La perception du temps et sa modulation par la température chez les guêpes parasitoïdes

Les modèles d'optimalité postulent que les animaux en quête de ressources utilisent le taux de gain de valeur adaptative pour optimiser plusieurs comportements tels que la répartition du temps lors de l’exploitation d‘un agrégat et l'investissement en progénitures. Bien que la durée de plusieurs comportements doit être régulée, peu d’évidences de la perception du temps sont actuellement disponibles pour les insectes et aucune pour les guêpes parasitoïdes, et ce malgré leur importance en tant que modèles écologiques. De plus, puisque les guêpes parasitoïdes sont poïkilothermes, cette capacité pourrait être affectée par la température. Nous avons supposé que les guêpes parasitoïdes auraient la capacité de percevoir le temps, à la fois de façon prospective (mesure du temps écoulé) et rétrospective (durée d'un événement passé), afin d'optimiser les décisions liées à l'exploitation d’agrégats d’hôtes et à la reproduction. Nous avons également émis l'hypothèse que la température aurait une incidence sur la perception du temps des guêpes parasitoïdes. Pour la mesure prospective du temps, nous avons utilisé la capacité d’apprentissage associatif de Microplitis croceipes (Hymenoptera: Braconidae). Les guêpes ont été entraînées à associer une odeur à la durée d'un intervalle entre des hôtes. Après leur entraînement, elles ont été testées dans un tunnel de vol avec un choix d’odeurs. Les guêpes ont choisi majoritairement l'odeur associée à l'intervalle de temps auquel elles étaient testées. Nous avons également investigué le rôle de la dépense énergétique sur la mesure du temps. Suite à une restriction de mouvement des guêpes pendant l'intervalle de temps entre les hôtes, elles choisissaient aléatoirement dans le tunnel de vol. L'absence de dépense énergétique les aurait rendues incapables de mesurer le temps. La dépense d'énergie est donc un substitut essentiel pour mesurer le temps. Pour la mesure rétrospective du temps, nous avons utilisé le processus d'évaluation de l'hôte de Trichogramma euproctidis (Hymenoptera: Trichogrammatidae). Certains trichogrammes utilisent la durée du transit initial sur l'œuf hôte afin d’en évaluer la taille et d’ajuster le nombre d’œufs à y pondre. Nous avons augmenté artificiellement la durée de transit initiale de T. euproctidis en suspendant l'œuf hôte pour le faire paraître plus gros qu'un œuf de taille similaire. Une augmentation de la durée de transit initiale a augmenté la taille de la ponte. Ceci démontre la capacité de T. euproctidis de mesurer la durée du transit initial, et donc d’une mesure du temps rétrospective. Pour déterminer si la température modifie la mesure du temps dans les espèces poïkilothermes, nous avons utilisé le comportement d’exploitation d’agrégats d’hôtes de T. euproctidis. Les modèles d’optimalités prédisent que les guêpes devraient rester plus longtemps et quitter à un faible taux de gain de valeur adaptative suite à un déplacement de longue durée plutôt que pour un déplacement de courte durée. Nous avons testé l'impact d'un déplacement de 24 h à différentes températures sur l'exploitation d’agrégats d’hôtes. Un déplacement à température chaude augmente le temps de résidence dans l’agrégat et diminue le taux de gain de valeur adaptative au moment de quitter ; ces comportements sont associés à un trajet de longue durée. L'inverse a été observé lors d’un déplacement à une température froide. Les températures chaude et froide ont modulé la mesure du temps en accélérant ou ralentissant l'horloge biologique, faisant paraître le déplacement respectivement plus long ou plus court qu’il ne l’était réellement. Ces résultats démontrent clairement que les guêpes parasitoïdes ont la capacité de mesurer le temps, autant rétrospectivement que prospectivement. Des preuves directes de leur capacité sont maintenant disponibles pour au moins deux espèces de guêpes parasitoïdes, une composante essentielle des modèles d'optimalité. Le rôle de la dépense énergétique dans la mesure du temps a aussi été démontré. Nos résultats fournissent également la preuve de l'impact de la température sur la perception du temps chez les insectes. L'utilisation de la dépense énergétique en tant que proxy pour mesurer le temps pourrait expliquer une partie de sa thermosensibilité, puisque les guêpes parasitoïdes sont poïkilothermes. Cette mesure du temps sensible à la température pourrait affecter des stratégies de lutte biologique. Sur le terrain, au début de la journée, la température de l'air sera similaire à la température de l'air autour des plantes infestées par des parasites, alors qu'elle sera plus chaude pendant la journée. En lutte biologique augmentative, les guêpes parasitoïdes libérées resteraient plus longtemps dans les agrégats d’hôtes que celles relâchées en début de journée.

