Forty-six mathematical scientists have been named recipients of AMS-Simons Research Enhancement Grants for Primarily Undergraduate Institution (PUI) Faculty. Each awardee will receive $3,000 per year for three years. 

The grants foster and support research collaboration by full-time mid-career mathematicians at US institutions that do not offer a mathematics doctoral degree.

This year’s grant recipients hail from 42 institutions across 21 US states. The grants will support their research in several different areas, from number theory to applied mathematics.

This is the grant program’s second cohort, said Sarah Bryant, associate vice president of programs. “Over the first two years, we’ve worked with faculty from 75 different institutions, including 19 minority-serving institutions, which shows just how much this program is expanding and making an impact,” Bryant said. She noted that “in the first year, the grants supported 87 trips, helped produce 70 publications and preprints, and gave awardees the resources needed to collaborate and advance their work.”

The grant allows for any activities that will further the awardee’s research program. Expenses include but are not limited to conference participation, institute visits, collaboration travel (awardee or collaborator), computer equipment or software, family-care expenses, and teaching assistants.

Administration of the award by the grantee’s institution is required; annual discretionary funds for a grantee’s department and administrative funds for a grantee's institution will be available at the end of each grant year.

The grants are made possible through funding from the Simons Foundation and the American Mathematical Society (AMS), as well as Eve, Kirsten, Lenore, and Ada of the Menger family.

Applications for the next cohort are anticipated to open on MathPrograms.org on January 9, 2025. Visit the AMS website to view an informational PowerPoint or sign up to receive email updates about the program. Faculty who applied for but did not receive the 2023 or 2024 awards are encouraged to reapply if they are still eligible for the grant. 

The Math Community Educational Outreach (Math CEO) program at the University of California, Irvine (UCI) will receive the 2025 AMS Award for an Exemplary Program or Achievement in a Mathematics Department.

Founded in 2014, UCI’s Math CEO is an after-school math enrichment program aimed at increasing the number of talented students in STEM from diverse backgrounds by fostering mathematical exploration, mentor development, and community engagement.

From the citation

The University of California, Irvine (UCI) Math CEO program is recognized for its exceptional contributions to the mathematics community and society at large. Established in 2014 by professors Alessandra Pantano and Li-Sheng Tseng, Math CEO targets students from Title I middle schools, providing them with a high-quality after-school math enrichment program. This program brings middle-school students to the UCI campus to work in small groups with undergraduate mentors, many of whom are also from historically marginalized groups, to engage in challenging mathematical tasks and encourage exploration. 

From September 2019 to June 2024, Math CEO engaged a total of 1,221 youth, with 48.6% identifying as female. The ethnic background of the participants was predominantly Latinx (93.5%), with smaller representations of Asian, white, and multiethnic students. In the same five-year period, Math CEO engaged 553 undergraduate mentors, 62.2% of whom were female. The mentors’ ethnic backgrounds were diverse, with significant representation of Asian (52%) and Latinx (30%) students. The undergraduate mentors, many of whom pursue careers in education, receive training in culturally responsive teaching practices and equity in education, significantly impacting their professional development. In a post-survey, 52.3% of the undergraduate mentors expressed interest in teaching or working in education and 45.9% were likely to pursue professions working with children or families.

Recognizing the central role of families in supporting Latinx youth, Math CEO involves parents through bilingual workshops that enhance community awareness of college pathways and financial opportunities. 

Math CEO has been the foundation for numerous research projects in mathematics education, supported by NSF grants, leading to publications and program growth. The program’s success is evident in its expansion to high schools and other regions in Southern California, including a new branch at California State University, Dominguez Hills. Math CEO continues to make a substantial impact on underserved youth, demonstrating a model of systemic, reproducible change that can be implemented by others.

