Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during a time-course of myogenesis in cell culture. We observed wide-spread changes in the abundance of several important lectins and enzymes facilitating glycan biosynthesis. Glycomics-based quantification of released N-linked glycans confirmed remodeling of the glycome consistent with the regulation of glycosyltransferases and glycosidases responsible for their formation including a previously unknown di-galactose-to-sialic acid switch supporting a functional role of these glycoepitopes in myogenesis. Furthermore, dynamic quantitative glycoproteomic analysis with multiplexed stable isotope labelling and analysis of enriched glycopeptides with multiple fragmentation approaches identified glycoproteins modified by these regulated glycans including several integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins most notably the up-regulation of galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early functional role of galectin-1 in the myogenic program. Importantly, similar changes in N-glycosylation and the up-regulation of galectin-1 during postnatal skeletal muscle development were observed in mice. Treatment of new-born mice with recombinant adeno-associated viruses to overexpress galectin-1 in the musculature resulted in enhanced muscle mass. Our data form a valuable resource to further understand the glycobiology of myogenesis and will aid the development of intervention strategies to promote healthy muscle development or regeneration.

CD4+ T cell responses are crucial for inducing and maintaining effective anti-cancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17 and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared to interferon gamma (IFN) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor-antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire.

Glycosylation is a highly diverse set of co- and post-translational modification of proteins. For mammalian glycoproteins, glycosylation is often site-, tissue- and species-specific, and diversified by microheterogeneity. Multitudinous biochemical, cellular, physiological and organismic effects of their glycans have been revealed, either intrinsic to the carrier proteins or mediated by endogenous reader proteins with carbohydrate recognition domains. Furthermore, glycans frequently form the first line of access by or defense from foreign invaders, and new roles for nucleocytoplasmic glycosylation are blossoming. We now know enough to conclude that the same general principles apply in invertebrate animals and unicellular eukaryotes – different branches of which spawned the plants or fungi and animals. The two major driving forces for exploring the glycomes of invertebrates and protists are (i) to understand the biochemical basis of glycan-driven biology in these organisms, especially of pathogens, and (ii) to uncover the evolutionary relationships between glycans, their biosynthetic enzyme genes, and biological functions for new glycobiological insights. With an emphasis on emerging areas of protist glycobiology, here we offer an overview of glycan diversity and evolution, to promote future access to this treasure trove of glycobiological processes.

The glycoprotein spike (S) on the surface of SARS-CoV-2 is a determinant for viral invasion and host immune response. Herein, we characterized the site-specific N-glycosylation of S protein at the level of intact glycopeptides. All 22 potential N-glycosites were identified in the S-protein protomer and were found to be preserved among the 753 SARS-CoV-2 genome sequences. The glycosites exhibited glycoform heterogeneity as expected for a human cell-expressed protein subunit. We identified masses that correspond to 157 N-glycans, primarily of the complex type. In contrast, the insect cell-expressed S protein contained 38 N-glycans, completely of the high-mannose type. Our results revealed that the glycan types were highly determined by the differential processing of N-glycans among human and insect cells, regardless of the glycosites’ location. Moreover, the N-glycan compositions were conserved among different sizes of subunits. Our study indicate that the S protein N-glycosylation occurs regularly at each site, albeit the occupied N-glycans were diverse and heterogenous. This N-glycosylation landscape and the differential N-glycan patterns among distinct host cells are expected to shed light on the infection mechanism and present a positive view for the development of vaccines and targeted drugs.

The choice for adjuvant chemotherapy in stage II colorectal cancer (CRC) is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high-risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II CRC tissue samples. The cancer cells, compared to normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.

Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock which has seen a rapid rise in prevalence throughout Western Europe in recent years. Following ingestion of metacercariae (parasite cysts) by the mammalian host, newly-excysted juveniles (NEJs) emerge and invade the duodenal submucosa which causes significant pathology in heavy infections. The immature larvae then migrate upwards, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients and to avoid the host immune response. Here, transcriptome analysis of four intra-mammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic disease respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that whilst a family of cathepsins B with varying S2 sub-site residues (indicating distinct substrate specificities) are differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is up-regulated in adult worms, although they are underrepresented in the secretome. The most abundant proteins in adult fluke secretions were helminth defence molecules (HDMs) that likely establish an immune environment permissive to fluke survival and/or neutralise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognise antigens from other helminths commonly found as co-infections with rumen fluke.

The complexity and dynamics of the immensely heterogeneous glycoproteome of the prostate cancer (PCa) tumour micro-environment remain incompletely mapped, a knowledge gap that impedes our molecular-level understanding of the disease. To this end, we have used sensitive glycomics and glycoproteomics to map the protein-, cell- and tumour grade-specific N- and O-glycosylation in surgically-removed PCa tissues spanning five histological grades (n = 10/grade) and tissues from patients with benign prostatic hyperplasia (n = 5). Quantitative glycomics revealed PCa grade-specific alterations of the oligomannosidic-, paucimannosidic- and branched sialylated complex-type N-glycans, and dynamic remodelling of the sialylated core 1- and core 2-type O-glycome. Deep quantitative glycoproteomics identified ~7,400 unique N-glycopeptides from 500 N-glycoproteins and ~500 unique O-glycopeptides from nearly 200 O-glycoproteins. With reference to a recent Tissue and Blood Atlas, our data indicate that paucimannosidic glycans of the PCa tissues arise mainly from immune cell-derived glycoproteins. Further, the grade-specific PCa glycosylation arises primarily from dynamics in the cellular makeup of the PCa tumour microenvironment across grades involving increased oligomannosylation of prostate-derived glycoproteins and decreased bisecting GlcNAcylation of N-glycans carried by the extracellular matrix proteins. Further, elevated expression of several oligosaccharyltransferase subunits and enhanced N-glycoprotein site occupancy were observed associated with PCa progression. Finally, correlations between the protein-specific glycosylation and PCa progression were observed including increased site-specific core 2-type O-glycosylation of collagen VI. In conclusion, integrated glycomics and glycoproteomics have enabled new insight into the complexity and dynamics of the tissue glycoproteome associated with PCa progression generating an important resource to explore the underpinning disease mechanisms.

Modulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver bacterial proteins, termed ‘effector proteins’ into the host cell during infection by sophisticated protein translocation systems, which manipulate cellular processes and functions. The functional contribution of individual effectors is poorly characterised, particularly in intracellular bacterial pathogens with large effector protein repertoires. Technical caveats have limited the capacity to study these proteins during a native infection, with many effector proteins having only been demonstrated to be translocated during over-expression of tagged versions. Here we developed a novel strategy to examine effector proteins in the context of infection. We coupled a broad, unbiased proteomics-based screen with organelle purification to study the host-pathogen interactions occurring between the host cell mitochondrion and the Gram-negative, Q fever pathogen Coxiella burnetii. We identify 4 novel mitochondrially-targeted C. burnetii effector proteins, renamed Mitochondrial Coxiella effector protein (Mce) B to E. Examination of the subcellular localisation of ectopically expressed proteins confirmed their mitochondrial localisation, demonstrating the robustness of our approach. Subsequent biochemical analysis and affinity enrichment proteomics of one of these effector proteins, MceC, revealed the protein localises to the inner membrane and can interact with components of the mitochondrial quality control machinery. Our study adapts high-sensitivity proteomics to study intracellular host-pathogen interactions, providing a robust strategy to examine the sub-cellular localisation of effector proteins during native infection. This approach could be applied to a range of pathogens and host cell compartments to provide a rich map of effector dynamics throughout infection.

Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in mature medaka testis. As for the interaction with TGFβ-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid (Y2H) screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired Y2H assay. Co-immunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastrutural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (TGFβ and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA which may be fundamentally conserved across phyla during sexual differentiation.

Staphylococcus aureus is a major cause of infections worldwide and infection results in a variety of diseases. As of no surprise, protein phosphorylation is an important game player in signaling cascades and has been shown to be involved in S. aureus virulence. Albeit long neglected, eukaryotic-type serine/threonine kinases in S. aureus have been implicated in this complex signaling cascades. Due to the sub-stoichiometric nature of protein phosphorylation and a lack of suitable analysis tools, the knowledge of these cascades is however, to date, still limited.

Here, were apply an optimized protocol for efficient phosphopeptide enrichment via Fe3+-IMAC followed by LC-MS/MS to get a better understanding of the impact of protein phosphorylation on the complex signaling networks involved in pathogenicity. By profiling a serine/threonine kinase and phosphatase mutant from a methicillin-resistant S. aureus mutant library, we generated the most comprehensive phosphoproteome dataset of S. aureus to date, aiding a better understanding of signaling in bacteria. With the identification of 3800 class I p-sites we were able to increase the number of identifications by more than 21 times compared to recent literature. In addition, we were able to identify 74 downstream targets of the only reported eukaryotic-type Ser/Thr kinase of the S. aureus strain USA300, Stk1. This work allowed an extensive analysis of the bacterial phosphoproteome and indicates that Ser/Thr kinase signaling is far more abundant than previously anticipated in S. aureus.

The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics.

Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for primary cultured glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome datasets, 38 DEPs were organized; only 10 DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multi-sample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.

Data independent acquisition (DIA) is now an emerging method in bottom-up proteomics and capable of achieving deep proteome coverage and accurate label-free quantification. However, for post-translational modifications (PTM), such as glycosylation, DIA methodology is still in the early stage of development. The full characterization of glycoproteins requires site specific glycan identification as well as subsequent quantification of glycan structures at each site. The tremendous complexity of glycosylation represents a significant analytical challenge in glycoproteomics. This review focuses on the development and perspectives of DIA methodology for N- and O- glycoproteomics and posits that DIA-based glycoproteomics could be a method of choice to address some of the challenging aspects of glycoproteomics. First, the current challenges in glycoproteomics and the basic principles of DIA is briefly introduced. DIA based glycoproteomics is then summarized and described into four aspects based on the actual samples. Lastly, we discussed the important challenges and future perspectives in the field. We believe that DIA can significantly facilitate glycoproteomic studies and contribute to the development of future advanced tools and approaches in the field of glycoproteomics.

Cells continually degrade and replace damaged proteins. However, the high energetic demand of protein turnover generates reactive oxygen species (ROS) that compromise the long-term health of the proteome. Thus, the relationship between aging, protein turnover and energetic demand remains unclear. Here, we used a proteomic approach to measure rates of protein turnover within primary fibroblasts isolated from a number of species with diverse lifespans including the longest-lived mammal, the bowhead whale. We show that organismal lifespan is negatively correlated with turnover rates of highly abundant proteins. In comparison to mice, cells from long-lived naked mole rats have slower rates of protein turnover, lower levels of ATP production and reduced ROS levels. Despite having slower rates of protein turnover, naked mole rat cells tolerate protein misfolding stress more effectively than mouse cells. We suggest that in lieu of rapid constitutive turnover, long-lived species may have evolved more energetically efficient mechanisms for selective detection and clearance of damaged proteins.

Alpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases and some changes appear to be disease-specific, thus it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers and enable better understanding of AGP’s role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96 well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography based solid-phase extraction and analyzed by RP-LC-ESI-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in 3 time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP’s second glycosylation site and lower sialylation of N-glycans on AGP’s third and AGP1’s fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes.

