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A.F. Branco and Joe Dan Gorman discuss The debate, Tony’s toons and related issues, along with some videos and some..

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Toni Annala, Marc Hoyois and Ryomei Iwasa
J. Amer. Math. Soc. 38 (), 243-289.
Abstract, references and article information

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.

Celebrating Black History Month at Chatham House 24 October 2024 — 6:00PM TO 8:00PM Anonymous (not verified) 2 October 2024 Chatham House

Join us for the ‘Beyond expectations: The impact and legacy of migration exhibition 2024’ exhibition and drinks reception.

About the Photographer  

Neil Kenlock, a photographer and media professional, has lived in London since arriving from Jamaica in 1963 to join his parents. He spent the early years of his career as a professional photographer, specialising in fashion, beauty, celebrities, and the cultural lifestyles of Black people in the UK. In the late 1960s and 1970s, he captured images of the UK Black Panther movement and documented demonstrations and anti-racism protests across the country.

“Neil Kenlock helps us to better understand the story of London’s Black communities and to appreciate the huge artistic and cultural impact they have had on all our lives. He is a significant photographer whose work documents a key chapter in London’s post-war history.” — Mike Seaborne, former curator of photographs at the Museum of London.

About the exhibition

This exhibition unveils a collection of photographs by Neil Kenlock, capturing Black British individuals who migrated from their homelands and settled in the UK. Curated by his daughter Emelia Kenlock, the series explores the theme of ‘expectations’ and its enduring legacy, featuring African and Caribbean subjects who brought their skills, passions, and dreams—contributions that have profoundly shaped British culture today.

Reflecting on the work, Kenlock stated: “Over 50 years since the concept of ‘black excellence’ first manifested, and more than 70 years since the Windrush, I truly hope this exhibition will add to the national cultural narrative and resonate with new audiences.” 

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.

A Digital India Must Embrace the Circular Economy Expert comment sysadmin 15 January 2018

A growing amount of e-waste should draw attention to the broader sustainability of a digital society.

The latest Global E-Waste Monitor places India as one of the highest contributors to global e-waste, generating over 2 million metric tonnes in 2016. Posing serious health and environmental risks, growing e-waste represents the hidden cost of increasingly digital lives in an information society.

With just 33 per cent of the population owning a smart phone, India already has the second largest number of smart phone users in the world, nearly 4 times that of the United States. The amount of e-waste generated will exponentially increase in the coming decade as the cost of consumer electronics decline, middle-class incomes rise, and the frequency at which devices are discarded increases.

As governance instruments are increasingly digitized and industry re-repositions itself to leverage Industry 4.0 solutions, the generation of e-waste will become a byproduct of institutional choices rather than consumer consumption and behaviour alone.

India is already a leader in the management and recycling of e-waste. But over 90 per cent is managed in the unorganized sector by small businesses and individual entrepreneurs, typically from low-income marginalized communities, and often women. E-waste contains various toxic substances such as mercury and lead, prolonged exposure to which can lead to major health problems.

Almost 80 per cent of e-waste workers in India suffer from respiratory ailments due to improper standards and nearly 500,000 children are engaged in e-waste collection without adequate protection and safeguards. The bulk of the dirty and dangerous work supporting India’s march towards an increasingly digital society is done by those who have the least access to technology gains. Government regulations for the management of e-waste, on the other hand, are becoming more relaxed, presumably as a result of industry pressure. To streamline e-waste management, the government notified Electronic Waste Rules in 2011, based on the concept of extended producer responsibility (EPR).

EPR makes manufacturers of electronic products responsible for the end-of-life management of their products, including setting up collection centres. By shifting the burden to manufacturers, the EPR framework, in theory, creates incentives for more environmentally friendly design. But the impact of EPR rules on manufacturers has been minimal, at best. The recently released Draft Notification (2017) by the Ministry of Environment, Forest and Climate Change further relaxes the EPR rule by reducing the e-waste collection targets for industries.

While the efficiency and productivity gains of Digital India are to be welcomed, growing e-waste should draw attention to the broader sustainability of a digital society. Data centres, for example, are one the largest contributors to global warming, contributing a similar amount to global greenhouse emissions as the aviation industry.

