate whether a self-selection bias with respect to ethical values exists among students enrolled as business majors when compared with students planning to enter the engineering profession. Engineering students are exposed to a similar technical orientation in academic curricula and also supply the market for managers.A survey instrument was administered to 195 students enrolled (...) in undergraduate business and engineering programs and a graduate business program. The research instrument measured how business and engineering students perceive their own ethical beliefs and actions and how they perceived the ethical beliefs and actions of their peers. (shrink)

O artigo traz resultados de uma investigação de mestrado que teve por objetivo pesquisar as concepções de um grupo de professores a respeito das funções que os mesmos exercem frente à sociedade contemporânea. Partiu-se da premissa de que suas concepções guardam relação com suas práticas educativas e pedagógicas. Trata-se de uma pesquisa desenvolvida na perspectiva qualitativa, com cinquenta e um professores que atuam em seis escolas estaduais da cidade de Ponta Grossa-PR. Elegeu-se como aporte teórico autores que tratam da formação (...) de professores e da profissão docente, como Freire, Imbernón, Ens e Behrens, Tozetto, Sacristán e Tedesco. Os dados foram coletados por meio de questionários, categorizados e analisados seguindo os pressupostos na Análise de Conteúdo. Três categorias foram configuradas a partir de significantes presentes nas respostas dos professores participantes: Categoria I – Professor como um sujeito transformador: educação em uma forma ampla, Categoria II – Professor como profissional do conhecimento, e Categoria III – Professor enquanto sujeito que desempenha vários papéis sociais. Essas categorias nos possibilitaram inferir que as concepções dos professores em relação ao seu papel na sociedade contemporânea vão além da função social da escola, pois centram-se primeiramente na figura de um profissional transformador do mundo; seguida da noção de profissional do conhecimento e, por fim, da ideia de um profissional que desempenha vários papéis sociais. A pesquisa também apontou uma necessária redefinição da profissão docente para que os professores assumam novas competências profissionais na contemporaneidade. Palavras-chave: Profissão docente. Função dos professores. Sociedade contemporânea. Concepções. (shrink)

Acidity, generated in hypoxia or hypermetabolic states, perturbs homeostasis and is a feature of solid tumors. That acid peripherally disperses lysosomes is a three‐decade‐old observation, yet one little understood or appreciated. However, recent work has recognized the inhibitory impact this spatial redistribution has on mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of metabolism. This finding argues for a paradigm shift in localization of mTORC1 activator Ras homolog enriched in brain (RHEB), a conclusion several others have now independently (...) reached. Thus, mTORC1, known to sense amino acids, mitogens, and energy to restrict biosynthesis to times of adequate resources, also senses pH and, via dampened mTOR‐governed synthesis of clock proteins, regulates the circadian clock to achieve concerted responses to metabolic stress. While this may allow cancer to endure metabolic deprivation, immune cell mTOR signaling likewise exhibits pH sensitivity, suggesting that suppression of antitumor immune function by solid tumor acidity may additionally fuel cancers, an obstacle potentially reversible through therapeutic pH manipulation. (shrink)

MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub (...) that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology. (shrink)

It is widely held in contemporary philosophy of mind that states with underived representational content are ipso facto psychological states. This view—the Content View—underlies a number of interesting philosophical projects, such as the attempt to pick out a psychological level of explanation, to demarcate genuinely psychological from non-psychological states, and to limn the class of states with phenomenal character. The most detailed and influential theories of underived representation in philosophy are the tracking theories developed by Fodor, Dretske, Millikan and others. (...) Tracking theorists initially hoped to ‘naturalize’ underived representation by showing that although it is distinctively psychological it is not irreducibly so, yet they ended up developing theories of representation that by their own lights don’t pick out a distinctively psychological phenomenon at all. Burge sets out to develop a theory of underived representation that does pick out a distinctively psychological phenomenon. His theory promises to vindicate the Content View and the various philosophical projects that depend on it. In this paper I argue that Burge’s theory dementalizes representation for the same reason tracking theories do: These theories hold that representations are states with underived accuracy conditions, yet such states are found in all sorts of mindless systems, like plants. (shrink)

Recently, Bechtel and Abrahamsen have argued that mathematical models study the dynamics of mechanisms by recomposing the components and their operations into an appropriately organized system. We will study this claim through the practice of combinational modeling in circadian clock research. In combinational modeling, experiments on model organisms and mathematical/computational models are combined with a new type of model—a synthetic model. We argue that the strategy of recomposition is more complicated than what Bechtel and Abrahamsen indicate. Moreover, synthetic modeling (...) as a kind of material recomposition strategy also points beyond the mechanistic paradigm. (shrink)

