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1.
Philos Trans A Math Phys Eng Sci ; 381(2262): 20220188, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37866389

RESUMO

Continuous measurements of the Atlantic meridional overturning circulation (AMOC) and meridional ocean heat transport at 26.5° N began in April 2004 and are currently available through December 2020. Approximately 90% of the total meridional heat transport (MHT) at 26.5° N is carried by the zonally averaged overturning circulation, and an even larger fraction of the heat transport variability (approx. 95%) is explained by the variability of the zonally averaged overturning. A physically based separation of the heat transport into large-scale AMOC, gyre and shallow wind-driven overturning components remains challenging and requires new investigations and approaches. We review the major interannual changes in the AMOC and MHT that have occurred over the nearly two decades of available observations and their documented impacts on North Atlantic heat content. Changes in the flow-weighted temperature of the Florida Current (Gulf Stream) over the past two decades are now taken into account in the estimates of MHT, and have led to an increased heat transport relative to the AMOC strength in recent years. Estimates of the MHT at 26.5° N from coupled models and various surface flux datasets still tend to show low biases relative to the observations, but indirect estimates based on residual methods (top of atmosphere net radiative flux minus atmospheric energy divergence) have shown recent promise in reproducing the heat transport and its interannual variability. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.

2.
Biochemistry ; 60(4): 289-302, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33440120

RESUMO

Pseudokinases play important roles in signal transduction and cellular processes similar to those of catalytically competent kinases. However, pseudokinase pharmacological tractability and conformational space accessibility are poorly understood. Pseudokinases have only recently been suggested to adopt "inactive" conformations or interact with conformation-specific kinase inhibitors (e.g., type II compounds). In this work, the heavily substituted pseudokinase STRADα, which possesses a DFG → GLR substitution in the catalytic site that permits nucleotide binding while impairing divalent cation coordination, is used as a test case to demonstrate the potential applicability of conformation-specific, type II compounds to pseudokinase pharmacology. Integrated structural modeling is employed to generate a "GLR-out" conformational ensemble. Likely interacting type II compounds are identified through virtual screening against this ensemble model. Biophysical validation of compound binding is demonstrated through protein thermal stabilization and ATP competition. Localization of a top-performing compound through surface methylation strongly suggests that STRADα can adopt the "GLR-out" conformation and interact with compounds that comply with the standard type II pharmacophore. These results suggest that, despite a loss of catalytic function, some pseudokinases, including STRADα, may retain the conformational switching properties of conventional protein kinases.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/química , Trifosfato de Adenosina/química , Humanos , Domínios Proteicos , Estabilidade Proteica
3.
Science ; 345(6193): 184-7, 2014 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-25013068

RESUMO

Observed distributions of high-speed plasma flows at distances of 10 to 30 Earth radii (R(E)) in Earth's magnetotail neutral sheet are highly skewed toward the premidnight sector. The flows are a product of the magnetic reconnection process that converts magnetic energy stored in the magnetotail into plasma kinetic and thermal energy. We show, using global numerical simulations, that the electrodynamic interaction between Earth's magnetosphere and ionosphere produces an asymmetry consistent with observed distributions in nightside reconnection and plasmasheet flows and in accompanying ionospheric convection. The primary causal agent is the meridional gradient in the ionospheric Hall conductance which, through the Cowling effect, regulates the distribution of electrical currents flowing within and between the ionosphere and magnetotail.

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