In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles.

Constantin Carle and Marlis Hochbruck
Math. Comp. 93 (), 2611-2641.
Abstract, references and article information

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Review: Decolonization and its discontents The World Today mhiggins.drupal 1 August 2022

Jenna Marshall on a lively if flawed argument to find a way forward in a debate that has descended ‘into acrimony’.

Against Decolonization: Taking African Agency Seriously
Olufemi Taiwo, Hurst, £14.99

Decolonization was once heralded as a moment of potential and possibility for the formerly imperial world to chart a new way forward no longer tied to the apparatus of empire.

It marked a period of transition to nation states – and an expansion of a rights-based international community that would dispense with the morally bankrupt regime of racism, dispossession and subjugation that characterized colonialism.  
 

The descent of the decolonization debate

Half a century later, the debate surrounding decolonization has descended into acrimony. Some factions cast the issue of decolonization as a sustained attack on British and western culture writ large; other disparate voices coalesce around related social justice issues such as inequality, climate change and education. 

Decolonization has become ubiquitous in the public domain – and its ubiquity is the problem. In Against Decolonization, Olufemi Taiwo renounces a concept he conceives as having been emptied of serious study and analytical purchase; one incapable of addressing the complexities of modern global politics and more importantly, Africa’s place in it. 

Although the book attacks the inexhaustible ways in which the ‘trope of decolonization’ has been deployed, Taiwo is less bothered by the purported failures of scholars he deems ‘decolonizers’ and focuses his attention instead on the political landscape of African countries, past and present. 

Central to the book’s argument are two distinct scholarly strands on decolonization. The first, legal focus, centres on the political and economic forces of state-building. The second essays an ‘ideology’ of decolonization that rests on ‘forcing an ex-colony to forswear on pain of being forever under the yoke of colonization any and every cultural, political, intellectual, social and linguistic artefact, idea, process, institution and practice that retains even the slightest whiff of the colonial past’. 

Whether one should characterize the latter as simply a field of study or a potential set of policy arrangements remains unclear – yet what is certain is that it is too nebulous, too elastic, too open-ended to offer any substantive model or mechanism to understand postcolonial Africa. 
 

Correcting Eurocentric narcissism

 The decolonization research agenda in Africa came to prominence during the Cold War period of national liberation struggles.

The intellectual project that followed centred on dismantling Eurocentrism as colonial subjugation through its promotion of the West as the crucible of legitimate and scientific knowledge. Since then, scholars have argued that decolonization itself has become compromised by its enduringly Eurocentric gaze at the expense of the agency of African thinkers, creatives and statesmen and women. 

Taiwo seeks to correct this narcissism – and the omissions left in its wake – by introducing lesser-known Africans and pan-African scholars and cultural figures. These voices, he hopes, will illuminate issues often ignored by ‘decolonizers’ and spark a ‘renewed interest in an appreciation of the many different ways in which African thinkers have responded to the colonial experience’.
 

The decolonization of language

Taiwo challenges the decolonization of language as an oversold promise.

Romanticizing an imagined, pristine African pre-colonial past, he says, ultimately leads to nativism and atavism. As a case in point, Taiwo highlights bureaucratic instances of ‘language policy planning’ to deploy African languages in places such as Niger, Mali, Cameroon, Senegal and Nigeria that were hindered by multilingualism, education and high rates of illiteracy.

The author goes on to confront the abstract language of decolonization, which, he says, allows western scholars to unproblematically engage with the concept without any serious consideration of their own complicity in upholding systems of exclusion. It entrenches their own institutional power within the academy, amplifies their perspectives at the expense of others, and limits the possibilities for understanding the problems of world politics with deleterious effects on policy.

It is a serious claim, but there are issues to be addressed: Taiwo assumes there is coherence among scholars of decolonization, which is not the case. 

When Taiwo approaches how to foster political systems that cater to the needs of their citizens he dismantles the binary of ‘West as modern’ v ‘Africa as traditional’. Chieftaincies as traditional African governance, he points out, were the product of colonial anthropology, not Africans themselves. From the Fanti Confederation of 1871 to the Egba United Government in what is now Nigeria, Taiwo demonstrates that there has been a sustained tradition towards demands for democratic values. 

