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Origin of life models based on “energized assemblages of building blocks” are untenable in principle. This is fundamentally a consequence of the fact that any living system is in a physical state that is extremely far from equilibrium, a condition it must itself build and sustain. This in turn requires that it carries out all of its molecular transformations–obligatorily those that convert, and thereby...
The metabolic requirements of differentiated neurons are significantly different from that of neuronal precursor and neural stem cells. While a re‐programming of metabolism is tightly coupled to the neuronal differentiation process, whether shifts in mitochondrial mass, glycolysis, and oxidative phosphorylation are required (or merely consequential) in differentiation is not yet certain. In addition...
Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually...
No overarching hypotheses tie the basic mechanisms of mitochondrial reactive oxygen species (ROS) production to activity dependent synapse pruning—a fundamental biological process in health and disease. Neuronal activity divergently regulates mitochondrial ROS: activity decreases whereas inactivity increases their production, respectively. Placing mitochondrial ROS as innate synaptic activity sentinels...
Life, Branscomb and Russell argue in article number 1700179, owes its existence not to chemistry but to engines; engines of disequilibria conversion. And it therefore owes its emergence to a context that can abiotically provide both the needed engines and the disequilibria to drive them. Only the Alkaline Hydrothermal Vent model of abiogenesis provides that context ‐‐“Of which vertu engendered is the flour...
The convergence of morphogenesis into viable organisms under variable conditions suggests closed‐loop dynamics involving multiscale functional feedback. We develop the idea that morphogenesis is based on synergy between mechanical and bio‐signaling processes, spanning all levels of organization: molecular, cellular, tissue, up to the whole organism. This synergy provides feedback within and between...
The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non‐pathological)...
An intriguing question in the field of stress is what makes an individual more likely to be susceptible or resilient to stress‐induced depression. Predisposition to stress susceptibility is believed to be influenced by genetic factors and early adversity. However, beyond genetics and life experiences, recent evidence has highlighted social rank as a key determinant of susceptibility to stress, underscoring...
Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum‐Golgi intermediate compartment (ERGIC). These membranous vesicular‐tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII‐coated transport carriers. In contrast to many unicellular...
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...
In article number 1800012, Sandi and Larrieu review and analyze rodent protocols addressing the relevance of social rank to predict vulnerability to chronic social stress. The authors also discuss whether a specific social status (i.e., dominance or subordination) is the appropriate predictor of vulnerability to develop stress‐induced depression or rather, the loss of social rank and resources.
Mitochondrial function and biogenesis depend on the transport of a large variety of proteins, ions, and metabolites across the two surrounding membranes. While several specific transporters are present in the inner membrane, transport processes across the outer membrane are less understood. Recent studies reveal that the number of outer membrane channels and their transport mechanisms are more diverse...
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