Gene regulatory networks are intensively studied in biology. One of the main aims of these studies is to gain an understanding of how the structure of genetic networks relates to specific functions such as chemotaxis and the circadian clock. Scientists have examined this question by using model organisms such as Drosophila and mathematical models. In the last years, synthetic models—engineered genetic networks—have become more and more important in the exploration of gene regulation. What is the potential of this new (...) approach in the investigation of gene network structures? How do synthetic models relate to model organisms and mathematical models? (shrink)

I examine to what extent accounts of mechanisms based on formal interventionist theories of causality can adequately represent biological mechanisms with complex dynamics. Using a differential equation model for a circadian clock mechanism as an example, I first show that there exists an iterative solution that can be interpreted as a structural causal model. Thus, in principle, it is possible to integrate causal difference-making information with dynamical information. However, the differential equation model itself lacks the right modularity properties for (...) a full integration. A formal mechanistic model will therefore have to leave out either noncausal or causal explanatory relations. (shrink)

The functions of sleep are still unknown, but are probably related to cellular and molecular aspects of neural function. To better understand the benefits that sleep may bring at the cellular level, recent studies have employed Drosophila melanogaster as a model system and shown that fruit flies share the fundamental features of mammalian sleep. As in mammals, sleep in Drosophila is characterized by increased arousal threshold and by changes in brain electrical activity. Fly sleep is homeostatically regulated independent of the (...) circadian clock, is modulated by stimulants and hypnotics, and is affected by age. Also, fly sleep is associated with changes in brain gene expression similar to those observed in mammals. While Drosophila neurobiology is sufficiently complex to permit meaningful generalizations to mammals and humans, Drosophila genetics is simple enough to allow a rapid mutagenesis screening. An ongoing mutagenesis study has screened ∼5000 mutant Drosophila lines and found that sleep amount, sleep pattern, and the homeostatic regulation of sleep are highly conserved phenotypes in flies. So far, this study has identified 10 short sleeper lines and 4 lines that show no sleep rebound after sleep deprivation. Ultimately, the characterization of these lines should help identifying crucial cellular pathways involved in the regulatory mechanisms of sleep and its functional consequences. BioEssays 25:940–949, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Philosophers have traditionally held that propositions mark the domain of rational thought and inference. Many philosophers have held that only conceptually sophisticated creatures like us could have propositional attitudes. But in recent decades, philosophers have adopted increasingly liberal views of propositional attitudes that encompass the mental states of various non-human animals. These views now sit alongside more traditional views within the philosophical mainstream. In this paper I argue that liberalized views of propositional attitudes are so liberal that they encompass states (...) of all sorts of apparently mindless systems like circadian clocks in plants. I begin by arguing that on the most well-developed and widely endorsed theories of underived representation in philosophy, circadian clocks qualify as representations. I then argue that standard reasons for thinking that perceptual states and pictures have propositional content carry over to circadian clocks. Finally, I argue that circadian representations in plants play the kind of functional role that is widely taken to be partly constitutive of belief-like attitudes. So according to mainstream theories of representation, propositions, and attitudes, plants have propositional attitudes. Yet on other more traditional views, this conclusion would seem absurd. So, contrary to appearances, there is no shared, stable understanding of what propositional attitudes are in contemporary philosophy. (shrink)

We describe a recent approach for distinguishing between stochastic and deterministic sources of variability, focusing on the mammalian cell cycle. Variability between cells is often attributed to stochastic noise, although it may be generated by deterministic components. Interestingly, lineage information can be used to distinguish between variability and determinism. Analysis of correlations within a lineage of the mammalian cell cycle duration revealed its deterministic nature. Here, we discuss the sources of such variability and the possibility that the underlying deterministic process (...) is due to the circadian clock. Finally, we discuss the “kicked cell cycle” model and its implication on the study of the cell cycle in healthy and cancerous tissues. (shrink)