Physical Design Methodologies for Low Power and Reliable 3D ICs

As the semiconductor industry struggles to maintain its momentum down the path following the Moore's Law, three dimensional integrated circuit (3D IC) technology has emerged as a promising solution to achieve higher integration density, better performance, and lower power consumption. However, despite its significant improvement in electrical performance, 3D IC presents several serious physical design challenges. In this dissertation, we investigate physical design methodologies for 3D ICs with primary focus on two areas: low power 3D clock tree design, and reliability degradation modeling and management. Clock trees are essential parts for digital system which dissipate a large amount of power due to high capacitive loads. The majority of existing 3D clock tree designs focus on minimizing the total wire length, which produces sub-optimal results for power optimization. In this dissertation, we formulate a 3D clock tree design flow which directly optimizes for clock power. Besides, we also investigate the design methodology for clock gating a 3D clock tree, which uses shutdown gates to selectively turn off unnecessary clock activities. Different from the common assumption in 2D ICs that shutdown gates are cheap thus can be applied at every clock node, shutdown gates in 3D ICs introduce additional control TSVs, which compete with clock TSVs for placement resources. We explore the design methodologies to produce the optimal allocation and placement for clock and control TSVs so that the clock power is minimized. We show that the proposed synthesis flow saves significant clock power while accounting for available TSV placement area. Vertical integration also brings new reliability challenges including TSV's electromigration (EM) and several other reliability loss mechanisms caused by TSV-induced stress. These reliability loss models involve complex inter-dependencies between electrical and thermal conditions, which have not been investigated in the past. In this dissertation we set up an electrical/thermal/reliability co-simulation framework to capture the transient of reliability loss in 3D ICs. We further derive and validate an analytical reliability objective function that can be integrated into the 3D placement design flow. The reliability aware placement scheme enables co-design and co-optimization of both the electrical and reliability property, thus improves both the circuit's performance and its lifetime. Our electrical/reliability co-design scheme avoids unnecessary design cycles or application of ad-hoc fixes that lead to sub-optimal performance. Vertical integration also enables stacking DRAM on top of CPU, providing high bandwidth and short latency. However, non-uniform voltage fluctuation and local thermal hotspot in CPU layers are coupled into DRAM layers, causing a non-uniform bit-cell leakage (thereby bit flip) distribution. We propose a performance-power-resilience simulation framework to capture DRAM soft error in 3D multi-core CPU systems. In addition, a dynamic resilience management (DRM) scheme is investigated, which adaptively tunes CPU's operating points to adjust DRAM's voltage noise and thermal condition during runtime. The DRM uses dynamic frequency scaling to achieve a resilience borrow-in strategy, which effectively enhances DRAM's resilience without sacrificing performance. The proposed physical design methodologies should act as important building blocks for 3D ICs and push 3D ICs toward mainstream acceptance in the near future.

A Hardware Implementation of a Run-Time Scheduler for Reconfigurable Systems

New generation embedded systems demand high performance, efficiency and flexibility. Reconfigurable hardware can provide all these features. However the costly reconfiguration process and the lack of management support have prevented a broader use of these resources. To solve these issues we have developed a scheduler that deals with task-graphs at run-time, steering its execution in the reconfigurable resources while carrying out both prefetch and replacement techniques that cooperate to hide most of the reconfiguration delays. In our scheduling environment task-graphs are analyzed at design-time to extract useful information. This information is used at run-time to obtain near-optimal schedules, escaping from local-optimum decisions, while only carrying out simple computations. Moreover, we have developed a hardware implementation of the scheduler that applies all the optimization techniques while introducing a delay of only a few clock cycles. In the experiments our scheduler clearly outperforms conventional run-time schedulers based on As-Soon-As-Possible techniques. In addition, our replacement policy, specially designed for reconfigurable systems, achieves almost optimal results both regarding reuse and performance.

