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Cancer Cell Aug 2022Metastasis, the major cause of cancer death, represents one of the major challenges in oncology. Scientists are still trying to understand the biological basis...
Metastasis, the major cause of cancer death, represents one of the major challenges in oncology. Scientists are still trying to understand the biological basis underlying the dissemination and outgrowth of tumor cells, why these cells can remain dormant for years, how they become resistant to the immune system or cytotoxic effects of systemic therapy, and how they interact with their new microenvironment. We asked experts to discuss some of the unknowns, advances, and areas of opportunity related to cancer metastasis.
Topics: Humans; Immune System; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 35944497
DOI: 10.1016/j.ccell.2022.07.010 -
Current Opinion in Immunology Aug 2014
Topics: Aging; Cellular Senescence; Humans; Periodicals as Topic
PubMed: 24996928
DOI: 10.1016/j.coi.2014.06.005 -
Cell Metabolism Jan 2022Metabolite identification represents a major challenge, and opportunity, for biochemistry. The collective characterization and quantification of metabolites in living... (Review)
Review
Metabolite identification represents a major challenge, and opportunity, for biochemistry. The collective characterization and quantification of metabolites in living organisms, with its many successes, represents a major biochemical knowledgebase and the foundation of metabolism's rebirth in the 21 century; yet, characterizing newly observed metabolites has been an enduring obstacle. Crystallography and NMR spectroscopy have been of extraordinary importance, although their applicability in resolving metabolism's fine structure has been restricted by their intrinsic requirement of sufficient and sufficiently pure materials. Mass spectrometry has been a key technology, especially when coupled with high-performance separation technologies and emerging informatic and database solutions. Even more so, the collective of artificial intelligence technologies are rapidly evolving to help solve the metabolite characterization conundrum. This perspective describes this challenge, how it was historically addressed, and how metabolomics is evolving to address it today and in the future.
Topics: Artificial Intelligence; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolomics
PubMed: 34986335
DOI: 10.1016/j.cmet.2021.11.005 -
Frontiers in Robotics and AI 2022We AI researchers are concerned about the potential impact of artificially intelligent systems on humanity. In the first half of this essay, I argue that ethics is an...
We AI researchers are concerned about the potential impact of artificially intelligent systems on humanity. In the first half of this essay, I argue that ethics is an evolved body of cultural knowledge that (among other things) encourages individual behavior that promotes the welfare of the society (which in turn promotes the welfare of its individual members). The causal paths involved suggest that and play key roles in this process. In the second half of the essay, I consider whether the key role of trust exposes our society to existential threats. This possibility arises because decision-making agents (humans, AIs, and others) necessarily rely on simplified models to cope with the unbounded complexity of our physical and social world. By selecting actions to maximize a utility measure, a well-formulated game theory model can be a powerful and valuable tool. However, a poorly-formulated game theory model may be uniquely harmful, in cases where the action it recommends deliberately exploits the vulnerability and violates the trust of cooperative partners. Widespread use of such models can erode the overall levels of trust in the society. Cooperation is reduced, resources are constrained, and there is less ability to meet challenges or take advantage of opportunities. Loss of trust will affect humanity's ability to respond to existential threats such as climate change.
PubMed: 35572370
DOI: 10.3389/frobt.2022.676767 -
The British Journal of General Practice... Apr 2021
Topics: Humans; Learning Disabilities; Psychiatry
PubMed: 33771791
DOI: 10.3399/bjgp21X715325 -
Frontiers in Immunology 2020LAG3 is an important immune checkpoint with relevance in cancer, infectious disease and autoimmunity. However, despite LAG3's role in immune exhaustion and the great... (Review)
Review
LAG3 is an important immune checkpoint with relevance in cancer, infectious disease and autoimmunity. However, despite LAG3's role in immune exhaustion and the great potential of LAG3 inhibition as treatment, much remains unknown about its biology, particularly its mechanism of action. This review describes the knowns, unknowns and controversies surrounding LAG3. This includes examination of how LAG3 is regulated transcriptionally and post-translationally by endocytosis and proteolytic cleavage. We also discuss the interactions of LAG3 with its ligands and the purpose thereof. Finally, we review LAG3's mechanism of action, including the roles of LAG3 intracellular motifs and the lack of a role for CD4 competition. Overall, understanding the biology of LAG3 can provide greater insight on LAG3 function, which may broaden the appreciation for LAG3's role in disease and potentially aid in the development of targeted therapies.
