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Current Opinion in Chemical Biology Aug 2022Complex carbohydrates (glycans) are the most abundant and versatile biopolymers in nature. The broad diversity of biochemical functions that carbohydrates cover is a... (Review)
Review
Complex carbohydrates (glycans) are the most abundant and versatile biopolymers in nature. The broad diversity of biochemical functions that carbohydrates cover is a direct consequence of the variety of 3D architectures they can adopt, displaying branched or linear arrangements, widely ranging in sizes, and with the highest diversity of building blocks of any other natural biopolymer. Despite this unparalleled complexity, a common denominator can be found in the glycans' inherent flexibility, which hinders experimental characterization, but that can be addressed by high-performance computing (HPC)-based molecular simulations. In this short review, I present and discuss the state-of-the-art of molecular simulations of complex carbohydrates and glycoconjugates, highlighting methodological strengths and weaknesses, important insights through emblematic case studies, and suggesting perspectives for future developments.
Topics: Carbohydrates; Glycoconjugates; Polysaccharides
PubMed: 35728307
DOI: 10.1016/j.cbpa.2022.102175 -
Frontiers in Immunology 2022Inflammation and a dysregulated immune system are common denominators of cancer and cardiovascular disease (CVD). Immuno-cardio-oncology addresses the interconnected... (Review)
Review
Inflammation and a dysregulated immune system are common denominators of cancer and cardiovascular disease (CVD). Immuno-cardio-oncology addresses the interconnected immunological aspect in both cancer and CVD and the integration of immunotherapies and anti-inflammatory therapies in both distinct disease entities. Building on prominent examples of convergent inflammation (IL-1ß biology) and immune disbalance (CD20 cells) in cancer and CVD/heart failure, the review tackles both the roadblocks and opportunities of repurposed use of IL-1ß drugs and anti-CD20 antibodies in both fields, and discusses the use of advanced therapies e.g. chimeric antigen receptor (CAR) T cells, that can address the raising burden of both cancer and CVD. Finally, it is discussed how inspired by precision medicine in oncology, the use of biomarker-driven patient stratification is needed to better guide anti-inflammatory/immunomodulatory therapeutic interventions in cardiology.
Topics: Humans; Medical Oncology; Heart; Immunotherapy; Cardiovascular Diseases; Inflammation
PubMed: 36466820
DOI: 10.3389/fimmu.2022.1018772 -
Proceedings. Biological Sciences Sep 2019In conditions of constant illumination, the eye pupil diameter indexes the modulation of arousal state and responds to a large breadth of cognitive processes, including... (Review)
Review
In conditions of constant illumination, the eye pupil diameter indexes the modulation of arousal state and responds to a large breadth of cognitive processes, including mental effort, attention, surprise, decision processes, decision biases, value beliefs, uncertainty, volatility, exploitation/exploration trade-off, or learning rate. Here, I propose an information theoretic framework that has the potential to explain the ensemble of these findings as reflecting pupillary response to information processing. In short, updates of the brain's internal model, quantified formally as the Kullback-Leibler (KL) divergence between prior and posterior beliefs, would be the common denominator to all these instances of pupillary dilation to cognition. I show that stimulus presentation leads to pupillary response that is proportional to the amount of information the stimulus carries about itself and to the quantity of information it provides about other task variables. In the context of decision making, pupil dilation in relation to uncertainty is explained by the wandering of the evidence accumulation process, leading to large summed KL divergences. Finally, pupillary response to mental effort and variations in tonic pupil size are also formalized in terms of information theory. On the basis of this framework, I compare pupillary data from past studies to simple information-theoretic simulations of task designs and show good correspondance with data across studies. The present framework has the potential to unify the large set of results reported on pupillary dilation to cognition and to provide a theory to guide future research.
