Towards just transition in Africa: Green financing for urban energy solutions and job creation 9 June 2022 — 7:30AM TO 11:00AM Anonymous (not verified) 18 May 2022 Nairobi and online

This event explores the major openings and potential impediments to the development of a just transition policy in Africa.

Global climate policies towards a ‘just transition’ under the Paris Agreement should also align with and support African states’ national sustainable development priorities. In particular, the need for decent and fair job creation and the establishment of sufficient, resilient and sustainable power supply, accessible to all, and efficient energy use.

Achieving green growth requires innovative and more accessible financing models, especially as wealthy nations’ financial pledges have fallen short. Ahead of the ‘African COP27’ set to take place in Egypt in November 2022, there is a need for transformational strategic thinking and context-specific action from African governments, civil society, businesses and financiers in their green financing demands and national implementation plans.

Sustainable urban energy solutions represent a critical zone of opportunity for the development of new and more reliable green finance pathways. Africa’s rapidly expanding cities present a significant economic opportunity and source of growth. However, urban centres are also where income and energy inequalities are at their starkest. The acceleration of sustainable energy generation and use could have a transformative impact on SMEs and livelihoods across value chains.

At this event, participants will discuss the major openings and potential impediments to the development of a credible ‘just transition’ policy in Africa towards net zero goals, with a particular focus on establishing and enhancing links between green financing innovation, employment creation, sustainable power supply and generation, and sustainable energy usage and consumption in an urban environment.

This event is held in partnership with the Pan African Climate Justice Alliance (PACJA). It is part of a series on Towards Just Transition: Connecting Green Financing and Sustainable Job Creation in Africa, supported by the Chatham House Sustainability Accelerator.

This event will be held in English and French with simultaneous interpretation.

How is the war in Ukraine affecting perceptions of Russia in Africa? Explainer Video NCapeling 10 June 2022

Aanu Adeoye outlines how the invasion of Ukraine is affecting perceptions of Russia across the Africa region.

He says the voting patterns at the United Nations (UN) shows that the majority of African countries are unhappy about Russia’s actions, but there is not a united voice as there is in the European Union (EU) and North America.

Certain countries are heavily influenced by historical ties with Russia going back to the Soviet era and their own struggles for liberation, while others tend to remain non-aligned whenever possible.

Towards just transition in Africa: Green financing for nature-based solutions and rural resilience 21 July 2022 — 9:30AM TO 1:00PM Anonymous (not verified) 30 June 2022 Libreville and online

This hybrid event in Libreville explores just transition policy and green financing for nature-based solutions, with a particular focus on the integration of job creation priorities in conservation and rural resilience.

Global climate policies towards a ‘just transition’ under the Paris Agreement should align with and support African states’ national sustainable development priorities – in particular, the need for decent and fair job creation, as well as resilient and sustainable land, environment, and ecosystem management policies.

Achieving green growth requires innovative and more accessible financing models, especially as wealthy nations’ financial pledges have fallen short. Ahead of the ‘African COP27’ set to take place in Egypt in November 2022, there is a need for transformational strategic thinking and context-specific action from African governments, civil society, businesses and financiers, in their green financing demands and national implementation plans.

Preservation of biodiversity and nature is not only critical in the global fight against climate change but is also vital for conservation-based economic development. Natural capital stocks, such as terrestrial and marine ecosystems and biodiversity, produce benefits that support societal and individual well-being and economic prosperity, such as clean air, fresh water, regulation of water flows and pollination of crops – while also acting as important carbon sinks. Financing environmental protection must go beyond compensation and contribute to creating fair social and economic conditions for incentivizing conservation.

At this hybrid event in Libreville, participants will discuss green financing for nature-based solutions, particularly the integration of plans for job creation in conservation and rural resilience within just transition planning.

This event is part of a series on Towards Just Transition: Connecting Green Financing and Sustainable Job Creation in Africa, supported by the Chatham House Sustainability Accelerator.

This event will be held in French and English with simultaneous interpretation.

This event will also be broadcast live on the Chatham House Africa Programme’s Facebook page.

Now is the moment to launch an African vaccine industry The World Today mhiggins.drupal 31 July 2022

The continent plans to make 60 per cent of its vaccines by 2040. After the failure of the world to help in the pandemic, it’s high time, says Ngozi Erondu.

