M el-Saadani
Apr 1, 1989; 30:627-630
Articles

DL Brasaemle
Nov 1, 1997; 38:2249-2263
Articles

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles

JE Hixson
Mar 1, 1990; 31:545-548
Articles

Announcing Design Resonance in an Age of Crisis News Release sysadmin 1 June 2020

London Design Biennale and Chatham House announce Design Resonance in an Age of Crisis, which calls for action by designers around the world to create radical design solutions to critical problems across four key areas: Health, Environment, Society and Work.

Design In An Age of Crisis - Open Call News Release sysadmin 21 July 2020

Chatham House and London Design Biennale announce full details of 'Design In An Age of Crisis,' a global Open Call for radical design thinking.

Design in an Age of Crisis Launches News Release jon.wallace 13 January 2021

Design open call receives 500 submissions from over 50 countries across six continents.

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Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage? 23 January 2020 — 8:30AM TO 10:00AM Anonymous (not verified) 6 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

In the context of the feasibility of reducing greenhouse gas emissions to net zero, policymakers are beginning to pay more attention to options for removing carbon dioxide from the atmosphere. A wide range of potential carbon dioxide removal (CDR) options are currently being discussed and modelled though the most prominent among them are bioenergy with carbon capture and storage (BECCS) and afforestation and reforestation.

There are many reasons to question the reliance on BECCS assumed in the models including the carbon balances achievable, its substantial needs for land, water and other inputs and technically and economically viable carbon capture and storage technologies.

This meeting will examine the potentials and challenges of BECCS in the context of other CDR and emissions abatement options. It will discuss the requisite policy and regulatory frameworks to minimize sustainability and socio-political risks of CDR approaches while also avoiding overshooting climate goals.

Attendance at this event is by invitation only.

Moving Food up the Political Agenda 14 December 2020 — 3:00PM TO 4:30PM Anonymous (not verified) 8 December 2020 Online

How can food system transformation be woven into high level biodiversity, nutrition and climate forums in 2021?

Adverse impacts on food security are expected to worsen as global temperatures continue to rise. As well as feeling the impacts of climate change, food systems drive it in a number of ways. Not only do food systems contribute more to greenhouse gas emissions than any other parts of our lives, they are also the leading driver of biodiversity loss, the largest cause of deforestation and occupy the most land globally.

On our current trajectory, 1.5°C of warming could become a reality in the next 5-10 years. Transforming food systems to meet climate, biodiversity and food security goals is crucial. If left to continue, food alone could take us over 1.5°C this century – even with maximum efforts in the energy sector.

Unprecedented levels of action to transform food systems is required over the next decade. The coming year is described as a ‘super year’ given the numerous high-level global events taking place that cover climate, biodiversity and food security. The year ahead has also been identified as the final opportunity to bring global commitments in line with the goals of the Paris Agreement.

What can be achieved in the super year? How can food system transformation be woven into high level biodiversity, nutrition and climate forums during the super year? How can momentum from the super year be built upon, to ensure meaningful action is taken over the next decade?

Sand: Monitoring and management for a sustainable future 2 March 2021 — 1:00PM TO 2:00PM Anonymous (not verified) 18 February 2021 Online

In partnership with the Global Sand Observatory Initiative, this event outlines the sand challenge, what actions are currently underway to address it, and what else needs to be done.

Please complete your registration on Zoom:

After water, sand is the raw material that the world consumes in the greatest quantity. It is no exaggeration to say that fine sand and coarser materials – the medium-to-coarse-grained pebbles, gravel and rock fragments used in construction – are the building blocks of the modern world.

When bound with cement, sand becomes concrete; when mixed with bitumen, it becomes asphalt; and when heated, it becomes glass. Without sand, we would have no highways, high-rises or high-speed trains. Yet sand – which is used here as shorthand for sand, gravel and crushed rock together – is a resource that is both abundant and finite.

In global terms, it is abundant, especially when compared with many other raw materials, albeit often not available close to where it is needed. It is finite in that the rate at which we are using it far exceeds the natural rate at which it is being replenished by the weathering of rocks by wind and water.

