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Frontiers in Neuroscience 2022Neuromorphic engineering aims to build (autonomous) systems by mimicking biological systems. It is motivated by the observation that biological organisms-from algae to... (Review)
Review
Neuromorphic engineering aims to build (autonomous) systems by mimicking biological systems. It is motivated by the observation that biological organisms-from algae to primates-excel in sensing their environment, reacting promptly to their perils and opportunities. Furthermore, they do so more resiliently than our most advanced machines, at a fraction of the power consumption. It follows that the performance of neuromorphic systems should be evaluated in terms of real-time operation, power consumption, and resiliency to real-world perturbations and noise using task-relevant evaluation metrics. Yet, following in the footsteps of conventional machine learning, most neuromorphic benchmarks rely on recorded datasets that foster sensing accuracy as the primary measure for performance. Sensing accuracy is but an arbitrary proxy for the actual system's goal-taking a good decision in a timely manner. Moreover, static datasets hinder our ability to study and compare closed-loop sensing and control strategies that are central to survival for biological organisms. This article makes the case for a renewed focus on closed-loop benchmarks involving real-world tasks. Such benchmarks will be crucial in developing and progressing neuromorphic Intelligence. The shift towards dynamic real-world benchmarking tasks should usher in richer, more resilient, and robust artificially intelligent systems in the future.
PubMed: 35237122
DOI: 10.3389/fnins.2022.813555 -
Nature Aging Jan 2021Aging has largely been defined by analog measures of organ and organismal dysfunction. This has led to the characterization of aging processes at the molecular and...
Aging has largely been defined by analog measures of organ and organismal dysfunction. This has led to the characterization of aging processes at the molecular and cellular levels that underlie these gradual changes. However, current knowledge does not fully explain the growing body of data emerging from large epidemiological, systems biology, and single cell studies of entire organisms pointing to varied rates of aging between individuals (different functionality and lifespan), across lifespan (asynchronous aging), and within an organism at the tissue and organ levels (aging mosaicism). Here we consider these inhomogeneities in the broader context of the rate of aging and from the perspective of underlying cellular changes. These changes reflect genetic, environmental, and stochastic factors that cells integrate to adopt new homeostatic, albeit less functional, states, such as cellular senescence. In this sense, cellular aging can be viewed, at least in part, as a quantal process we refer to as "digital aging". Nevertheless, analog declines of tissue dysfunction and organ failure with age could be the sum of underlying digital events. Importantly, cellular aging, digital or otherwise, is not uniform across time or space within the organism or between organisms of the same species. Certain tissues may exhibit earliest signs of cellular aging, acting as drivers for organismal aging as signals from those driver cells within those tissues may accelerate the aging of other cells locally or even systemically. Advanced methodologies at the systems level and at the single cell level are likely to continue to refine our understanding to the processes of how cells and tissues age and how the integration of those processes leads to the complexities of individual, organismal aging.
Topics: Humans; Aging; Cellular Senescence; Longevity
PubMed: 34223194
DOI: 10.1038/s43587-020-00015-1 -
Frontiers in Cardiovascular Medicine 2020The close association among cardiovascular, metabolic, and kidney diseases suggests a common pathological basis and significant interaction among these diseases.... (Review)
Review
The close association among cardiovascular, metabolic, and kidney diseases suggests a common pathological basis and significant interaction among these diseases. Metabolic syndrome and cardiorenal syndrome are two examples that exemplify the interlinked development of disease or dysfunction in two or more organs. Recent studies have been sorting out the mechanisms responsible for the crosstalk among the organs comprising the cardiovascular, metabolic, and renal systems, including heart-kidney and adipose-liver signaling, among many others. However, it is also becoming clear that this crosstalk is not limited to just pairs of organs, and in addition to organ-organ crosstalk, there are also organ-system and organ-body interactions. For instance, heart failure broadly impacts various organs and systems, including the kidney, liver, lung, and nervous system. Conversely, systemic dysregulation of metabolism, immunity, and nervous system activity greatly affects heart failure development and prognosis. This is particularly noteworthy, as more and more patients present with two or more coexisting chronic diseases or conditions (multimorbidity) due in part to the aging of society. Advances in treatment also contribute to the increase in multimorbidity, as exemplified by cardiovascular disease in cancer survivors. To understand the mechanisms underlying the increasing burden of multimorbidity, it is vital to elucidate the multilevel crosstalk and communication within the body at the levels of organ systems, tissues, and cells. In this article, we focus on chronic inflammation as a key common pathological basis of cardiovascular and metabolic diseases, and discuss emerging mechanisms that drive chronic inflammation in the context of multimorbidity.
