27 August 2020

COP27: Navigating a difficult road to Sharm El-Sheikh Expert comment NCapeling 6 July 2022

Against a backdrop of rising urgency, COP27 in Egypt will bring all aspects of climate action into the spotlight – but especially the role of the host country.

As COP26 drew to a close in Glasgow, Egyptian officials announced their priorities for COP27, emphasizing climate finance and climate adaptation – a new approach given previous COPs mainly focused on mitigation, reducing emissions to limit climate damage.

This was followed by the COP27 presidency outlining its vision at MENA Climate Week 2022 to achieve ‘substantive and equal progress’ on all aspects of the negotiations, and Egypt emphasizing its intention to focus on implementing existing carbon reduction targets rather than pushing for further carbon cuts.

Egypt argues it is hosting COP27 on behalf of African nations and that, while it is promoting the interests of the developing world, it will be an impartial arbiter. However it is also useful to consider its priorities from the Egyptian government’s perspective.

Agenda drivers

Egypt has long prioritized climate finance and adaptation because it remains in need of technical and financial support to adapt, especially in agriculture and tourism.

It plans to expand its access to climate funding and investment, an area in which Egypt has been relatively successful as it currently receives 27 per cent of all multilateral climate finance in the MENA region and has issued the region’s first sovereign green bonds.

With public debt currently 94 per cent of GDP, Egyptian officials have also called for debt relief for Egypt and other developing countries.

Egypt’s Climate Change Strategy reflects this approach, aiming to enhance Egypt’s rank on the Climate Change Performance Index in order to ‘attract more investments and acquire more climate funding’.

Limiting the mitigation scope and the focus on finance also echoes Egypt’s own reluctance to make carbon reduction commitments. The Egyptian nationally determined contribution (NDC) – its 2030 pledge under the Paris Agreement – does not include any quantifiable emission reduction targets.

Egypt is one of only a few countries which failed to submit an updated NDC in 2021 and its upcoming update will not include an economy-wide carbon reduction target.

Egypt has also never published a long-term strategy and has no decarbonization plans despite independent estimates it should cut rising emissions by one-quarter by 2030, and by two-thirds by 2050 to be aligned with the Paris Agreement. This partly explains why observers rate Egypt’s climate action as highly insufficient.

Furthermore, Egypt’s championing of ‘moving from pledges to implementation’ without having quantifiable carbon reduction pledges of its own effectively exempts it from both pledging and implementation.

As a developing country, Egypt’s negotiating position is supported by UNFCCC provisions which recognize differentiated responsibilities and respective capabilities of nations.

Its proposal to focus COP27 on the implementation of climate action and finance pledges is important in consolidating progress. But not pushing for more emission reductions at this critical moment risks derailing global decarbonization momentum and undermining global climate action.

According to optimistic estimates, if current climate pledges were implemented the world would still remain on track for 2°C of warming by the end of the century, with far worse impacts than if warming was curbed at 1.5°C.

Under a 2°C scenario, 37 per cent of the global population could regularly be exposed to extreme heat waves compared to 14 per cent in a 1.5°C warmer world, with developing countries expected to be worst-affected.

A 2°C trajectory also runs the risk of tipping points such as the melting of ice sheets in Antarctica and Greenland, triggering runaway climate change. Time to change the warming trajectory is running out as the latest IPCC assessment warns the window of opportunity is now ‘brief and rapidly closing’, and the UN Secretary General recently called for faster carbon cuts by the end of 2022 to avoid a ‘climate catastrophe’.

A different energy transition

Egypt opted not to join any of the voluntary sectoral coalitions at COP26 on reducing methane, clean energy transition, transition to zero-emissions vehicles, or moving beyond oil and gas.

This position is explained by its growing role as an exporter and advocate for fossil gas in the energy transition. Egypt is the second-largest producer of natural gas in Africa and is emerging as a fossil gas hub for the eastern Mediterranean, which is shaping its domestic energy policy.

Its 59GW electricity generation capacity is almost double the peak demand and is dominated by gas-powered electricity generation, which currently represents 42 per cent of all Africa’s gas generation.

Egypt’s climate policy is also shaped by fossil gas, and its national Climate Change Strategy encourages the expansion of gas use by promoting a transition to compressed natural gas for vehicles, the expansion of its domestic natural gas network – despite having universal access to electricity – and shifting to a gas-fuelled shipping sector.

Egypt also voiced support for other African countries to extract and deploy fossil gas and oil resources, making it one of the protagonists of the ‘great fossil gas pushback’. These advocates defend the right of developing countries to deploy fossil gas as a ‘transition fuel’ and champion its necessity to solve energy poverty.

But their position is not shared by all African and developing countries, and is rejected by some civil society groups, who argue it risks locking in greenhouse gases and local emissions for decades as well as delaying future development of low carbon energy systems.

Egypt’s huge spare generation capacity has contributed to a slowdown in renewable energy projects over the past two years. With renewables representing just 6GW, Egypt is expected to miss its renewable energy target for 2022, set at 20 per cent of generating capacity.