Response of Alessandra Pantano, UCI Math CEO

I am deeply honored to receive the AMS Award for an Exemplary Program in a Mathematics Department on behalf of the UCI Math CEO team. This wonderful award recognizes the work of many colleagues, graduate students, and undergraduate students in developing and delivering the UCI Math Community Educational Outreach (Math CEO) program. For over a decade, Math CEO has provided creative and culturally responsive math enrichment opportunities for hundreds of underprivileged middle-school students, many of which have since “graduated” to high school or even college. Leading this exceptional and dedicated team of volunteers has been the highest pride of my professional life. A special thanks to my partners-in-crime, Prof. Li-Sheng Tseng, codirector of Math CEO, and former graduate student Andres Forero Cuervo, academic coordinator for Math CEO: We could have never done this without you. I look forward to pushing this activity forward and continuing to dedicate my energy to help kids in our county find the way to express their potential – in math and in life! A big thanks to the colleagues who nominated us and to the AMS for recognizing our efforts.  

History of the program

The UC Irvine Math Community Educational Outreach (Math CEO) program was founded in 2014 by math faculty Alessandra Pantano and Li-Sheng Tseng in collaboration with Santa Ana Unified math teacher Jasmina Matasovic. The founders shared a belief that low standardized test scores in underserved communities do not reflect students’ interest and potential to succeed in STEM. Math CEO runs free, weekly, after-school math enrichment sessions, welcoming all youth regardless of math achievement. Starting with only 25 students from one middle school, the program has grown and engaged nearly two thousand students in all, from multiple school districts in Southern California.

About the award

The annual AMS Award for an Exemplary Program or Achievement in a Mathematics Department was established in 2004 and first given in 2006. This award recognizes a department which has distinguished itself by undertaking an unusual or particularly effective program of value to the mathematics community, internally or in relation to the rest of society. Departments of mathematical sciences in North America that offer at least a bachelor’s degree in mathematical sciences are eligible. The award amount is currently $5,000. The award will be presented at the 2025 Joint Mathematics Meetings in Seattle.

Learn more about the award and previous recipients.

Contact: AMS Communications.

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The American Mathematical Society is dedicated to advancing research and connecting the diverse global mathematical community through our publications, meetings and conferences, MathSciNet, professional services, advocacy, and awareness programs.
 

Conroy Overdose's 'Life of a Star' birthday bash sizzled recently at Cool Breeze Entertainment Complex in Church Pen, St Catherine. Glamorous ladies and dapper gents gathered for a night of high fashion and revelry. The Sharper Lane venue pulsed...

TODAY KINGSTON...

TODAY KINGSTON...

An 18-year-old woman has been left with a gunshot wound to her left leg following a shooting incident in Central Village in St Catherine Sunday night.

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

Programmed cell death protein 1 (PD-1) is a critical inhibitory receptor that limits excessive T cell responses. Cancer cells have evolved to evade these immunoregulatory mechanisms by upregulating PD-1 ligands and preventing T cell–mediated anti-tumor responses. Consequently, therapeutic blockade of PD-1 enhances T cell–mediated anti-tumor immunity, but many patients do not respond and a significant proportion develop inflammatory toxicities. To improve anti-cancer therapy, it is critical to reveal the mechanisms by which PD-1 regulates T cell responses. We performed global quantitative phosphoproteomic interrogation of PD-1 signaling in T cells. By complementing our analysis with functional validation assays, we show that PD-1 targets tyrosine phosphosites that mediate proximal T cell receptor signaling, cytoskeletal organization, and immune synapse formation. PD-1 ligation also led to differential phosphorylation of serine and threonine sites within proteins regulating T cell activation, gene expression, and protein translation. In silico predictions revealed that kinase/substrate relationships engaged downstream of PD-1 ligation. These insights uncover the phosphoproteomic landscape of PD-1–triggered pathways and reveal novel PD-1 substrates that modulate diverse T cell functions and may serve as future therapeutic targets. These data are a useful resource in the design of future PD-1–targeting therapeutic approaches.

Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity.

Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit.

Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre–mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation.

VAR2CSA is the placental-malaria–specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum-infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ∼310 kDa ectodomain of VAR2CSA is a multidomain protein that requires a minimum 12-mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor-binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative-stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative locations of the domains creates two distinct pores that can each accommodate the 12-mer of chondroitin-4-sulfate, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of infected red blood cells and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria.

The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets.

