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Article ; Online: Realization of Paris Agreement pledges may limit warming just below 2 °C.

Meinshausen, Malte / Lewis, Jared / McGlade, Christophe / Gütschow, Johannes / Nicholls, Zebedee / Burdon, Rebecca / Cozzi, Laura / Hackmann, Bernd

Nature

2022 Volume 604, Issue 7905, Page(s) 304–309

Abstract: Over the last five years prior to the Glasgow Climate ... ...

Abstract	Over the last five years prior to the Glasgow Climate Pact
MeSH term(s)	Earth, Planet ; Environmental Policy/legislation & jurisprudence ; Global Warming/legislation & jurisprudence ; Global Warming/prevention & control ; Global Warming/statistics & numerical data ; History, 21st Century ; International Cooperation/legislation & jurisprudence ; Paris ; Retrospective Studies ; Temperature ; Time Factors ; United Nations/legislation & jurisprudence
Language	English
Publishing date	2022-04-13
Publishing country	England
Document type	Historical Article ; Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-04553-z
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Article ; Online: SLAP2 Adaptor Binding Disrupts c-CBL Autoinhibition to Activate Ubiquitin Ligase Function.

Wybenga-Groot, Leanne E / Tench, Andrea J / Simpson, Craig D / Germain, Jonathan St / Raught, Brian / Moran, Michael F / McGlade, C Jane

Journal of molecular biology

2021 Volume 433, Issue 8, Page(s) 166880

Abstract: CBL is a RING type E3 ubiquitin ligase that functions as a negative regulator of tyrosine kinase signaling and loss of CBL E3 function is implicated in several forms of leukemia. The Src-like adaptor proteins (SLAP/SLAP2) bind to CBL and are required for ...

Abstract	CBL is a RING type E3 ubiquitin ligase that functions as a negative regulator of tyrosine kinase signaling and loss of CBL E3 function is implicated in several forms of leukemia. The Src-like adaptor proteins (SLAP/SLAP2) bind to CBL and are required for CBL-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling. Despite the established role of SLAP/SLAP2 in regulating CBL activity, the nature of the interaction and the mechanisms involved are not known. To understand the molecular basis of the interaction between SLAP/SLAP2 and CBL, we solved the crystal structure of CBL tyrosine kinase binding domain (TKBD) in complex with SLAP2. The carboxy-terminal region of SLAP2 adopts an α-helical structure which binds in a cleft between the 4H, EF-hand, and SH2 domains of the TKBD. This SLAP2 binding site is remote from the canonical TKBD phospho-tyrosine peptide binding site but overlaps with a region important for stabilizing CBL in its autoinhibited conformation. In addition, binding of SLAP2 to CBL in vitro activates the ubiquitin ligase function of autoinhibited CBL. Disruption of the CBL/SLAP2 interface through mutagenesis demonstrated a role for this protein-protein interaction in regulation of CBL E3 ligase activity in cells. Our results reveal that SLAP2 binding to a regulatory cleft of the TKBD provides an alternative mechanism for activation of CBL ubiquitin ligase function.
MeSH term(s)	Adaptor Proteins, Signal Transducing/chemistry ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Binding Sites ; Down-Regulation ; Humans ; Molecular Conformation ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins c-cbl/chemistry ; Proto-Oncogene Proteins c-cbl/genetics ; Proto-Oncogene Proteins c-cbl/metabolism ; Proto-Oncogene Proteins pp60(c-src)/chemistry ; Proto-Oncogene Proteins pp60(c-src)/genetics ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Sequence Alignment ; Signal Transduction ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; src Homology Domains
Chemical Substances	Adaptor Proteins, Signal Transducing ; SLA2 protein, human ; Ubiquitin ; Proto-Oncogene Proteins c-cbl (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Proto-Oncogene Proteins pp60(c-src) (EC 2.7.10.2) ; CBL protein, human (EC 6.3.2.-)
Language	English
Publishing date	2021-02-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2021.166880
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Article: SLAP2 Adaptor Binding Disrupts c-CBL Autoinhibition to Activate Ubiquitin Ligase Function

Wybenga-Groot, Leanne E / Tench, Andrea J / Simpson, Craig D / Germain, Jonathan St / Raught, Brian / Moran, Michael F / McGlade, C. Jane