Industrialization, population growth and urbanization have fuelled explosive growth in the demand for sand. Precise data on sand extraction are hard to come by and the lack of data compounds the challenge of managing the resource sustainably.

However, the UN estimates that overall extraction could be in the region of 40 billion tonnes per year, driven primarily by construction sector demand. That equates to 18 kilograms of sand each day for every person on the planet and signals how strategically important these resources are for future sustainable development. Post-COVID-19 recovery investment in infrastructure, digital technologies, tourism and other economic activities are dependent on sand resources.

Current efforts to improve the management of sand resources at local, national and global levels are uneven. This is partly due to unique geological features and geography, but also differences in local manifestations of the ‘sand challenge’, national and regional demand for sand resources, as well as capacities to enforce or implement best practice assessment procedures, extractive practices, environmental management and restoration requirements.

We must put stronger conditions in place for a rapid, just and scaled transition to sustainable sand management. But where to focus our efforts for the greatest positive impact?

Loss and damage: Where are we now and what happens next? 25 January 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 17 January 2022 Online

This event discusses the progress of the loss and damage agenda within climate negotiations. 

Loss and damage refers to harms and destruction caused by climate change impacts that cannot be avoided through mitigation or adaptation.

While it has gained increasing recognition in international climate change negotiations, turning the concept of loss and damage into tangible action for climate-vulnerable countries has been contentious.

Loss and damage is interwoven with issues of fairness and equity. The issue is highly disputed due to its connection with the historical responsibility of developed countries in causing climate change, as well as associated calls for compensation from developing countries.

At COP26, Scotland became the first government to pledge funds for loss and damage for countries in the Global South. However, most climate-vulnerable countries left disappointed by the failure of the Glasgow Climate Pact to secure the establishment of a dedicated loss and damage financing facility.

Developing countries have made it clear that they will continue to push for a new financing facility in the Glasgow Dialogue, a set of international discussions on loss and damage kicking off in June.

The Environment and Society Discussion Series is hosting two events on loss and damage ahead of that date. This first event outlines the key debates and discuss what progress has been made on advancing the loss and damage agenda within climate negotiations to date.

The second event focuses on solutions and possible ways forward, looking ahead to the COP27 negotiations in Egypt later in 2022, where loss and damage is expected to be a high-profile agenda item.

A deep dive into loss and damage solutions 8 February 2022 — 1:00PM TO 2:15PM Anonymous (not verified) 31 January 2022 Online

This second event of our loss and damage series cuts through polarized debate by bringing together international experts to discuss innovative legal and financial approaches.

This event will focus on a deep dive into constructive solutions and progress made to address loss and damage.

Following the first event of this two-part series, ‘Loss and Damage – where are we now and what happens next’, this event focuses on a deep dive into constructive solutions and progress made to address loss and damage.

Loss and damage refers to harms and destruction caused by climate change impacts that cannot be avoided through mitigation or adaptation. While it has gained increasing recognition in international climate change negotiations, turning the concept of loss and damage into tangible action for climate-vulnerable countries has been contentious.

Loss and damage is interwoven with issues of fairness and equity. The issue is highly disputed due to its connection with the historical responsibility of developed countries in causing climate change, as well as associated calls for compensation from developing countries.

At COP26, Scotland became the first government to pledge funds for loss and damage for countries in the Global South. However, most climate-vulnerable countries left disappointed by the failure of the Glasgow Climate Pact to secure the establishment of a dedicated loss and damage financing facility.

Developing countries have made it clear that they will continue to push for a new financing facility in the Glasgow Dialogue, a set of international discussions on loss and damage kicking off in June. The Environment and Society Discussion Series is hosting two events on loss and damage ahead of that date.

This second event convenes a deep dive into the progress and potential on loss and damage solutions, while also examining the hurdles that are still to overcome to make loss and damage support a reality.