Giardia lamblia (G. lamblia) disease is a zoonosis with a-infection rate affecting the general population of the world. Despite the constant possibility of damage due to their own metabolism, G. lamblia have survived and evolved to adapt to various environments. However, research on energy-metabolism conversion in G. lamblia is limited. This study aimed to reveal the dynamic metabolism-conversion mechanism in G. lamblia under sugar starvation by detecting global lysine acetylation and 2-hydroxyisobutyrylation sites combined with quantitative proteome analyses. A total of 2999 acetylation sites on 956 proteins and 8877 2-hydroxyisobutyryl sites on 1546 proteins were quantified under sugar starvation. Integrated Kac and Khib data revealed that modified proteins were associated with arginine biosynthesis, glycolysis/gluconeogenesis, and alanine, aspartate, and glutamate metabolism. These findings suggested that lysine acetylation and 2-hydroxyisobutyrylation were ubiquitous and provided deep insight into the metabolism-conversion mechanism in G. lamblia under sugar starvation. Overall, these results can help understand the biology of G. lamblia infections and reveal the evolution rule from prokaryote to eukaryote.

Recent advances in MS-based proteomics have vastly increased the quality and scope of biological information that can be derived from human samples. These advances have rendered current workflows increasingly applicable in biomedical and clinical contexts. As proteomics is poised to take an important role in the clinic, associated ethical responsibilities increase in tandem with the impact on the health, privacy, and well-being of individuals. Here we conducted and report a systematic literature review of ethical issues in clinical proteomics. We add our perspectives from a background of bioethics, the results of our accompanying paper extracting individual-sensitive results from patient samples, and the literature addressing similar issues in genomics. The spectrum of potential issues ranges from patient re-identification to incidental findings of clinical significance. The latter can be divided into actionable and unactionable findings. Some of these have the potential to be employed in discriminatory or privacy-infringing ways. However, incidental findings may also have great positive potential. A plasma proteome profile, for instance, could inform on the general health or disease status of an individual regardless of the narrow diagnostic question that prompted it. We suggest that early discussion of ethical issues in clinical proteomics is important to ensure that eventual regulations reflect the considered judgment of the community as well as to anticipate opportunities and problems that may arise as the technology matures further.

Drones and the European Union: Prospects for a Common Future Research paper sysadmin 30 January 2018

The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.

Summary

• The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.
• Countries would benefit from working together to identify accountability gaps arising from fundamental elements of military cooperation, including the role of intelligence transfers in joint operations, and the distribution of responsibility for lethal actions in the context of coalition operations.
• Transparency in investigation procedures, as well as devoting sufficient resources towards ensuring that mistakes are identified, will improve the perception of drone use among domestic audiences.
• Identifying and communicating common standards and practices of mitigating complicity should be a priority for countries to ensure that they do not unwittingly become complicit in unlawful lethal operations.
• Although operational safety may hinder the ability of states to be completely transparent, understanding among the general public could be improved through the communication of policies and procedures regarding non-lethal assistance to partner states conducting lethal operations, both inside and outside the context of an armed conflict.

Libya’s War Economy: Predation, Profiteering and State Weakness Research paper sysadmin 9 April 2018

As Libya’s war economy persists, prospects for the restoration of functioning central governance become more distant.

Summary

• Libya suffers from interlinked political, security and economic crises that are weakening state institutions, damaging its economy and facilitating the continued existence of non-state armed groups. As rival authorities continue to compete for power, the resulting fragmentation and dysfunction have provided a fertile environment for the development of a pervasive war economy dependent on violence.
• This war economy is dynamic and constantly in flux. Relative to earlier problems, there were signs of progress on several fronts in 2017: a reduction in human smuggling, a tripling in oil revenues, and increased local action against fuel smuggling. Yet the dynamics that have supported the war economy’s rise remain.
• Libya’s war economy is highly damaging for the future of the state for three reasons:
  • First, it provides an enabling environment for networks of armed groups, criminal networks, corrupt businessmen and political elites to sustain their activities through illicit sales and predatory practices. Their operations are closely linked to the dispensation of violence, and are thus a spur for further conflict.
  • Second, the war economy perpetuates negative incentives for those who profit from the state’s dysfunction. Only effective governance, supported by a durable political settlement, can tackle the foundations of Libya’s war economy. But neither a return to functioning central governance nor the development of a security sector that is fit for purpose is in the interests of war economy profiteers, who are therefore motivated to act as powerful spoilers of reform.
  • Third, the political contestation and resource predation practised by those engaged in the war economy are having a disastrous impact on Libya’s formal economy, undermining what remains of its institutions. As the war economy persists, therefore, the prospects for the restoration of functioning central governance become more distant. This threatens to create a vicious cycle that accelerates further state collapse.
• Due to the limited capacity for coercion available to any actor or entity connected with the state, a strategy of co-opting networks of war economy profiteers has almost exclusively prevailed. This has failed. Drawing on the lessons from these attempts, a more successful policy must pursue targeted measures to combat the enabling structures of Libya’s war economy where possible, and to co-opt war economy profiteers only where necessary.
• In this, state authorities can do more to utilize what power they have to name and shame war economy profiteers in order to weaken the local legitimacy critical to profiteers’ survival. The state must present credible alternative livelihood opportunities to those engaged in, or benefiting from, the war economy. Progress will depend in part on the creation of positive incentives to abandon such activity. Where profiteers cannot be incentivized to move towards more legitimate economic activities, greater and more effective efforts must be made to reduce the profit margins of illicit schemes.
• The international community can do more to support Libyan efforts in countering the war economy. Cooperation over the targeting of criminal groups’ overseas assets, support for increased transparency over the dispensation of state funds, and measures to reduce the viability of illicit activities can all help to strengthen the position of state authorities.

Further reading

Discover the six things you need to know about Libya’s war economy

Dance of the Trillions: Developing Countries and Global Finance Book sysadmin 6 July 2018

David Lubin tells the story of what makes money flow from high-income countries to lower-income ones; what makes it flow out again; and how developing countries have sought protection against the volatility of international capital flows.