Journal of molecular biology. 2021 Apr. 16, v. 433, no. 8

2021

Abstract	CBL is a RING type E3 ubiquitin ligase that functions as a negative regulator of tyrosine kinase signaling and loss of CBL E3 function is implicated in several forms of leukemia. The Src-like adaptor proteins (SLAP/SLAP2) bind to CBL and are required for CBL-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling. Despite the established role of SLAP/SLAP2 in regulating CBL activity, the nature of the interaction and the mechanisms involved are not known. To understand the molecular basis of the interaction between SLAP/SLAP2 and CBL, we solved the crystal structure of CBL tyrosine kinase binding domain (TKBD) in complex with SLAP2. The carboxy-terminal region of SLAP2 adopts an α-helical structure which binds in a cleft between the 4H, EF-hand, and SH2 domains of the TKBD. This SLAP2 binding site is remote from the canonical TKBD phospho-tyrosine peptide binding site but overlaps with a region important for stabilizing CBL in its autoinhibited conformation. In addition, binding of SLAP2 to CBL in vitro activates the ubiquitin ligase function of autoinhibited CBL. Disruption of the CBL/SLAP2 interface through mutagenesis demonstrated a role for this protein-protein interaction in regulation of CBL E3 ligase activity in cells. Our results reveal that SLAP2 binding to a regulatory cleft of the TKBD provides an alternative mechanism for activation of CBL ubiquitin ligase function.
Keywords	antigens ; crystal structure ; cytokine receptors ; leukemia ; molecular biology ; mutagenesis ; peptides ; protein-protein interactions ; receptor protein-tyrosine kinase ; tyrosine ; ubiquitin-protein ligase
Language	English
Dates of publication	2021-0416
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2021.166880
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Article ; Online: The geographical distribution of fossil fuels unused when limiting global warming to 2 °C.

McGlade, Christophe / Ekins, Paul

Nature

2015 Volume 517, Issue 7533, Page(s) 187–190

Abstract: ... by greenhouse gas emissions should not exceed 2 °C above the average global temperature of pre-industrial times. It has been ... estimated that to have at least a 50 per cent chance of keeping warming below 2 °C throughout the twenty ... of all current fossil fuel reserves is incompatible with a warming limit of 2 °C. Here we use a single integrated ...

Abstract	Policy makers have generally agreed that the average global temperature rise caused by greenhouse gas emissions should not exceed 2 °C above the average global temperature of pre-industrial times. It has been estimated that to have at least a 50 per cent chance of keeping warming below 2 °C throughout the twenty-first century, the cumulative carbon emissions between 2011 and 2050 need to be limited to around 1,100 gigatonnes of carbon dioxide (Gt CO2). However, the greenhouse gas emissions contained in present estimates of global fossil fuel reserves are around three times higher than this, and so the unabated use of all current fossil fuel reserves is incompatible with a warming limit of 2 °C. Here we use a single integrated assessment model that contains estimates of the quantities, locations and nature of the world's oil, gas and coal reserves and resources, and which is shown to be consistent with a wide variety of modelling approaches with different assumptions, to explore the implications of this emissions limit for fossil fuel production in different regions. Our results suggest that, globally, a third of oil reserves, half of gas reserves and over 80 per cent of current coal reserves should remain unused from 2010 to 2050 in order to meet the target of 2 °C. We show that development of resources in the Arctic and any increase in unconventional oil production are incommensurate with efforts to limit average global warming to 2 °C. Our results show that policy makers' instincts to exploit rapidly and completely their territorial fossil fuels are, in aggregate, inconsistent with their commitments to this temperature limit. Implementation of this policy commitment would also render unnecessary continued substantial expenditure on fossil fuel exploration, because any new discoveries could not lead to increased aggregate production.
MeSH term(s)	Arctic Regions ; Atmosphere/chemistry ; Carbon Dioxide/analysis ; Coal/economics ; Coal/supply & distribution ; Coal/utilization ; Databases, Factual ; Fossil Fuels/economics ; Fossil Fuels/supply & distribution ; Fossil Fuels/utilization ; Geography ; Global Warming/prevention & control ; Global Warming/statistics & numerical data ; Greenhouse Effect/prevention & control ; Greenhouse Effect/statistics & numerical data ; Models, Theoretical ; Oil and Gas Fields ; Time Factors
Chemical Substances	Coal ; Fossil Fuels ; Carbon Dioxide (142M471B3J)
Language	English
Publishing date	2015-01-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature14016
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Article: Engineering P450 TamI as an Iterative Biocatalyst for Selective Late-Stage C-H Functionalization and Epoxidation of Tirandamycin Antibiotics.

Espinoza, Rosa V / Haatveit, Kersti Caddell / Grossman, S Wald / Tan, Jin Yi / McGlade, Caylie A / Khatri, Yogan / Newmister, Sean A / Schmidt, Jennifer J / Garcia-Borràs, Marc / Montgomery, John / Houk, K N / Sherman, David H

ACS catalysis

2021 Volume 11, Issue 13, Page(s) 8304–8316

Abstract: Iterative P450 enzymes are powerful biocatalysts for selective late-stage C-H oxidation of complex ...