Webinar: Hong Kong: Dissent in the Age of Coronavirus 17 April 2020 — 12:00PM TO 1:00PM Anonymous (not verified) 8 April 2020

Street protests demanding greater autonomy and democratization in Hong Kong upended the city for seven months last year. However, with the outbreak of the coronavirus in China in late January, the protests quickly died out. What does this mean for the city’s protest movement?

The speaker will argue that, despite the lack of high-profile street rallies, protest in the city is continuing. It is building on and evolving from last year’s protest movement albeit in different forms. At the same time, the Hong Kong authorities, emboldened by a hard line from Beijing, have begun cracking down on activists and protesters in the city as they seek to put a lid on dissent ahead of important Legislative Council elections scheduled for this September.

In this webinar, the speaker will look at the current state of dissent in Hong Kong and prospects for Hong Kong’s future.

This event will be held on the record.

The 2020 Inner Mongolia Language Protests: Wider Meanings for China and the Region 24 November 2020 — 3:00PM TO 4:00PM Anonymous (not verified) 12 November 2020 Online

Speakers discuss the historical roots of the language issue, as well as the wider significance of the protests in China.

Please note this is an online event. Please register on Zoom using the link below to secure your registration.

In September thousands of people protested in Inner Mongolia in opposition to a government move to replace Mongolian language with Standard Mandarin in three school subjects – history, politics and Chinese language.

Announced less than a week before the start of the new school year, the policy also requires schools to use new national textbooks in Chinese, instead of regional textbooks. The mass protests and classroom walk-outs reflect ethnic Mongolian’s anxiety that their native language may be eliminated. What has the government’s response to the protests been?

Ricardo Bermudez-Otero and Tobias Galla discuss the mathematics describing the evolution of human languages. The sounds and structures of the world's approximately 7,000 languages never stop changing. Just compare the English in Romeo and Juliet or the Spanish in Don Quixote to the modern forms. But historical records give an incomplete view of language evolution. Increasingly, linguists draw upon mathematical models to figure out which features of a language change often and which ones change more rarely over the course of thousands of years. A new model inspired by physics assigns a "temperature" to many sounds and grammatical structures. Features with higher temperatures are less stable, so they change more often as time goes on. The linguistic thermometer will help researchers reconstruct how our languages came to be, and how they might change in future generations.

Malena Espanol explains how she and others use linear algebra to correct blurry images. Imagine snapping a quick picture of a flying bird. The image is likely to come out blurry. But thanks to mathematics, you might be able to use software to improve the photo. Scientists often deal with blurry pictures, too. Linear algebra and clever numerical methods allow researchers to fix imperfect photos in medical imaging, astronomy, and more. In a computer, the pixels that make up an image can be represented as a column of numbers called a vector. Blurring happens when the light meant for each pixel spills into the adjacent pixels, changing the numbers in a way that can be mathematically represented as an enormous matrix. But knowing that matrix is not enough if you want to reconstruct the original (non-blurry) image.

Reggae crooner D'Yani has exclaimed surprise at the momentum building up for his upcoming United Kingdom (UK) tour. "I'm still in shock that the early bird tickets were sold out so quickly, " he told THE WEEKEND STAR. D'Yani, born Andre...

Staff at the Secrets and Breathless resorts in Montego Bay, St James, walked off the job this morning complaining of overwork, low wages, lack of overtime pay and disrespect.

α-Linked galactose is a common carbohydrate motif in nature that is processed by a variety of glycoside hydrolases from different families. Terminal Galα1–3Gal motifs are found as a defining feature of different blood group and tissue antigens, as well as the building block of the marine algal galactan λ-carrageenan. The blood group B antigen and linear α-Gal epitope can be processed by glycoside hydrolases in family GH110, whereas the presence of genes encoding GH110 enzymes in polysaccharide utilization loci from marine bacteria suggests a role in processing λ-carrageenan. However, the structure–function relationships underpinning the α-1,3-galactosidase activity within family GH110 remain unknown. Here we focus on a GH110 enzyme (PdGH110B) from the carrageenolytic marine bacterium Pseudoalteromonas distincta U2A. We showed that the enzyme was active on Galα1–3Gal but not the blood group B antigen. X-ray crystal structures in complex with galactose and unhydrolyzed Galα1–3Gal revealed the parallel β-helix fold of the enzyme and the structural basis of its inverting catalytic mechanism. Moreover, an examination of the active site reveals likely adaptations that allow accommodation of fucose in blood group B active GH110 enzymes or, in the case of PdGH110, accommodation of the sulfate groups found on λ-carrageenan. Overall, this work provides insight into the first member of a predominantly marine clade of GH110 enzymes while also illuminating the structural basis of α-1,3-galactoside processing by the family as a whole.