Desarrollo de un dispositivo confiable y de bajo costo para adquirir señales electro cardíacas, con capacidad de almacenamiento de datos y generación de registros

Generalidades anatómicas del musculo cardíaco -- Miocardio ventricular -- Génesis de la actividad -- eléctrica del corazón -- Señal eléctrica del corazón -- Representación vectorial -- El electrocardiograma --Intervalos y segmentos del electrocardiograma --Formas estándares de medición en el electrocardiograma -- Derivaciones bipolares -- Derivaciones monopolares --Posicionamiento adecuado de los electrodos-- Etapa de amplificación, filtrado y adaptación --Circuito de adecuación de la señal – Microcomputadora --Touchscreen display -- Shiel SD -- RTC (Real Time Clock) -- Thermal printer arduino -- Análisis de redes e interpretación del circuito de prueba -- Descripción, condiciones y resultados de la experimentación -- Desarrollo del dispositivo -- Interfaz de usuario -- Sistema de digitalización -- Sistema de Almacenamiento

A Hardware Task-Graph Scheduler for Reconfigurable Multi-tasking Systems

Reconfigurable hardware can be used to build a multitasking system where tasks are assigned to HW resources at run-time according to the requirements of the running applications. These tasks are frequently represented as direct acyclic graphs and their execution is typically controlled by an embedded processor that schedules the graph execution. In order to improve the efficiency of the system, the scheduler can apply prefetch and reuse techniques that can greatly reduce the reconfiguration latencies. For an embedded processor all these computations represent a heavy computational load that can significantly reduce the system performance. To overcome this problem we have implemented a HW scheduler using reconfigurable resources. In addition we have implemented both prefetch and replacement techniques that obtain as good results as previous complex SW approaches, while demanding just a few clock cycles to carry out the computations. We consider that the HW cost of the system (in our experiments 3% of a Virtex-II PRO xc2vp30 FPGA) is affordable taking into account the great efficiency of the techniques applied to hide the reconfiguration latency and the negligible run-time penalty introduced by the scheduler computations.

Engineering a Quantum Many-body Hamiltonian with Trapped Ions

While fault-tolerant quantum computation might still be years away, analog quantum simulators offer a way to leverage current quantum technologies to study classically intractable quantum systems. Cutting edge quantum simulators such as those utilizing ultracold atoms are beginning to study physics which surpass what is classically tractable. As the system sizes of these quantum simulators increase, there are also concurrent gains in the complexity and types of Hamiltonians which can be simulated. In this work, I describe advances toward the realization of an adaptable, tunable quantum simulator capable of surpassing classical computation. We simulate long-ranged Ising and XY spin models which can have global arbitrary transverse and longitudinal fields in addition to individual transverse fields using a linear chain of up to 24 Yb+ 171 ions confined in a linear rf Paul trap. Each qubit is encoded in the ground state hyperfine levels of an ion. Spin-spin interactions are engineered by the application of spin-dependent forces from laser fields, coupling spin to motion. Each spin can be read independently using state-dependent fluorescence. The results here add yet more tools to an ever growing quantum simulation toolbox. One of many challenges has been the coherent manipulation of individual qubits. By using a surprisingly large fourth-order Stark shifts in a clock-state qubit, we demonstrate an ability to individually manipulate spins and apply independent Hamiltonian terms, greatly increasing the range of quantum simulations which can be implemented. As quantum systems grow beyond the capability of classical numerics, a constant question is how to verify a quantum simulation. Here, I present measurements which may provide useful metrics for large system sizes and demonstrate them in a system of up to 24 ions during a classically intractable simulation. The observed values are consistent with extremely large entangled states, as much as ~95% of the system entangled. Finally, we use many of these techniques in order to generate a spin Hamiltonian which fails to thermalize during experimental time scales due to a meta-stable state which is often called prethermal. The observed prethermal state is a new form of prethermalization which arises due to long-range interactions and open boundary conditions, even in the thermodynamic limit. This prethermalization is observed in a system of up to 22 spins. We expect that system sizes can be extended up to 30 spins with only minor upgrades to the current apparatus. These results emphasize that as the technology improves, the techniques and tools developed here can potentially be used to perform simulations which will surpass the capability of even the most sophisticated classical techniques, enabling the study of a whole new regime of quantum many-body physics.