Selected by the Financial Times as one of the best economics books of 2018, Dance of the Trillions traces an arc from the 1970s, when developing countries first gained access to international financial markets, to the present day.

Underlying this story is a discussion of how the relationship between developing countries and global finance appears to be moving from one governed by the ‘Washington Consensus’ to one more likely to be shaped by Beijing.

This book is part of the Insights series.

Praise for Dance of the Trillions

About the author

David Lubin is managing director and head of emerging markets economics at Citi, an American bank, where he is responsible for a team of more than 30 economists in 15 locations globally.

Purchase

• UK (via Amazon)
• Rest of world (via Brookings Institution Press)
• Students (via Browns Books)

Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches Research paper sysadmin 5 October 2018

Combating illegal wildlife trade and further pursuing conservation-development models could help generate considerable economic benefits for African countries, while ensuring the long-term preservation of Africa’s wealth of natural capital.

Summary

• The illegal wildlife trade (IWT) significantly impacts African economies by destroying and corroding natural, human and social capital stocks. This hinders the achievement of the Sustainable Development Goals (SDGs) and has an impact on national budgets. Illicit financial flows from IWT deny revenue to governments where legal wildlife product trade exists and perpetuate cash externalization. IWT diverts national budgets away from social or development programmes, increases insecurity and threatens vulnerable populations.
• In expanding wildlife economies and pursuing conservation-driven development models, governments can protect their citizens, derive revenue from wildlife products, and establish world class tourism offerings. The illegal exploitation of wildlife is often due to a failure to enforce rights over those resources, where rights are unclearly defined or not fully exercised. Southern African countries have defined these rights in various ways, contributing to regional differences in conservation practices and the socio-economic benefits derived from wildlife resources. Combating IWT is an important step towards allowing legitimate business and communities to develop livelihoods that incentivize stewardship and connect people to conservation.
• The Southern African Development Community (SADC) has several framework policies for the establishment of transfrontier conservation areas (TFCAs). These promote local stewardship across multiple land-use areas to conserve biodiversity and increase the welfare and socioeconomic development of rural communities. Private-sector partnerships also increase skills transfer, improve access to investment finance, and expand economic opportunities, including through the promotion of local procurement. The economic benefits of TFCAs extend beyond tourism.
• The economic value of African ecosystems is often under-recognized because they remain unquantified, partly due to the lack of available data on the broader economic costs of IWT. Improved monitoring and evaluation with key performance indicators would help governments and citizens to appreciate the economic value of combating IWT.

The Role of Sub-state and Non-state Actors in International Climate Processes: Corporate Sector Research paper sysadmin 27 November 2018

Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• The corporate sector has traditionally engaged governments at national rather than international level in lobbying for action related to climate change. Where it has engaged at an international level, this has often been to restrain regulation and ambition, such as in air transport. Over time, many businesses have increasingly understood that there is more commercial opportunity in a strong, consistent approach to tackling climate mitigation and adaptation, and an increasing number are willing to speak up on the issue. The Paris Climate Conference in 2015 demonstrated this positive engagement.
• Businesses are more powerful when engaging directly with national governments on detailed policies – by demonstrating what is possible and indirectly influencing national governments’ international pledges. Traditional trade/industry sector associations and groups have tended to suffer from the ‘lowest common denominator’ effect of their least progressive members. Progressive business groups coalescing around climate ambition can help to counter this.
• Unlike at the Copenhagen climate talks in 2009, the business community provided a positive, supportive backdrop to the 2015 Paris talks, mindful of the public relations opportunities in taking a progressive stance and of the benefits of targets that reflected the science. The carbon market was a particular focus for corporates, which succeeded in getting emissions trading options and market mechanisms included in Article 6 of the Paris Agreement.
• Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made. With increasing awareness of resource scarcity, businesses are pursuing ever more creative solutions.
• Wide recognition that the avoidance of future emissions is increasingly dependent on developing and emerging economies means that business voices from these countries will potentially be more influential in the next few years.

Proportionality in the Conduct of Hostilities: The Incidental Harm Side of the Assessment Research paper sysadmin 6 December 2018

Clarification of international humanitarian law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups is also crucial.

Summary

• Military operations are taking place with increasing frequency in densely populated areas. Such operations result in loss of life and harm to civilians, as well as damage to civilian objects, (including infrastructure providing essential services). In order to protect civilians, it is imperative that armed forces and groups comply with the rules of international humanitarian law on the conduct of hostilities, including the rule of proportionality.
• The rule of proportionality prohibits attacks which may be expected to cause incidental loss of civilian life, injury to civilians, damage to civilian objects or a combination thereof, which would be excessive in relation to the concrete and direct military advantage anticipated. This research paper analyses the key steps that belligerents must take to give effect to the rule, with a particular focus on one side of proportionality assessments – the expected incidental harm.
• Those undertaking proportionality assessments before or during an attack must consider whether the expected harm will be caused by the attack, and whether that harm could be expected (that is, was it reasonably foreseeable).
• For the purpose of proportionality assessments, injury to civilians includes disease, and there is no reason in principle to exclude mental harm, even though it is currently challenging to identify and quantify it. Damage to civilian objects includes damage to elements of the natural environment.
• Once the incidental harm to be considered has been identified, a value or weight must be assigned to it. This is then balanced against the value or weight of the military advantage anticipated from the attack to determine whether the harm would be excessive.
• In the determination of whether the expected incidental harm would be excessive compared to the anticipated military advantage, ‘excessive’ is a wide but not indeterminate standard.
• Belligerents should develop methodologies so that those planning and deciding attacks are provided with all necessary information on expected incidental harm, and to assist them in assigning weight to the incidental harm to be considered.
• If it becomes apparent that the rule of proportionality will be contravened, the attack in question must be cancelled or suspended.
• Clarification of the law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups, inculcated by their leaders, is also crucial.

