Hyperglycosylation of glycopeptidolipid of mycobacterium smegmatis under nutrient starvation: structural studies

The presence of a polar species of glycopeptidolipid (GPL) in carbon-starved Mycobacterium smegmatis has been reported previously. In this study, the complete structure of this GPL is established with the help of MALDI-TOF (matrix assisted laser desorption/ionization time of flight) and ESI (electrospray ionization) -MS, 13C-SEFT (spin echo Fourier transform) -NMR spectroscopy, and HPLC analysis. In the molecule, two units of a 3,4-di-O-methyl derivative of rhamnose are attached to L-alaninol via a 1 → 2 linkage. Various methyl derivatives of rhamnose and 6-deoxytalose were synthesized as standards to establish this structure. The accumulation of this polar GPL in M. smegmatis is sigB dependent, as a SigB-overproducing strain of M. smegmatis shows the presence of this spot in the exponential phase, and a sigB-knockout strain of M. smegmatis does not show the presence of any polar GPLs

Hominin reactions to herbivore distribution in the Lower Palaeolithic of the Southern Levant

We explore the relationship between the edaphic potential of soils and the mineral properties of the underlying geology as a means of mapping the differential productivity of different areas of the Pleistocene landscape for large herbivores. These factors strongly control the health of grazing animals irrespective of the particular types of vegetation growing on them, but they have generally been neglected in palaeoanthropological studies in favour of a more general emphasis on water and vegetation, which provide an incomplete picture. Taking the Carmel-Galilee-Golan region as an example, we show how an understanding of edaphic potential provides insight into how animals might have exploited the environment. In order to simplify the analysis, we concentrate on the Lower Palaeolithic period and the very large animals that dominate the archaeofaunal assemblages of this period. Topography and the ability of soils to retain water also contribute to the differential productivity and accessibility of different regions and to patterns of seasonal movements of the animals, which are essential to ensure a supply of healthy fodder throughout the year, especially for large animals such as elephants, which require substantial regions of good grazing and browsing. Other animals migrating in groups have similar needs. The complex topography of the Southern Levant with frequent sudden and severe changes in gradient, and a wide variety of landforms including rocky outcrops, cliffs, gorges, and ridges, places major limits on these patterns of seasonal movements. We develop methods of mapping these variables, based on the geology and our substantial field experience, in order to create a framework of landscape variation that can be compared with the locations and contents of archaeological sites to suggest ways in which early hominins used the variable features of the landscape to target animal prey, and we extend the analysis to the consideration of smaller mammals that were exploited more intensively after the disappearance of the elephants. We consider some of the ways in which this regional-scale approach can be further tested and refined, and advocate the development of such studies as an essential contribution to understanding the wider pattern of hominin dispersal

Expression of P. falciparum var Genes Involves Exchange of the Histone Variant H2A.Z at the Promoter

Plasmodium falciparum employs antigenic variation to evade the human immune response by switching the expression of different variant surface antigens encoded by the var gene family. Epigenetic mechanisms including histone modifications and sub-nuclear compartmentalization contribute to transcriptional regulation in the malaria parasite, in particular to control antigenic variation. Another mechanism of epigenetic control is the exchange of canonical histones with alternative variants to generate functionally specialized chromatin domains. Here we demonstrate that the alternative histone PfH2A.Z is associated with the epigenetic regulation of var genes. In many eukaryotic organisms the histone variant H2A.Z mediates an open chromatin structure at promoters and facilitates diverse levels of regulation, including transcriptional activation. Throughout the asexual, intraerythrocytic lifecycle of P. falciparum we found that the P. falciparum ortholog of H2A.Z (PfH2A.Z) colocalizes with histone modifications that are characteristic of transcriptionally-permissive euchromatin, but not with markers of heterochromatin. Consistent with this finding, antibodies to PfH2A.Z co-precipitate the permissive modification H3K4me3. By chromatin-immunoprecipitation we show that PfH2A.Z is enriched in nucleosomes around the transcription start site (TSS) in both transcriptionally active and silent stage-specific genes. In var genes, however, PfH2A.Z is enriched at the TSS only during active transcription in ring stage parasites. Thus, in contrast to other genes, temporal var gene regulation involves histone variant exchange at promoter nucleosomes. Sir2 histone deacetylases are important for var gene silencing and their yeast ortholog antagonises H2A.Z function in subtelomeric yeast genes. In immature P. falciparum parasites lacking Sir2A or Sir2B high var transcription levels correlate with enrichment of PfH2A.Z at the TSS. As Sir2A knock out parasites mature the var genes are silenced, but PfH2A.Z remains enriched at the TSS of var genes; in contrast, PfH2A.Z is lost from the TSS of de-repressed var genes in mature Sir2B knock out parasites. This result indicates that PfH2A.Z occupancy at the active var promoter is antagonized by PfSir2A during the intraerythrocytic life cycle. We conclude that PfH2A.Z contributes to the nucleosome architecture at promoters and is regulated dynamically in active var genes

Colonial lives of the carceral archipelago: rethinking the neoliberal security state