PubMed: 32411724
DOI: 10.3389/fcvm.2020.00064 -
BioDrugs : Clinical Immunotherapeutics,... Jan 2023Kidney transplantation is a life-saving strategy for patients with end-stage renal disease. Although progress has been made in the field of transplantation medicine in... (Review)
Review
Kidney transplantation is a life-saving strategy for patients with end-stage renal disease. Although progress has been made in the field of transplantation medicine in recent decades in terms of surgical techniques and immunosuppression, long-term organ survival remains a challenge. Also, for reasons of organ shortage, there is an unmet need for new therapeutic approaches to improve the long-term survival of transplants. There is increasing evidence that the complement system plays a crucial role in various pathological events after transplantation, including ischemia/reperfusion injury as well as rejection episodes. The complement system is part of the innate immune system and plays a crucial role in the defense against pathogens but is also involved in tissue homeostasis. However, the tightly regulated complement system can become dysregulated or activated by non-infectious stimuli, then targeting the organism's own cells and leading to inflammatory tissue damage that exacerbates injury. In this review, we will highlight the role of the complement system after transplantation and discuss ongoing and potential therapeutic approaches.
Topics: Humans; Kidney Transplantation; Graft Rejection; Complement System Proteins; Reperfusion Injury
PubMed: 36512315
DOI: 10.1007/s40259-022-00567-1 -
Alcohol Research : Current Reviews 2021Chronic, heavy alcohol consumption disrupts normal organ function and causes structural damage in virtually every tissue of the body. Current diagnostic terminology... (Review)
Review
Chronic, heavy alcohol consumption disrupts normal organ function and causes structural damage in virtually every tissue of the body. Current diagnostic terminology states that a person who drinks alcohol excessively has alcohol use disorder. The liver is especially susceptible to alcohol-induced damage. This review summarizes and describes the effects of chronic alcohol use not only on the liver, but also on other selected organs and systems affected by continual heavy drinking-including the gastrointestinal tract, pancreas, heart, and bone. Most significantly, the recovery process after cessation of alcohol consumption (abstinence) is explored. Depending on the organ and whether there is relapse, functional recovery is possible. Even after years of heavy alcohol use, the liver has a remarkable regenerative capacity and, following alcohol removal, can recover a significant portion of its original mass and function. Other organs show recovery after abstinence as well. Data on studies of both heavy alcohol use among humans and animal models of chronic ethanol feeding are discussed. This review describes how (or whether) each organ/tissue metabolizes ethanol, as metabolism influences the organ's degree of injury. Damage sustained by the organ/tissue is reviewed, and evidence for recovery during abstinence is presented.
Topics: Alcohol Abstinence; Alcohol Drinking; Alcoholism; Animals; Bone and Bones; Ethanol; Gastrointestinal Tract; Heart; Humans; Liver; Liver Diseases, Alcoholic; Mice; Pancreatitis, Alcoholic; Rats
PubMed: 33868869
DOI: 10.35946/arcr.v41.1.05 -
International Journal of Molecular... Mar 2019Circadian timekeeping allows appropriate temporal regulation of an organism's internal metabolism to anticipate and respond to recurrent daily changes in the... (Review)
Review
Circadian timekeeping allows appropriate temporal regulation of an organism's internal metabolism to anticipate and respond to recurrent daily changes in the environment. Evidence from animal genetic models and from humans under circadian misalignment (such as shift work or jet lag) shows that disruption of circadian rhythms contributes to the development of obesity and metabolic disease. Inappropriate timing of food intake and high-fat feeding also lead to disruptions of the temporal coordination of metabolism and physiology and subsequently promote its pathogenesis. This review illustrates the impact of genetically or environmentally induced molecular clock disruption (at the level of the brain and peripheral tissues) and the interplay between the circadian system and metabolic processes. Here, we discuss some mechanisms responsible for diet-induced circadian desynchrony and consider the impact of nutritional cues in inter-organ communication, with a particular focus on the communication between peripheral organs and brain. Finally, we discuss the relay of environmental information by signal-dependent transcription factors to adjust the timing of gene oscillations. Collectively, a better knowledge of the mechanisms by which the circadian clock function can be compromised will lead to novel preventive and therapeutic strategies for obesity and other metabolic disorders arising from circadian desynchrony.
