Standard of civilization, nomadism and territoriality in nineteenth-century international society

In this chapter, the encounter between the Russian Empire and the nomads of the Eurasian steppe in the nineteenth century is analyzed using the theoretical framework of the standard of civilization. The creation of the Westphalian state-model in Europe in the seventeenth century, linked to the later emergence of the notion of the standard of civilization led to the ‘othering’ of the nomads of the Eurasian steppe as barbarians, as a threat to the borders of civilized Europe. The chapter presents also an argument to define ‘territoriality’ as not only an institution of international society of the time but also as a distinctive quality and requirement for being considered ‘civilized’. In this analytical framework, the nomads become the ‘other’, the ‘alien’, the ‘menace’, onto which projections of rationality and modernity were cast in order to prevent threats to Russia’s European and civilized identity. The chapter sheds light on the encounter between ‘fixed’ and ‘mobile’ units in the course of expansion of international society; contextualizes the role played by nomadic tribes in resisting the application of Westphalian spatial categories in the Eurasian space; and scrutinizes what the role of nomads was in constructing a European, civilized identity.PostprintPeer reviewe

Clash of pans: pan-Africanism and pan-Anglo-Saxonism and the global colour line, 1919–1945

The article demonstrates both conceptually and empirically that pan-Anglo-Saxonist knowledge networks reconstructed and reimagined an apparently de-racialised, scientific, sober and liberal world order that outwardly abandoned, but did not eradicate the twin phenomena of racism and imperialism. Rather the new liberal (imperial) internationalists, organised in newly formed “think tanks” such as Chatham House and the Council on Foreign Relations, and through their increasingly global elite networks, mounted a top-down battle for minds at home and in the wider world. Operating in state-private elite networks, they drove the movement to manage change and develop a new liberal world order particularly to contain pan-Africanists who combatted the domination and exploitation of Africans worldwide. More broadly, we indicate that the pragmatic response to the extremes of Nazi ideology and a countering movement from the cadres of Asian, African and African American intellectuals, anti-colonial and anti-racist struggles within the national and global context, forced the Anglo-centric elites to promote change, albeit limited

CCL25/CCR9 Interactions Regulate Large Intestinal Inflammation in a Murine Model of Acute Colitis

CCL25/CCR9 is a non-promiscuous chemokine/receptor pair and a key regulator of leukocyte migration to the small intestine. We investigated here whether CCL25/CCR9 interactions also play a role in the regulation of inflammatory responses in the large intestine.Acute inflammation and recovery in wild-type (WT) and CCR9(-/-) mice was studied in a model of dextran sulfate sodium (DSS)-induced colitis. Distribution studies and phenotypic characterization of dendritic cell subsets and macrophage were performed by flow cytometry. Inflammatory bowel disease (IBD) scores were assessed and expression of inflammatory cytokines was studied at the mRNA and the protein level.CCL25 and CCR9 are both expressed in the large intestine and are upregulated during DSS colitis. CCR9(-/-) mice are more susceptible to DSS colitis than WT littermate controls as shown by higher mortality, increased IBD score and delayed recovery. During recovery, the CCR9(-/-) colonic mucosa is characterized by the accumulation of activated macrophages and elevated levels of Th1/Th17 inflammatory cytokines. Activated plasmacytoid dendritic cells (DCs) accumulate in mesenteric lymph nodes (MLNs) of CCR9(-/-) animals, altering the local ratio of DC subsets. Upon re-stimulation, T cells isolated from these MLNs secrete significantly higher levels of TNFα, IFNγ, IL2, IL-6 and IL-17A while down modulating IL-10 production.Our results demonstrate that CCL25/CCR9 interactions regulate inflammatory immune responses in the large intestinal mucosa by balancing different subsets of dendritic cells. These findings have important implications for the use of CCR9-inhibitors in therapy of human IBD as they indicate a potential risk for patients with large intestinal inflammation

Cardiovascular risk assessment - From individual risk prediction to estimation of global risk and change in risk in the population

Cardiovascular disease is the most common cause of death and risk prediction formulae such as the Framingham Risk Score have been developed to easily identify patients at high risk that may require therapeutic interventions. Using cardiovascular risk formulae at a population level to estimate and compare average cardiovascular risk among groups has been recently proposed as a way to facilitate surveillance of net cardiovascular risk and target public health interventions. Risk prediction formulas may help to compare interventions that cause effects of different magnitudes and directions in several cardiovascular risk factors, because these formulas assess the net change in risk using easily obtainable clinical variables. Because of conflicting data estimates of the incidence and prevalence of cardiovascular disease, risk prediction formulae may be a useful tool to estimate such risk at a population level

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Proteome-wide identification of SUMO modification sites by mass spectrometry

The protein called 'small ubiquitin-like modifier' (SUMO) is post-translationally linked to target proteins at the varepsilon-amino group of lysine residues. This 'SUMOylation' alters the behavior of the target protein, a change that is utilized to regulate diverse cellular processes. Understanding the target-specific consequences of SUMO modification requires knowledge of the location of conjugation sites, and we have developed a straightforward protocol for the proteome-wide identification of SUMO modification sites using mass spectrometry (MS). The approach described herein requires the expression of a mutant form of SUMO, in which the residue preceding the C-terminal Gly-Gly (diGly) is replaced with a lysine (SUMO(KGG)). Digestion of SUMO(KGG) protein conjugates with endoproteinase Lys-C yields a diGly motif attached to target lysines. Peptides containing this adduct are enriched using a diGly-Lys (K-varepsilon-GG)-specific antibody and identified by MS. This diGly signature is characteristic of SUMO(KGG) conjugation alone, as no other ubiquitin-like protein (Ubl) yields this adduct upon Lys-C digestion. We have demonstrated the utility of the approach in SUMOylation studies, but, in principle, it may be adapted for the site-specific identification of proteins modified by any Ubl. Starting from cell lysis, this protocol can be completed in approximately 5 d