The Costs of Fuelling Humanitarian Aid Research paper sysadmin 7 December 2018

As humanitarian crises become more protracted and aid budgets face unprecedented scrutiny, agencies could save millions by switching from diesel and oil fuels to cleaner energy sources.

Download the accompanying toolkit

Most refugee and internal displacement camps are in remote locations, so humanitarian agencies consume large amounts of fuel on the transport of staff, equipment, and goods such as food and water.

Operations tend to rely on on-site electricity generation to power reception centres, clinics, schools, food storage, water-pumping and street lighting. Despite the essential role of energy in humanitarian action, and the UN’s stated commitment to carbon neutrality by 2020, there is no concerted effort to move away from fossil fuel to date.

Summary points

• Agencies are paying too much for the energy they consume. They are overwhelmingly dependent on oil fuel for electricity generation, even though renewable energy solutions are reducing costs for those deploying them in similar conditions. Well-below-optimum standards of efficiency in buildings, generator use and fleet management are also the norm.
• Agencies typically have few incentives to do things better. There is rarely motivation to conserve fuel, nor performance indicators for energy or fuel use. In addition, energy spending and use lacks transparency.
• Few agencies collect and report on energy use. Where numbers are available, they are usually partial and unverified. Energy costs are rarely transparent in budgets; and donors do not know how much is being spent.
• We estimate that around 5 per cent of humanitarian agencies’ expenditure goes on diesel, petrol and associated costs such as fixing generators. That would mean that the sector spent some $1.2 billion on polluting fuel in 2017.
• Based on current best-practice, the sector could save at least 10 per cent of fuel costs on ground transport, 37 per cent through behaviour change and more efficient technologies, and 60 per cent on generation – all using currently available, affordable and proven practice and technology changes.
• At current prices, this could mean operational savings of over $517 million a year for the humanitarian sector, roughly equal to 5 per cent of UNHCR’s funding gap for 2017.
• In Kenya, annual spending on diesel and petrol for the seven agencies surveyed was $6.7 million in 2017. Replacing gensets with solar systems could create significant savings due the costs of diesel, the likelihood of protracted camp situations, and the opportunities that off-grid solar would offer for extending electricity access to refugees and local populations in Garissa and Turkana counties.
• In Jordan, solar energy now powers the majority of camp facilities and many households. However, the use of grid electricity by humanitarian agencies’ large head offices in Amman remains high and expensive. Improving the energy efficiency of buildings is a priority for savings.
• In Burkina Faso’s Goudoubo camp, NGO offices are desperately short of power – they have no computers or air-conditioning. Investment in renewable forms of energy for this and other camp services such as street lighting and water pumping would enable better service provision, and could drive increased rural energy access among host populations across this area of the Sahel.

Toolkit

An accompanying toolkit, Powering Ahead: Improving How We Use and Account for Energy in Humanitarian Operations, provides practical guidance for humanitarian agencies that want to make energy cost savings and reduce their carbon and emissions footprint.

Moscow Rules: What Drives Russia to Confront the West Book sysadmin 17 January 2019

Keir Giles surveys Russia’s history and the present day to explain why its current leadership feels it has no choice but to challenge and attack the West. Recognising and accepting that this will not change in the near future will help the West find a way of dealing with Russia without risking a deeper conflict.

This book is for anyone that cannot understand why Russia and its leaders behave as they do.

The relationship between Russia and the West is once again deep in crisis. A major reason is that Western leaders have too often believed or hoped that Russia sees the world as they do — but things look very different from Moscow. This book shows that efforts at engagement with Russia that do not take this into account are a key reason for repeated disappointment and crisis.

In confronting the West, Russia is implementing strategic and doctrinal approaches that have been consistent for centuries. The roots of current Russian behaviour and demands can be traced not just to the Soviet era, but back into Tsarist foreign and domestic policy, and further to the structure and rules of Russian society. But this also gives the US and the West pointers for how to behave — and how not to — in order to manage the challenge of Russia effectively, based on past experience of both successful and unsuccessful engagement with Moscow.

The book recognizes the reality of confrontation and provides an essential introduction to grasping why Russia sees it as inevitable. Consequently, it offers a basis for building a less crisis-prone relationship with Russia.

This book is part of the Insights series.

Praise for Moscow Rules

About the author

Keir Giles is a senior consulting fellow at Chatham House, the Royal Institute of International Affairs. He also works with the Conflict Studies Research Centre (CSRC), a group of subject matter experts in Eurasian security with a particular focus on the wide range of security challenges coming from Russia.

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Cooking in Displacement Settings: Engaging the Private Sector in Non-wood-based Fuel Supply Research paper sysadmin 22 January 2019

In displacement settings, providing cooking solutions that reduce negative impacts on the environment and health remains a challenge for local governments, humanitarian agencies, businesses and refugees.

Summary

• Providing adequate cooking fuel and clean-burning, fuel-efficient stoves in displacement settings has long been a major challenge for local authorities, humanitarian agencies, non-governmental organizations, local communities and refugees themselves. Refugees generally have limited access to modern cooking solutions. Most either depend on insufficient humanitarian agency handouts of ‘in-kind’ firewood or have to travel long distances to collect firewood.
• There is significant potential for private-sector engagement in this context – which, though largely overlooked to date, could result in win-win scenarios for all stakeholders. Refugee camps and other displacement settings present opportunities for private-sector cooking fuel companies to expand their customer bases, with the added advantage for vendors of offering concentrated demand and scope for economies of scale.
• For the Kakuma refugee camp complex in Kenya, the Moving Energy Initiative (MEI) decided to engage with the private sector directly. The MEI requested expressions of interest from local private-sector companies for expanding sales and distribution of fuels in the complex through the concession. The winning company – National Oil Corporation of Kenya – is to receive a prize of $50,000 for its proposed concession to supply liquefied petroleum gas both to refugees in the Kakuma complex and to the surrounding host community.
• The MEI also conducted interviews with various stakeholders in other contexts and countries who are engaged in efforts to develop market-based approaches to providing clean, fuel-efficient cooking solutions to refugees.
• Based on the interviews and the concession process, the MEI recommends greater donor investment and longer-term guaranteed funding for cooking interventions. This is needed to allow sufficient time to build sustainable markets and secure the requisite engagement and investments from the private sector.
• Larger, longer-term investments by the private sector – supported through partnerships with donors and humanitarian agencies – in infrastructure and demand creation (both in and outside the refugee community) can reduce the price of alternative solutions and support a gradual transition away from subsidies.

