-
Liver International : Official Journal... Jan 2021Mature transfer RNAs (tRNA) charged with amino acids decode mRNA to synthesize proteins. Dysregulation of translational machineries has a fundamental impact on cancer...
BACKGROUND & AIMS
Mature transfer RNAs (tRNA) charged with amino acids decode mRNA to synthesize proteins. Dysregulation of translational machineries has a fundamental impact on cancer biology. This study aims to map the tRNAome landscape in liver cancer patients and to explore potential therapeutic targets at the interface of charging amino acid with tRNA.
METHODS
Resected tumour and paired tumour-free (TFL) tissues from hepatocellular carcinoma (HCC) patients (n = 69), and healthy liver tissues from organ transplant donors (n = 21), HCC cell lines, and cholangiocarcinoma (CC) patient-derived tumour organoids were used.
RESULTS
The expression levels of different mature tRNAs were highly correlated and closely clustered within individual tissues, suggesting that different members of the tRNAome function cooperatively in protein translation. Interestingly, high expression of tRNA-Lys-CUU in HCC tumours was associated with more tumour recurrence (HR 1.1; P = .022) and worse patient survival (HR 1.1; P = .0037). The expression of Lysyl-tRNA Synthetase (KARS), the enzyme catalysing the charge of lysine to tRNA-Lys-CUU, was significantly upregulated in HCC tumour tissues compared to tumour-free liver tissues. In HCC cell lines, lysine deprivation, KARS knockdown or treatment with the KARS inhibitor cladosporin effectively inhibited overall cell growth, single cell-based colony formation and cell migration. This was mechanistically mediated by cell cycling arrest and induction of apoptosis. Finally, these inhibitory effects were confirmed in 3D cultured patient-derived CC organoids.
CONCLUSIONS
The biological process of charging tRNA-Lys-CUU with lysine sustains liver cancer cell growth and migration, and is clinically relevant in HCC patients. This process can be therapeutically targeted and represents an unexplored territory for developing novel treatment strategies against liver cancer.
Topics: Biological Phenomena; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Lysine; Neoplasm Recurrence, Local; Transfer RNA Aminoacylation
PubMed: 33084231
DOI: 10.1111/liv.14692 -
Physical Biology May 2021Biological organisms experience constantly changing environments, from sudden changes in physiology brought about by feeding, to the regular rising and setting of the... (Review)
Review
Biological organisms experience constantly changing environments, from sudden changes in physiology brought about by feeding, to the regular rising and setting of the Sun, to ecological changes over evolutionary timescales. Living organisms have evolved to thrive in this changing world but the general principles by which organisms shape and are shaped by time varying environments remain elusive. Our understanding is particularly poor in the intermediate regime with no separation of timescales, where the environment changes on the same timescale as the physiological or evolutionary response. Experiments to systematically characterize the response to dynamic environments are challenging since such environments are inherently high dimensional. This roadmap deals with the unique role played by time varying environments in biological phenomena across scales, from physiology to evolution, seeking to emphasize the commonalities and the challenges faced in this emerging area of research.
Topics: Biological Evolution; Environment; Physiological Phenomena; Time Factors
PubMed: 33477124
DOI: 10.1088/1478-3975/abde8d -
PloS One 2017Biological networks pervade nature. They describe systems throughout all levels of biological organization, from molecules regulating metabolism to species interactions...
Biological networks pervade nature. They describe systems throughout all levels of biological organization, from molecules regulating metabolism to species interactions that shape ecosystem dynamics. The network thinking revealed recurrent organizational patterns in complex biological systems, such as the formation of semi-independent groups of connected elements (modularity) and non-random distributions of interactions among elements. Other structural patterns, such as nestedness, have been primarily assessed in ecological networks formed by two non-overlapping sets of elements; information on its occurrence on other levels of organization is lacking. Nestedness occurs when interactions of less connected elements form proper subsets of the interactions of more connected elements. Only recently these properties began to be appreciated in one-mode networks (where all elements can interact) which describe a much wider variety of biological phenomena. Here, we compute nestedness in a diverse collection of one-mode networked systems from six different levels of biological organization depicting gene and protein interactions, complex phenotypes, animal societies, metapopulations, food webs and vertebrate metacommunities. Our findings suggest that nestedness emerge independently of interaction type or biological scale and reveal that disparate systems can share nested organization features characterized by inclusive subsets of interacting elements with decreasing connectedness. We primarily explore the implications of a nested structure for each of these studied systems, then theorize on how nested networks are assembled. We hypothesize that nestedness emerges across scales due to processes that, although system-dependent, may share a general compromise between two features: specificity (the number of interactions the elements of the system can have) and affinity (how these elements can be connected to each other). Our findings suggesting occurrence of nestedness throughout biological scales can stimulate the debate on how pervasive nestedness may be in nature, while the theoretical emergent principles can aid further research on commonalities of biological networks.
