7,573 research outputs found
In Synch but Not in Step: Circadian Clock Circuits Regulating Plasticity in Daily Rhythms
The suprachiasmatic nucleus (SCN) is a network of neural oscillators that program daily rhythms in mammalian behavior and physiology. Over the last decade much has been learned about how SCN clock neurons coordinate together in time and space to form a cohesive population. Despite this insight, much remains unknown about how SCN neurons communicate with one another to produce emergent properties of the network. Here we review the current understanding of communication among SCN clock cells and highlight a collection of formal assays where changes in SCN interactions provide for plasticity in the waveform of circadian rhythms in behavior. Future studies that pair analytical behavioral assays with modern neuroscience techniques have the potential to provide deeper insight into SCN circuit mechanisms
Circadian rhythms and hormonal homeostasis: Pathophysiological implications
Over recent years, a deeper comprehension of the molecular mechanisms that control biological clocks and circadian rhythms has been achieved. In fact, many studies have contributed to unravelling the importance of the molecular clock for the regulation of our physiology, including hormonal and metabolic homeostasis. Here we will review the structure, organisation and molecular machinery that make our circadian clock work, and its relevance for the proper functioning of physiological processes. We will also describe the interconnections between circadian rhythms and endocrine homeostasis, as well as the underlying consequences that circadian dysregulations might have in the development of several pathologic affections. Finally, we will discuss how a better knowledge of such relationships might prove helpful in designing new therapeutic approaches for endocrine and metabolic diseases
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
Designer Gene Networks: Towards Fundamental Cellular Control
The engineered control of cellular function through the design of synthetic
genetic networks is becoming plausible. Here we show how a naturally occurring
network can be used as a parts list for artificial network design, and how
model formulation leads to computational and analytical approaches relevant to
nonlinear dynamics and statistical physics.Comment: 35 pages, 8 figure
Cytoskeleton and Cell Motility
The present article is an invited contribution to the Encyclopedia of
Complexity and System Science, Robert A. Meyers Ed., Springer New York (2009).
It is a review of the biophysical mechanisms that underly cell motility. It
mainly focuses on the eukaryotic cytoskeleton and cell-motility mechanisms.
Bacterial motility as well as the composition of the prokaryotic cytoskeleton
is only briefly mentioned. The article is organized as follows. In Section III,
I first present an overview of the diversity of cellular motility mechanisms,
which might at first glance be categorized into two different types of
behaviors, namely "swimming" and "crawling". Intracellular transport, mitosis -
or cell division - as well as other extensions of cell motility that rely on
the same essential machinery are briefly sketched. In Section IV, I introduce
the molecular machinery that underlies cell motility - the cytoskeleton - as
well as its interactions with the external environment of the cell and its main
regulatory pathways. Sections IV D to IV F are more detailed in their
biochemical presentations; readers primarily interested in the theoretical
modeling of cell motility might want to skip these sections in a first reading.
I then describe the motility mechanisms that rely essentially on
polymerization-depolymerization dynamics of cytoskeleton filaments in Section
V, and the ones that rely essentially on the activity of motor proteins in
Section VI. Finally, Section VII is devoted to the description of the
integrated approaches that have been developed recently to try to understand
the cooperative phenomena that underly self-organization of the cell
cytoskeleton as a whole.Comment: 31 pages, 16 figures, 295 reference
Complex and unexpected dynamics in simple genetic regulatory networks
Peer reviewedPublisher PD
Widespread depolarization during expiration: A source of respiratory drive?
Respiration influences various pacemakers and rhythms of the body during inspiration and expiration but the underlying mechanisms are relatively unknown. Understanding this phenomenon is important, as breathing disorders, breath holding, and hyperventilation can lead to significant medical conditions. We discuss the physiological modulation of heart rhythm, blood pressure, sympathetic nerve activity, EEG, and other changes observed during inspiration and expiration. We also correlate the intracellular mitochondrial respiratory metabolic processes with real-time breathing and correlate membrane potential changes with inspiration and expiration. We propose that widespread minor hyperpolarization occurs during inspiration and widespread minor depolarization occurs during expiration. This depolarization is likely a source of respiratory drive. Further knowledge of intracellular and extracellular ionic changes associated with respiration will enhance our understanding of respiration and its role as a modulator of cellular membrane potential. This could expand treatment options for a wide range of health conditions, such as breathing disorders, stress-related disorders, and further our understanding of the Hering–Breuer reflex and respiratory sinus arrhythmia
A Multi-scale View of the Emergent Complexity of Life: A Free-energy Proposal
We review some of the main implications of the free-energy principle (FEP) for the study of the self-organization of living systems – and how the FEP can help us to understand (and model) biotic self-organization across the many temporal and spatial scales over which life exists. In order to maintain its integrity as a bounded system, any biological system - from single cells to complex organisms and societies - has to limit the disorder or dispersion (i.e., the long-run entropy) of its constituent states. We review how this can be achieved by living systems that minimize their variational free energy. Variational free energy is an information theoretic construct, originally introduced into theoretical neuroscience and biology to explain perception, action, and learning. It has since been extended to explain the evolution, development, form, and function of entire organisms, providing a principled model of biotic self-organization and autopoiesis. It has provided insights into biological systems across spatiotemporal scales, ranging from microscales (e.g., sub- and multicellular dynamics), to intermediate scales (e.g., groups of interacting animals and culture), through to macroscale phenomena (the evolution of entire species). A crucial corollary of the FEP is that an organism just is (i.e., embodies or entails) an implicit model of its environment. As such, organisms come to embody causal relationships of their ecological niche, which, in turn, is influenced by their resulting behaviors. Crucially, free-energy minimization can be shown to be equivalent to the maximization of Bayesian model evidence. This allows us to cast natural selection in terms of Bayesian model selection, providing a robust theoretical account of how organisms come to match or accommodate the spatiotemporal complexity of their surrounding niche. In line with the theme of this volume; namely, biological complexity and self-organization, this chapter will examine a variational approach to self-organization across multiple dynamical scales
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