This amount is expected to triple in the next decade. In many ways, the sustainability challenge is a ‘wicked problem’ – where possible solutions create a new set of additional challenges and the choice between available alternatives is largely about competing values.

For example, data centres powered by renewable sources of energy such as solar provide a greener alternative, but will also create new forms of e-waste in the form of photovoltaic cells and panels. An unverified estimate suggests that India’s projected solar capacity of 100 gigawatts by 2022 will create 7.76 million tonnes of e-waste. Without adequate and preemptive consideration of how this waste should be disposed and recycled, renewable energy solutions can create new negative externalities.

For Digital India to be sustainable, we need to develop anticipatory knowledge for preemptive solutions. It is an opportune moment to think of the broader architecture of a digital society, one that avoids getting locked into unsustainable models of production and consumption, as is the case with many industrialized economies.

The argument that such considerations are premature for India, given high levels of poverty and unemployment, are misplaced. Enquiries into the sustainability of Digital India are no less urgent than the need for sustained job-creating economic growth. These issues should not be addressed in a sequential or linear manner, but in parallel, or else we will be only partially aware of available choices and their consequences, creating new forms of technological and economic lock-ins.

The value-based choice demanded by the ‘wicked problem’ at hand is one that embraces the idea of a circular economy — one that departs from the linear economic growth model predicated on ‘take, make, dispose’ to embrace a growth model based on creating closed loops of production, consumption and re-use. A circular economy model is built on the idea of designing out waste and pollution; keeping products and materials in use; and regenerating natural systems. In many ways, India is already a leader in the circular economy.

Alongside, the management of e-waste and other forms of recycling, high levels of repair and reuse are distinctly observable. A number of reports note that the informal waste management sector in India works better than systems in many industrialized economies.

A circular economy vision for Digital India would include organizing informal waste management systems, including safety and social protection initiatives for workers; revising and tightening existent e-waste rules for increased accountability by manufacturers both in terms of durable design and responsible disposal; green data centres; and building future smart cities with a view towards energy and water efficiency, among others.

A recent report by the Ellen McArthur Foundation and the World Economic Forum also estimates that a circular economy path to development could bring India annual benefits of $624 billion by 2050. Greenhouse gas emissions could also be 44 per cent lower in 2050, compared with current development path.

Unsurprisingly, Nordic countries are leading the way in promoting the idea of a circular economy. Sweden recently announced tax breaks for repair related activities and Finland hosted the first global conference on the circular economy earlier this year. The circular economy provides an opportunity for India to capitalize and leverage an already existing culture of circular activities, and promote it as a policy agenda that will create new forms of employment while facilitating sustainable environmental management.

This article was originally published in the Indian Express.

Dongmei Cheng
Jun 1, 2006; 5:1158-1170
Datasets

Ilka Wittig
Jul 1, 2007; 6:1215-1225
Research

Independent Thinking: Lula wins in Brazil, US midterms Audio NCapeling 4 November 2022

The third episode of our new podcast analyses the results from the Brazil presidential election, and looks ahead to the crucial midterm elections in the US next week.

Bronwen Maddox and her guests examine the tight election result from Brazil and its impact on both the country and the region, and preview the US midterm elections being held on 8 November and the start of COP27.

In Brazil, former president Luiz Inácio Lula da Silva beat incumbent Jair Bolsonaro by the narrowest of margins. Meanwhile in the US, the Democrats are fighting to retain the House and Senate from a resurgent Republican Party still enamoured with Donald Trump.

Joining Bronwen Maddox this week are Leslie Vinjamuri, director of Chatham House’s US and Americas programme, Christopher Sabatini, senior fellow on Latin America in the same programme, and Ana Yang, executive director of Chatham House’s Sustainability Accelerator.

Independent Thinking: Insurrections and elections in Brazil and the US Audio NCapeling 20 January 2023

Episode 11 examines disinformation in the US and Brazil, the role played by social media platforms, and how conspiracy theories percolate online.

The storming in Brasilia of government institutions by supporters of former president Jair Bolsonaro echoed the events seen at the US Capitol building on 6 January 2021. This week’s guests discuss the impact on Brazil.