The lack of an African vaccine industry has been a glaring concern for decades. Before the pandemic, 99 per cent of Africa’s vaccines were manufactured outside the continent. As well as endangering the lives of millions, this situation has inhibited social and economic progress on the continent.

In response, the Africa Centres for Disease Control and Prevention (Africa CDC) has undertaken an ambitious plan, outlined in the Partnerships for African Vaccine Manufacturing (PAVM) Framework for Action, to develop the nascent African vaccine manufacturing sector into an end-to-end industry by 2040. The framework aims to raise the share of African-manufactured vaccines used across the continent to 60 per cent by 2040, or the equivalent to up to 1.7 billion doses annually.

Seven of every 10 vaccines used in Africa are currently donated through Gavi, the Vaccine Alliance. Most are administered within childhood immunization programmes and are largely manufactured either in India, or by  multinational vaccine manufacturers in North America or Japan.

Vaccine donations have inhibited the development in Africa of vaccines and other countermeasures against diseases.

Though the Ebola virus was discovered in Central Africa in 1976, vaccine development was not adequately funded until it emerged in Europe in 2014. Human monkeypox resurfaced in Nigeria in 2017, yet the global Coalition for Epidemic Preparedness Innovations only targeted it for vaccine development in July this year.

The pandemic highlighted Africa’s fatal dependency on imported vaccines. Only 20 per cent of Africans are fully vaccinated against Covid-19, due to the failure of countries in the Global North to ensure the equitable distribution of vaccines via the COVAX facility to 40 per cent of the world’s most vulnerable people. 

The pandemic also confirmed that Africa could not rely on fellow states of the Global South. At the height of the Delta variant outbreak in early 2021, India halted vaccine exports to Africa, where only 1.5 per cent of the population had at that time received any vaccine doses.

After decades of discussions, there are signs that Africa could soon succeed in creating its own vaccine industry. First, the 55-member African Union is in the process of establishing the African Medicines Agency, a regional regulatory body. 
 

‘The new public health order’

Additionally, the African Export-Import Bank and African Development Bank (AfDB) have established a foundation to provide financial and strategic support for the development of the pharmaceutical industry and the consolidation of regional vaccination programmes in Africa (the foundation would potentially negotiate intellectual property rights and licensing issues but that remains to be seen).

Second, studies show there is an emerging middle class in Africa. In a 2011 report by the AfDB, this was estimated at some 56 million households. Potentially, this means many people will be able to buy vaccines and medicines made in Africa.

About a third of African countries currently pay for their vaccine needs. According to PAVM forecasts, the value of the total African market could reach between $3 billion and $17 billion by 2040.

The recent entry into effect of the African Continental Free Trade Area should also prove conducive to African vaccine development. Through economic integration, free movement and harmonized regional standards, countries that invest in their biopharmaceutical and medical technology sectors may attract employees, regional and international businesses, and investment. Further, the pandemic has encouraged people to relocate to countries with, or planning for, universal healthcare.

Building an African pharmaceutical industry from the ground up could take much longer than two decades and cost tens of billions of dollars. Nevertheless, the moment seems ripe, and timely support has been forthcoming from influential regional actors, including Rwandan President Paul Kagame, South Africa’s Cyril Ramaphosa, and private sector business executives, including the Zimbabwean-born billionaire Strive Masiyiwa.

With a pandemic treaty embedding equity in prevention, preparedness and response some way off, and given the limitations surrounding the recent World Trade Organization compromise on the TRIPS waiver – which temporarily waives Covid-19 vaccine patent protections for poorer countries – it is doubly important for Africa to build up its own pharmaceutical industry and emergency systems. 

In 2021, John Nkengasong, then director of Africa CDC, wrote of the necessity of a post-pandemic ‘new public health order’ for Africa. Such a change may threaten the global health organizations, industries and institutes who derive payment from ‘saving Africa’ during emergencies. Additionally, through strengthening Africa CDC, other actors such as the World Health Organization may find that they have a diminished strategic role on the continent.
 
While Africa should not dismiss these valuable and long-standing partnerships, it must take the opportunity to advance its interests and to assume leadership in this important area.