Holistic Design In High-Speed Optical Interconnects

Integrated circuit scaling has enabled a huge growth in processing capability, which necessitates a corresponding increase in inter-chip communication bandwidth. As bandwidth requirements for chip-to-chip interconnection scale, deficiencies of electrical channels become more apparent. Optical links present a viable alternative due to their low frequency-dependent loss and higher bandwidth density in the form of wavelength division multiplexing. As integrated photonics and bonding technologies are maturing, commercialization of hybrid-integrated optical links are becoming a reality. Increasing silicon integration leads to better performance in optical links but necessitates a corresponding co-design strategy in both electronics and photonics. In this light, holistic design of high-speed optical links with an in-depth understanding of photonics and state-of-the-art electronics brings their performance to unprecedented levels. This thesis presents developments in high-speed optical links by co-designing and co-integrating the primary elements of an optical link: receiver, transmitter, and clocking.

In the first part of this thesis a 3D-integrated CMOS/Silicon-photonic receiver will be presented. The electronic chip features a novel design that employs a low-bandwidth TIA front-end, double-sampling and equalization through dynamic offset modulation. Measured results show -14.9dBm of sensitivity and energy efficiency of 170fJ/b at 25Gb/s. The same receiver front-end is also used to implement source-synchronous 4-channel WDM-based parallel optical receiver. Quadrature ILO-based clocking is employed for synchronization and a novel frequency-tracking method that exploits the dynamics of IL in a quadrature ring oscillator to increase the effective locking range. An adaptive body-biasing circuit is designed to maintain the per-bit-energy consumption constant across wide data-rates. The prototype measurements indicate a record-low power consumption of 153fJ/b at 32Gb/s. The receiver sensitivity is measured to be -8.8dBm at 32Gb/s.

Next, on the optical transmitter side, three new techniques will be presented. First one is a differential ring modulator that breaks the optical bandwidth/quality factor trade-off known to limit the speed of high-Q ring modulators. This structure maintains a constant energy in the ring to avoid pattern-dependent power droop. As a first proof of concept, a prototype has been fabricated and measured up to 10Gb/s. The second technique is thermal stabilization of micro-ring resonator modulators through direct measurement of temperature using a monolithic PTAT temperature sensor. The measured temperature is used in a feedback loop to adjust the thermal tuner of the ring. A prototype is fabricated and a closed-loop feedback system is demonstrated to operate at 20Gb/s in the presence of temperature fluctuations. The third technique is a switched-capacitor based pre-emphasis technique designed to extend the inherently low bandwidth of carrier injection micro-ring modulators. A measured prototype of the optical transmitter achieves energy efficiency of 342fJ/bit at 10Gb/s and the wavelength stabilization circuit based on the monolithic PTAT sensor consumes 0.29mW.

Lastly, a first-order frequency synthesizer that is suitable for high-speed on-chip clock generation will be discussed. The proposed design features an architecture combining an LC quadrature VCO, two sample-and-holds, a PI, digital coarse-tuning, and rotational frequency detection for fine-tuning. In addition to an electrical reference clock, as an extra feature, the prototype chip is capable of receiving a low jitter optical reference clock generated by a high-repetition-rate mode-locked laser. The output clock at 8GHz has an integrated RMS jitter of 490fs, peak-to-peak periodic jitter of 2.06ps, and total RMS jitter of 680fs. The reference spurs are measured to be –64.3dB below the carrier frequency. At 8GHz the system consumes 2.49mW from a 1V supply.

