Structure, function and inhibition of the phosphoinositide 3-kinase p110α enzyme

2014 ◽  
Vol 42 (1) ◽  
pp. 120-124 ◽  
Author(s):  
Jack U. Flanagan ◽  
Peter R. Shepherd
Keyword(s):  
Structure Function ◽  
Present Article ◽  
Recent Progress ◽  
Pi3k Pathway ◽  
Structure And Function ◽  
Selective Inhibitors ◽  
Oncogenic Mutations ◽  
Phosphoinositide 3 Kinase ◽  
And Function

The PI3K (phosphoinositide 3-kinase) p110α isoform is activated by oncogenic mutations in many cancers. This has stimulated intense interest in identifying inhibitors of the PI3K pathway as well as p110α-selective inhibitors, and understanding the mechanisms underlying activation by the oncogenic mutations. In the present article, we review recent progress in the structure and function of the p110α enzyme and two of its most common oncogenic mutations, the development of isoform-selective inhibitors, and p110α pharmacology.

Chemically targeting the PI3K family

2007 ◽  
Vol 35 (2) ◽  
pp. 245-249 ◽  
Author(s):  
Z.A. Knight ◽  
K.M. Shokat
Keyword(s):  
Cell Growth ◽  
Recent Progress ◽  
Pi3k Pathway ◽  
Selective Inhibitors ◽  
Growth Metabolism ◽  
Phosphoinositide 3 Kinase ◽  
Widespread Interest

PI3K (phosphoinositide 3-kinase) is a key regulator of cell growth, metabolism and survival. The frequent activation of the PI3K pathway in cancer has stimulated widespread interest in identifying potent and selective inhibitors of PI3K isoforms. The present paper highlights recent progress in identifying such molecules and the challenges that remain for efforts to pharmacologically target the PI3K family.

Structure, Function, and Tort Law

2020 ◽  
Vol 13 (1) ◽  
pp. 31-79
Author(s):  
Dan Priel
Keyword(s):  
Structure Function ◽  
Tort Law ◽  
Structure And Function ◽  
Vicarious Liability ◽  
Causal Uncertainty ◽  
Popular View ◽  
And Function

AbstractA popular view among tort theorists is that an explanation of tort law must take account its “structure,” since this structure constitutes the law’s “self-understanding.” This view is used to both criticize competing functional accounts of tort law, especially economic ones, that are said to ignore tort law’s structure, and, more constructively, as a basis for explaining various tort doctrines. In this essay, I consider this argument closely and conclude that it is faulty. To be valid, one needs a non-question begging way of identifying the essence of tort law. I argue that law’s “self-understanding” can only make sense if it means the understanding of certain people. Examining those, I conclude that the claim of structuralists is false, for there are many people who take its function to be central. I then further show that if one wishes to understand the development of tort law’s doctrine one must take both structure and function into account. I demonstrate this claim by examining the development of the doctrine dealing with causal uncertainty and vicarious liability.

Recent Progress in Hormone Research, Vol. XIV. The Proceedings of the Laurentian Hormone Conference

PEDIATRICS ◽  
1959 ◽  
Vol 23 (5) ◽  
pp. 961-961
Author(s):  
LYTT I. GARDNER
Keyword(s):  
Special Interest ◽  
Growth And Development ◽  
Recent Progress ◽  
Structure And Function ◽  
Hormone Research ◽  
And Function

This is the 14th volume of this valuable series of the Laurentian Hormone Conference. The editor continues the same excellent format as in the previous volumes. There are 14 monographs on various aspects of endocrinology each followed by a bibliography and verbatim record of the discussion. The volume is divided into five sections: I. Hormone Structure and Function; II. Hormones in Growth and Development; III. Aspects of Reproduction; IV. Hormones and Metabolism; and V. Neurohumors. Of special interest to pediatricians is the section on cytologic tests of chromosomal sex by Grumbach and Barr.

Endogenous ion channel complexes: the NMDA receptor

2011 ◽  
Vol 39 (3) ◽  
pp. 707-718 ◽  
Author(s):  
René A.W. Frank
Keyword(s):  
Nmda Receptor ◽  
Ion Channel ◽  
Present Article ◽  
Neuronal Excitability ◽  
Structure And Function ◽  
Current Understanding ◽  
Ionotropic Receptors ◽  
Receptor Complexes ◽  
Aspartate Receptor ◽  
And Function

Ionotropic receptors, including the NMDAR (N-methyl-D-aspartate receptor) mediate fast neurotransmission, neurodevelopment, neuronal excitability and learning. In the present article, the structure and function of the NMDAR is reviewed with the aim to condense our current understanding and highlight frontiers where important questions regarding the biology of this receptor remain unanswered. In the second part of the present review, new biochemical and genetic approaches for the investigation of ion channel receptor complexes will be discussed.

