TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Time-Series Data in Circadian Biology Research.

The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms' performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.

Introduction to Chronobiology.

A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate regular environmental rhythms promotes optimal performance and survival. Herein we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s.

Methods in field chronobiology.

Chronobiological research has seen a continuous development of novel approaches and techniques to measure rhythmicity at different levels of biological organization from locomotor activity (e.g. migratory restlessness) to physiology (e.g. temperature and hormone rhythms, and relatively recently also in genes, proteins and metabolites). However, the methodological advancements in this field have been mostly and sometimes exclusively used only in indoor laboratory settings. In parallel, there has been an unprecedented and rapid improvement in our ability to track animals and their behaviour in the wild. However, while the spatial analysis of tracking data is widespread, its temporal aspect is largely unexplored. Here, we review the tools that are available or have potential to record rhythms in the wild animals with emphasis on currently overlooked approaches and monitoring systems. We then demonstrate, in three question-driven case studies, how the integration of traditional and newer approaches can help answer novel chronobiological questions in free-living animals. Finally, we highlight unresolved issues in field chronobiology that may benefit from technological development in the future. As most of the studies in the field are descriptive, the future challenge lies in applying the diverse technologies to experimental set-ups in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.

Sleep research goes wild: new methods and approaches to investigate the ecology, evolution and functions of sleep.

Despite being a prominent aspect of animal life, sleep and its functions remain poorly understood. As with any biological process, the functions of sleep can only be fully understood when examined in the ecological context in which they evolved. Owing to technological constraints, until recently, sleep has primarily been examined in the artificial laboratory environment. However, new tools are enabling researchers to study sleep behaviour and neurophysiology in the wild. Here, we summarize the various methods that have enabled sleep researchers to go wild, their strengths and weaknesses, and the discoveries resulting from these first steps outside the laboratory. The initial studies to 'go wild' have revealed a wealth of interindividual variation in sleep, and shown that sleep duration is not even fixed within an individual, but instead varies in response to an assortment of ecological demands. Determining the costs and benefits of this inter- and intraindividual variation in sleep may reveal clues to the functions of sleep. Perhaps the greatest surprise from these initial studies is that the reduction in neurobehavioural performance resulting from sleep loss demonstrated in the laboratory is not an obligatory outcome of reduced sleep in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.

XVII Congreso SEINAP. Ritmos circadianos y crononutrición / XVII Congreso SEINAP. Circadian rhythms and chrononutrition

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Cronobiología del sistema inmune / Immune system chronobiology

La cronobiología es la disciplina que ha estudiado la organización temporal de los procesos que ocurren en los seres vivos, los mecanismos que las originan y sus alteraciones. En 1832, Agustín de Candolle demostró que bajo condiciones constantes el período de los ciclos de movimientos de las plantas duraba unas 24 horas, con lo que añadió una evidencia de la naturaleza endógena de los ritmos biológicos. En los mamíferos, se ha estimado que aproximadamente el 10 por ciento del genoma está bajo un control circadiano. Desde la década de los años 70´s se observó que la respuesta inmune dependía de la hora del día en la cual se analizaba y que la susceptibilidad a las infecciones dependía también de la hora en la cual el organismo fuera infectado. Recientemente se ha establecido una relación entre el ciclo circadiano y la respuesta inmune. Este trabajo trata las ventajas del conocimiento del ritmo circadiana de los mecanismos inmunitarios y la importancia del uso de la cronoterapia sobre los osciladores de las células del sistema inmune en los trastornos inmunitarios, lo cual pudiera evitar complicaciones en los pacientes(AU)

Chronobiology is the science that studies temporary organization of the processes that happen in organisms, the mechanisms that originate them and its disorders. Austin of Candolle demonstrated that under constant conditions the period of the cycles of the plants' movements it lasted some 24 hour, adding an evidence of the endogenous nature of the biological rhythms in 1832. In mammals, has been considered approximately 10 percent of genome under circadian control. Since decade of 70´s, was observed that immune response depends of day´s hours in which it was analyzed, and the susceptibility to infections also depends of the hour in which an organism is infected. It has begun to establish relationship between circadian cycle and immune response recently. This work intends to give us the advantages of the knowledge of circadian rhythms of immune mechanisms and the importance of the chronotherapy´s use on the oscillators of the immune system´s cells in immunity dysfunctions and it would avoid complications in the patients(AU)