Processamento de Dados GNSS em Modo Cinemático

O princípio do posicionamento por GNSS baseia-se, resumidamente, na resolução de um problema matemático que envolve a observação das distâncias do utilizador a um conjunto de satélites com coordenadas conhecidas. A posição resultante pode ser calculada em modo absoluto ou relativo. O posicionamento absoluto necessita apenas de um recetor para a determinação da posição. Por sua vez, o posicionamento relativo implica a utilização de estações de referência e envolve a utilização de mais recetores para além do pertencente ao próprio utilizador. Assim, os métodos mais utilizados na determinação da posição de uma plataforma móvel, com exatidão na ordem dos centímetros, baseiam-se neste último tipo de posicionamento. Contudo, têm a desvantagem de estarem dependentes de estações de referência, com um alcance limitado, e requerem observações simultâneas dos mesmos satélites por parte da estação e do recetor. Neste sentido foi desenvolvida uma nova metodologia de posicionamento GNSS em modo absoluto, através da modelação ou remoção dos erros associados a cada componente das equações de observação, da utilização de efemérides precisas e correções aos relógios dos satélites. Este método de posicionamento tem a designação Precise Point Positioning (PPP) e permite manter uma elevada exatidão, equivalente à dos sistemas de posicionamento relativo. Neste trabalho, após um estudo aprofundado do tema, foi desenvolvida uma aplicação PPP, de índole académica, com recurso à biblioteca de classes C++ do GPS Toolkit, que permite determinar a posição e velocidade do recetor em modo cinemático e em tempo real. Esta aplicação foi ensaiada utilizando dados de observação de uma estação estática (processados em modo cinemático) e de uma estação em movimento instalada no NRP Auriga. Os resultados obtidos permitiram uma exatidão para a posição na ordem decimétrica e para a velocidade na ordem do cm/s.

Learning math through movement: physical education as another alternative

The purpose of this study was to determine the cognitive effects of applying physical recreational activities to two groups of pre-school students, related to mathematics to one of the groups and recreational games to the other.  A total of 27 subjects (13 girls and 14 boys) of 5 and a half and 6 and half years of age participated in the study.  The instrument used was a questionnaire including basic math concepts such as geometry, basic operations with concrete elements, and how to read the clock, based on the topics established by the Costa Rican Ministry of Public Education.  Once the instrument was developed, a plan of physical recreational activities related to math was prepared and applied to the experimental group (pre-school B) for one and a half months, while the other group played recreational games.  Data was analyzed using descriptive and inferential statistics.  Positive and significant effects were found in the physical recreational activity program regarding student performance in 10 of the 12 items that were applied to assess mastery of basic math concepts.  In conclusion, using physical education as another instrument to teach other disciplines represents an excellent alternative for pre-school teachers that try to satisfy the learning needs of children that will soon be attending school.  Using movement as part of guided and planned activities plays an indispensable role in children’s lives; therefore, learning academic subjects should be adapted to their needs to explore and know their environment.

Detecting KaiC Phosphorylation Rhythms of the Cyanobacterial Circadian Oscillator In Vitro and In Vivo

The central oscillator of the cyanobacterial circadian clock is unique in the biochemical simplicity of its components and the robustness of the oscillation. The oscillator is composed of three cyanobacterial proteins: KaiA, KaiB, and KaiC. If very pure preparations of these three proteins are mixed in a test tube in the right proportions and with ATP and MgCl2, the phosphorylation states of KaiC will oscillate with a circadian period, and these states can be analyzed simply by SDS-PAGE. The purity of the proteins is critical for obtaining robust oscillation. Contaminating proteases will destroy oscillation by degradation of Kai proteins, and ATPases will attenuate robustness by consumption of ATP. Here, we provide a detailed protocol to obtain pure recombinant proteins from Escherichia coli to construct a robust cyanobacterial circadian oscillator in vitro. In addition, we present a protocol that facilitates analysis of phosphorylation states of KaiC and other phosphorylated proteins from in vivo samples.

Nanosecond-level time synchronization of autonomous radio detector stations for extensive air showers

To exploit the full potential of radio measurements of cosmic-ray air showers at MHz frequencies, a detector timing synchronization within 1 ns is needed. Large distributed radio detector arrays such as the Auger Engineering Radio Array (AERA) rely on timing via the Global Positioning System (GPS) for the synchronization of individual detector station clocks. Unfortunately, GPS timing is expected to have an accuracy no better than about 5 ns. In practice, in particular in AERA, the GPS clocks exhibit drifts on the order of tens of ns. We developed a technique to correct for the GPS drifts, and an independent method is used to cross-check that indeed we reach a nanosecond-scale timing accuracy by this correction. First, we operate a "beacon transmitter" which emits defined sine waves detected by AERA antennas recorded within the physics data. The relative phasing of these sine waves can be used to correct for GPS clock drifts. In addition to this, we observe radio pulses emitted by commercial airplanes, the position of which we determine in real time from Automatic Dependent Surveillance Broadcasts intercepted with a software-defined radio. From the known source location and the measured arrival times of the pulses we determine relative timing offsets between radio detector stations. We demonstrate with a combined analysis that the two methods give a consistent timing calibration with an accuracy of 2 ns or better. Consequently, the beacon method alone can be used in the future to continuously determine and correct for GPS clock drifts in each individual event measured by AERA.

