Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

Arabinomannan (AM) polysaccharides are clinical biomarkers for Mycobacterium tuberculosis (MTB) infections due to their roles in the interaction with host cells and interference with macrophage activation. Collections of defined AM oligosaccharides can help to improve the understanding of these polysaccharides and the development of novel therapeutical and diagnostic agents. Automated glycan assembly (AGA) was employed to prepare the core structure of AM from MTB, containing α-(1,6)-Man, α-(1,5)-Ara, and α-(1,2)-Man linkages. The introduction of a capping step after each glycosylation and further optimized reaction conditions allowed for the synthesis of a series of oligosaccharides, ranging from hexa- to branched dodecasaccharides.

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Indexicality of Grammar: The Case of Japanese Transgender Speakers

The Oxford Handbook of Language and Sexuality ◽

10.1093/oxfordhb/9780190212926.013.16 ◽

2019 ◽

Author(s):

Hideko Abe

Keyword(s):

Gender Identity ◽

Gender Identity Disorder ◽

Grammatical Gender ◽

Core Structure ◽

Subject Positions ◽

Transgender Identity ◽

The Core ◽

History Of ◽

History Of Scholarship ◽

Grammatical Structures

This article discusses how the intersection of grammatical gender and social gender, entwined in the core structure of language, can be analyzed to understand the dynamic status of selfhood. After reviewing a history of scholarship that demonstrates this claim, the discussion analyzes the language practices of transgender individuals in Japan, where transgender identity is currently understood in terms of sei-dōitsusei-shōgai (gender identity disorder). Based on fieldwork conducted between 2011 and 2017, the analysis reveals how individuals identifying with sei-dōitsusei-shōgai negotiate subject positions by manipulating the specific indexical meanings attached to grammatical structures.

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Evolutionary Genetics of Mycobacterium tuberculosis and HIV-1: “The Tortoise and the Hare”

Microorganisms ◽

10.3390/microorganisms9010147 ◽

2021 ◽

Vol 9 (1) ◽

pp. 147

Author(s):

Ana Santos-Pereira ◽

Carlos Magalhães ◽

Pedro M. M. Araújo ◽

Nuno S. Osório

Keyword(s):

Genetic Diversity ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Evolutionary Dynamics ◽

Evolutionary Genetics ◽

Host Cells ◽

Whole Genome Sequencing Data ◽

Host Immune System ◽

Viral Mutant ◽

Hiv 1

The already enormous burden caused by Mycobacterium tuberculosis and Human Immunodeficiency Virus type 1 (HIV-1) alone is aggravated by co-infection. Despite obvious differences in the rate of evolution comparing these two human pathogens, genetic diversity plays an important role in the success of both. The extreme evolutionary dynamics of HIV-1 is in the basis of a robust capacity to evade immune responses, to generate drug-resistance and to diversify the population-level reservoir of M group viral subtypes. Compared to HIV-1 and other retroviruses, M. tuberculosis generates minute levels of genetic diversity within the host. However, emerging whole-genome sequencing data show that the M. tuberculosis complex contains at least nine human-adapted phylogenetic lineages. This level of genetic diversity results in differences in M. tuberculosis interactions with the host immune system, virulence and drug resistance propensity. In co-infected individuals, HIV-1 and M. tuberculosis are likely to co-colonize host cells. However, the evolutionary impact of the interaction between the host, the slowly evolving M. tuberculosis bacteria and the HIV-1 viral “mutant cloud” is poorly understood. These evolutionary dynamics, at the cellular niche of monocytes/macrophages, are also discussed and proposed as a relevant future research topic in the context of single-cell sequencing.

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Solvent-free and efficient synthesis of bicyclic 2-pyridone derivatives for endoplasmic reticulum imaging

Organic Chemistry Frontiers ◽

10.1039/d1qo00350j ◽

2021 ◽

Author(s):

Xiaoyun Ran ◽

Qian Zhou ◽

Jin Zhang ◽

Shanqiang Wang ◽

Gui Wang ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Citric Acid ◽

Core Structure ◽

Solvent Free ◽

Efficient Synthesis ◽

The Core ◽

Catalyst Free ◽

Synthesis Approach ◽

Ethylenediamine Derivatives

Started from citric acid (CA) and ethylenediamine derivatives, a solvent-free, catalyst-free and highly yield synthesis approach for bicyclic 2-pyridones was presented. Continuing to modify the core structure, a series of...

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Pore-forming Esx proteins mediate toxin secretion by Mycobacterium tuberculosis

Nature Communications ◽

10.1038/s41467-020-20533-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Uday Tak ◽

Terje Dokland ◽

Michael Niederweis

Keyword(s):

Mycobacterium Tuberculosis ◽

Pore Formation ◽

Molecular Switches ◽

Water Soluble ◽

Host Cells ◽

Solvent Exposure ◽

Membrane Channel ◽

Toxin Secretion ◽

Outer Membrane Channel ◽

Membrane Spanning

AbstractMycobacterium tuberculosis secretes the tuberculosis necrotizing toxin (TNT) to kill host cells. Here, we show that the WXG100 proteins EsxE and EsxF are essential for TNT secretion. EsxE and EsxF form a water-soluble heterodimer (EsxEF) that assembles into oligomers and long filaments, binds to membranes, and forms stable membrane-spanning channels. Electron microscopy of EsxEF reveals mainly pentameric structures with a central pore. Mutations of both WXG motifs and of a GXW motif do not affect dimerization, but abolish pore formation, membrane deformation and TNT secretion. The WXG/GXW mutants are locked in conformations with altered thermostability and solvent exposure, indicating that the WXG/GXW motifs are molecular switches controlling membrane interaction and pore formation. EsxF is accessible on the bacterial cell surface, suggesting that EsxEF form an outer membrane channel for toxin export. Thus, our study reveals a protein secretion mechanism in bacteria that relies on pore formation by small WXG proteins.

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