Towards democracy in Sudan: Reflections on the transitional period 20 September 2022 — 2:00PM TO 4:00PM Anonymous (not verified) 31 August 2022 Online

In this webinar, panellists discuss the key outcomes of the evaluation workshop and reflect on how the experience of the transition to date should inform the realization of Sudan’s democratic aspirations going forward.

The military coup on 25 October 2021 halted Sudan’s transition to democracy and prospects for sustainable peace. Since then, members of the former regime have regained political influence, with many reinstated to senior positions.

The coup has provoked a strong reaction from the country’s pro-democracy movement and youth-led resistance committees who have led continuous peaceful protests demanding civilian democratic transition, despite a brutal crackdown by state security forces.

Those supportive of the coup have blamed the Forces of Freedom and Change (FFC), a wide coalition of pro-democracy political and civilian groups, for the mistakes of the transitional government.

However, the country’s political, security and economic situation has sharply deteriorated since the military’s action, and the progress achieved by the transitional government has been reversed, leading to an accelerating economic crisis, increased food insecurity and political instability.

The FFC, which played a key role in appointing the transitional government, has acknowledged its errors. In July 2022, it held a workshop in Khartoum, which was broadcast on social media, to evaluate its performance and identify lessons learned, in discussion with civil society actors and activists.

In this webinar, leading pro-democracy movement figures and independent experts discuss the key outcomes of the evaluation workshop and reflect on how the experience of the transition to date should inform the realization of Sudan’s democratic aspirations going forward.

This event is part of a Chatham House Africa programme project on supporting Sudan’s civilian-led democratic transition.

Towards just transition in Africa: Continental coordination on green financing and job creation 6 October 2022 — 7:00AM TO 3:30PM Anonymous (not verified) 8 September 2022 Addis Ababa and online

At this hybrid conference in Addis Ababa, speakers take stock of preparations ahead of the ‘African COP27’ in November and discuss the key priorities for streamlining continental cooperation on policy approaches to just transition.

At this hybrid conference in Addis Ababa, speakers will take stock of policy efforts and preparations ahead of the ‘African COP27’ in November and discuss the key priorities for streamlining continental cooperation on policy approaches to just transition.

Global climate policies towards a ‘just transition’ under the Paris Agreement should align with and support African states’ national sustainable development priorities – in particular, the need for decent and fair job creation, as well as resilient and sustainable land, environment and ecosystem management policies.

They must also be cognizant of African nations’ urgent requirements for sustainable and accessible energy to underpin economic development. Achieving green growth requires innovative and more accessible financing models, especially as wealthy nations’ financial pledges have fallen short. It also requires clarity and cooperation to unlock investment in both renewable and transitional energy.

African countries face collective climate and employment-related challenges. However, policymaking often remains regionally siloed according to differing political, energy sector and ecological realities. There is a need for transformational strategic thinking and context-specific action from African governments, civil society, businesses and financiers, in their green financing demands and national implementation plans.

At this hybrid conference in Addis Ababa, speakers will take stock of policy efforts and preparations ahead of the ‘African COP27’ in November and discuss the key priorities for streamlining continental cooperation on policy approaches to just transition, job creation and green financing.

This event is the third in a series on Towards just transition: Connecting green financing and sustainable job creation in Africa, supported by the Chatham House Sustainability Accelerator.

Towards just transition in Africa Interview Video NCapeling 23 December 2022

Highlighting key interventions from African policymakers, business leaders, researchers, and civil society voices on green financing and implementation plans.

African countries face collective climate and employment-related challenges. However, policymaking often remains regionally siloed according to differing political, energy sector, and ecological realities.

There is a need for transformational strategic thinking and context-specific action from African governments, civil society, businesses, and financiers, in their green financing demands and national implementation plans.

This video highlights key interventions from policymakers, business leaders, researchers, and civil society voices at a series of events hosted by the Chatham House Africa programme in Nairobi, Libreville, and Addis Ababa in the lead-up to COP27.

The events series, Towards just transition: Connecting green financing and sustainable job creation in Africa, was supported by the Chatham House Sustainability Accelerator and the United Nations Development Programme.

Africa Aware: Towards just transition in Africa Audio NCapeling 1 March 2023

African countries face collective climate and job creation-related challenges, yet policymaking often remains regionally siloed.

This podcast reflects on the key policy messages from the Africa programme’s series on Towards just transition: Connecting green financing and sustainable job creation in Africa.