Cronobiología del sistema inmune / Immune system chronobiology

La cronobiología es la disciplina que ha estudiado la organización temporal de los procesos que ocurren en los seres vivos, los mecanismos que las originan y sus alteraciones. En 1832, Agustín de Candolle demostró que bajo condiciones constantes el período de los ciclos de movimientos de las plantas duraba unas 24 horas, con lo que añadió una evidencia de la naturaleza endógena de los ritmos biológicos. En los mamíferos, se ha estimado que aproximadamente el 10 por ciento del genoma está bajo un control circadiano. Desde la década de los años 70´s se observó que la respuesta inmune dependía de la hora del día en la cual se analizaba y que la susceptibilidad a las infecciones dependía también de la hora en la cual el organismo fuera infectado. Recientemente se ha establecido una relación entre el ciclo circadiano y la respuesta inmune. Este trabajo trata las ventajas del conocimiento del ritmo circadiana de los mecanismos inmunitarios y la importancia del uso de la cronoterapia sobre los osciladores de las células del sistema inmune en los trastornos inmunitarios, lo cual pudiera evitar complicaciones en los pacientes(AU)

Chronobiology is the science that studies temporary organization of the processes that happen in organisms, the mechanisms that originate them and its disorders. Austin of Candolle demonstrated that under constant conditions the period of the cycles of the plants' movements it lasted some 24 hour, adding an evidence of the endogenous nature of the biological rhythms in 1832. In mammals, has been considered approximately 10 percent of genome under circadian control. Since decade of 70´s, was observed that immune response depends of day´s hours in which it was analyzed, and the susceptibility to infections also depends of the hour in which an organism is infected. It has begun to establish relationship between circadian cycle and immune response recently. This work intends to give us the advantages of the knowledge of circadian rhythms of immune mechanisms and the importance of the chronotherapy´s use on the oscillators of the immune system´s cells in immunity dysfunctions and it would avoid complications in the patients(AU)

Data graphs and mechanistic explanation.

It is a widespread assumption in philosophy of science that representations of data are not explanatory-that they are mere stepping stones towards an explanation, such as a representation of a mechanism. I draw on instances of representational and explanatory practice from mammalian chronobiology to suggest that this assumption is unsustainable. In many instances, biologists employ representations of data in explanatory ways that are not reducible to constraints on or evidence for representations of mechanisms. Data graphs are used to represent relationships between quantities across conditions, and often these representations are necessary for explaining particular aspects of the phenomena under study. The benefit of the analysis is two-fold. First, it provides a more accurate account of explanatory practice in broadly mechanistic investigation in biology. Second, it suggests that there is not an explanatorily "fundamental" type of representation in biology. Rather, the practice of explanation consists in the construction of different types of representations and their employment for distinct explanatory purposes.

Phenotyping Circadian Rhythms in Mice.

Circadian rhythms take place with a periodicity of 24 hr, temporally following the rotation of the earth around its axis. Examples of circadian rhythms are the sleep/wake cycle, feeding, and hormone secretion. Light powerfully entrains the mammalian clock and assists in keeping animals synchronized to the 24-hour cycle of the earth by activating specific neurons in the "central pacemaker" of the brain, the suprachiasmatic nucleus. Absolute periodicity of an animal can deviate slightly from 24 hr as manifest when an animal is placed into constant dark or "free-running" conditions. Simple measurements of an organism's activity in free-running conditions reveal its intrinsic circadian period. Mice are a particularly useful model for studying circadian rhythmicity due to the ease of genetic manipulation, thus identifying molecular contributors to rhythmicity. Furthermore, their small size allows for monitoring locomotion or activity in their homecage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are presented here including the process of entrainment, determination of tau (period length) in free-running conditions, determination of circadian periodicity in response to light disruption (e.g., jet lag studies), and evaluation of clock plasticity in non-24-hour conditions (T-cycles). Studying the properties of circadian periods such as their phase, amplitude, and length in response to photic perturbation, can be particularly useful in understanding how humans respond to jet lag, night shifts, rotating shifts, or other transient or chronic disruption of environmental surroundings.