Adopting a Market-based Approach to Boost Energy Access in Displaced Contexts Research paper sysadmin 25 March 2019

This paper evaluates the market-based approaches adopted in the MEI projects in Kenya and Burkina Faso. It articulates how such commercial strategies can be applied to the delivery of energy in displacement settings and compares this to real world examples.

• Development of long-term energy solutions in displacement settings tends to be perceived as investment that falls outside the remit of emergency responses. In addition, when emergency energy supply measures are implemented they often result in expensive, unreliable and unhealthy energy provision for those in protracted or recurrent crises.
• There is widespread agreement among humanitarian and development experts that an effective refugee response should include long-term development solutions as well as emergency relief.
• The energy access imperative is more pronounced when considering the need for effective energy distribution in practically all camp activities and basic necessities: pumping and treatment of clean water; heating and cooling for food storage and cooking; energy for livelihood activities; and provision of light for schooling, hospitals and the prevention of violence against women and children.
• Minor shifts in household energy use to basic solar lighting options and non-wood fuels would save $303 million annually on refugee fuel costs.
• Within refugee contexts in Kenya and Burkina Faso, the MEI sought to examine opportunities to use market interventions, rather than in-kind distributions, to improve clean energy access over the long-term and test the delivery of market-based approaches.

Infrastructure Management Contracts: Improving Energy Asset Management in Displacement Settings Research paper sysadmin 17 April 2019

This paper highlights a number of options for managing electricity infrastructure in refugee camps and outlines the challenges, opportunities and operational implications associated with them. It takes the Kalobeyei settlement in Kenya as a case study.

• Building and maintaining electricity infrastructure to power offices, businesses, households and other operations in displacement settings is difficult. It is especially challenging for the Office of the United Nations High Commissioner for Refugees (UNHCR) and its partner agencies, because supplying electricity is not their core business.
• Private-sector companies exist that are willing and able to develop infrastructure management contracts to provide energy as a service in displacement settings. However, institutional barriers within humanitarian agencies persist, with short budgeting cycles in particular preventing humanitarian agencies from entering into the sorts of long-term service agreements required by the private sector.
• A number of options exist to leverage the expertise of the private sector through ‘public–private partnership’ (P3) structures. Such mechanisms can promote more efficient management of infrastructure by drawing on private-sector experience and expertise, incentivizing appropriate risk-sharing and providing options to leverage private capital in project development.
• Field work from the Kalobeyei settlement in Kenya suggests that a solar/diesel hybrid mini-grid solution was the most economical option to power camp services and infrastructure there. Compared to distributed diesel generation, the annual savings in operating costs were estimated at $49,880, with the additional investment paid back within 3.6 years.
• Humanitarian agencies need to be willing to change their policies to enable long-term service agreements. Alternatively (or, more likely, in conjunction with this option), financial mechanisms such as partial risk guarantees need to be developed to offset some of the risks. This change will need high-level support from donors and humanitarian agencies.
• Once the first infrastructure management contracts can be signed and tested in displacement locations (through the use of donor funding or otherwise) and associated data collected, it will ease the way for future investments in these types of projects.

Artificial Intelligence Prediction and Counterterrorism Research paper sysadmin 6 August 2019

The use of AI in counterterrorism is not inherently wrong, and this paper suggests some necessary conditions for legitimate use of AI as part of a predictive approach to counterterrorism on the part of liberal democratic states.

Summary

• The use of predictive artificial intelligence (AI) in countering terrorism is often assumed to have a deleterious effect on human rights, generating spectres of ‘pre-crime’ punishment and surveillance states. However, the well-regulated use of new capabilities may enhance states’ abilities to protect citizens’ right to life, while at the same time improving adherence to principles intended to protect other human rights, such as transparency, proportionality and freedom from unfair discrimination. The same regulatory framework could also contribute to safeguarding against broader misuse of related technologies.
• Most states focus on preventing terrorist attacks, rather than reacting to them. As such, prediction is already central to effective counterterrorism. AI allows higher volumes of data to be analysed, and may perceive patterns in those data that would, for reasons of both volume and dimensionality, otherwise be beyond the capacity of human interpretation. The impact of this is that traditional methods of investigation that work outwards from known suspects may be supplemented by methods that analyse the activity of a broad section of an entire population to identify previously unknown threats.
• Developments in AI have amplified the ability to conduct surveillance without being constrained by resources. Facial recognition technology, for instance, may enable the complete automation of surveillance using CCTV in public places in the near future.
• The current way predictive AI capabilities are used presents a number of interrelated problems from both a human rights and a practical perspective. Where limitations and regulations do exist, they may have the effect of curtailing the utility of approaches that apply AI, while not necessarily safeguarding human rights to an adequate extent.
• The infringement of privacy associated with the automated analysis of certain types of public data is not wrong in principle, but the analysis must be conducted within a robust legal and policy framework that places sensible limitations on interventions based on its results.
• In future, broader access to less intrusive aspects of public data, direct regulation of how those data are used – including oversight of activities by private-sector actors – and the imposition of technical as well as regulatory safeguards may improve both operational performance and compliance with human rights legislation. It is important that any such measures proceed in a manner that is sensitive to the impact on other rights such as freedom of expression, and freedom of association and assembly.