As he concedes an intellectual neglect of African philosophers that underlies the design and operations of Africa’s political institutions, Taiwo’s initial dismissal of the significance of cultural decolonization deserves another look. How should political and economic drives toward self-determination be advanced in the absence of knowledge shaped and mediated through African lived experiences?

In this respect, the tale of two decolonizations – the legal alongside the ideological – suggest an unhelpful, if not false, binary.
 

The problem of reconciling modernity and colonialism

What resonates throughout the book is the idea that Europe cannot profess to hold an exclusive intellectual claim to modernity. Its universal aspirations are open to all of humanity, allowing those who have historically been marginalized to be worldmakers. 

The idea that modernity and colonialism are irreconcilable is problematic. For instance, Taiwo argues that the curtailment of capitalism in Africa by restricting the growth of the middle classes while limiting competition between African capitalists and the metropole is the consequence of colonialism.

Yet the celebrated cultural anthropologist Sidney Mintz established an understanding that the matter for debate is not whether non-westerners were part of the modern system, but how and to what degree they were included and able to actualise its ideals. 

The emerging capitalist world economy needed non-western lands and labour, and so they were conscripted to this end. Recent abolitionist and black radical scholarship has built on this argument to maintain that capitalism not only requires inequality for it to function but that race – as a mechanism for producing ‘difference’ – enshrines it.

Acknowledging the unacknowledged

In the end, Taiwo communicates a palpable frustration at the state of academic discourses on contemporary Africa under the guise of emancipatory and radical scholarship. He offers an alternative approach whereby African students might rid themselves of a faddism that is ‘at best unsatisfactory’ and at worst produces ‘confusion, obscurantism, if not outright distortion and falsification’.

Yet out of this irritation, Taiwo’s greatest contribution in Against Decolonization might be to urge an acknowledgement of how and to what degree decolonization has become subdued and its political possibilities curtailed. He ultimately urges us to reconsider the purpose of the decolonization academic movement as an ethics to abide by rather than a social theory of the postcolonial world. 

This requires those ‘decolonizers’ on whose careers the term is built to adopt greater intellectual humility – to resist the posture of the anarchist radical scholar armed for the ‘good fight’. Instead, they should apply a scholarly curiosity to genuinely engage with those already on the battlefield, so to speak; those ‘doing the work’ in practice, but who have been unacknowledged until now.

Toma Keser
Dec 29, 2020; 0:RA120.002433v1-mcp.RA120.002433
Research

Ji Eun Kim
Dec 20, 2020; 0:RA120.002159v1-mcp.RA120.002159
Research

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

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

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

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

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

Summary

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

Review: Rediscovering Milan Kundera’s European tragedy The World Today mhiggins.drupal 28 March 2023

The Czech writer’s 40-year-old essay on the roots of Russia’s empire-building, ‘A Kidnapped West’, reads all too presciently, writes Stefan Auer.

A Kidnapped West: The Tragedy of Central Europe
Milan Kundera, Faber, £10

‘In November 1956, the director of the Hungarian News Agency, shortly before his office was flattened by artillery fire, sent a telex to the entire world with a desperate message announcing that the Russian attack against Budapest had begun. The dispatch ended with these words: “We are going to die for Hungary and for Europe.”’ Thus, Milan Kundera began his 1983 essay for the French journal Le Débat, reflecting on the 1956 Hungarian Uprising.

A seminal essay

The Czech author might well have written a near-identical passage about the fraught hours immediately after Russia’s invasion of Ukraine in 2022. In the event, Russian tanks failed to occupy Kyiv, unlike Budapest in 1956. Nevertheless, Faber has chosen this moment, 40 years later, to republish Kundera’s seminal essay on Europe and Russian aggression in its original translation for the New York Review of Books by Edmund White. How salient are its observations today?

The essay’s original French title, ‘Un Occident kidnappé ou la tragédie de l’Europe centrale’ (The Kidnapped West, or the Tragedy of Central Europe), described the fate of Hungary, Czechoslovakia in 1968 and, to an extent, Poland in 1980-81 at the hands of the Soviet Union. Owing to the Cold War division of Europe, the countries of Central Europe were denied their true destiny, Kundera thought, to be an integral part of the liberal, democratic West. Kundera himself fled Czechoslovakia for France in 1975.