Topics: Arousal; Attention; Cognition; Decision Making; Humans; Learning; Photic Stimulation; Pupil; Uncertainty
PubMed: 31530143
DOI: 10.1098/rspb.2019.1593 -
Journal of Biosciences 2023The past few decades have seen a rise in research on vertebrate cilia and ciliopathy, with interesting collaborations between basic and clinical scientists. This work... (Review)
Review
The past few decades have seen a rise in research on vertebrate cilia and ciliopathy, with interesting collaborations between basic and clinical scientists. This work includes studies on ciliary architecture, composition, evolution, and organelle generation and its biological role. The human body has cells that harbour any of the following four types of cilia: 9+0 motile, 9+0 immotile, 9+2 motile, and 9+2 immotile. Depending on the type, cilia play an important role in cell/fluid movement, mating, sensory perception, and development. Defects in cilia are associated with a wide range of human diseases afflicting the brain, heart, kidneys, respiratory tract, and reproductive system. These are commonly known as ciliopathies and affect millions of people worldwide. Due to their complex genetic etiology, diagnosis and therapy have remained elusive. Although model organisms like have been a useful source for ciliary research, reports of a fascinating and rewarding translation of this research into mammalian systems, especially humans, are seen. The current review peeks into one of the complex features of this organelle, namely its birth, the common denominators across the formation of both 9+0 and 9+2 ciliary types, the molecules involved in ciliogenesis, and the steps that go towards regulating their assembly and disassembly.
Topics: Animals; Humans; Cilia; Ciliopathies; Cell Movement; Organelles; Cell Communication; Mammals
PubMed: 36924208
DOI: 10.1007/s12038-023-00326-6 -
Cancers Oct 2022Endocrine and neuroendocrine tumors (NETs) represent a group of heterogeneous malignancies that have endocrine cell onset as a common denominator [...].
Endocrine and neuroendocrine tumors (NETs) represent a group of heterogeneous malignancies that have endocrine cell onset as a common denominator [...].
PubMed: 36291777
DOI: 10.3390/cancers14204994 -
Neuroscience of Consciousness 2021Over the last years, a surge of empirical studies converged on complexity-related measures as reliable markers of consciousness across many different conditions, such as... (Review)
Review
Over the last years, a surge of empirical studies converged on complexity-related measures as reliable markers of consciousness across many different conditions, such as sleep, anesthesia, hallucinatory states, coma, and related disorders. Most of these measures were independently proposed by researchers endorsing disparate frameworks and employing different methods and techniques. Since this body of evidence has not been systematically reviewed and coherently organized so far, this positive trend has remained somewhat below the radar. The aim of this paper is to make this consilience of evidence in the science of consciousness explicit. We start with a systematic assessment of the growing literature on complexity-related measures and identify their common denominator, tracing it back to core theoretical principles and predictions put forward more than 20 years ago. In doing this, we highlight a consistent trajectory spanning two decades of consciousness research and provide a provisional taxonomy of the present literature. Finally, we consider all of the above as a positive ground to approach new questions and devise future experiments that may help consolidate and further develop a promising field where empirical research on consciousness appears to have, so far, naturally converged.
PubMed: 38496724
DOI: 10.1093/nc/niab023 -
Frontiers in Cell and Developmental... 2021Nucleophagy is an organelle-selective subtype of autophagy that targets nuclear material for degradation. The macroautophagic delivery of micronuclei to the vacuole,... (Review)
Review
Nucleophagy is an organelle-selective subtype of autophagy that targets nuclear material for degradation. The macroautophagic delivery of micronuclei to the vacuole, together with the nucleus-vacuole junction-dependent microautophagic degradation of nuclear material, were first observed in yeast. Nuclear pore complexes and ribosomal DNA are typically excluded during conventional macronucleophagy and micronucleophagy, indicating that degradation of nuclear cargo is tightly regulated. In mammals, similarly to other autophagy subtypes, nucleophagy is crucial for cellular differentiation and development, in addition to enabling cells to respond to various nuclear insults and cell cycle perturbations. A common denominator of all nucleophagic processes characterized in diverse organisms is the dependence on the core autophagic machinery. Here, we survey recent studies investigating the autophagic processing of nuclear components. We discuss nucleophagic events in the context of pathology, such as neurodegeneration, cancer, DNA damage, and ageing.