Topics: Animals; Circadian Clocks; Circadian Rhythm Signaling Peptides and Proteins; Energy Metabolism; Humans; Metabolic Diseases
PubMed: 30935034
DOI: 10.3390/ijms20071597 -
International Journal of Molecular... Mar 2021CRISPR/Cas (clustered regularly interspaced short palindromic repeats linked to Cas nuclease) technology has revolutionized many aspects of genetic engineering research.... (Review)
Review
CRISPR/Cas (clustered regularly interspaced short palindromic repeats linked to Cas nuclease) technology has revolutionized many aspects of genetic engineering research. Thanks to it, it became possible to study the functions and mechanisms of biology with greater precision, as well as to obtain genetically modified organisms, both prokaryotic and eukaryotic. The changes introduced by the CRISPR/Cas system are based on the repair paths of the single or double strand DNA breaks that cause insertions, deletions, or precise integrations of donor DNA. These changes are crucial for many fields of science, one of which is the use of animals (pigs) as a reservoir of tissues and organs for xenotransplantation into humans. Non-genetically modified animals cannot be used to save human life and health due to acute immunological reactions resulting from the phylogenetic distance of these two species. This review is intended to collect and summarize the advantages as well as achievements of the CRISPR/Cas system in pig-to-human xenotransplantation research. In addition, it demonstrates barriers and limitations that require careful evaluation before attempting to experiment with this technology.
Topics: Animals; CRISPR-Cas Systems; DNA Breaks, Double-Stranded; DNA Repair; Gene Editing; Genetic Engineering; Graft Rejection; Graft Survival; Heterografts; Humans; Models, Animal; Organ Transplantation; Swine; Transplantation, Heterologous
PubMed: 33801123
DOI: 10.3390/ijms22063196 -
EMBO Reports Sep 2019Multidirectional interactions between metabolic organs in the periphery and the central nervous system have evolved concomitantly with multicellular organisms to... (Review)
Review
Multidirectional interactions between metabolic organs in the periphery and the central nervous system have evolved concomitantly with multicellular organisms to maintain whole-body energy homeostasis and ensure the organism's adaptation to external cues. These interactions are altered in pathological conditions such as obesity and type 2 diabetes. Bioactive peptides and proteins, such as hormones and cytokines, produced by both peripheral organs and the central nervous system, are key messengers in this inter-organ communication. Despite the early discovery of the first hormones more than 100 years ago, recent studies taking advantage of novel technologies have shed light on the multiple ways used by cells in the body to communicate and maintain energy balance. This review briefly summarizes well-established concepts and focuses on recent advances describing how specific proteins and peptides mediate the crosstalk between gut, brain, and other peripheral metabolic organs in order to maintain energy homeostasis. Additionally, this review outlines how the improved knowledge about these inter-organ networks is helping us to redefine therapeutic strategies in an effort to promote healthy living and fight metabolic disorders and other diseases.
Topics: Animals; Diabetes Mellitus, Type 2; Energy Metabolism; Homeostasis; Humans; Models, Biological; Obesity
PubMed: 31423716
DOI: 10.15252/embr.201947903 -
Frontiers in Immunology 2019The skin and intestine are active organs of the immune system that are constantly exposed to the outside environment. They support diverse microbiota, both commensal and... (Review)
Review
The skin and intestine are active organs of the immune system that are constantly exposed to the outside environment. They support diverse microbiota, both commensal and pathogenic, which encompass bacteria, viruses, fungi, and parasites. The skin and intestine must maintain homeostasis with the diversity of commensal organisms present on epithelial surfaces. Here we review the current literature pertaining to epithelial barrier formation, microbial composition, and the complex regulatory mechanisms governing the interaction between the innate immune system and microbiota in the skin and intestine. We also compare and contrast the skin and intestine-two different organ systems responsible creating a protective barrier against the external environment, each of which has unique mechanisms for interaction with commensal populations and host repair.
Topics: Gastrointestinal Microbiome; Humans; Immunity, Innate; Intestines; Organ Specificity; Skin
PubMed: 31921196
DOI: 10.3389/fimmu.2019.02950 -
Medical Law Review May 2022It is often claimed that a legitimate approach to organ donation is an opt-out system, also known as 'presumed consent', 'deemed consent', or 'deemed authorisation',...
It is often claimed that a legitimate approach to organ donation is an opt-out system, also known as 'presumed consent', 'deemed consent', or 'deemed authorisation', whereby individuals are presumed or deemed willing to donate at least some of their organs and tissues after death unless they have explicitly refused permission. While sharing a default in favour of donation, such systems differ in several key respects, such as the role and importance assigned to the family members of prospective donors and their preferences, and exclusions and safeguards which often specify the demographic groups, purposes, or organs and tissues that will remain outside the scope of the opt-out system. Using the recent shift to opt-out in England, Scotland, and Northern Ireland as case studies, and by reference to the key goals motivating this shift across the UK, this article asks whether and, if so, why, and how, opt-out systems for post-mortem organ donation should restrict the types of organs and tissues for which consent is deemed. In other words, ought opt-out systems for PMOD presume dissent regarding the donation of certain organs and tissues?
Topics: Dissent and Disputes; Humans; Organ Transplantation; Presumed Consent; Prospective Studies; Tissue Donors; Tissue and Organ Procurement
PubMed: 35171293
DOI: 10.1093/medlaw/fwac001