Methods for monitoring the functional status of the circadian system in dietary surveys studies: application criteria and interpretation of results

To evaluate the circadian system status of the subject may be of special interest in nutrition. Particularly for those studies related to the assessment of diseases related to malnutrition, as it is the case of most of the degenerative diseases such as obesity, cancer, or cardiovascular diseases. For this purpose, one of the approaches consists to measure a) the external synchronizers of the internal clock, such as light intensity, and changes from fasting to eating and from resting to activity. Indeed, "chronodisruptors" have been defined as "exogenous and endogenous exposures or effectors which are chronobiologically active and can thus disrupt the timing and order". Another approach to assess the circadian system health is to measure the b) outputs of the internal clock (circadian marker rhythms). Among such outputs, the rhythm of body temperature, motor activity, melatonin, cortisol and clock gene expression are the most commonly used. From the genetic perspective, we are now able to measure failures in the internal clock, in order to assess c) the genetics of the molecular clock. Indeed, new nutrigenetics techniques are giving us the opportunity to measure the association between different genetic variants of our clock genes and several illnesses such as obesity, cardiovascular diseases, diabetes or cancer. In addition to these techniques, self-reported questionnaires based in the morning-evening preferences have been developed as complementary procedures to assess human chronotypes (AU)

Evaluar el estado del sistema circadiano del sujeto puede ser de especial interés en la nutrición. En particular, para los estudios relativos a la evaluación de las enfermedades relacionadas con la malnutrición como es el caso de la mayoría de las enfermedades degenerativas tales como la obesidad, cáncer, o enfermedades cardiovasculares. Para este propósito, uno de los enfoques consiste en medir a) los sincronizadores externos del reloj interno, tales como intensidad de la luz, y los cambios de ayuno/ingesta y de reposo/actividad. De hecho, se ha definido el término de "cronodisruptor" que se refiere a "exposiciones o efectores exógenos y endógenos que son cronobiológicamente activos y que por lo tanto pueden interrumpir el tiempo". Otro enfoque para evaluar la salud del sistema circadiano es medir b) las salidas del reloj interno (ritmos circadianos). Entre ellos las más utilizadas son la medición del ritmo de la temperatura corporal, la actividad motora, la melatonina, el cortisol y la expresión de genes reloj. Desde el punto de vista genético, ahora somos capaces de medir c) las alteraciones del reloj interno, con el fin de evaluar la genética del reloj molecular. De hecho, las nuevas técnicas de nutrigenética nos están dando la oportunidad de medir la asociación entre las diferentes variantes genéticas de nuestros genes reloj y varias enfermedades como la obesidad, las enfermedades cardiovasculares, la diabetes o el cáncer. Además de estas técnicas, se han desarrollado cuestionarios basados en las preferencias de mañana-tarde como procedimientos complementarios para evaluar cronotipos humanos (AU)

Métodos cronobiológicos en las encuestas alimentarias: criterios de aplicación e interpretación de resultados / Methods for monitoring the functional status of the circadian system in dietary surveys studies: application criteria and interpretation of results

En 1996, la Cumbre Mundial sobre la Alimentación reafirmó el derecho inalienable de los habitantes del mundo a tener acceso a una alimentación adecuada, inocua y nutritiva, y se planteó como meta disminuir a la mitad el número de personas subnutridas en el mundo para el año 2015, es decir, este año que iniciamos. Diversos países y organizaciones se plantean la necesidad de consensuar y desarrollar indicadores para la medición de la inseguridad alimentaria en los hogares. Disponer de un método de medición simple pero con base científica para identificar los grupos de población de mayor vulnerabilidad nutricional, se considera una herramienta básica para poder implementar estrategias que permitan afrontar el problema de un forma efectiva (AU)