African countries face collective climate and job creation-related challenges. Yet policymaking often remains regionally siloed according to differing political, energy sector and ecological realities.

This output is part of a stream of work supported by the Chatham House Sustainability Accelerator and the United Nations Development Programme (UNDP). 

Visual Abstract

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

Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-κB [NF-κB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-κB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-κB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was down-regulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-κB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3'UTR, causing its down-regulation. This in-creased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-κB(p65) promotion of miR-99b can aggravate ALI in mice by down-regulating the expression of PRDM1.

Chiara Pavanello
Dec 1, 2020; 61:1784-1788
Patient-Oriented and Epidemiological Research

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

Akemi Kakino
Nov 3, 2020; 0:jlr.RA120000767v1-jlr.RA120000767
Research Articles

Amanda D.V. MacCannell
Nov 18, 2020; 0:jlr.ILR120001204v1-jlr.ILR120001204
Images in Lipid Research

In SAS Business Rules Manager 3.3, the initial loading of a rule set and a rule flow takes significantly longer than it does in release 3.2. When this problem happens, long time gaps are evident in the local

You might see the following error messages: "ERROR: Connection failed. Server returned: SAS Logon Manager authentication failed: Access denied." and "ERROR: Unable to connect to Cloud Analytic Services host-name on port 5570. Veri

Editing and/or saving an action column can take up to a minute to display a window. There are no workarounds identified at this time.

In SAS Life Science Analytics Framework 4.6, group membership removal fails with an exception if a user is set as assignee, a candidate, or a notification recipient in a user task for a Process Flow . The Process

When you use SAS/ACCESS Interface to PostgreSQL to query a Yellowbrick database, the SAS OBS= option is not generating a limit clause on the query that is passed to the database. Click the

In SAS Customer Intelligence Studio,  when you add  Reply- node variable values in the Define Value dialog box, you might notice that two identically labeled data-grid variables are

In SAS Infrastructure for Risk Management, the message "ERROR: Could not move and link one or more files to..." occurs while running a job-flow instance if an orphaned folder exists in the persistent area.

In SAS Customer Intelligence, a decision campaign can become corrupted and impossible to open. When you try to open the campaign, an error message is displayed that asks you to check the SAS Customer Intel

When you log on to the SAS Risk Governance Framework and choose a solution, the web application might fail to load the solution content. When the problem occurs, you continue to see "Loading..." on the screen, an

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affects circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDL were isolated from patients with severe obesity (n=53) before, 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDL were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222 and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222 and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222 and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase (PON1) activity were increased and intracellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with increase in cholesterol efflux capacity (r=0.326, P=0.027 and r=0.349, P=0.017 respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction, and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.

The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRC), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine (PC), amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (VLC-PUFAs,n-3, ≥ 28 carbons) are at the sn-1 of this PC molecular species and interact with rhodopsin. PRC shed their tips (DHA-rich membrane disks) daily, which in turn are phagocytized by the retinal pigment epithelium (RPE), where DHA is recycled back to PRC inner segments to be used for the biogenesis of new photoreceptor membranes. Here, we review the structures and stereochemistry of novel elovanoid (ELV)-N32 and ELV-N34 to be ELV-N32: (14Z,17Z,20R,21E,23E,25Z,27S,29Z)-20,27-dihydroxydo-triaconta-14,17,21,23,25,29-hexaenoic acid; ELV-N34: (16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxytetra-triaconta-16,19,23,25,27,31-hexaenoic acid. ELVs are low-abundance, high-potency, protective mediators. Their bioactivity includes enhancing of anti-apoptotic and pro-survival protein expression with concomitant downregulation of pro-apoptotic proteins when RPE is confronted with uncompensated oxidative stress (UOS). ELVs also target PRC/RPE senescence gene programming, the senescence secretory phenotype in the interphotoreceptor matrix (IPM), as well as inflammaging (chronic, sterile, low-grade inflammation). An important lesson on neuroprotection is highlighted by the ELV mediators that target the terminally differentiated PRC and RPE, sustaining a beautifully synchronized renewal process. The role of ELVs in PRC and RPE viability and function uncovers insights on disease mechanisms and the development of therapeutics for age-related macular degeneration (AMD), Alzheimer’s disease (AD), and other pathologies.

Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL’s atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic responses similarly to copper-oxidized LDL (oxLDL). Unlike native LDL endocytosed via the LDL receptor, L5 and oxLDL are internalized by cells via the lectin-like oxidized LDL receptor-1 (LOX-1). Using enzyme-linked immunosorbent assays (ELISAs), we showed that adiponectin preferentially bound oxLDL but not native LDL. In Chinese hamster ovary (CHO) cells transfected with LOX-1 or LDL receptor, adiponectin selectively inhibited the uptake of oxLDL but not of native LDL, respectively. Furthermore, adiponectin suppressed the internalization of oxLDL in human coronary artery endothelial cells (HCAECs) and THP-1–derived macrophages. Western blot analysis of human plasma showed that adiponectin was abundant in L5 but not in L1, the least electronegative subfraction of LDL. Sandwich ELISAs with anti-adiponectin and anti–apolipoprotein B antibodies confirmed the binding of adiponectin to L5 and oxLDL. In LOX-1–expressing CHO cells, adiponectin inhibited cellular responses to oxLDL and L5, including nuclear factor-B activation and ERK phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and ERK phosphorylation. Conversely, oxLDL suppressed the adiponectin-induced activation of adenosine monophosphate–activated protein kinase in COS-7 cells expressing adiponectin receptor AdipoR1. Our findings suggest that adiponectin binds and inactivates atherogenic LDL, providing novel insight into the anti-atherogenic mechanisms of adiponectin.

Among the virulence factors in Neisseria infections, a major inducer of inflammatory cytokines is the lipooligosaccharide (LOS). The activation of NF-B via extracellular binding of LOS or lipopolysaccharide (LPS) to the toll-like receptor 4 and its coreceptor, MD-2, results in production of pro-inflammatory cytokines that initiate adaptive immune responses. LOS can also be absorbed by cells and activate intracellular inflammasomes, causing the release of inflammatory cytokines and pyroptosis. Studies of LOS and LPS have shown that their inflammatory potential is highly dependent on lipid A phosphorylation and acylation, but little is known on the location and pattern of these posttranslational modifications. Herein, we report on the localization of phosphoryl groups on phosphorylated meningococcal lipid A, which has two to three phosphate and zero to two phosphoethanolamine substituents. Intact LOS with symmetrical hexa-acylated and asymmetrical penta-acylated lipid A moieties was subjected to high-resolution ion mobility spectrometry MALDI-TOF MS. LOS molecular ions readily underwent in-source decay to give fragments of the oligosaccharide and lipid A formed by cleavage of the ketosidic linkage, which enabled performing MS/MS (pseudo-MS³). The resulting spectra revealed several patterns of phosphoryl substitution on lipid A, with certain species predominating. The extent of phosphoryl substitution, particularly phosphoethanolaminylation, on the 4'-hydroxyl was greater than that on the 1-hydroxyl. The heretofore unrecognized phosphorylation patterns of lipid A of meningococcal LOS that we detected are likely determinants of both pathogenicity and the ability of the bacteria to evade the innate immune system.

Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of ¹⁸F-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with β-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP1-mediated thermogenesis. In metabolic studies using radiolabeled tracers, we found that glucose uptake is increased in mildly cold-activated BAT of Ucp1^–/– versus WT mice kept at subthermoneutral temperature. Conversely, lower glucose disposal was detected after full thermogenic activation achieved by sustained cold exposure or CL treatment. In contrast, uptake of lipoprotein-derived fatty acids into chronically activated thermogenic adipose tissues was substantially increased in UCP1-deficient mice. This effect is linked to higher sympathetic tone in adipose tissues of Ucp1^–/– mice, as indicated by elevated levels of thermogenic genes in BAT and WAT. Thus, glucose and lipoprotein handling does not necessarily reflect UCP1-dependent thermogenic activity, but especially lipid uptake rather mirrors sympathetic activation of adipose tissues.