Abstract	Iterative P450 enzymes are powerful biocatalysts for selective late-stage C-H oxidation of complex natural product scaffolds. These enzymes represent useful tools for selectivity and cascade reactions, facilitating direct access to core structure diversification. Recently, we reported the structure of the multifunctional bacterial P450 TamI and elucidated the molecular basis of its substrate binding and strict reaction sequence at distinct carbon atoms of the substrate. Here, we report the design and characterization of a
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article
ISSN	2155-5435
ISSN	2155-5435
DOI	10.1021/acscatal.1c01460
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Article ; Online: Cerebrospinal fluid neurofilament light chain is elevated in Niemann-Pick type C compared to psychiatric disorders and healthy controls and may be a marker of treatment response.

Eratne, Dhamidhu / Loi, Samantha M / Li, Qiao-Xin / Varghese, Shiji / McGlade, Amelia / Collins, Steven / Masters, Colin L / Velakoulis, Dennis / Walterfang, Mark

The Australian and New Zealand journal of psychiatry

2019 Volume 54, Issue 6, Page(s) 648–649

Language	English
Publishing date	2019-12-11
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	221140-3
ISSN	1440-1614 ; 0004-8674
ISSN (online)	1440-1614
ISSN	0004-8674
DOI	10.1177/0004867419893431
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Article ; Online: Response to Letter to the Editor for "'stacked stitch' for efficient closure of deep cutaneous defects".

Glade, Daniel C / Krunic, Aleksandar L / Owen, Joshua L

JAAD international

2024 Volume 15, Page(s) 32

Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Journal Article
ISSN	2666-3287
ISSN (online)	2666-3287
DOI	10.1016/j.jdin.2023.12.007
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Article ; Online: How particle shape affects granular segregation in industrial and geophysical flows.

Cúñez, Fernando David / Patel, Div / Glade, Rachel C

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 6, Page(s) e2307061121

Abstract: Industrial and environmental granular flows commonly exhibit a phenomenon known as "granular segregation," in which grains separate according to physical characteristics (size, shape, density), interfering with industrial applications (cement mixing, ... ...

Abstract	Industrial and environmental granular flows commonly exhibit a phenomenon known as "granular segregation," in which grains separate according to physical characteristics (size, shape, density), interfering with industrial applications (cement mixing, medicine, and food production) and fundamentally altering the behavior of geophysical flows (landslides, debris flows, pyroclastic flows, riverbeds). While size-induced segregation has been well studied, the role of grain shape has not. Here we conduct numerical experiments to investigate how grain shape affects granular segregation in dry and wet flows. To isolate the former, we compare dry, bidisperse mixtures of spheres alone with mixtures of spheres and cubes in a rotating drum. Results show that while segregation level generally increases with particle size ratio, the presence of cubes decreases segregation levels compared to cases with only spheres. Further, we find differences in the segregation level depending on which shape makes up each size class, reflecting differences in mobility when smaller grains are cubic or spherical. We find similar dynamics in simulations of a shear-driven coupled fluid-granular flow (e.g., a simulated riverbed), demonstrating that this phenomenon is not unique to rotating drums; however, in contrast to the dry system, we find that the segregation level increases in the presence of cubic grains, and fluid drag effects can qualitatively change segregation trends. Our findings demonstrate competing shape-induced segregation patterns in wet and dry flows that are independent from grain size controls, with implications for many industrial and geophysical processes.
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2307061121
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Article: Review and Analysis of Heat Transfer in Spacer-Filled Channels of Membrane Distillation Systems.

Schilling, Sebastian / Glade, Heike

Membranes

2023 Volume 13, Issue 10

Abstract: ... solutions in a wide range of salinities, between 1 g/kg and 95 g/kg, and temperatures, between 30 °C and 80 ... °C, yielding high heat transfer coefficients in a range of 1500 to 8300 W/(m ...

Abstract	Membrane distillation (MD) is an attractive process for the concentration of seawater brines. Modelling and simulation of membrane distillation processes requires a better knowledge of the heat transfer coefficients in spacer-filled channels which are usually determined by applying empirical correlations for the Nusselt number. In this study, first, a comprehensive literature review on heat transfer correlations was conducted. It was found that the empirical correlations often used for MD simulation result in strongly varying Nusselt numbers that differ by up to an order of magnitude at low Reynolds numbers. Then, heat transfer in spacer-filled channels was investigated experimentally in a membrane distillation system using an aluminum plate instead of a flat-sheet membrane. Numerous tests were carried out with sodium chloride solutions in a wide range of salinities, between 1 g/kg and 95 g/kg, and temperatures, between 30 °C and 80 °C, yielding high heat transfer coefficients in a range of 1500 to 8300 W/(m
Language	English
Publishing date	2023-10-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2614641-1
ISSN	2077-0375
ISSN	2077-0375
DOI	10.3390/membranes13100842
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Article ; Online: "Stacked Stitch" for efficient closure of deep cutaneous defects.

Glade, Daniel C / Krunic, Aleksandar L / Owen, Joshua L

JAAD international

2023 Volume 12, Page(s) 1–2

Language	English
Publishing date	2023-01-26
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2666-3287
ISSN (online)	2666-3287
DOI	10.1016/j.jdin.2023.01.008
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