From Machine and Tape to Structure and Function: Formulation of a Reflexively Computing System

2006 ◽  
Vol 12 (4) ◽  
pp. 487-512 ◽  
Author(s):  
Chris Salzberg
Keyword(s):  
Structure Function ◽  
Computing System ◽  
Structure And Function ◽  
Structural Constraints ◽  
Static Information ◽  
Biochemical Systems ◽  
Uniform Medium ◽  
Simple Mapping ◽  
Function Relationship ◽  
And Function

The relationship between structure and function is explored via a system of labeled directed graph structures upon which a single elementary read/write rule is applied locally. Boundaries between static (information-carrying) and active (information-processing) objects, imposed by mandate of the rules or physics in earlier models, emerge instead as a result of a structure-function dynamic that is reflexive: objects may operate directly on their own structure. A representation of an arbitrary Turing machine is reproduced in terms of structural constraints by means of a simple mapping from tape squares and machine states to a uniform medium of nodes and links, establishing computation universality. Exploiting flexibility of the formulation, examples of other unconventional “self-computing” structures are demonstrated. A straightforward representation of a kinematic machine system based on the model devised by Laing is also reproduced in detail. Implications of the findings are discussed in terms of their relation to other formal models of computation and construction. It is argued that reflexivity of the structure-function relationship is a critical informational dynamic in biochemical systems, overlooked in previous models but well captured by the proposed formulation.

scholarly journals Gradients of structure–function tethering across neocortex

2019 ◽  
Vol 116 (42) ◽  
pp. 21219-21227 ◽  
Author(s):  
Bertha Vázquez-Rodríguez ◽  
Laura E. Suárez ◽  
Ross D. Markello ◽  
Golia Shafiei ◽  
Casey Paquola ◽  
...  
Keyword(s):  
Structure Function ◽  
Present Report ◽  
Brain Regions ◽  
Structure And Function ◽  
Spatial Proximity ◽  
Functional Networks ◽  
Functional Connection ◽  
Brain Structure And Function ◽  
And Function ◽  
The Brain

The white matter architecture of the brain imparts a distinct signature on neuronal coactivation patterns. Interregional projections promote synchrony among distant neuronal populations, giving rise to richly patterned functional networks. A variety of statistical, communication, and biophysical models have been proposed to study the relationship between brain structure and function, but the link is not yet known. In the present report we seek to relate the structural and functional connection profiles of individual brain areas. We apply a simple multilinear model that incorporates information about spatial proximity, routing, and diffusion between brain regions to predict their functional connectivity. We find that structure–function relationships vary markedly across the neocortex. Structure and function correspond closely in unimodal, primary sensory, and motor regions, but diverge in transmodal cortex, particularly the default mode and salience networks. The divergence between structure and function systematically follows functional and cytoarchitectonic hierarchies. Altogether, the present results demonstrate that structural and functional networks do not align uniformly across the brain, but gradually uncouple in higher-order polysensory areas.

Native Mass Spectrometry: Recent Progress and Remaining Challenges

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Kelly R. Karch ◽  
Dalton T. Snyder ◽  
Sophie R. Harvey ◽  
Vicki H. Wysocki
Keyword(s):  
Mass Spectrometry ◽  
Gas Phase ◽  
Structural Biology ◽  
Recent Progress ◽  
Native Mass Spectrometry ◽  
Structure And Function ◽  
Annual Review ◽  
Publication Date ◽  
Analysis Software ◽  
And Function

Native mass spectrometry (nMS) has emerged as an important tool in studying the structure and function of macromolecules and their complexes in the gas phase. In this review, we cover recent advances in nMS and related techniques including sample preparation, instrumentation, activation methods, and data analysis software. These advances have enabled nMS-based techniques to address a variety of challenging questions in structural biology. The second half of this review highlights recent applications of these technologies and surveys the classes of complexes that can be studied with nMS. Complementarity of nMS to existing structural biology techniques and current challenges in nMS are also addressed. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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