To evaluate the circadian system status of the subject may be of special interest in nutrition. Particularly for those studies related to the assessment of diseases related to malnutrition, as it is the case of most of the degenerative diseases such as obesity, cancer, or cardiovascular diseases. For this purpose, one of the approaches consists to measure a) the external synchronizers of the internal clock, such as light intensity, and changes from fasting to eating and from resting to activity. Indeed, “chronodisruptors” have been defined as “exogenous and endogenous exposures or effectors which are chronobiologically active and can thus disrupt the timing and order. Another approach to assess the circadian system health is to measure the b) outputs of the internal clock (circadian marker rhythms). Among such outputs, the rhythm of body temperature, motor activity, melatonin, cortisol and clock gene expression are the most commonly used. From the genetic perspective, we are now able to measure failures in the internal clock, in order to assess c) the genetics of the molecular clock. Indeed, new nutrigenetics techniques are giving us the opportunity to measure the association between different genetic variants of our clock genes and several illnesses such as obesity, cardiovascular diseases, diabetes or cancer. In addition to these techniques, selfreported questionnaires based in the morning-evening preferences have been developed as complementary procedures to assess human chronotypes (AU)

Utilidad y aplicación práctica de los resultados obtenidos en las encuestas alimentarias, de estimación de la actividad física y otros estilos de vida a nivel poblacional / Uses and applications of the results from food surveys, physical activity estimates and other lifestyle related surveys at a population level

Los resultados y las conclusiones de los estudios nutricionales bien diseñados, utilizando la metodología adecuada para lograr los objetivos planteados, con la mayor validez y precisión posible, son de gran utilidad en los sistemas de vigilancia nutricional, alimentaria y toxicológica, en la planificación, seguimiento y evaluación de políticas nutricionales y proporcionan información de gran interés en el planteamiento de ingestas de referencia, objetivos nutricionales y guías alimentarias (AU)

The results and conclusions of well design nutrition studies, using the appropriate methods to achieve the intended aims with the best validity and precision possible are of great value for nutritional, food and toxicological surveillance systems; also in the planning, follow-up and evaluation of nutrition and health policies and providing high value information for the formulation of recommended reference intakes, nutritional objectives and food based dietary guidelines (AU)

Evaluación de la atención en deportistas de artes marciales. Expertos vs. novatos / Measuring attention in martial art athletes. Experts versus novices / Avaliação da atenção em desportistas de artes marciais: especialistas vs. iniciantes

El objetivo del estudio fue determinar las diferencias en el desempeño de una tarea de atención en relación con la pericia en artes marciales. Participaron 12 deportistas de artes marciales expertos y 13 novatos. Se les aplicó el Test of Variables of Attention (Greenberg, 1996) y se analizaron los datos de la prueba para cada variable, condición y segmentos en los que se divide, con un método estadístico no-paramétrico de permutaciones. Las comparaciones intergrupos indicaron una tendencia a que el puntaje global de Trastorno por Déficit de Atención e Hiperactividad (TDAH) de la prueba fuera mejor en los expertos que en los novatos. Se hizo un análisis intragrupo para conocer el comportamiento de cada grupo a lo largo de la prueba; los resultados indicaron que los deportistas expertos muestran mayor consistencia en el número de aciertos y tiempos de reacción a lo largo de la prueba, lo que se traduce como un mejor desempeño cuando se compara con la forma en que los deportistas novatos responden a la tarea. Los resultados sugieren que el entrenamiento físico y mental de las disciplinas de artes marciales podría producir una mejora en las capacidades de atención de los deportistas

The aim of this study is to determine differences in the performance of an attention-related task involving martial arts skills. 12 expert martial arts athletes and 13 novices took part, performing the Test of Variables of Attention (Leark, Greenberg, Kindschi, Dupuy and Hughes, 2007). Using a non-parametric statistical permutation method, the test data for each variable, condition and segment of the test was analysed. Comparisons of the groups showed a trend toward a higher global Attention Deficit Hyperactivity Disorder (ADHD) score by the expert athletes as compared with the novices. In order to find out each group’s performance during the test, a statistical intra-group analysis was performed. Generally, the results revealed more consistent accuracy and response times by the experts than by the novice athletes. The results suggest that physical and mental training in the martial arts may increase the attention skills of sportsmen and women