The author of The Unbearable Lightness of Being might no longer be as well-known as he was at the height of his fame in the 1980s, but his novels and essays still deserve attention. So, it is pleasing to see Kundera’s masterpiece republished, even as it is awful to witness the enduring relevance of the questions it raises.

What did the Hungarian journalist mean when he declared his willingness to die for Europe, Kundera asked? That ‘Russians, in attacking Hungary, were attacking Europe itself. He was ready to die so that Hungary might remain Hungary and European’. The journalist did indeed die in the uprising.

It is a line that President Volodymyr Zelenskyy and his supporters abroad have echoed time and again: that Ukrainian soldiers are not just dying for their country, they are dying for Europe at large.

The ‘tragedy’ in Kundera’s essay was that the West didn’t care. ‘Europe hasn’t noticed the disappearance of its cultural home,’ Kundera wrote, ‘because Europe no longer perceives its unity as a cultural unity.’

In other words, as the cultural sphere in Central Europe continued to defy the political restrictions imposed by the Soviet empire, it embodied the western values of freedom and democracy more than the West itself did. The extent to which this analysis remains relevant today will prove decisive for Europe’s future.

As timely as ever

Kundera’s essay is as timely as ever but in ways that both vindicate and challenge his key arguments. His suspicion of Russia has been validated. His frustration about the indifference of the West less so. But the true tragedy of Ukraine would be if the West has not changed sufficiently. So far, the West appears to be doing enough to enable Ukraine to defend itself, but not enough to defeat the aggressor.

Faber has made an excellent decision in combining The Tragedy of Central Europe with a lesser-known text by Kundera: his 1967 speech to the Czech Writers’ Congress given the year before the ill-fated Prague Spring. In it, Kundera addressed what was to become a lifelong preoccupation: the fate of small nations. ‘For Czechs’, Kundera wrote, ‘nothing has ever constituted an indisputable possession – neither their language nor their belonging to Europe.’

Rather than reflecting the size of its territory or population, a small nation ‘is one whose very existence can be put in question at any moment; a small nation can disappear, and it knows it.’ In this way Ukraine, Europe’s largest country, apart from Russia, is fighting to avoid the fate of Kundera’s ‘small nation’.

Historically, the ‘small’ nations of Central Europe were threatened by both Germany and Russia. But after the Second World War, the threat was from the Soviet Union, which for Kundera was indistinguishable from Russia (tacitly including Ukraine). In its expansiveness, Russia was the opposite of Central Europe. While the latter was based on the principle of ‘the greatest variety within the smallest space’, the former represented ‘the smallest variety within the greatest space’.

In this sense, authoritarian communism was the fulfilment of Russian history, Kundera argued, writing that ‘Russian communism vigorously reawakened Russia’s old anti-western obsessions and turned it brutally against Europe’. Vladimir Putin’s Russia appears to build on these same pernicious impulses.

Kundera was widely criticized for observations in his essay that smack of civilizational racism (including by me) describing Russians as fundamentally different from us: ‘Russia knows another (greater) dimension of disaster, another image of space (a space so immense that entire nations are swallowed up in it), another sense of time (slow and patient), another way of laughing, living, and dying’.

The wreckage of the U.S. destroyer USS Edsall, sunk by Japanese forces more than 80 years ago during World War II, has been found at the bottom of the Indian Ocean, according to the U.S. Navy.

The switch to remote learning in rural New Mexico has left some students profoundly isolated—cut off from others and the grid by sheer distance.

Resurrecting an old idea about assessing school quality could allow schools to examine a broad range of data on performance and practices and lead to improvement.

The switch to remote learning in rural New Mexico has left some students profoundly isolated—cut off from others and the grid by sheer distance.