Familial LCAT deficiency (FLD) is a rare genetic disorder of HDL metabolism, caused by loss-of-function mutations in the LCAT gene and characterized by a variety of symptoms including corneal opacities and kidney failure. Renal disease represents the leading cause of morbidity and mortality in FLD cases. However, the prognosis is not known and the rate of deterioration of kidney function is variable and unpredictable from patient to patient. In this article, we present data from a follow-up of the large Italian cohort of FLD patients, who have been followed for an average of 12 years. We show that renal failure occurs at the median age of 46 years, with a median time to a second recurrence of 10 years. Additionally, we identify high plasma unesterified cholesterol level as a predicting factor for rapid deterioration of kidney function. In conclusion, this study highlights the severe consequences of FLD, underlines the need of correct early diagnosis and referral of patients to specialized centers, and highlights the urgency for effective treatments to prevent or slow renal disease in patients with LCAT deficiency.

HMG-CoA reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing nonsterol isoprenoids, such as dolichol, ubiquinone, and farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on nonsterol isoprenoids in the liver. We have generated new genetic models to acutely delete genes in the mevalonate pathway in the liver using AAV-mediated delivery of Cre-recombinase (AAV-Cre) or CRISPR/Cas9 (AAV-CRISPR). The genetic deletion of Hmgcr by AAV-Cre resulted in extensive hepatocyte apoptosis and compensatory liver regeneration. At the biochemical level, we observed decreased levels of sterols and depletion of the nonsterol isoprenoids, dolichol and ubiquinone. At the cellular level, Hmgcr-null hepatocytes showed ER stress and impaired N-glycosylation. We further hypothesized that the depletion of dolichol, essential for N-glycosylation, could be responsible for ER stress. Using AAV-CRISPR, we somatically disrupted dehydrodolichyl diphosphate synthase subunit (Dhdds), encoding a branch point enzyme required for dolichol biosynthesis. Dhdds-null livers showed ER stress and impaired N-glycosylation, along with apoptosis and regeneration. Finally, the combined deletion of Hmgcr and Dhdds synergistically exacerbated hepatocyte ER stress. Our data show a critical role for mevalonate-derived dolichol in the liver and suggest that dolichol depletion is at least partially responsible for ER stress and apoptosis upon potent Hmgcr inhibition.

Small admixtures in water, e.g. of metal ions, often act as cell growth regulators. Here we report that enrichment of deuterium content in water, normally found at 8 mm concentration, two-three folds increases cell proliferation and lowers the oxidative stress level as well. Acting as an anti-oxidant, deuterium-enriched water prevents the toxic effect of such oxidative agents as hydrogen peroxide and auranofin. This action is opposite to that of deuterium depletion that is known to suppress cell growth and induce oxidative stress in mitochondria. We thus hypothesize that deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. Because growth acceleration is reduced approximately by half by addition to water a minute amount (0.15%) of ¹⁸O isotope, at least part of the deuterium effect on cell growth can be explained by the isotopic resonance phenomenon. A slight (2-fold) enrichment of deuterium in water accelerates human cell growth. Quantitative MS based proteomics determined changes in protein abundances and redox states and found that deuterium-enriched water acts mainly through decreasing ROS production in mitochondria. This action is opposite to that of deuterium depletion that suppresses cell growth by inducing oxidative stress. Thus deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. The role of isotopic resonance in this effect was validated by further experiments on bacteria.

High-speed analysis of large (prote)omics sample sets at the rate of thousands or millions of samples per day on a single platform has been a challenge since the beginning of proteomics. For many years, ESI-based MS methods have dominated proteomics because of their high sensitivity and great depth in analyzing complex proteomes. However, despite improvements in speed, ESI-based MS methods are fundamentally limited by their sample introduction, which excludes off-line sample preparation/fractionation because of the time required to switch between individual samples/sample fractions, and therefore being dependent on the speed of on-line sample preparation methods such as liquid chromatography. Laser-based ionization methods have the advantage of moving from one sample to the next without these limitations, being mainly restricted by the speed of modern sample stages, i.e. 10 ms or less between samples. This speed matches the data acquisition speed of modern high-performing mass spectrometers whereas the pulse repetition rate of the lasers (>1 kHz) provides a sufficient number of desorption/ionization events for successful ion signal detection from each sample at the above speed of the sample stages. Other advantages of laser-based ionization methods include the generally higher tolerance to sample additives and contamination compared with ESI MS, and the contact-less and pulsed nature of the laser used for desorption, reducing the risk of cross-contamination. Furthermore, new developments in MALDI have expanded its analytical capabilities, now being able to fully exploit high-performing hybrid mass analyzers and their strengths in sensitivity and MS/MS analysis by generating an ESI-like stable yield of multiply charged analyte ions. Thus, these new developments and the intrinsically high speed of laser-based methods now provide a good basis for tackling extreme sample analysis speed in the omics.