Topics: Animals; Biological Phenomena; Humans; Models, Biological; Neural Networks, Computer
PubMed: 28166284
DOI: 10.1371/journal.pone.0171691 -
Biointerphases Jul 2018The genesis for this topical review stems from the interdisciplinary Biointerfaces International conference 2016 (BI 2016) in Zurich, Switzerland, wherein the need for... (Review)
Review
The genesis for this topical review stems from the interdisciplinary Biointerfaces International conference 2016 (BI 2016) in Zurich, Switzerland, wherein the need for advances in analytical tools was both expressed and addressed. Pushing the limits of detection for characterizing individual components, such as single proteins, single drug-delivery vehicles, or probing single living cells in a more natural environment, will contribute to the understanding of the complex biomolecular systems central to a number of applications including medical diagnostics, tissue engineering, and drug screening and delivery. Accordingly, the authors begin with an overview of single nanoparticle analytics highlighting two emerging techniques and how they compare with existing techniques. The first is based on single particle tracking of nanoparticles tethered to a mobile supported lipid bilayer, enabling the simultaneous characterization of both size and composition of individual nanoparticles. The second technique is based on probing variations in the ionic conduction across nanoscale apertures for detection of not only nanoparticles but also membrane-tethered proteins, thereby allowing a multiparameter characterization of individual nanoscopic objects, addressing their size, shape, charge, and dipole moment. Subsequently, the authors lead into an example of an area of application that stands to benefit from such advances in bioanalytics, namely, the development of biomimetic lipid- and polymer-based assemblies as stimuli-responsive artificial organelles and nanocarriers designed to optimize delivery of next generation high-molecular-weight biological drugs. This in turn motivates the need for additional advanced techniques for investigating the cellular response to drug delivery, and so the review returns again to bioanalytics, in this case single-cell analysis, while highlighting a technique capable of probing and manipulating the content of individual living cells via fluidic force microscopy. In presenting a concerted movement in the field of bioinspired bioanalytics, positioned in the context of drug delivery, while also noting the critical role of surface modifications, it is the authors' aim to evaluate progress in the field of single component bioanalytics and to emphasize the impact of initiating and maintaining a fruitful dialogue among scientists, together with clinicians and industry, to guide future directions in this area and to steer innovation to successful translation.
Topics: Biological Phenomena; Cytological Techniques; Nanotechnology
PubMed: 30049219
DOI: 10.1116/1.5037582 -
Topics in Cognitive Science Oct 2017In many fields of biology, both the phenomena to be explained and the mechanisms proposed to explain them are commonly presented in diagrams. Our interest is in how...
In many fields of biology, both the phenomena to be explained and the mechanisms proposed to explain them are commonly presented in diagrams. Our interest is in how scientists construct such diagrams. Researchers begin with evidence, typically developed experimentally and presented in data graphs. To arrive at a robust diagram of the phenomenon or the mechanism, they must integrate a variety of data to construct a single, coherent representation. This process often begins as the researchers create a first sketch, and it continues over an extended period as they revise the sketch until they arrive at a diagram they find acceptable. We illustrate this process by examining the sketches developed in the course of two research projects directed at understanding the generation of circadian rhythms in cyanobacteria. One identified a new aspect of the phenomenon itself, whereas the other aimed to develop a new mechanistic account. In both cases, the research resulted in a paper in which the conclusion was presented in a diagram that the authors deemed adequate to convey it. These diagrams violate some of the normative "cognitive design principles" advanced by cognitive scientists as constraints on successful visual communication. We suggest that scientists' sketching is instead governed by norms of success that are broadly explanatory: conveying the phenomenon or mechanism.
Topics: Biological Phenomena; Biology; Humans; Learning
PubMed: 28914494
DOI: 10.1111/tops.12290 -
Frontiers in Bioscience (Landmark... Jun 2014Fracture healing is a complex event that involves the coordination of different processes: initial inflammatory response, soft and hard callus formation, initial bony... (Review)
Review
Fracture healing is a complex event that involves the coordination of different processes: initial inflammatory response, soft and hard callus formation, initial bony union and bone remodeling. This well-orchestrated series of biological events follows a specific temporal and spatial sequence that can be affected by biological factors, such as age and bone quality. There is some evidence that increased age is a considerable factor in the inhibition of fracture repair in human subjects. During aging there is an accumulation of damage that depends on the activation of inflammation processes and on changes in the circulating levels of inflammatory cytokines. In addition to the physiological slow down in the repair process, other conditions such as multiple comorbidities leading to polymedication are a frequent occurrence in elderly patients and can have an influence on this process. A further factor that affects bone metabolism is nutrition: bone quality, fragility fractures risk and fracture healing process are all influenced by the nutritional status. This review provides a summary of the immunological aspects of physiological fracture healing and of those nutritional factors which might play an important role in this process.
