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Frontiers in Cell and Developmental... 2017The long-term maintenance of an organism's homeostasis and health relies on the accurate regulation of organ-organ communication. Recently, there has been growing... (Review)
Review
The long-term maintenance of an organism's homeostasis and health relies on the accurate regulation of organ-organ communication. Recently, there has been growing interest in using the gastrointestinal tract to elucidate the regulatory programs that underlie the complex interactions between organs. Data obtained in this field have dramatically improved our understanding of how organ-organ communication contributes to the regulation of various aspects of the intestine, including its metabolic and physiological status. However, although research uncovering regulatory programs associated with interorgan communication has provided key insights, the underlying mechanisms have not been extensively explored. In this review, we highlight recent findings describing gut-neighbor and neighbor-neighbor communication models in adults and larvae, respectively, with a special focus on how a range of critical strategies concerning continuous interorgan communication and adjustment can be used to manipulate different aspects of biological processes. Given the high degree of similarity between the and mammalian intestinal epithelia, it can be anticipated that further analyses of the gastrointestinal tract will facilitate the discovery of similar mechanisms underlying organ-organ communication in other mammalian organs, such as the human intestine.
PubMed: 28421183
DOI: 10.3389/fcell.2017.00029 -
Annual Review of Cell and Developmental... Oct 2022Although tissue homeostasis-the steady state-implies stability, our organs are in a state of continual, large-scale cellular flux. This flux underpins an organ's ability... (Review)
Review
Although tissue homeostasis-the steady state-implies stability, our organs are in a state of continual, large-scale cellular flux. This flux underpins an organ's ability to homeostatically renew, to non-homeostatically resize upon altered functional demand, and to return to homeostasis after resizing or injury-in other words, to be dynamic. Here, I examine the basic unit of organ-scale cell dynamics: the cellular life cycle of birth, differentiation, and death. Focusing on epithelial organs, I discuss how spatial patterns and temporal kinetics of life cycle stages depend upon lineage organization and tissue architecture. I review how signaling between stages coordinates life cycle dynamics to enforce homeostasis, and I highlight how particular stages are transiently unbalanced to drive organ resizing or repair. Finally, I offer that considering organs as a collective of not cells but rather cell life cycles provides a powerful vantage for deciphering homeostatic and non-homeostatic tissue states.
Topics: Cell Differentiation; Homeostasis; Signal Transduction
PubMed: 35850152
DOI: 10.1146/annurev-cellbio-120420-114855 -
European Journal of Clinical Nutrition Feb 2019Body mass in humans and animals is strongly associated with the rate of heat production as defined by resting energy expenditure (REE). Beginning with the ancient Greeks... (Review)
Review
Body mass in humans and animals is strongly associated with the rate of heat production as defined by resting energy expenditure (REE). Beginning with the ancient Greeks up to the present time, philosophers and scientists have endeavored to understand the nature and sources of bodily heat. Today we recognize that body mass consists of organs and tissues, each of which produces a specified amount of heat at rest. An individual organ's REE can now be estimated in vivo as the product of its assumed mass-specific metabolic rate and its imaging-derived mass; whole-body REE reflects the sum of organ and tissue metabolic rates. The sizes of organs and total body mass in adults are governed by two main factors, a person's stature or height, and their level of adiposity. With greater body size, as represented by adult height independent of adiposity, organs remain stable or increase in mass according to distinct "scaling" patterns. Similarly, with greater relative adiposity organs adaptively accommodate to the increase in imposed mechanical and metabolic loading conditions. Through a detailed analysis of these stature and adiposity effects, we show how classical statistical REE prediction models can be mechanistically understood at the anatomic body composition level.
Topics: Body Composition; Energy Metabolism; Humans
PubMed: 30254244
DOI: 10.1038/s41430-018-0319-3 -
Comptes Rendus Biologies 2016Genomes and genes continuously evolve. Gene sequences undergo substitutions, deletions or nucleotide insertions; mobile genetic elements invade genomes and interleave in... (Review)
Review
Genomes and genes continuously evolve. Gene sequences undergo substitutions, deletions or nucleotide insertions; mobile genetic elements invade genomes and interleave in genes; chromosomes break, even within genes, and pieces reseal in reshuffled order. To maintain functional gene products and assure an organism's survival, two principal strategies are used - either repair of the gene itself or of its product. I will introduce common types of gene aberrations and how gene function is restored secondarily, and then focus on systematically fragmented genes found in a poorly studied protist group, the diplonemids. Expression of their broken genes involves restitching of pieces at the RNA-level, and substantial RNA editing, to compensate for point mutations. I will conclude with thoughts on how such a grotesquely unorthodox system may have evolved, and why this group of organisms persists and thrives since tens of millions of years.