Call recognition and individual identification of fish vocalizations based on automatic speech recognition: An example with the Lusitanian toadfish

The study of acoustic communication in animals often requires not only the recognition of species specific acoustic signals but also the identification of individual subjects, all in a complex acoustic background. Moreover, when very long recordings are to be analyzed, automatic recognition and identification processes are invaluable tools to extract the relevant biological information. A pattern recognition methodology based on hidden Markov models is presented inspired by successful results obtained in the most widely known and complex acoustical communication signal: human speech. This methodology was applied here for the first time to the detection and recognition of fish acoustic signals, specifically in a stream of round-the-clock recordings of Lusitanian toadfish (Halobatrachus didactylus) in their natural estuarine habitat. The results show that this methodology is able not only to detect the mating sounds (boatwhistles) but also to identify individual male toadfish, reaching an identification rate of ca. 95%. Moreover this method also proved to be a powerful tool to assess signal durations in large data sets. However, the system failed in recognizing other sound types.

Hardware processors for pairing-based cryptography

Bilinear pairings can be used to construct cryptographic systems with very desirable properties. A pairing performs a mapping on members of groups on elliptic and genus 2 hyperelliptic curves to an extension of the finite field on which the curves are defined. The finite fields must, however, be large to ensure adequate security. The complicated group structure of the curves and the expensive field operations result in time consuming computations that are an impediment to the practicality of pairing-based systems. The Tate pairing can be computed efficiently using the ɳT method. Hardware architectures can be used to accelerate the required operations by exploiting the parallelism inherent to the algorithmic and finite field calculations. The Tate pairing can be performed on elliptic curves of characteristic 2 and 3 and on genus 2 hyperelliptic curves of characteristic 2. Curve selection is dependent on several factors including desired computational speed, the area constraints of the target device and the required security level. In this thesis, custom hardware processors for the acceleration of the Tate pairing are presented and implemented on an FPGA. The underlying hardware architectures are designed with care to exploit available parallelism while ensuring resource efficiency. The characteristic 2 elliptic curve processor contains novel units that return a pairing result in a very low number of clock cycles. Despite the more complicated computational algorithm, the speed of the genus 2 processor is comparable. Pairing computation on each of these curves can be appealing in applications with various attributes. A flexible processor that can perform pairing computation on elliptic curves of characteristic 2 and 3 has also been designed. An integrated hardware/software design and verification environment has been developed. This system automates the procedures required for robust processor creation and enables the rapid provision of solutions for a wide range of cryptographic applications.

Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalk

Disruptions to circadian rhythm in mice and humans have been associated with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiological regulators of host circadian gene expression. We utilised a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equivalent tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addition oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and associated genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression. Disruptions to circadian rhythm in mice and humans have been associated with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiological regulators of host circadian gene expression. We utilised a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equivalent tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addition oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and associated genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression.

Melatonin for cardioprotection in ST elevation myocardial infarction: Are we ready for the challenge?

Melatonin, an endocrine product of the pineal gland, is formed predominantly during the nighttime. Light has an inhibitory effect on pineal melatonin secretion. Pineal melatonin release is synchronised by this daily light-dark cycle via a multisynaptic pathway between the eyes and the pineal gland. Light stimulates the retina to modulate the activity of the suprachiasmatic nucleus, the master biological clock.1 The suprachiasmatic nucleus controls pineal melatonin synthesis and the concentrations of melatonin in the sera of healthy subjects, which reach values of 10−10 to 10−9 mol/L during the night, with much lower concentrations being present during the day. Many publications have shown that melatonin has an important role in a variety of cardiovascular pathophysiologic processes: the indoleamine has anti-inflammatory, antioxidant, antihypertensive, antithrombotic and antilipaemic properties.