Engaging Egypt better

But these positions are more malleable than they seem, and Egypt is open to dialogue – not just on refining the COP27 agenda but also on reviewing its own climate priorities and leveraging its energy sector for a more ambitious transition.

Visual Abstract

Researchers use dynamic PET imaging with target-selective tracer molecules to probe molecular processes. Kinetic models have been developed to describe these processes. The models are typically fitted to the measured PET data with the assumption that the brain is in a steady-state condition for the duration of the scan. The end results are quantitative parameters that characterize the molecular processes. The most common kinetic modeling endpoints are estimates of volume of distribution or the binding potential of a tracer. If the steady state is violated during the scanning period, the standard kinetic models may not apply. To address this issue, time-variant kinetic models have been developed for the characterization of dynamic PET data acquired while significant changes (e.g., short-lived neurotransmitter changes) are occurring in brain processes. These models are intended to extract a transient signal from data. This work in the PET field dates back at least to the 1990s. As interest has grown in imaging nonsteady events, development and refinement of time-variant models has accelerated. These new models, which we classify as belonging to the first, second, or third generation according to their innovation, have used the latest progress in mathematics, image processing, artificial intelligence, and statistics to improve the sensitivity and performance of the earliest practical time-variant models to detect and describe nonsteady phenomena. This review provides a detailed overview of the history of time-variant models in PET. It puts key advancements in the field into historical and scientific context. The sum total of the methods is an ongoing attempt to better understand the nature and implications of neurotransmitter fluctuations and other brief neurochemical phenomena.

Visual Abstract

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Sophos X-Ops unveils five-year investigation tracking China-based groups targeting perimeter devices

Tricia Rowlison
Dec 1, 2020; 19:2090-2103
Research

Simone Kurz
Dec 29, 2020; 0:RA120.002266v1-mcp.RA120.002266
Research

Toma Keser
Dec 29, 2020; 0:RA120.002433v1-mcp.RA120.002433
Research

Xiao-Ting Wen
Dec 17, 2020; 0:RA120.002119v1-mcp.RA120.002119
Research

Kyle Swovick
Dec 28, 2020; 0:RA120.002301v1-mcp.RA120.002301
Research

Eugen Netz
Dec 1, 2020; 19:2157-2167
Technological Innovation and Resources

Alison M. Kurimchak
Dec 1, 2020; 19:2068-2089
Research

Peter Lasch
Dec 1, 2020; 19:2125-2138
Technological Innovation and Resources

Sylwia Struk
Dec 28, 2020; 0:RA119.001766v1-mcp.RA119.001766
Research

Weixian Deng
Dec 22, 2020; 0:RA120.002411v1-mcp.RA120.002411
Research

Julia Knöckel
Dec 22, 2020; 0:RA120.002432v1-mcp.RA120.002432
Research

David Durán
Nov 19, 2020; 0:RA120.002276v1-mcp.RA120.002276
Research

Xinting Zhang
Dec 8, 2020; 0:RA120.002306v1-mcp.RA120.002306
Research

Qin Zhang
Nov 17, 2020; 0:RA120.002325v1-mcp.RA120.002325
Research

Juntuo Zhou
Nov 30, 2020; 0:RA120.002384v1-mcp.RA120.002384
Research

Ka-Won Kang
Nov 30, 2020; 0:RA120.002169v1-mcp.RA120.002169
Research

Laura F Fielden
Nov 11, 2020; 0:RA120.002370v1-mcp.RA120.002370
Research

Congcong Lu
Nov 17, 2020; 0:R120.002257v1-mcp.R120.002257
Review

Daniel J. Geiszler
Dec 1, 2020; 0:TIR120.002216v1-mcp.TIR120.002216
Technological Innovation and Resources

Jianhua Wang
Nov 4, 2020; 0:RA120.002375v1-mcp.RA120.002375
Research

Philipp Emanuel Geyer
Dec 17, 2020; 0:RA120.002359v1-mcp.RA120.002359
Research

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

Transient receptor potential vanilloid 1 (TRPV1) channel is a multimodal receptor that is responsible for nociceptive, thermal, and mechanical sensations. However, which biomolecular partners specifically interact with TRPV1 remains to be elucidated. Here, we used cDNA library screening of genes from mouse dorsal root ganglia combined with patch-clamp electrophysiology to identify the voltage-gated potassium channel auxiliary subunit Kvβ1 physically interacting with TRPV1 channel and regulating its function. The interaction was validated in situ using endogenous dorsal root ganglia neurons, as well as a recombinant expression model in HEK 293T cells. The presence of Kvβ1 enhanced the expression stability of TRPV1 channels on the plasma membrane and the nociceptive current density. Surprisingly, Kvβ1 interaction also shifted the temperature threshold for TRPV1 thermal activation. Using site-specific mapping, we further revealed that Kvβ1 interacted with the membrane-distal domain and membrane-proximal domain of TRPV1 to regulate its membrane expression and temperature-activation threshold, respectively. Our data therefore suggest that Kvβ1 is a key element in the TRPV1 signaling complex and exerts dual regulatory effects in a site-specific manner.