Topics: Aging; Bone Remodeling; Cytokines; Fracture Healing; Fractures, Bone; Humans; Inflammation Mediators; Models, Biological; Nutritional Physiological Phenomena; Osteoporotic Fractures
PubMed: 24896342
DOI: 10.2741/4273 -
ELife Jul 2015Theoretical ideas have a rich history in many areas of biology, and new theories and mathematical models have much to offer in the future.
Theoretical ideas have a rich history in many areas of biology, and new theories and mathematical models have much to offer in the future.
Topics: Biological Phenomena; Biomedical Research; Models, Biological; Models, Theoretical
PubMed: 26173204
DOI: 10.7554/eLife.07158 -
Biological Research For Nursing Mar 2018For precision health care to be successful, an in-depth understanding of the biological mechanisms for symptom development and severity is essential. Omics-based... (Review)
Review
For precision health care to be successful, an in-depth understanding of the biological mechanisms for symptom development and severity is essential. Omics-based research approaches facilitate identification of the biological underpinnings of symptoms. We reviewed literature for omics-based approaches and exemplar symptoms (sleep disruption, cognitive impairment, fatigue, gastrointestinal [GI] distress, and pain) to identify genes associated with the symptom or symptoms across disease processes. The review yielded 27 genes associated with more than one symptom. ABCB1 (MDR1), APOE, BDNF, CNR1, COMT, DAT1 (SLC6A3), DRD4, ESR1, HLA-DRB1, IL10, IL1B, IL6, LTA, PTGS2 (COX-2), SLC6A4, and TNF were associated with cognitive impairment and pain, which had the most genes in common. COMT and TNF were related to all symptoms except sleep disruption. IL1B was associated with all symptoms except cognitive impairment. IL10, IL1A, IL1B, IL1RN, IL6, and IL8 (CXCL8) were linked with all the exemplar symptoms in various combinations. ABCB1 (MDR1) and SLC6A4 were associated with cognitive impairment, GI distress, and pain. IL10 and IL6 were linked to cognitive impairment, fatigue, and pain. APOE and BDNF were associated with sleep disruption, cognitive impairment, and pain. The 27 genes were associated with canonical pathways including immune, inflammatory, and cell signaling. The pathway analysis generated a 15-gene model from the 27 as well as 3 networks, which incorporated new candidate genes. The findings support the hypothesis of overlapping biological underpinnings across the exemplar symptoms. Candidate genes may be targeted in future omics research to identify mechanisms of co-occurring symptoms for potential precision treatments.
Topics: Biological Phenomena; Disease; Female; Humans; Syndrome; Virulence
PubMed: 29325450
DOI: 10.1177/1099800417751069 -
Berichte Zur Wissenschaftsgeschichte Sep 2022This essay considers the mid-twentieth century adoption of genetic explanations for three biological phenomena: nutritional adaptation, antibiotic resistance, and...
This essay considers the mid-twentieth century adoption of genetic explanations for three biological phenomena: nutritional adaptation, antibiotic resistance, and antibody production. This occurred at the same time as the hardening of the neo-Darwinian Synthesis in evolutionary theory. I argue that these concurrent changes reflect an ascendant narrative of genetic selfhood, which prioritized random hereditary variation and selection through competition, and marginalized physiological or environmental adaptation. This narrative was further reinforced by the Central Dogma of molecular biology and fit well with liberal political thought, with its focus on the autonomous individual. However, bringing biological findings into line with this narrative required modifying the notion of the gene to account for various kinds of non-Mendelian inheritance. Hans-Jörg Rheinberger's reflections on narrative and experiment are valuable in thinking about the friction between the postwar ideal of genetic selfhood and actual observations of how organisms adapt in response to the environment.
Topics: Biological Evolution; Selection, Genetic
PubMed: 36086835
DOI: 10.1002/bewi.202200022 -
Frontiers in Immunology 2022
Topics: Biological Phenomena; Immunity; Nanoparticles; Signal Transduction
PubMed: 35634330
DOI: 10.3389/fimmu.2022.927733