6 July 2020

9 July 2020

15 July 2020

16 July 2020

14 September 2020

Peptidoglycan (PG) is an essential constituent of the bacterial cell wall. During cell division, the machinery responsible for PG synthesis localizes mid-cell, at the septum, under the control of a multiprotein complex called the divisome. In Escherichia coli, septal PG synthesis and cell constriction rely on the accumulation of FtsN at the division site. Interestingly, a short sequence of FtsN (Leu75–Gln93, known as EFtsN) was shown to be essential and sufficient for its functioning in vivo, but what exactly this sequence is doing remained unknown. Here, we show that EFtsN binds specifically to the major PG synthase PBP1b and is sufficient to stimulate its biosynthetic glycosyltransferase (GTase) activity. We also report the crystal structure of PBP1b in complex with EFtsN, which demonstrates that EFtsN binds at the junction between the GTase and UB2H domains of PBP1b. Interestingly, mutations to two residues (R141A/R397A) within the EFtsN-binding pocket reduced the activation of PBP1b by FtsN but not by the lipoprotein LpoB. This mutant was unable to rescue the ΔponB-ponAts strain, which lacks PBP1b and has a thermosensitive PBP1a, at nonpermissive temperature and induced a mild cell-chaining phenotype and cell lysis. Altogether, the results show that EFtsN interacts with PBP1b and that this interaction plays a role in the activation of its GTase activity by FtsN, which may contribute to the overall septal PG synthesis and regulation during cell division.

Priorities for implementing Ethiopia's national dialogue 11 May 2022 — 1:00PM TO 3:00PM Anonymous (not verified) 3 May 2022 Online

Experts discuss challenges and priorities in shaping an inclusive and effective national dialogue in Ethiopia.

Ethiopia is grappling with numerous contentious national issues – not least persistent conflict in several parts of the country – which underscore the need for large-scale dialogue and reconciliation efforts to address the country’s deep-rooted societal and political divisions. Ethiopia’s newly established National Dialogue Commission – whose 11 commissioners were appointed in February 2022 – has begun a four-phased process of preparations for a dialogue, with its initial stage focused on stakeholder engagement and local knowledge mobilization.

There are major challenges, however, in ensuring inclusivity amidst ongoing conflict and questions on how a country-wide process will sit alongside local dialogue initiatives and wider mediation and peacebuilding efforts. Linking the process to constitutional bodies will also be an important priority to ensure dialogue outcomes are effectively implemented.

At this public event, panellists will exchange perspectives on how to shape an effective national dialogue in Ethiopia, including priorities for building a credible National Dialogue Commission and the roles and responsibilities of other national, regional and local-level actors. They will also discuss key implementation mechanisms and long-term priorities for trust-building and cultivating a conducive environment for inclusive dialogue.

This webinar is part of a series of events and outputs on Ethiopia’s political transition.

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

Enhancing the role of women in peacebuilding and politics in Ethiopia 29 June 2022 — 1:00PM TO 2:30PM Anonymous (not verified) 16 June 2022 Online

Panellists discuss the priorities for promoting the agency of women in politics and peacebuilding in Ethiopia and approaches for combatting gender-based discrimination and violence.

The war in northern Ethiopia and conflicts elsewhere have disproportionately affected women and girls – including through the infliction of physical and sexual violence, the heightened impacts of displacement and disruptions to education, and the co-option of women’s experiences in narratives by aggressors of conflict.

Hard-won political gains in women’s rights have been undermined and deep-rooted gender inequalities exacerbated. Despite this, women remain central actors in politics, as well as in conflict resolution and mediation efforts. However, more needs to be done to promote the security and inclusion of women in finding sustainable solutions for Ethiopia’s long-term recovery and to institutionalize reforms for gender equity and development.

At this public event, panellists will discuss the priorities for improving women’s participation and equality in public decision-making in Ethiopia and how to strengthen the implementation of legislation on women’s rights. They will also discuss what societal shifts and approaches are needed to combat gender-based discrimination and violence and to promote the agency of women in peacebuilding.

This webinar is part of a series of events and outputs on Ethiopia’s political transition.

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.

Review: the rise of Africa’s superwomen The World Today mhiggins.drupal 1 August 2022

From foster care in England to colonialism’s legacy in Zimbabwe, this set of essays on race, feminism and identity is searingly honest, says Masiyaleti Mbewe.