PubMed: 35047516
DOI: 10.3389/fcell.2021.814955 -
Frontiers in Medicine 2023Immune complex (IC) vasculitides present inflammations of vessel walls associated with perivascular deposition of immunoglobulins (Igs), mostly ICs. They encompass... (Review)
Review
Immune complex (IC) vasculitides present inflammations of vessel walls associated with perivascular deposition of immunoglobulins (Igs), mostly ICs. They encompass systemic and skin-limited variants of IgA vasculitis (IgAV), cryoglobulinemic vasculitis (CV), rheumatoid, lupus, and hypocomplementemic vasculitides, serum sickness cutaneous IgM/IgG (non-IgA) vasculitis, and recurrent macular (hypergammaglobulinemic or exertion-induced) vasculitis. Serum sickness and CV fulfill the criteria of a type III hypersensitivity immune reaction as large lattices of the IC precipitate at vessel walls and activate polymorphonuclear neutrophils (PMNs). Immunoglobulin-A vasculitis differs with regard to the causes of perivascular deposition of ICs since here many IgA1 molecules are hypoglycosylated (Gd-IgA1), which appears to facilitate their perivascular deposition in skin and mesangium (via e.g. CD71). The reasons for increased generation of immunoglobulins or formation of IC and their perivascular deposition in either skin or systemic organs are different and not fully explored. A common denominator of OC vasculitides is the activation of PMNs near the vessel wall Fcy or Fcα receptors. Acute episodes of IgAV additionally require PMNs to become preactivated by IgA1 or by IC already in circulation. This intravascular priming results in increased adherence and subsequently vessel-destructive NETosis when they encounter IgA deposited at the vessel walls. Binding of IgA1 to PMNs in blood stream is associated with increased serum levels of hypogalactosidated IgA1. The characteristic clinical picture of IgAV (and also of so-called IgG/IgM vasculitis) comprises palpable or retiform purpura with a clear predilection for lower legs, probably due to stasis-related reduction in blood velocity, while in other IC vasculitides, additional factors influence the sites of vasculitides. Our knowledge of distinct forms and different pathophysiological pathways of IC vasculitides may lead to in efficacious or targeted therapies. Antibodies to complement components or intestinal budesonide for IgAV are promising agents (the latter suppresses the pathophysiologically related IgA nephropathy by reducing the generation of mucosal IgA.
PubMed: 36936215
DOI: 10.3389/fmed.2023.1103065 -
Current Opinion in Cardiology May 2023Here, we review recent findings on the role of long noncoding RNAs (lncRNAs) in cardiovascular disease (CVD). In addition, we highlight some of the latest findings in... (Review)
Review
PURPOSE OF REVIEW
Here, we review recent findings on the role of long noncoding RNAs (lncRNAs) in cardiovascular disease (CVD). In addition, we highlight some of the latest findings in lncRNA biology, providing an outlook for future avenues of lncRNA research in CVD.
RECENT FINDINGS
Recent publications provide translational evidence from patient studies and animal models for the role of specific lncRNAs in CVD. The molecular effector mechanisms of these lncRNAs are diverse. Overall, cell-type selective modulation of gene expression is the largest common denominator. New methods, such as single-cell profiling and CRISPR/Cas9-screening, reveal additional novel mechanistic principles: For example, many lncRNAs establish RNA-based spatial compartments that concentrate effector proteins. Also, RNA modifications and splicing features can be determinants of lncRNA function.
SUMMARY
lncRNA research is passing the stage of enumerating lncRNAs or recording simplified on-off expression switches. Mechanistic analyses are starting to reveal overarching principles of how lncRNAs can function. Exploring these principles with decisive genetic testing in vivo remains the ultimate test to discern how lncRNA loci, by RNA motifs or DNA elements, affect CVD pathophysiology.
Topics: Animals; Humans; RNA, Long Noncoding; Cardiovascular Diseases
PubMed: 36930221
DOI: 10.1097/HCO.0000000000001041 -
International Journal of Tryptophan... 2020Nicotinamide homeostasis is a candidate common denominator to explain smooth transitions, whether demographic, epidemiological or economic. This 'NAD world', dependent... (Review)
Review
Nicotinamide homeostasis is a candidate common denominator to explain smooth transitions, whether demographic, epidemiological or economic. This 'NAD world', dependent on hydrogen-based energy, is not widely recognised as it is neither measured nor viewed from a sufficiently multi-genomic or historical perspective. Reviewing the importance of meat and nicotinamide balances during our co-evolution, recent history suggests that populations only modernise and age well with low fertility on a suitably balanced diet. Imbalances on the low meat side lead to an excess of infectious disease, short lives and boom-bust demographics. On the high side, meat has led to an excess of degenerative, allergic and metabolic disease and low fertility. A 'Goldilocks' diet derived from mixed and sustainable farming (preserving the topsoil) allows for high intellectual capital, height and good health with controlled population growth resulting in economic growth and prosperity. Implementing meat equity worldwide could lead to progress for future generations on 'spaceship' earth by establishing control over population quality, thermostat and biodiversity, if it is not already too late.
PubMed: 32327922
DOI: 10.1177/1178646920910159