Many philosophers and psychologists have attempted to elucidate the nature of mental representation by appealing to notions like isomorphism or abstract structural resemblance. The ‘structural representations’ that these theorists champion are said to count as representations by virtue of functioning as internal models of distal systems. In his 2007 book, Representation Reconsidered, William Ramsey endorses the structural conception of mental representation, but uses it to develop a novel argument against representationalism, the widespread view that cognition essentially involves the manipulation of (...) mental representations. Ramsey argues that although theories within the ‘classical’ tradition of cognitive science once posited structural representations, these theories are being superseded by newer theories, within the tradition of connectionism and cognitive neuroscience, which rarely if ever appeal to structural representations. Instead, these theories seem to be explaining cognition by invoking so-called ‘receptor representations’, which, Ramsey claims, aren’t genuine representations at all—despite being called representations, these mechanisms function more as triggers or causal relays than as genuine stand-ins for distal systems. I argue that when the notions of structural and receptor representation are properly explicated, there turns out to be no distinction between them. There only appears to be a distinction between receptor and structural representations because the latter are tacitly conflated with the ‘mental models’ ostensibly involved in offline cognitive processes such as episodic memory and mental imagery. While structural representations might count as genuine representations, they aren’t distinctively mental representations, for they can be found in all sorts of non-intentional systems such as plants. Thus to explain the kinds of offline cognitive capacities that have motivated talk of mental models, we must develop richer conceptions of mental representation than those provided by the notions of structural and receptor representation. (shrink)

In the 1960’s Brian Goodwin published a couple of mathematical models showing how feedback inhibition can lead to oscillations and discussed possible implications of this behaviour for the physiology of the cell. He also presented key ideas about the rich dynamics that may result from the coupling between such biochemical oscillators. Goodwin’s work motivated a series of theoretical investigations aiming at identifying minimal mechanisms to generate limit cycle oscillations and deciphering design principles of biological oscillators. The three-variable Goodwin model (adapted (...) by Griffith) can be seen as a core model for a large class of biological systems, ranging from ultradian to circadian clocks. We summarize here main ideas and results brought by Goodwin and review a couple of modeling works directly or indirectly inspired by Goodwin’s findings. (shrink)

Many plants are adapted to flower at particular times of year, to ensure optimal pollination and seed maturation. In these plants flowering is controlled by environmental signals that reflect the changing seasons, particularly daylength and temperature. The response to daylength varies, so that plants isolated at higher latitudes tend to flower in response to long daylengths of spring and summer, while plants from lower latitudes avoid the extreme heat of summer by responding to short days. Such responses require a mechanism (...) for measuring time, and the circadian clock that regulates daily rhythms in behaviour also acts as the timer in the measurement of daylength. Plants from high latitudes often also show an extreme response to temperature called vernalisation in which flowering is repressed until the plant is exposed to winter temperatures for an extended time. Genetic approaches in Arabidopsis have identified a number of genes that control vernalisation and daylength responses. These genes are described and models presented for how daylength might regulate flowering by controlling their expression by the circadian clock. BioEssays 22:38–47, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

Philosophers have traditionally held that propositions mark the domain of rational thought and inference. Many philosophers have held that only conceptually sophisticated creatures like us could have propositional attitudes. But in recent decades, philosophers have adopted increasingly liberal views of propositional attitudes that encompass the mental states of various non-human animals. These views now sit alongside more traditional views within the philosophical mainstream. In this paper I argue that liberalized views of propositional attitudes are so liberal that they encompass states (...) of all sorts of apparently mindless systems like circadian clocks in plants. I begin by arguing that on the most well-developed and widely endorsed theories of underived representation in philosophy, circadian clocks qualify as representations. I then argue that standard reasons for thinking that perceptual states and pictures have propositional content carry over to circadian clocks. Finally, I argue that circadian representations in plants play the kind of functional role that is widely taken to be partly constitutive of belief-like attitudes. So according to mainstream theories of representation, propositions, and attitudes, plants have propositional attitudes. Yet on other more traditional views, this conclusion would seem absurd. So, contrary to appearances, there is no shared, stable understanding of what propositional attitudes are in contemporary philosophy. (shrink)

This dissertation offers new proposals, based on a philosophical appraisal of scientific findings, to address old philosophical problems regarding our immediate acquaintance with time. It focuses on two topics: our capacity to determine the length of intervals and our acquaintance with the present moment. A review of the relevant scientific findings concerning these topics grounds the main contributions of this dissertation. Thus, this study introduces to the philosophical literature an empirically adequate way to talk about how the mind represents time (...) at the most fundamental level. In order to account for our immediate acquaintance with the duration of intervals, a theoretical framework for classifying clocks is used to explain why the representational outputs of the circadian clock and the stopwatch have metric structure. A philosophical analysis of these outputs is proposed to classify them and explain their properties. With respect to our immediate acquaintance with the present, a novel two-phase model of the present is proposed. This model shows that there are two forms of acquaintance with the present, which has consequences for contemporary debates in the philosophy of time. (shrink)