Black and Female
Tsitsi Dangarembga, Faber, £9.99

The 1988 novel Nervous Conditions by the Zimbabwean author Tsitsi Dangarembga is considered one of Africa’s finest literary exports. It won the Commonwealth Writers’ Prize and alongside The Book of Not (2006) and This Mournable Body (2018), shortlisted for the 2020 Booker Prize, forms a trilogy of semi-autobiographical novels that grapple with the gendered colonial oppression of young black girls and women from Southern Rhodesia through to Zimbabwe. 

In Black and Female, Dangarembga continues the interrogation of these intersections in an unflinchingly honest and personal, if occasionally dense, collection of essays. Along the way, she examines the sheer magnitude of colonialism’s effects on African people, and how they ripple through her early childhood in England and her formative years as a writer, filmmaker and feminist activist in post-independence Zimbabwe.

‘Writing While Black and Female’

In 1961 Dangarembga’s parents relocated from Southern Rhodesia to the UK. While they worked and studied in London, they put their two-year-old daughter, her older brother and, later, her younger sister into private foster care in Dover, Kent (as many Africans did – a fact that was new to me). The first essay, ‘Writing While Black and Female’, takes a painful look at the four years she spent with her foster parents, Mummy-Gran and Daddy Henry. 

Blackness, she learned in those years, was a consequence of her non-whiteness. So Dangarembga writes of the momentary elation she felt when a stranger addressed her as a ‘lovely little piccaninny’, giving her ‘a category I could wield against the void of no longer being’. To cope with this sort of racialization and her abandonment, the young Dangarembga turned to disassociation and self-harm. 

As she writes: ‘Blackness is a condition imposed on me, rather than being an experienced identity.’ Instead of ‘black’ people, therefore, Dangarembga prefers the term ‘highly melanated people’. It is a resonant phrase, highlighting the inherently ridiculous nature of racism.

Dangarembga’s ‘Africanness’ shifts into focus upon her return to Rhodesia in 1965. At first, other children refused to play with her and her siblings, calling them ‘varungu’ (white people). As she describes it: ‘The dance of my identities … became frenetic’. 

In ‘Black, Female and the Superwoman Black Feminist’, the second essay, Dangarembga is adamant about the urgent necessity of a black feminist practice that is centred on action to provide real, material change. Along the way, she makes a distinction – a slightly uneasy one to my mind – between the patriarchy that western colonization imposed, based on private ownership, and the patriarchy of pre-colonial African society with its foundations in kinship that devolved power to an extent.

‘Hence women could and did become rulers and warriors, and royal spirit mediums called mhondoro,’ Dangarembga writes approvingly. She is making a nuanced point; but the idea of a more accommodating sort of patriarchy jars a little nonetheless.

While independence may have arrived for Zimbabwe more than 40 years ago, Dangarembga argues strongly that the subjugation of women and feminists at the hands of the ruling Zanu-PF government continues as an extension of colonial rule. Indeed, beyond Zimbabwe, black feminists remain ‘a small, often embattled group’ across Africa, believes Dangarembga. 

As a young black feminist who is part of this ‘small, embattled group’, I should say we have been able to foster large communities digitally and otherwise to work around the hostility we are often faced with. Despite internet shutdowns and restrictions, we resist – an act Dangarembga encourages.  

Resistance, she says, starts with establishing community despite these difficulties. At the nucleus of Dangarembga’s argument is the ‘superwoman’ of the essay’s title, the African woman who doesn’t require external factors to be inspired to action but who continuously draws on what Dangarembga calls ‘internal agency’ that derives from ‘an unrelenting fight for survival and dignity’.

Pointedly, she criticizes global feminism’s greater focus on optics than activism in the practical sense. One only has to observe the performative allyship and ‘Instagram activism’ rampant on the internet today to see her point.
 

The complexities of decolonization

In the final essay, ‘Decolonization as Revolutionary Imagining’, Dangarembga turns her gaze upon the ‘highly stratified’ European societies that outsourced their violent inequality to their empires and ‘the work of decolonization’. However, decolonial discourse is complex, and it is here that the writing occasionally gets bogged down. Fewer recommendations with more elaboration perhaps would have helped.

She herself acknowledges the difficulties of decolonization. Centuries of the Enlightenment and its logic of ‘racism, slavery, genocide and colonization’ are hard to uproot ‘whatever one’s melanin concentration’, she writes.

