Pathological behavior of arithmetic invariants of unipotent groups

AbstractThe identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.

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Our Tau Tales from Normal to Pathological Behavior

Journal of Alzheimer s Disease ◽

10.3233/jad-179906 ◽

2018 ◽

Vol 64 (s1) ◽

pp. S507-S516 ◽

Cited By ~ 2

Author(s):

Alejandra D. Alonso ◽

Leah S. Cohen

Keyword(s):

Pathological Behavior

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Consolidating the Circuit Model for Addiction

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-092920-123905 ◽

2021 ◽

Vol 44 (1) ◽

Author(s):

Christian Lüscher ◽

Patricia H. Janak

Keyword(s):

Negative Reinforcement ◽

Circuit Model ◽

Annual Review ◽

Publication Date ◽

Early Model ◽

Negative Consequences ◽

Individual Vulnerability ◽

Core Components ◽

Natural Rewards ◽

Pathological Behavior

Addiction is a disease characterized by compulsive drug seeking and consumption observed in 20–30% of users. An addicted individual will favor drug reward over natural rewards, despite major negative consequences. Mechanistic research on rodents modeling core components of the disease has identified altered synaptic transmission as the functional substrate of pathological behavior. While the initial version of a circuit model for addiction focused on early drug adaptive behaviors observed in all individuals, it fell short of accounting for the stochastic nature of the transition to compulsion. The model builds on the initial pharmacological effect common to all addictive drugs—an increase in dopamine levels in the mesolimbic system. Here, we consolidate this early model by integrating circuits underlying compulsion and negative reinforcement. We discuss the genetic and epigenetic correlates of individual vulnerability. Many recent data converge on a gain-of-function explanation for circuit remodeling, revealing blueprints for novel addiction therapies. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Unipotent Groups

Introduction to Affine Group Schemes - Graduate Texts in Mathematics ◽

10.1007/978-1-4612-6217-6_8 ◽

1979 ◽

pp. 62-67

Author(s):

William C. Waterhouse

Keyword(s):

Unipotent Groups

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Palmitoylation as a Functional Regulator of Neurotransmitter Receptors

Neural Plasticity ◽

10.1155/2018/5701348 ◽

2018 ◽

Vol 2018 ◽

pp. 1-18 ◽

Cited By ~ 12

Author(s):

Vladimir S. Naumenko ◽

Evgeni Ponimaskin

Keyword(s):

Posttranslational Modifications ◽

Current Knowledge ◽

Point Of View ◽

Covalent Attachment ◽

Neurotransmitter Receptors ◽

Protein Palmitoylation ◽

Neuronal Proteins ◽

Functional Point ◽

Pathological Behavior ◽

Multiple Signaling

The majority of neuronal proteins involved in cellular signaling undergo different posttranslational modifications significantly affecting their functions. One of these modifications is a covalent attachment of a 16-C palmitic acid to one or more cysteine residues (S-palmitoylation) within the target protein. Palmitoylation is a reversible modification, and repeated cycles of palmitoylation/depalmitoylation might be critically involved in the regulation of multiple signaling processes. Palmitoylation also represents a common posttranslational modification of the neurotransmitter receptors, including G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LICs). From the functional point of view, palmitoylation affects a wide span of neurotransmitter receptors activities including their trafficking, sorting, stability, residence lifetime at the cell surface, endocytosis, recycling, and synaptic clustering. This review summarizes the current knowledge on the palmitoylation of neurotransmitter receptors and its role in the regulation of receptors functions as well as in the control of different kinds of physiological and pathological behavior.

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Linear Actions of Unipotent Groups

Algebraic Theory of Locally Nilpotent Derivations - Encyclopaedia of Mathematical Sciences ◽

10.1007/978-3-662-55350-3_6 ◽

2017 ◽

pp. 167-191

Author(s):

Gene Freudenburg

Keyword(s):

Unipotent Groups

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Whole Tumor Capsule is Prognostic of a Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab396 ◽

2021 ◽

Author(s):

Carlotta Giani ◽

Liborio Torregrossa ◽

Ramone Teresa ◽

Romei Cristina ◽

Antonio Matrone ◽

...

Keyword(s):

Thyroid Cancer ◽

Braf V600e ◽

Braf Mutations ◽

Biological Behaviour ◽

Non Invasive ◽

Good Outcome ◽

Predictive Role ◽

Pathological Behavior

Abstract Context Tumour capsule integrity is becoming a relevant issue to predict the biological behaviour of human tumours, including thyroid cancer. Aim To verify if a whole tumour capsule in the classical variant of PTC (CVPTC) could have a predictive role of a good outcome as for follicular variant (FVPTC). Methods FVPTC (n=600) and CVPTC (n=554) cases, were analysed. We distinguished encapsulated-FVPTC (E-FVPTC) and encapsulated-CVPTC (E-CVPTC) and, thereafter, invasive (Ei-FVPTC and Ei-CVPTC) and non-invasive (En-FVPTC and En-CVPTC) tumours, according to the invasion or integrity of tumour capsule, respectively. Cases without tumour capsule were indicated as invasive-FVPTC (I-FVPTC) and invasive-CVPTC (I-CVPTC). Sub-group of each variant was evaluated for BRAF mutations. Results E-FVPTC was more frequent than E-CVPTC (p<0.0001). No differences were found between En-FVPTC and En-CVPTC or between Ei-FVPTC and Ei-CVPTC. After 18 years of follow-up, a greater number of not-cured cases were observed in Ei-CVPTC with respect to Ei-FVPTC, but not in En-CVPTC to En-FVPTC. Multivariate clustering analysis showed that En-FVPTC, En-CVPTC, and Ei-FVPTC have similar features but different from I-FVPTC and I-CVPTC and, to a lesser extent, from Ei-CVPTC. 177/614 (28.8%) cases were BRAF V600E-mutated and 10/614(1.6%) carried BRAF-rare alterations. Significantly higher rate of En-CVPTC (22/49,44.9%) than En-FVPTC (15/195,7.7%) (p<0.0001) were BRAF V600E-mutated. Conclusions En-CVPTC is less prevalent than En-FVPTC. However, they have a good clinical/ pathological behavior comparable to En-FVPTC. This finding confirms the good prognostic role of a whole tumour capsule also in CVPTC. New nomenclature for En-CVPTC, similar to that introduced for En-FVPTC (i.e, NIFTP) could be envisaged.

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