Mineralogist Bob Hazen talks about what he loves about walking along the coast of the Chesapeake Bay, hunting for fossils and shark teeth hidden in the sand

Fossils found in Colombia indicate that a giant snake may have roamed the earth 60 million years ago

Kip Thorne, Rainer Weiss, Barry Barish and Ronald Drever | Smithsonian Magazine’s 2016 American Ingenuity Award Winners for Physical Sciences In February, physicists announced the first-ever detection of gravitational waves—a phenomenon Albert Einstein predicted back in 1915. The faint reverberation, from two merging black holes 1.3 billion light-years ago, registered in the two giant detectors that make up the Laser Interferometer Gravitational-Wave Observatory, or LIGO. It took decades for LIGO’s founders—Weiss, of MIT, and Thorne and Drever, of Cal Tech—to amass the necessary funding and brainpower. Barish, a particle physicist at CalTech, became LIGO’s director and expanded its work to include more than 1,000 researchers worldwide. Their revolutionary achievement opens the way for a new understanding of the universe, perhaps even a glimpse of the Big Bang. Read more about their work: http://smithmag.co/FZBFeP | #IngenuityAwards And more about the American Ingenuity Awards: http://smithmag.co/77xPqy

Video by David VanZandt

An incredible trove of archaeological artifacts has been unearthed once again at Saqqara—including 100 coffins, and incredibly rare statues dating back 4,500 years.

The 12,000 year old skeleton of a teenage girl was found in Hoyo Negro, an underwater cave system on the Yucatan Peninsula.

"Le Lyonnais" descended into the depths off the coast of Massachusetts after colliding with the "Adriatic," a sailing vessel that left the floundering steamship to fend for itself

New research suggests the sarcophagus' occupant, previously known only as "the horseman," is Joachim du Bellay, a French Renaissance poet who died in 1560

The energetic streams are together 23 million light-years in length—roughly as long as 140 Milky Way galaxies lined end to end

If the structures look familiar, it's probably because nature has been using them for a long time in places like nautilus shells, zebra stripes and onions

An A.I.-assisted study identified 303 previously unknown geoglyphs in the Peruvian desert. The art features surprising figures, like orcas holding knives

Unearthed last year, the remains could reveal new information on the extinct sea reptile, which crushed mollusks and shelled creatures with its large, round teeth

Called the Australasian narrow-nosed spookfish, the cryptic species lives deep in the ocean off the coasts of New Zealand and Australia

Using sound recordings, the team identified the largest known population of the night parrot, a secretive species known as the "Holy Grail of birdwatching"

For years, the owner's son had wondered about the artwork, which features the Spanish painter's signature. Now, some experts think it's the real deal

Orbiting Barnard's star, the nearest solo star to Earth, the world is too hot to be habitable—a scorching 257 degrees Fahrenheit

The USS Stewart was purposefully sunk off the coast of California after the war

At the site known as Oued Beht, archaeologists uncovered evidence of a large farming settlement where people used advanced techniques

Victor Ambros and Gary Ruvkun discovered microRNA, tiny molecules that play a crucial role in how cells develop, paving the way for new treatments for diseases

The 4,000-year-old burial chamber featured hieroglyphs referring to the woman, known as Idi, as the "lady of the house"

The recent excavation beneath the Treasury has revealed 12 complete human skeletons and a trove of grave goods dating back 2,000 years

In 1924, Andrew "Sandy" Irvine joined George Mallory’s expedition to the world’s highest peak. Now, Irvine’s recently found foot and boot hint at what might have happened on that ill-fated undertaking

Scientists aren't sure how the circular indentations some 450 feet below the surface formed, but they hope to investigate further

Hundreds of artifacts have been unearthed at a burial mound in the city of Chifeng, but researchers are particularly intrigued by the six-inch-long object

The structure—also the earliest of its kind in the Asian country—dates to around 350 C.E.

Called M136279841, the value belongs to a rare class of prime numbers called Mersenne primes and was found using a supercomputer system spread across 17 countries

History forgot about "Gibbet Hill" for more than a century—until a fan of the Gothic horror writer stumbled upon the haunting tale at the National Library of Ireland

The giant salmon carp was formally identified in 1991, and since then, fewer than 30 individuals had been documented

Despite its unusually small size, the newly unearthed House of Phaedra is covered in elaborate frescos depicting mythological scenes

Ne’Kiya Jackson and Calcea Johnson of Louisiana published a new study proving the Pythagorean theorem using trigonometry, a feat mathematicians long thought could not be done