The histopathological subtype of lung adenocarcinoma (LUAD) is closely associated with prognosis. Micropapillary or solid predominant LUAD tends to relapse after surgery at an early stage, whereas lepidic pattern shows a favorable outcome. However, the molecular mechanism underlying this phenomenon remains unknown. Here, we recruited 31 lepidic predominant LUADs (LR: low-risk subtype group) and 28 micropapillary or solid predominant LUADs (HR: high-risk subtype group). Tissues of these cases were obtained and label-free quantitative proteomic and bioinformatic analyses were performed. Additionally, prognostic impact of targeted proteins was validated using The Cancer Genome Atlas databases (n=492) and tissue microarrays composed of early-stage LUADs (n=228). A total of 192 differentially expressed proteins were identified between tumor tissues of LR and HR and three clusters were identified via hierarchical clustering excluding eight proteins. Cluster 1 (65 proteins) showed a sequential decrease in expression from normal tissues to tumor tissues of LR and then to HR and was predominantly enriched in pathways such as tyrosine metabolism and ECM-receptor interaction, and increased matched mRNA expression of 18 proteins from this cluster predicted favorable prognosis. Cluster 2 (70 proteins) demonstrated a sequential increase in expression from normal tissues to tumor tissues of LR and then to HR and was mainly enriched in pathways such as extracellular organization, DNA replication and cell cycle, and high matched mRNA expression of 25 proteins indicated poor prognosis. Cluster 3 (49 proteins) showed high expression only in LR, with high matched mRNA expression of 20 proteins in this cluster indicating favorable prognosis. Furthermore, high expression of ERO1A and FEN1 at protein level predicted poor prognosis in early-stage LUAD, supporting the mRNA results. In conclusion, we discovered key differentially expressed proteins and pathways between low-risk and high-risk subtypes of early-stage LUAD. Some of these proteins could serve as potential biomarkers in prognostic evaluation.

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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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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War Time: Temporality and the Decline of Western Military Power Book dora.popova 22 February 2021

In War Time the Western way of war, its pace and timing, are discussed and analysed by experts who question the West’s ability to maintain its military superiority given the political and strategic failures of interventions in Iraq and Afghanistan.

In War Time, war studies experts examine the trajectory of Western military power. They discuss conflicting perceptions of time anchored within Western political and military institutions, and the Western attachment to fast-paced warfare at the expense of longer-term political solutions.

Divided into three sections, the book covers ‘civic militarism’ and the trajectory of Western power, Western perceptions of time and the international normative order, and military operations and temporality. War Time explains why the West has been overwhelmingly powerful on the battlefield and yet strategically and politically weak as exemplified by the return of the Taliban and the hasty evacuation of troops and personnel from Afghanistan.

The book identifies policies that decision-makers must adopt to stave off the decline of Western military dominance.

This book is part of the Insights series.

Watch the event

A special event was held in March 2021 to mark the launch of the book. View the event here.

Praise for War Time

About the editors

Sten Rynning is professor of war studies at the University of Southern Denmark.

Olivier Schmitt is professor with special responsibilities at the Center for War Studies, University of Southern Denmark, and currently director of research and studies at the French Institute for Higher National Defence Studies.

Amelie Theussen is assistant professor at the Center for War Studies, University of 
Southern Denmark.

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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.

Phillies president Andy MacPhail opened a 28-minute press conference on Friday afternoon at Spectrum Field with facts and figures about investments the organization made the past few seasons as the team wallowed at the bottom of the National League. Then MacPhail talked a lot about Bryce Harper and Manny Machado as well as manager Gabe Kapler.

Jerad Eickhoff took his latest first step on Sunday morning at Spectrum Field. He threw a bullpen session, his first since sustaining a setback last month following carpal tunnel surgery in October.

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 2019 MLB season feels so close now. Spring Training has begun. Players are taking the field. So it's time to rank the best of the best.

The Angels will be without left fielder Justin Upton early in Spring Training, as he's dealing with right knee patellar tendinitis but is expected to be ready for Opening Day, manager Brad Ausmus said on Monday.