The bacterial enhancer-binding protein (bEBP) FlrC, controls motility and colonization of Vibrio cholerae by regulating the transcription of class-III flagellar genes in σ54-dependent manner. However, the mechanism by which FlrC regulates transcription is not fully elucidated. Although, most bEBPs require nucleotides to stimulate the oligomerization necessary for function, our previous study showed that the central domain of FlrC (FlrCC) forms heptamer in a nucleotide-independent manner. Furthermore, heptameric FlrCC binds ATP in “cis-mediated” style without any contribution from sensor I motif 285REDXXYR291 of the trans protomer. This atypical ATP binding raises the question of whether heptamerization of FlrC is solely required for transcription regulation, or if it is also critical for ATPase activity. ATPase assays and size exclusion chromatography of the trans-variants FlrCC-Y290A and FlrCC-R291A showed destabilization of heptameric assembly with concomitant abrogation of ATPase activity. Crystal structures showed that in the cis-variant FlrCC-R349A drastic shift of Walker A encroached ATP-binding site, whereas the site remained occupied by ADP in FlrCC-Y290A. We postulated that FlrCC heptamerizes through concentration-dependent cooperativity for maximal ATPase activity and upon heptamerization, packing of trans-acting Tyr290 against cis-acting Arg349 compels Arg349 to maintain proper conformation of Walker A. Finally, a Trp quenching study revealed binding of cyclic-di-GMP with FlrCC. Excess cyclic-di-GMP repressed ATPase activity of FlrCC through destabilization of heptameric assembly, especially at low concentration of protein. Systematic phylogenetic analysis allowed us to propose similar regulatory mechanisms for FlrCs of several Vibrio species and a set of monotrichous Gram-negative bacteria.

21 August 2020

27 August 2020

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

A new vision for African agency in sustainable development Expert comment LJefferson 18 October 2022

Change is necessary not only in global economic structures and attitudes – but in African governance too.

The conventional notion that Africa is mostly a consumer of norms and practices designed by the Global North has been repeatedly challenged and is increasingly being debunked. Increased African agency in international affairs is today a well-established and documented reality. But Africa’s influence still does not match the scale of the challenges that it faces on its pathway to sustainable development. 

Pushing for African agency in sustainable development also warrants a critical assessment of how ‘sustainable development’ should be defined, and how it can be achieved in terms of actual poverty reduction and real improvement in the lives of local poor Africans. Sustainable development has been a political catchphrase for over 30 years – but a genuine transition towards sustainability has yet to begin.

African agency today

Historically, there have been structural limitations on the agency of African stakeholders to shape development pathways. Chief among them, donor-recipient power dynamics have persistently promoted dependency and sustained institutional corruption. Many African countries are also challenged by economic incentives and infrastructure that have favoured the market demands and supply chains of former colonial powers, which largely remain reliant on natural resource extraction, and are marked by limited investment in value-addition activities and technology development.

Today, however, African agency is being exerted in a more assertive fashion. The African Union (AU), individual African states, civil society, the private sector and eminent and ordinary persons are all displaying Africa’s agency in steering global sustainable development priorities, namely by proposing their own development agenda, The African Union Agenda 2063, adopted in 2013. This was followed by the UN Sustainable Development Goals (Agenda 2030), which in many ways mirror Agenda 2063 – a clear demonstration of the influence of Africa in the global arena. 