Nevertheless, Dangarembga concludes with the radical determination to dismantle that is evident throughout this searing yet hopeful collection: ‘The trajectory of current and future generations depends on that uprooting.’

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.

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Visual Abstract

Visual Abstract

Visual Abstract

Sean A Burnap
Dec 7, 2020; 0:RA120.002305v1-mcp.RA120.002305
Research

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

Type I and III interferons induce expression of the “myxovirus resistance proteins” MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms cytoplasmic structures, whereas murine Mx1 forms nuclear bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). We previously reported that the cytoplasmic human GFP-MxA structures were phase-separated membraneless organelles (“biomolecular condensates”). In the present study, we investigated whether nuclear murine Mx1 structures might also represent phase-separated biomolecular condensates. The transient expression of murine GFP-Mx1 in human Huh7 hepatoma, human Mich-2H6 melanoma, and murine NIH 3T3 cells led to the appearance of Mx1 nuclear bodies. These GFP-MuMx1 nuclear bodies were rapidly disassembled by exposing cells to 1,6-hexanediol (5%, w/v), or to hypotonic buffer (40–50 mosm), consistent with properties of membraneless phase-separated condensates. Fluorescence recovery after photobleaching (FRAP) assays revealed that the GFP-MuMx1 nuclear bodies upon photobleaching showed a slow partial recovery (mobile fraction: ∼18%) suggestive of a gel-like consistency. Surprisingly, expression of GFP-MuMx1 in Huh7 cells also led to the appearance of GFP-MuMx1 in 20–30% of transfected cells in a novel cytoplasmic giantin-based intermediate filament meshwork and in cytoplasmic bodies. Remarkably, Huh7 cells with cytoplasmic murine GFP-MuMx1 filaments, but not those with only nuclear bodies, showed antiviral activity toward VSV. Thus, GFP-MuMx1 nuclear bodies comprised phase-separated condensates. Unexpectedly, GFP-MuMx1 in Huh7 cells also associated with cytoplasmic giantin-based intermediate filaments, and such cells showed antiviral activity toward VSV.

Melissa Gómez
Dec 1, 2020; 61:1658-1674
Research Articles

Elisa Vidal
Dec 1, 2020; 61:1733-1746
Research Articles

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

Amyloid fibrils are polymeric structures originating from aggregation of misfolded proteins. In vivo, proteolysis may modulate amyloidogenesis and fibril stability. In light chain (AL) amyloidosis, fragmented light chains (LCs) are abundant components of amyloid deposits; however, site and timing of proteolysis are debated. Identification of the N and C termini of LC fragments is instrumental to understanding involved processes and enzymes. We investigated the N and C terminome of the LC proteoforms in fibrils extracted from the hearts of two AL cardiomyopathy patients, using a proteomic approach based on derivatization of N- and C-terminal residues, followed by mapping of fragmentation sites on the structures of native and fibrillar relevant LCs. We provide the first high-specificity map of proteolytic cleavages in natural AL amyloid. Proteolysis occurs both on the LC variable and constant domains, generating a complex fragmentation pattern. The structural analysis indicates extensive remodeling by multiple proteases, largely taking place on poorly folded regions of the fibril surfaces. This study adds novel important knowledge on amyloid LC processing: although our data do not exclude that proteolysis of native LC dimers may destabilize their structure and favor fibril formation, the data show that LC deposition largely precedes the proteolytic events documentable in mature AL fibrils.

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This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98.

Since the publication of the Age-Related Eye Disease Study (AREDS2) in 2013, the macular pigment carotenoids lutein and zeaxanthin have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration (AMD). More recently, there has been growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of lutein and zeaxanthin supplementation at very young ages have been underappreciated. In this review, we examine the biochemical mechanisms and supportive data for lutein and zeaxanthin supplementation throughout the lifespan, with particular emphasis on prenatal supplementation. We propose that prenatal nutritional recommendations may aim at improving maternal and infant carotenoid status. Prenatal supplementation with lutein and zeaxanthin might enhance infant visual development and performance and may even prevent retinopathy of prematurity, possibilities that should be examined in future clinical studies.