Topics: ADAM10 Protein; ADAM17 Protein; Amino Acid Motifs; Antigens, CD; Clinical Trials as Topic; Dendritic Cells; Endocytosis; Gene Expression Regulation; Humans; Immune Checkpoint Inhibitors; Immune Checkpoint Proteins; Ligands; Lymphocyte Subsets; Molecular Targeted Therapy; Neoplasms; Neurons; Protein Biosynthesis; Protein Processing, Post-Translational; Receptors, Antigen, T-Cell; Transcription, Genetic; Lymphocyte Activation Gene 3 Protein
PubMed: 33488626
DOI: 10.3389/fimmu.2020.615317 -
Zoological Research Sep 2023Planarians represent the most primitive bilateral triploblastic animals. Most planarian species exhibit mechanisms for whole-body regeneration, exemplified by the... (Review)
Review
Planarians represent the most primitive bilateral triploblastic animals. Most planarian species exhibit mechanisms for whole-body regeneration, exemplified by the regeneration of their cephalic ganglion after complete excision. Given their robust whole-body regeneration capacity, planarians have been model organisms in regenerative research for more than 240 years. Advancements in research tools and techniques have progressively elucidated the mechanisms underlying planarian regeneration. Accurate cell-cell communication is recognized as a fundamental requirement for regeneration. In recent decades, mechanisms associated with such communication have been revealed at the cellular level. Notably, stem cells (neoblasts) have been identified as the source of all new cells during planarian homeostasis and regeneration. The interplay between neoblasts and somatic cells affects the identities and proportions of various tissues during homeostasis and regeneration. Here, this review outlines key discoveries regarding communication between stem cell compartments and other cell types in planarians, as well as the impact of communication on planarian regeneration. Additionally, this review discusses the challenges and potential directions of future planarian research, emphasizing the sustained impact of this field on our understanding of animal regeneration.
Topics: Animals; Planarians; Stem Cells; Cell Communication; Homeostasis; Regeneration
PubMed: 37721107
DOI: 10.24272/j.issn.2095-8137.2023.044 -
Viruses Feb 2022Viral aggregation is a complex and pervasive phenomenon affecting many viral families. An increasing number of studies have indicated that it can modulate critical... (Review)
Review
Viral aggregation is a complex and pervasive phenomenon affecting many viral families. An increasing number of studies have indicated that it can modulate critical parameters surrounding viral infections, and yet its role in viral infectivity, pathogenesis, and evolution is just beginning to be appreciated. Aggregation likely promotes viral infection by increasing the cellular multiplicity of infection (MOI), which can help overcome stochastic failures of viral infection and genetic defects and subsequently modulate their fitness, virulence, and host responses. Conversely, aggregation can limit the dispersal of viral particles and hinder the early stages of establishing a successful infection. The cost-benefit of viral aggregation seems to vary not only depending on the viral species and aggregating factors but also on the spatiotemporal context of the viral life cycle. Here, we review the of viral aggregation by focusing on studies with direct observations of viral aggregation and mechanistic studies of the aggregation process. Next, we chart the and discuss the biological implications of viral aggregation in their infection cycle. We conclude with a perspective on harnessing the therapeutic potential of this phenomenon and highlight several challenging questions that warrant further research for this field to advance.
Topics: Animals; Biological Evolution; Humans; Virion; Virus Diseases; Virus Replication
PubMed: 35216031
DOI: 10.3390/v14020438 -
The Malaysian Journal of Medical... Feb 2021The coronavirus disease 2019 (COVID-19) pandemic is severe and has not shown any signs of warning up to today. Biotech companies around the world have raced to come up...
The coronavirus disease 2019 (COVID-19) pandemic is severe and has not shown any signs of warning up to today. Biotech companies around the world have raced to come up with an acceptable vaccine and recently two mRNA vaccines have received emergency usage authorisation from regulatory bodies in several countries. mRNA vaccines, which consist of a new and revolutionary technology have not been previously tested widely on humans. Medium- and long-term safety data are not available. While many experts seem to support the start of a mass vaccination campaign, others feel there are too many unknowns to embark on a mass vaccination campaign. Concerns include uncertainties about the long-term effects of foreign mRNA on human cellular physiology and the possibility of vaccine-enhanced disease severity, which may not be unlikely with the current disease presentation of COVID-19.
PubMed: 33679230
DOI: 10.21315/mjms2021.28.1.17 -
Journal of Anxiety Disorders Apr 2016The current review and synthesis serves to define and contextualize fear of the unknown relative to related constructs, such as intolerance of uncertainty, and... (Review)
Review
The current review and synthesis serves to define and contextualize fear of the unknown relative to related constructs, such as intolerance of uncertainty, and contemporary models of emotion, attachment, and neuroticism. The contemporary models appear to share a common core in underscoring the importance of responses to unknowns. A recent surge in published research has explored the transdiagnostic impact of not knowing on anxiety and related pathologies; as such, there appears to be mounting evidence for fear of the unknown as an important core transdiagnostic construct. The result is a robust foundation for transdiagnostic theoretical and empirical explorations into fearing the unknown and intolerance of uncertainty.
Topics: Anxiety; Anxiety Disorders; Fear; Humans; Models, Psychological; Neuroticism; Uncertainty
PubMed: 26945765
DOI: 10.1016/j.janxdis.2016.02.007