The panel also examines the state of politics in the US going into 2023. How are things shaping up for Joe Biden’s presidency after the mid-terms now that a new Congress has been sworn in? And what are the challenges being faced more broadly by the American body politic two years on from the insurrection at Capitol Hill.

Joining guest host Leslie Vinjamuri this week from Chatham House is Christopher Sabatini, senior research fellow for Latin America, Serusha Govender, the Mo Ibrahim Foundation academy fellow, and Alex Krasodomski, senior research associate at the Digital Society Initiative.

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

K Schoonjans
May 1, 1996; 37:907-925
Reviews

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.

Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential.

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
Abstract, references and article information

Cheng Chu
Proc. Amer. Math. Soc. 152 (), 5289-5297.
Abstract, references and article information

YoungJu Choie, Winfried Kohnen and Yichao Zhang
Proc. Amer. Math. Soc. 152 (), 5025-5037.
Abstract, references and article information

Alin Bostan, Xavier Caruso and Julien Roques
Bull. Amer. Math. Soc. 61 (), 609-658.
Abstract, references and article information

The two branches of the Kennedy pathways (CDP-choline and CDP-ethanolamine) are the predominant pathways responsible for the synthesis of the most abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine, respectively, in mammalian membranes. Recently, hereditary diseases associated with single gene mutations in the Kennedy pathways have been identified. Interestingly, genetic diseases within the same pathway vary greatly, ranging from muscular dystrophy to spastic paraplegia to a childhood blinding disorder to bone deformations. Indeed, different point mutations in the same gene (PCYT1; CCTα) result in at least three distinct diseases. In this review, we will summarize and review the genetic diseases associated with mutations in genes of the Kennedy pathway for phospholipid synthesis. These single-gene disorders provide insight, indeed direct genotype-phenotype relationships, into the biological functions of specific enzymes of the Kennedy pathway. We discuss potential mechanisms of how mutations within the same pathway can cause disparate disease.

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

Bacterial low-copy-number plasmids require partition (par) systems to ensure their stable inheritance by daughter cells. In general, these systems consist of three components: a centromeric DNA sequence, a centromere-binding protein and a nucleotide hydrolase that polymerizes and functions as a motor. Type III systems, however, segregate plasmids using three proteins: the FtsZ/tubulin-like GTPase TubZ, the centromere-binding protein TubR and the MerR-like transcriptional regulator TubY. Although the TubZ filament is sufficient to transport the TubR-centromere complex in vitro, TubY is still necessary for the stable maintenance of the plasmid. TubY contains an N-terminal DNA-binding helix-turn-helix motif and a C-terminal coiled-coil followed by a cluster of lysine residues. This study determined the crystal structure of the C-terminal domain of TubY from the Bacillus cereus pXO1-like plasmid and showed that it forms a tetrameric parallel four-helix bundle that differs from the typical MerR family proteins with a dimeric anti-parallel coiled-coil. Biochemical analyses revealed that the C-terminal tail with the conserved lysine cluster helps TubY to stably associate with the TubR-centromere complex as well as to nonspecifically bind DNA. Furthermore, this C-terminal tail forms an amphipathic helix in the presence of lipids but must oligomerize to localize the protein to the membrane in vivo. Taken together, these data suggest that TubY is a component of the nucleoprotein complex within the partitioning machinery, and that lipid membranes act as mediators of type III systems.

15 July 2020

War in Ukraine: The world reaction - Brazil and Africa Audio NCapeling 9 June 2022

The ninth episode of our podcast mini-series examines perspectives from Brazil and the Africa region and the impact on their relations with Russia.

How have Brazil and Africa reacted to the war in Ukraine? With impending elections in Brazil, how is President Bolsonaro’s relationship with Putin received by the public? How will food insecurity affect African nations’ response to the war?

This episode was produced by David Dargahi and Anouk Millet of Earshot Strategies on behalf of Chatham House.

PREAMBLE

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.

The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated.

Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized.

These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, both the SNMMI and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question.

The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines.

The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment.

Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

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

Visual Abstract

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

Alba Simats
Dec 1, 2020; 19:1921-1935
Research

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

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

Hideaki Kuge
Dec 1, 2020; 61:1747-1763
Research Articles

Douglas A. Andres
Dec 1, 2020; 61:1537-1537
Images in Lipid Research