Mass incarceration, police brutality, and border controls are part and parcel of the everyday experiences of marginalized and racialized communities across the world. Recent scholarship in international relations, sociology, and geography has examined the prevalence of these coercive practices through the prism of “disciplinary,” “penal,” or “authoritarian” neoliberalism. In this collective discussion, we argue that although this literature has brought to the fore neoliberalism's reliance on state violence, it has yet to interrogate how these carceral measures are linked to previous forms of global racial ordering. To rectify this moment of “colonial unknowing,” the collective discussion draws on decolonial approaches, Indigenous studies, and theories of racial capitalism. It demonstrates that “new” and “neoliberal” forms of domestic control must be situated within the global longue durée of racialized and colonial accumulation by dispossession. By mapping contemporary modes of policing, incarceration, migration control, and surveillance onto earlier forms of racial–colonial subjugation, we argue that countering the violence of neoliberalism requires more than nostalgic appeals for a return to Keynesianism. What is needed is abolition—not just of the carceral archipelago, but of the very system of racial capitalism that produces and depends on these global vectors of organized violence and abandonment. L'incarcération de masse, la brutalité policière et les contrôles aux frontières constituent une partie intégrante des expériences quotidiennes des communautés marginalisées et racialisées du monde entier. Des études récentes en relations internationales, en sociologie et en géographie ont examiné la prévalence de ces pratiques coercitives par le prisme du néolibéralisme « disciplinaire », « pénal » ou « autoritaire ». Dans cet article, nous soutenons que bien que cette littérature ait mis en évidence la dépendance du néolibéralisme à la violence étatique, elle ne s'est pas encore interrogée sur le lien entre ces mesures carcérales et les formes précédentes d'ordre racial mondial. Cet article s'appuie sur le féminisme noir, les approches décoloniales, les études indigènes et les théories de capitalisme racial pour rectifier cette « ignorance coloniale » marquante. Il démontre que les formes « nouvelles » et « néolibérales » de contrôle national doivent se situer dans la longue durée globale de l'accumulation racialisée et coloniale par dépossession. Nous associons les modes contemporains de maintien de l'ordre, d'incarcération, de contrôle migratoire et de surveillance à des formes antérieures d'assujettissement racial/colonial pour soutenir que contrer la violence du néolibéralisme exige davantage que des appels nostalgiques au retour du keynésianisme. Ce qu'il faut, c'est une abolition : non seulement de l'archipel carcéral, mais aussi du système de capitalisme racial en lui-même qui produit et dépend de ces vecteurs globaux de violence organisée et d'abandon. El encarcelamiento masivo, la brutalidad policial y los controles fronterizos forman parte de las experiencias cotidianas de las comunidades marginadas y racializadas de todo el mundo. Estudios recientes en RI, Sociología y Geografía han examinado la prevalencia de estas prácticas coercitivas a través del prisma del neoliberalismo “disciplinario,” “penal” o “autoritario.” En este artículo, sostenemos que, si bien esta literatura puso en primer plano la dependencia del neoliberalismo de la violencia estatal, aún tiene que cuestionar la manera en que estas medidas carcelarias se vinculan a formas anteriores de ordenamiento racial global. Para rectificar este momento de “desconocimiento colonial,” el artículo recurre al feminismo negro, a los abordajes descoloniales, a los estudios indígenas y a las teorías del capitalismo racial. Demuestra que las formas “nuevas” y “neoliberales” de control interno se deben situar dentro de la longue durée global de la acumulación por desposesión racializada y colonial. Al trazar un mapa de los modos contemporáneos de vigilancia policial, encarcelamiento, control de la migración y vigilancia sobre las formas anteriores de subyugación racial-colonial, sostenemos que contrarrestar la violencia del neoliberalismo requiere algo más que apelaciones nostálgicas de retorno al keynesianismo. Lo que se necesita es la abolición, no solo del archipiélago carcelario, sino también del propio sistema de capitalismo racial que produce y depende de estos vectores globales de violencia y abandono organizados

Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence

Tuberculosis (TB), one of the oldest known human diseases. is still is one of the major causes of mortality, since two million people die each year from this malady. TB has many manifestations, affecting bone, the central nervous system, and many other organ systems, but it is primarily a pulmonary disease that is initiated by the deposition of Mycobacterium tuberculosis, contained in aerosol droplets, onto lung alveolar surfaces. From this point, the progression of the disease can have several outcomes, determined largely by the response of the host immune system. The efficacy of this response is affected by intrinsic factors such as the genetics of the immune system as well as extrinsic factors, e.g., insults to the immune system and the nutritional and physiological state of the host. In addition, the pathogen may play a role in disease progression since some M. tuberculosis strains are reportedly more virulent than others, as defined by increased transmissibility as well as being associated with higher morbidity and mortality in infected individuals. Despite the widespread use of an attenuated live vaccine and several antibiotics, there is more TB than ever before, requiring new vaccines and drugs and more specific and rapid diagnostics. Researchers are utilizing information obtained from the complete sequence of the M. tuberculosis genome and from new genetic and physiological methods to identify targets in M. tuberculosis that will aid in the development of these sorely needed antitubercular agents

Identification of an ABC Transporter Required for Iron Acquisition and Virulence in Mycobacterium tuberculosis

Iron availability affects the course of tuberculosis infection, and the ability to acquire this metal is known to be essential for replication of Mycobacterium tuberculosis in human macrophages. M. tuberculosis overcomes iron deficiency by producing siderophores. The relevance of siderophore synthesis for iron acquisition by M. tuberculosis has been demonstrated, but the molecules involved in iron uptake are currently unknown. We have identified two genes (irtA and irtB) encoding an ABC transporter similar to the YbtPQ system involved in iron transport in Yersinia pestis. Inactivation of the irtAB system decreases the ability of M. tuberculosis to survive iron-deficient conditions. IrtA and -B do not participate in siderophore synthesis or secretion but are required for efficient utilization of iron from Fe-carboxymycobactin, as well as replication of M. tuberculosis in human macrophages and in mouse lungs. We postulate that IrtAB is a transporter of Fe-carboxymycobactin. The irtAB genes are located in a chromosomal region previously shown to contain genes regulated by iron and the major iron regulator IdeR. Taken together, our results and previous observations made by other groups regarding two other genes in this region indicate that this gene cluster is dedicated to siderophore synthesis and transport in M. tuberculosis