Topics: Animals; Biological Evolution; DNA Fragmentation; Genes, Mitochondrial; Genetics; Humans; RNA; RNA Editing; Targeted Gene Repair
PubMed: 27180109
DOI: 10.1016/j.crvi.2016.04.004 -
Current Issues in Molecular Biology Jun 2023Recently, immense efforts have focused on improving the preservation of (sub)optimal donor organs by means of ex vivo perfusion, which enables the opportunity for organ... (Review)
Review
Recently, immense efforts have focused on improving the preservation of (sub)optimal donor organs by means of ex vivo perfusion, which enables the opportunity for organ reconditioning and viability assessment. However, there is still no biomarker that correlates with renal viability. Therefore, it is essential to explore new techniques for pre-transplant assessment of organ quality to guarantee successful long-term transplantation outcomes. The renal vascular compartment has received little attention in machine perfusion studies. In vivo, proper renal vascular and endothelial function is essential for maintaining homeostasis and long-term graft survival. In an ex vivo setting, little is known about vascular viability and its implications for an organ's suitability for transplant. Seeing that endothelial damage is the first step in a cascade of disruptions and maintaining homeostasis is crucial for positive post-transplant outcomes, further research is key to clarifying the (patho)physiology of the renal vasculature during machine perfusion. In this review, we aim to summarize key aspects of renal vascular physiology, describe the role of the renal vasculature in pathophysiological settings, and explain how ex vivo perfusion plays a role in either unveiling or targeting such processes. Additionally, we discuss potentially new vascular assessment tools during ex vivo renal perfusion.
PubMed: 37504261
DOI: 10.3390/cimb45070345 -
Human Molecular Genetics Oct 2016The genetic code is degenerate. With the exception of two amino acids (Met and Trp), all other amino acid residues are each encoded by multiple, so-called synonymous... (Review)
Review
The genetic code is degenerate. With the exception of two amino acids (Met and Trp), all other amino acid residues are each encoded by multiple, so-called synonymous codons. Synonymous codons were initially presumed to have entirely equivalent functions, however, the finding that synonymous codons are not present at equal frequencies in genes/genomes suggested that codon choice might have functional implications beyond amino acid coding. The pattern of non-uniform codon use (known as codon usage bias) varies between organisms and represents a unique feature of an organism. Organism-specific codon choice is related to organism-specific differences in populations of cognate tRNAs. This implies that, in a given organism, frequently used codons will be translated more rapidly than infrequently used ones and vice versa A theory of codon-tRNA co-evolution (necessary to balance accurate and efficient protein production) was put forward to explain the existence of codon usage bias. This model suggests that selection favours preferred (frequent) over un-preferred (rare) codons in order to sustain efficient protein production in cells and that a given un-preferred codon will have the same effect on an organism's fitness regardless of its position within an mRNA's open reading frame. However, many recent studies refute this prediction. Un-preferred codons have been found to have important functional roles and their effects appeared to be position-dependent. Synonymous codon usage affects the efficiency/stringency of mRNA decoding, mRNA biogenesis/stability, and protein secretion and folding. This review summarizes recent developments in the field that have identified novel functions of synonymous codons and their usage.
Topics: Codon; Evolution, Molecular; Genetic Code; Open Reading Frames; Protein Biosynthesis; RNA Stability; RNA, Messenger; RNA, Transfer
PubMed: 27354349
DOI: 10.1093/hmg/ddw207 -
Dose-response : a Publication of... 2012Organisms are perpetually facing noxious insults but exhibit surprising diverse reaction patterns. Depending on the strength, frequency and quality of the stress stimuli...
Organisms are perpetually facing noxious insults but exhibit surprising diverse reaction patterns. Depending on the strength, frequency and quality of the stress stimuli biological systems may react with increased vitality, future stress resistance or with injury and degeneration. Whereas a multitude of such specific stress responses has been observed in diverse biological systems the underlying molecular mechanisms are mainly unknown. These knowledge restrictions urge the exploration of specific molecular signaling reactions controlling the ambivalent responses of cells and organisms to noxious effects. The adaptive responses of signaling networks to defined stress stimuli need to be investigated in a time-and dose-resolved manner in cellular and organismic models. Anticipated results are expected to significantly advance the understanding of the molecular signatures of stress responses and may also promote ongoing efforts for the effective use of the organism's preventive and regenerative potentials in modern medicine.