Agenda 2063 is a strategic roadmap for Africa ‘to build an integrated, prosperous and peaceful Africa, driven and managed by its own citizens and development goals representing a dynamic force in the international arena’. Prepared following a broad-based participatory consultation, it advocates for inclusion and empowerment and provides an excellent vision for African countries and African people. The SDGs address several of the key shortcomings of their predecessor – the MDGs – and incorporate a broader and more transformative agenda that more adequately reflects the complex challenges of the 21st century and the need for structural reforms in the global economy and governance norms.

In international forums on sustainable development, African countries are increasingly using their collective voice to change the discourse on how development can and should be done. For instance, by championing innovative solutions for carbon markets, African policy leaders are enabling access to climate finance for development while preserving Africa’s natural wealth.

In the post-COVID era, championing investments in and leadership of Africa’s global health architecture demonstrates a desire that in the next pandemic, Africa CDC, AMA and continental manufacturers will play leading roles in determining Africa’s public health strategy and implementation.

In trade, building on the groundwork led by the regional economic commissions, the AfCFTA will catalyse and scale regional integration, trade and cooperation, leading to promising new modes of supply chain and self-sufficiency.

Encouraging signs, but persistent shortcomings

Encouraging signs that African agency is gaining momentum cannot disguise the fact that Africa has yet to move from rhetoric to implementation in the realm of sustainable development. Continental visions often fail to go beyond declarations of intent, and have only limited influence on governance systems or national structural transformation, and African states remain vulnerable to economic shocks emanating from the global system.

Change will require governance systems that are coordinated, transparent, efficient, and inclusive, as well as tools, processes, and means (material, technical, and human) for successful implementation. There is an urgent need for a new governance paradigm in Africa and internationally, dealing with long-term social change.

Notably, African agency should not be only seen as emanating from government, but also as being exerted by independent civil society organizations and committed ordinary individuals. Effective agency needs to be multi-faceted and multi-actor, and depends on the inclusiveness of African governments and their willingness to work with civil society in their strategic engagements with external partners.

Both Agenda 2063 and the SDGs hold the potential for transformation, but implementation will depend on continued advocacy to hold authorities to account and change the dominant discourse, logic and rules of engagement at global, regional, national, and local levels. There is a need for a dynamic new model of African ‘development’.

Time for a new vision

Africa’s economic landscape is changing rapidly, with new regional and local value chains, and integrated regional economic corridors to link countries, minimize the burden of high-cost production and logistics, and boost real incomes and international competitiveness. But Africa continues to face structural challenges, including the need for large investment projects – at a time when Africa remains a net exporter of capital.

Donors and development partners must reflect upon their prior modes of engagement and commit to genuine and equitable relationships with African states. Such partnerships must reflect mutual respect of ideas and accountability, and commit to making space in international forums and multi-lateral arrangements for African people and countries to realize their own visions for progress.

But African leaders and actors must also recognize that with the advent of resources and agency comes responsibility for results and outcomes, notably the need to improve governance. Gaps in accountability, widespread corruption, and lack of successful implementation and sustainability of projects must be addressed.

Africa’s maritime agency cannot be overlooked Expert comment LJefferson 3 November 2022

Increasing maritime awareness has already delivered impact, but consistency and continental leadership are needed to realize the sector’s full potential.

Africa’s 48,000 kilometres of coastline, shared among 38 coastal states, are resource rich and hold some of the world’s most strategic sea lanes, including the approaches to the Suez Canal, which carries 12 per cent of worldwide trade, and the Gulf of Guinea, a critical route for global energy. But despite the vast potential this represents, piracy and maritime insecurity have dominated the narrative of Africa’s coasts, and further propagated the image of African states as beholden to external intervention.

Yet African agency is established and evolving in the sector, with African littoral states enhancing their capacity to face collective security threats and exercising increasing autonomy in responding to the recent rush of external actors looking for port facilities and military bases. Enhanced continental coordination, consistency and leadership can help Africa’s maritime endowment become a resource that can bring sustainable benefit across the continent.  