Protein quality control is maintained by a number of integrated cellular pathways that monitor the folding and functionality of the cellular proteome. Defects in these pathways lead to the accumulation of misfolded or faulty proteins that may become insoluble and aggregate over time. Protein aggregates significantly contribute to the development of a number of human diseases such as amyotrophic lateral sclerosis, Huntington's disease, and Alzheimer's disease. In vitro, imaging-based, cellular studies have defined key biomolecular components that recognize and clear aggregates; however, no unifying method is available to quantify cellular aggregates, limiting our ability to reproducibly and accurately quantify these structures. Here we describe an ImageJ macro called AggreCount to identify and measure protein aggregates in cells. AggreCount is designed to be intuitive, easy to use, and customizable for different types of aggregates observed in cells. Minimal experience in coding is required to utilize the script. Based on a user-defined image, AggreCount will report a number of metrics: (i) total number of cellular aggregates, (ii) percentage of cells with aggregates, (iii) aggregates per cell, (iv) area of aggregates, and (v) localization of aggregates (cytosol, perinuclear, or nuclear). A data table of aggregate information on a per cell basis, as well as a summary table, is provided for further data analysis. We demonstrate the versatility of AggreCount by analyzing a number of different cellular aggregates including aggresomes, stress granules, and inclusion bodies caused by huntingtin polyglutamine expansion.

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause mitochondrial diseases and are implicated in aging. The mtDNA within cells is organized into nucleoids within the mitochondrial matrix, but how mtDNA nucleoids are formed and regulated within cells remains incompletely resolved. Visualization of mtDNA within cells is a powerful means by which mechanistic insight can be gained. Manipulation of the amount and sequence of mtDNA within cells is important experimentally and for developing therapeutic interventions to treat mitochondrial disease. This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify, and manipulate the properties of mtDNA within cells.

RAS genes are the most commonly mutated in human cancers and play critical roles in tumor initiation, progression, and drug resistance. Identification of targets that block RAS signaling is pivotal to develop therapies for RAS-related cancer. As RAS translocation to the plasma membrane (PM) is essential for its effective signal transduction, we devised a high-content screening assay to search for genes regulating KRAS membrane association. We found that the tyrosine phosphatase PTPN2 regulates the plasma membrane localization of KRAS. Knockdown of PTPN2 reduced the proliferation and promoted apoptosis in KRAS-dependent cancer cells, but not in KRAS-independent cells. Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling. Consistently, analysis of the TCGA database demonstrates that high expression of PTPN2 is significantly associated with poor prognosis of patients with KRAS-mutant pancreatic adenocarcinoma. These results indicate that PTPN2 is a key regulator of KRAS and may serve as a new target for therapy of KRAS-driven cancer.

The kinesin-3 family contains the fastest and most processive motors of the three neuronal transport kinesin families, yet the sequence of states and rates of kinetic transitions that comprise the chemomechanical cycle and give rise to their unique properties are poorly understood. We used stopped-flow fluorescence spectroscopy and single-molecule motility assays to delineate the chemomechanical cycle of the kinesin-3, KIF1A. Our bacterially expressed KIF1A construct, dimerized via a kinesin-1 coiled-coil, exhibits fast velocity and superprocessivity behavior similar to WT KIF1A. We established that the KIF1A forward step is triggered by hydrolysis of ATP and not by ATP binding, meaning that KIF1A follows the same chemomechanical cycle as established for kinesin-1 and -2. The ATP-triggered half-site release rate of KIF1A was similar to the stepping rate, indicating that during stepping, rear-head detachment is an order of magnitude faster than in kinesin-1 and kinesin-2. Thus, KIF1A spends the majority of its hydrolysis cycle in a one-head-bound state. Both the ADP off-rate and the ATP on-rate at physiological ATP concentration were fast, eliminating these steps as possible rate-limiting transitions. Based on the measured run length and the relatively slow off-rate in ADP, we conclude that attachment of the tethered head is the rate-limiting transition in the KIF1A stepping cycle. Thus, KIF1A's activity can be explained by a fast rear-head detachment rate, a rate-limiting step of tethered-head attachment that follows ATP hydrolysis, and a relatively strong electrostatic interaction with the microtubule in the weakly bound post-hydrolysis state.

Stephanie E. Hood
Dec 1, 2020; 61:1720-1732
Research Articles

Marco De Giorgi
Dec 1, 2020; 61:1675-1686
Research Articles

Auguste Dargent
Dec 1, 2020; 61:1776-1783
Research Articles

Junhwan Kim
Dec 1, 2020; 61:1707-1719
Research Articles

Anja Jaeschke
Dec 9, 2020; 0:jlr.RA120001141v1-jlr.RA120001141
Research Articles

Gerhard Liebisch
Dec 1, 2020; 61:1539-1555
Special Report

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