Online Disinformation and Political Discourse: Applying a Human Rights Framework Research paper sysadmin 5 November 2019

Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law.

This paper examines how human rights frameworks should guide digital technology.

Summary

• Online political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.
• Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.
• International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.
• The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.
• The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.
• Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.
• The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.
• The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse.

Secrets and Spies: UK Intelligence Accountability After Iraq and Snowden Book sysadmin 15 January 2020

How can democratic governments hold intelligence and security agencies to account when what they do is largely secret? Jamie Gaskarth explores how intelligence professionals view accountability in the context of 21st century politics.

Using the UK as a case study, this book provides the first systematic exploration of how accountability is understood inside the secret world. It is based on new interviews with current and former UK intelligence practitioners, as well as extensive research into the performance and scrutiny of the UK intelligence machinery.

The result is the first detailed analysis of how intelligence professionals view their role, what they feel keeps them honest, and how far external overseers impact on their work.

The UK gathers material that helps inform global decisions on such issues as nuclear proliferation, terrorism, transnational crime, and breaches of international humanitarian law. On the flip side, the UK was a major contributor to the intelligence failures leading to the Iraq war in 2003, and its agencies were complicit in the widely discredited U.S. practices of torture and ‘rendition’ of terrorism suspects. UK agencies have come under greater scrutiny since those actions, but it is clear that problems remain.

Secrets and Spies is the result of a British Academy funded project (SG151249) on intelligence accountability. The book is published as part of the Insights series.

Praise for Secrets and Spies

About the author

Jamie Gaskarth is Professor of Foreign Policy and International Relations at The Open University. He was previously senior lecturer at the University of Birmingham where he taught strategy and decision-making. His research focused on the ethical dilemmas of leadership and accountability in intelligence, foreign policy, and defence. He is author/editor or co-editor of six books and served on the Academic Advisory panel for the 2015 UK National Security Strategy and Strategic Defence and Security Review.

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COP26: What happened, what does this mean, and what happens next? Chatham House briefing NCapeling 15 November 2021

Analysing a crucial opportunity for enhancing ambitions on climate finance, adaptation, and ‘loss and damage’, and the implementation of the Paris Agreement.

Key findings

Raising the ambition of national emission reduction targets (nationally determined contributions – NDCs) was a critical task for COP26. On this front, governments fell short: although over 120 parties have submitted new or updated NDCs, the new targets only narrow the gap to 1.5°C by 15–17 per cent, and are, if fully implemented (and this is far from certain), projected to result in warming of 2.4°C by the end of the century.

If warming is to be limited to 1.5°C above pre-industrial levels, additional emissions reductions before 2030, over and above current NDC pledges, will need to equate to reducing emissions by the equivalent of two years of current annual emissions. To keep warming to 2°C, the equivalent reductions would be needed of one year’s total emissions.

The Glasgow Climate Pact – the main political outcome of COP26 – requests governments to revisit and strengthen their NDCs before the end of 2022 to bring these in line with the Paris Agreement’s temperature goal. To keep 1.5°C within reach, it will be absolutely essential that governments return to the table with significantly enhanced offers ahead of COP27, which will take place at Sharm El-Sheikh, Egypt, in 2022.

Another key feature of the Glasgow Climate Pact is the reference to ‘accelerating efforts towards the phasedown of unabated coal power and phase-out of inefficient fossil fuel subsidies’. Although the language was watered down over the course of the negotiations, COP26 marks the first time ever reducing fossil fuels is mentioned in a COP decision.

Discussions around climate finance, adaptation, and loss and damage were centre stage in Glasgow, and were critical points of contention. Although the Glasgow Climate Pact urges developed countries to ‘fully’ deliver on the $100 billion annual climate finance pledge through to 2025, it remains unclear when this sum will actually be raised in full – and if a total of $500 billion will be mobilized between 2020 and 2025 to make up for initial shortfalls.

And while the Pact urges developed countries to double their adaptation finance by 2025, and establishes a dialogue on loss and damage finance, much more will need to be done to address the needs of climate-vulnerable developing countries. 

COP26 saw a flurry of plurilateral deals on key issues such as phasing out various forms of fossil fuels and ending deforestation. These initiatives have the potential to accelerate decarbonization, but monitoring their implementation and holding governments and other institutions to account will be critical. Future COPs provide a platform for doing this, and governments should seek to incorporate the pledges made outside the formal remits of the UNFCCC process in their NDCs.

While some progress was made at COP26, the next 12 months will be crucial in determining if the formal agreements reached in Glasgow provide grounds for optimism that 1.5°C remains firmly in sight, and are sufficient to build trust between countries and between citizens and governments.

Read the full analysis

Diagnosing social behavioural dynamics of corruption Other resource dora.popova 8 December 2021

This interactive toolkit identifies the types of social expectations which sustain selected corrupt practices and provides behaviourally-informed recommendations for changing them.

When tackling a problem as complex as corruption, it is important to understand why and how people behave in different situations where corruption occurs. In contexts where it is easier to engage in corruption than avoid it, identifying the social expectations and informal rules which sustain corrupt practices can advance corruption prevention and deepen collective action.  

Behavioural approaches to corruption offer a better understanding of diverse social settings, group dynamics, power distribution, social motivations, and expectations that contribute to a more tolerant environment for certain forms of the phenomenon. They are also highly complementary to traditional corruption measures, which tend to focus on the enforcement of legal sanctions and deterrents. Behavioural approaches, especially those inspired by social norms theory, highlight complex social characteristics and informal rules of specific corrupt practices, and effectively support implementation of more dynamic context-specific anti-corruption interventions.

Since 2016, the Chatham House Africa programme’s Social Norms and Accountable Governance (SNAG) project has adopted a behavioural approach based on social norms methodology to investigate the social beliefs which motivate different forms of corruption. Drawing on the project’s extensive evidence-gathering and analysis, this toolkit offers users navigable behavioural mapping of contextual factors, beliefs, and expectations surrounding common corrupt practices. 