Agency beyond piracy: the Gulf of Aden and Western Indian Ocean

Piracy became the dominant frame of reference for the East African maritime space as a result of the crisis off the coast of Somalia, which peaked between 2008 and 2012. In 2008, the UN Security Council (UNSC) took the unprecedented step of authorizing international naval operations in Somali territorial waters, contributing to a gradual reduction in attacks. There have been no successful hijackings reported since 2017.

But progress has not just been down to international assistance. Somalia is prioritizing increased domestic enforcement capacity – as demonstrated in the establishment of  a new specialized maritime unit and the wider region enhanced collaboration and information sharing through the Djibouti Code of Conduct of 2009, amended in 2017.

South Africa’s recent admission as a new signatory demonstrates its continued relevance. In March 2022, the UNSC authorization lapsed, following pressure from the Somali government. Although it is not yet clear whether Somali efforts will be sufficient to repress piracy in the long term, this reverse was a clear statement of Somalia’s agency at a level unthinkable during the outset of the crisis.

As the immediate threat of piracy has quietened, broader geopolitical dynamics have come to the fore, notably in a surge by external actors to establish strategic ports and military bases. Here too, African states have demonstrated enhanced agency, for better or worse. Consider Djibouti’s unilateral seizure of a container terminal from an Emirati firm, Sudan’s review of Russian and Turkish deals for maritime facilities, Tanzania’s rejection of a Chinese-led port investment, or the Seychelles withdrawing agreement for an Indian naval base.

Such examples point to a growing awareness of the value of maritime resources within African states, alongside a willingness and ability to push back against external imposition – and indeed to innovate in finding solutions beyond infrastructure and ‘hard’ security. In 2018, the Seychelles launched the world’s first sovereign blue bond to fund sustainable marine projects. That other countries are seeking to replicate this model points to the potentially global impact of African leadership on maritime issues.

Regional cooperation or competition in the Gulf of Guinea?

The Gulf of Guinea is likewise resource rich and geographically strategic, and has faced diverse maritime security threats including piracy, smuggling, illegal fishing, oil theft and pollution. Gulf of Guinea states put in place several initiatives to promote security, including the Yaoundé Code of Conduct (YCoC), signed by 25 states in 2013, that led to information-sharing and cooperation on interdiction, investigation and prosecution. But crime in the Gulf of Guinea nonetheless reached an all-time high in 2020, suffering 130 of the 135 maritime kidnappings recorded worldwide, due to the non-binding nature of the YCoC and gaps in capacity and finance.

Though external actors have become increasingly engaged, including the EU, US, France, Denmark, and the G7++ Group of Friends of the Gulf of Guinea (FOGG), states within the region, especially those most affected by piracy and armed robbery, have nonetheless demonstrated leadership. Nigeria, Ghana, and Cote D’Ivoire have all developed maritime security strategies; Nigeria launched its Deep Blue Project to secure Nigerian waters; Ghana has strengthened its navy; and Togo has changed its laws and judicial system to allow the arrest and prosecution of ships and persons. Maritime security incidents have consequently reduced in 2022.

Visual Abstract

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Felicia Grasso
Dec 1, 2020; 19:1986-1996
Research

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

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

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

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

Jenny E. Kanter
Dec 8, 2020; 0:jlr.ILR120001217v1-jlr.ILR120001217
Images in Lipid Research

For data that is being loaded from a SAS Stored Process Server, an insertion process might fail to a MySQL database with a warning, as well as an error message that says "During insert: Incorrect datetime value…"

You encounter this issue when the table metadata matches the data source. In this scenario, no metadata update is required.

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

In SAS Retail Space Management, it should be possible to click on any location object, then Show Properties, and change the location fill color. This can be done on the gray-filled objects. However, w

If the OBSMARGINS= or OM= option is specified in an LSMEANS, LSMESTIMATE, or SLICE statement and a user-defined format is applied to any of the effect variables in the OM-data-set , PROC PLM incorrectly stops proce

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