PubMed: 22423231
DOI: 10.2203/dose-response.11-012.Wetzker -
Annual Review of Neuroscience Jul 2020While neurons and circuits are almost unequivocally considered to be the computational units and actuators of behavior, a complete understanding of the nervous system... (Review)
Review
While neurons and circuits are almost unequivocally considered to be the computational units and actuators of behavior, a complete understanding of the nervous system must incorporate glial cells. Far beyond a copious but passive substrate, glial influence is inextricable from neuronal physiology, whether during developmental guidance and synaptic shaping or through the trophic support, neurotransmitter and ion homeostasis, cytokine signaling and immune function, and debris engulfment contributions that this class provides throughout an organism's life. With such essential functions, among a growing literature of nuanced roles, it follows that glia are consequential to behavior in adult animals, with novel genetic tools allowing for the investigation of these phenomena in living organisms. We discuss here the relevance of glia for maintaining circadian rhythms and also for serving functions of sleep.
Topics: Animals; Circadian Rhythm; Drosophila; Humans; Neuroglia; Neurons; Neurotransmitter Agents; Sleep
PubMed: 32075519
DOI: 10.1146/annurev-neuro-091819-094557 -
Molecular Biology of the Cell May 2019Organoids derived from stem cells or tissues in culture can develop into structures that resemble the in vivo anatomy and physiology of intact organs. Human organoid...
Organoids derived from stem cells or tissues in culture can develop into structures that resemble the in vivo anatomy and physiology of intact organs. Human organoid cultures provide the potential to study human development and model disease processes with the same scrutiny and depth of analysis customary for research with nonhuman model organisms. Resembling the complexity of the actual tissue or organ, patient-derived human organoid studies may accelerate medical research, creating new opportunities for tissue engineering and regenerative medicine, generating knowledge and tools for preclinical studies, including drug development and testing. Biologists are drawn to this system as a new "model organism" to study complex disease phenotypes and genetic variability among individuals using patient-derived tissues. The American Society for Cell Biology convened a task force to report on the potential, challenges, and limitations for human organoid research. The task force suggests ways to ease the entry for new researchers into the field and how to facilitate broader use of this new model organism within the research community. This includes guidelines for reproducibility, culturing, sharing of patient materials, patient consent, training, and communication with the public.
Topics: Animals; Biomedical Research; Cell Culture Techniques; Humans; Models, Biological; Organoids; Regenerative Medicine; Reproducibility of Results; Stem Cells; Tissue Engineering
PubMed: 31034354
DOI: 10.1091/mbc.E19-03-0135 -
Journal of Medical Toxicology :... Dec 2018The gap between the number of patients on transplant waiting lists and patients receiving transplants is growing. Use of organs from donors who have died following... (Review)
Review
INTRODUCTION
The gap between the number of patients on transplant waiting lists and patients receiving transplants is growing. Use of organs from donors who have died following pesticide exposure remains controversial. This study reviews the literature related to transplantation from this group.
METHODS
A literature search was undertaken on PubMed using the following keywords: 'insecticide', 'pesticide', 'rodenticide', 'organophosphate', 'carbamate', 'paraquat', 'poisoning', 'toxicity', 'overdose', 'intoxication', 'ingestion', 'organ donation or procurement', 'transplant', 'allograft transplant', and 'expanded criteria organ donation'; 21 specific pesticides/insecticides were also added to the search; the indexes for EAPCCT/NACCT meeting abstracts 2008-2017 were also searched. Identified publications were reviewed and if described human donation/transplantation of ≥ 1 solid organ(s), the following was extracted: (i) compound(s) ingested; (ii) donor demographics; (iii) organ(s) transplanted; and (iv) graft function at follow-up.
RESULTS
Ten papers were identified describing 20 fatalities (1999-2017) related to the following pesticide exposures: organophosphate, 8 cases; aldicarb, 4; paraquat, 3; parathion, 1; malathion, 1; carbofuran/carbamate, 1; carbamate, 1; and brodifacoum, 1 and no further cases were identified from EAPCCT/NACCT abstracts. Donors were aged 12-50 (25.9 ± 11.9) years. Forty-four organs were transplanted: 28 kidneys, 7 livers, 6 corneas, and 3 hearts. Forty recipients had outcome reported: 3 (7.5%) patients died, 3 (7.5%) had graft failure/dysfunction and 34 (85.0%) had good graft function. Overall survival with good function was 96%, 71%, 83%, and 67% for kidneys, livers, corneas and hearts respectively.
CONCLUSION
Review of the published literature suggests that solid organ donation following exposure to a pesticide is associated with good short-to-medium-term graft organ function following transplantation, particularly for transplanted kidneys and corneas.
Topics: Humans; Organ Transplantation; Pesticides; Tissue Donors; Treatment Outcome
PubMed: 29987646
DOI: 10.1007/s13181-018-0673-5