It aims to support anti-corruption actors in diagnosing informal rules and social expectations which sustain corruption in some societies. It also proposes behavioural-informed guidance for developing or adapting anti-corruption interventions and activities, so they account for informal rules of behaviour such as social norms. 
 
The toolkit supports users to:

• Identify whether and how widespread corrupt practices are motivated by social beliefs and expectations.

• Understand how society influences the types of corrupt activity individuals engage in, or avoid, and the factors informing these choices

• Integrate empirical evidence and behavioural insights into anti-corruption strategies from diagnostics to design, and eventual implementation and evaluation

The toolkit presents evidence from SNAG’s research into three key corrupt practices – bribery, embezzlement, and electoral fraud. Each was examined in the context of typical situations in which they occur, such as law enforcement, healthcare, the power sector, voting, and education while critical factors such as religion, gender, and ethnicity were considered. 

The toolkit presents an overview of specific contexts and behavioural features of the practices and provides behavioural-informed recommendations. It also contains pop-up features with definitions and explanations of key concepts. The toolkit is designed to be expandable, allowing further content and behavioural dynamics to be added.   

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

Homologous recombination (HR) repairs DNA double-strand breaks using intact homologous sequences as template DNA. Broken DNA and intact homologous sequences form joint molecules (JMs), including Holliday junctions (HJs), as HR intermediates. HJs are resolved to form crossover and noncrossover products. A mismatch repair factor, MLH3 endonuclease, produces the majority of crossovers during meiotic HR, but it remains elusive whether mismatch repair factors promote HR in nonmeiotic cells. We disrupted genes encoding the MLH3 and PMS2 endonucleases in the human B cell line, TK6, generating null MLH3−/− and PMS2−/− mutant cells. We also inserted point mutations into the endonuclease motif of MLH3 and PMS2 genes, generating endonuclease death MLH3DN/DN and PMS2EK/EK cells. MLH3−/− and MLH3DN/DN cells showed a very similar phenotype, a 2.5-fold decrease in the frequency of heteroallelic HR-dependent repair of restriction enzyme–induced double-strand breaks. PMS2−/− and PMS2EK/EK cells showed a phenotype very similar to that of the MLH3 mutants. These data indicate that MLH3 and PMS2 promote HR as an endonuclease. The MLH3DN/DN and PMS2EK/EK mutations had an additive effect on the heteroallelic HR. MLH3DN/DN/PMS2EK/EK cells showed normal kinetics of γ-irradiation–induced Rad51 foci but a significant delay in the resolution of Rad51 foci and a 3-fold decrease in the number of cisplatin-induced sister chromatid exchanges. The ectopic expression of the Gen1 HJ re-solvase partially reversed the defective heteroallelic HR of MLH3DN/DN/PMS2EK/EK cells. Taken together, we propose that MLH3 and PMS2 promote HR as endonucleases, most likely by processing JMs in mammalian somatic cells.

Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase SMURF2 plays a critical tumor suppressing role via its interaction with RNF20 (ring finger protein 20) in shaping chromatin landscape and preserving genomic stability. However, the mechanism that mobilizes SMURF2 in response to DNA damage remains unclear. Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. We demonstrate that a SMURF2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ataxia telangiectasia mutated–induced phosphorylation at Ser384 constitutes a negative feedback loop that regulates DSB repair.

Fans and analysts spend the entire offseason speculating where the top free agents could go, but sometimes an under-the-radar pickup can end up making a world of difference. As positional competitions begin to heat up at Spring Training camps this month, MLB.com's beat writers were asked to identify one potentially overlooked acquisition for each of the 30 clubs. Here's who they came up with.

The Phillies introduced J.T. Realmuto, their new All-Star catcher, in a news conference Tuesday at the team's Spring Training complex in Clearwater, Fla.

A slimmed down Maikel Franco and a bulked up Scott Kingery will compete for playing time at third base this season.

Phillies manager Gabe Kapler believes the two most important spots in a lineup are the Nos. 2 and 4 holes. Rhys Hoskins and Carlos Santana hit there most of last season. But with J.T. Realmuto, Andrew McCutchen and Jean Segura joining the Phillies in the offseason, Kapler has more options.

Jean Segura became one of the Phillies' most notable offseason acquisitions, a two-time All-Star expected to give the organization its best overall production at shortstop since Jimmy Rollins left town, in part because of a little brawl he had late last season with Mariners teammate Dee Gordon.

Maikel Franco followed the endless and often mind-numbing speculation the past few months from the Dominican Republic. Franco knows that Manny Machado could show up at Spectrum Field at any moment. The Phillies entertained him at Citizens Bank Park just before Christmas. They have made him at least one contract offer. If the Phillies sign him, Franco also knows he could be traded.

Fans and analysts spend the entire offseason speculating where the top free agents could go, but sometimes an under-the-radar pickup can end up making a world of difference. As positional competitions begin to heat up at Spring Training camps this month, MLB.com's beat writers were asked to identify one potentially overlooked acquisition for each of the 30 clubs. Here's who they came up with.

After undergoing surgery in late June to repair a torn left labrum in his left shoulder that required nine anchors to be inserted to keep everything in place, Zack Cozart is healthy and looking for a bounce-back season with the Angels.

The Angels announced their Minor League coaching staffs on Saturday, including former Major League catcher Lou Marson being named the new manager of Triple-A Salt Lake and former big leaguer David Newhan as the new skipper at Double-A Birmingham.

Mike Trout and owner Arte Moreno met separately with the media on Monday, but neither would confirm that extension talks have begun between the Angels and Trout's agent, Craig Landis.

The Angels have a new closer in Cody Allen and there isn't any manager in baseball who knows him better than Indians skipper Terry Francona.