O objectivo do estudo foi determinar as diferenças no desempenho de uma tarefa atencional tendo em conta a perícia em artes marciais. Participaram no estudo 12 desportistas especialistas em artes marciais e 13 iniciantes. Foi aplicado aos participantes o Test of Variables of Attention (Greenberg, 1996) e analisaram-se os dados do teste para cada variável, condição e segmentos em que se dividem, através de um método estatístico nãoparamétrico de permutações. As comparações intergrupos indicaram uma tendência para que a pontuação global de Transtorno do Défice de Atenção e Hiperactividade (TDAH) fosse maior nos especialistas do que nos iniciantes. Foi realizada uma análise intragrupo para conhecer o comportamento de cada grupo ao longo da prova; os resultados indicaram que os desportistas especialistas revelaram maior consistência no número de acertos e tempos de reacção ao longo da prova, o que se traduz num melhor desempenho quando comparados com a forma como os desportistas iniciantes respondem à tarefa. Os resultados sugerem que o treino físico e mental das disciplinas de artes marciais poderia produzir uma melhoria nas capacidades atencionais dos desportistas

Cefalea y sueño / No disponible

Introducción: la relación entre cefalea y sueño es conocida desde hace muchos años. El sueño y la cefalea tienen una fuerte interacción bidireccional, y comparten elementos anatómicos y fisiológicos. La intención de la presente revisión es presentar los distintos tipos de cefaleas relacionadas con el sueño y su aproximación fisiopatológica. Desarrollo: exponemos los distintos tipos de cefaleas relacionadas con el sueño, es decir aquellas que ocurren durante la noche o en las primeras horas de la mañana, la migraña, la cefalea en racimo, la hemicránea crónica paroxística y la cefalea hípnica. También, desarrollamos el síndrome de la cabeza que explota o síndrome del estallido cefálico, puesto que en la práctica clínica debe ser valorado en el diagnóstico diferencial de las cefaleas relacionadas con el sueño. Conclusión: se necesita una mayor investigación en el tema para establecer conclusiones, esclarecer los mecanismos fisiopatológicos entre cefalea y sueño, así como entender cómo los cambios en la biología del sueño provocan dolor de cabeza y por qué los distintos tipos de cefaleas afectan a la biología del sueño (AU)

Introduction: the link between cephalalgia and sleep has been known for many years. Sleep and cephalalgia have a strong bidirectional interaction and share anatomical and physiological aspects. The intention of this paper is to present the different types of cephalalgias related with sleep and their physiopathological closeness. Discussion: different types of cephalalgia related with sleep will be exposed. That is, cephalalgia that occurs at night time or first time in the morning: migraine, cluster headache, chronic hemicrania continua and hypnic headaches. We also review the exploding head syndrome since it should be assessed in differential diagnosis when looking at sleep-related cephalalgias. Conclusions: further research is needed on this subject in order to establish conclusions, to clarify physiopathological mechanisms between cephalalgia and sleep and to understand how changes in sleep biology cause headaches and why different types of cephalalgias affect sleep biology (AU)

From molecules to behavior and the clinic: Integration in chronobiology.

Chronobiology, especially the study of circadian rhythms, provides a model scientific field in which philosophers can study how investigators from a variety of disciplines working at different levels of organization are each contributing to a multi-level account of the responsible mechanism. I focus on how the framework of mechanistic explanation integrates research designed to decompose the mechanism with efforts directed at recomposition that relies especially on computation models. I also examine how recently the integration has extended beyond basic research to the processes through which the disruption of circadian rhythms contributes to disease, including various forms of cancer. Understanding these linkages has been facilitated by discoveries about how circadian mechanisms interact with mechanisms involved in other physiological processes, including the cell cycle and the immune system.

Perception of intersensory synchrony: a tutorial review.

For most multisensory events, observers perceive synchrony among the various senses (vision, audition, touch), despite the naturally occurring lags in arrival and processing times of the different information streams. A substantial amount of research has examined how the brain accomplishes this. In the present article, we review several key issues about intersensory timing, and we identify four mechanisms of how intersensory lags might be dealt with: by ignoring lags up to some point (a wide window of temporal integration), by compensating for predictable variability, by adjusting the point of perceived synchrony on the longer term, and by shifting one stream directly toward the other.