Ultrathin passive films effectively prevent the chemical attack of stainless steel grades in corrosive environments; their stability depends on the interplay between structure and chemistry of the ...constituents iron, chromium, and molybdenum (Fe-Cr-Mo). Carbon (C), and eventually boron (B), are also important constituents of steels, although in small quantities. In particular, nanoscale inhomogeneities along the surface can have an impact on material failure but are still poorly understood. Addressing a stainless-type glass-forming Fe 50 Cr 15 Mo 14 C 15 B 6 alloy and using a combination of complementary high-resolution analytical techniques, we relate near-atomistic insights into increasingly inhomogeneous nanostructures with time- and element-resolved dissolution behavior. The progressive elemental partitioning on the nanoscale determines the degree of passivation. A detrimental transition from Cr-controlled passivity to Mo-controlled breakdown is dissected atom by atom, demonstrating the importance of nanoscale knowledge for understanding corrosion.
Adipose tissue (AT) has previously been identified as an extra-medullary reservoir for normal hematopoietic stem cells (HSCs) and may promote tumor development. Here, we show that a subpopulation of ...leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis chronic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT. GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the fatty acid transporter CD36. CD36+ LSCs have unique metabolic properties, are strikingly enriched in AT, and are protected from chemotherapy by the GAT microenvironment. CD36 also marks a fraction of human blast crisis CML and acute myeloid leukemia (AML) cells with similar biological properties. These findings suggest striking interplay between leukemic cells and AT to create a unique microenvironment that supports the metabolic demands and survival of a distinct LSC subpopulation.
Display omitted
•Gonadal adipose tissue (GAT) serves as a reservoir for LSCs•Interplay between leukemia cells and GAT fuels leukemia cell fatty acid metabolism•CD36 segregates LSCs into two metabolically and functionally distinct subsets•GAT provides a niche that confers chemo-resistance for CD36+ LSCs
Ye et al. show that LSCs co-opt the adipose tissue niche to create a microenvironment that supports leukemic growth and resistance to chemotherapy. They also detect metabolically and functionally distinct mouse and human LSC subpopulations delineated by expression of the fatty acid transporter CD36.
The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella ...enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.
The "Ending Cholera: A Global Roadmap to 2030" (Roadmap) was launched in October 2017. Following its launch, it became clear that additional evidence is needed to assist countries in controlling ...cholera and that a prioritized list of research questions is required to focus the limited resources to address the issues most relevant to the implementation of the Roadmap.
A comprehensive list of research questions was developed based on inputs from the Working Groups of the Global Taskforce for Cholera Control and other experts. The Child Health and Nutrition Research Initiative methodology was adapted to identify the relevant assessment criteria and assign weights to each criterion. The assessment criteria were applied to each research question by cholera experts to derive a score based on which they were prioritized.
The consultation process involved 177 experts and stakeholders representing different constituencies and geographies with research priority scores ranging from 88·8 to 65·7% and resulted in the prioritization of the top 20 research questions across all Roadmap pillars, the top five research questions for each Roadmap pillar, and three discovery research questions. This resulted in 32 non-duplicative research questions that considers both immediate and long-term Roadmap goals.
The transparent, inclusive, and rigorous process to develop a Research Agenda is aimed to secure broad buy-in and serve as a guide for funding agencies and researchers to focus their efforts to fill the evidence gaps plaguing cholera-endemic countries.
Bloodstream infections by Salmonella enterica serovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by ...isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA.
Multi-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. ...Typhi in many regions. Here we have undertaken a detailed genomic analysis of typhoid in urban Dhaka, Bangladesh to unravel the population structure and antimicrobial resistance patterns in S. Typhi isolated between 2004-2016.
Whole genome sequencing of 202 S. Typhi isolates obtained from three study locations in urban Dhaka revealed a diverse range of S. Typhi genotypes and AMR profiles. The bacterial population within Dhaka were relatively homogenous with little stratification between different healthcare facilities or age groups. We also observed evidence of exchange of Bangladeshi genotypes with neighboring South Asian countries (India, Pakistan and Nepal) suggesting these are circulating throughout the region. This analysis revealed a decline in H58 (genotype 4.3.1) isolates from 2011 onwards, coinciding with a rise in a diverse range of non-H58 genotypes and a simultaneous rise in isolates with reduced susceptibility to fluoroquinolones, potentially reflecting a change in treatment practices. We identified a novel S. Typhi genotype, subclade 3.3.2 (previously defined only to clade level, 3.3), which formed two localized clusters (3.3.2.Bd1 and 3.3.2.Bd2) associated with different mutations in the Quinolone Resistance Determining Region (QRDR) of gene gyrA.
Our analysis of S. Typhi isolates from urban Dhaka, Bangladesh isolated over a twelve year period identified a diverse range of AMR profiles and genotypes. The observed increase in non-H58 genotypes associated with reduced fluoroquinolone susceptibility may reflect a change in treatment practice in this region and highlights the importance of continued molecular surveillance to monitor the ongoing evolution of AMR in Dhaka. We have defined new genotypes and lineages of Bangladeshi S. Typhi which will facilitate the identification of these emerging AMR clones in future surveillance efforts.
Superabsorbent polymers (SAP) are a new, promising class of chemical admixtures which offer new possibilities in respect of influencing the properties of cement-based materials in the fresh, ...hardening, and hardened states. Much research work has been done in the last two decades to set the stage for introducing this truly multipurpose agent into the practice of construction. In particular, three RILEM Technical Committees: 196-ICC, 225-SAP and 260-RSC contributed considerably to the related progress by coordinating and combining the efforts of international experts in the field. The major product of the RILEM TC 225-SAP work was the State-of-the-Art Report published in 2012. This comprehensive document covered all topics relevant to the application of SAP as a concrete admixture. Since then further important progress has been made in understanding the working mechanisms of SAP in concrete and the effects of SAP-addition on various concrete properties. The article at hand presents an update on the state-of-the-art and is the concluding document delivered by the RILEM TC 260-RSC.
Quality control of endoplasmic reticulum proteins involves the identification and engagement of misfolded proteins, dislocation of the misfolded protein across the endoplasmic reticulum (ER) ...membrane, and ubiquitin-mediated targeting to the proteasome for degradation. Ancient ubiquitous protein 1 (AUP1) physically associates with the mammalian HRD1-SEL1L complex, and AUP1 depletion impairs degradation of misfolded ER proteins. One of the functions of AUP1 in ER quality control is to recruit the soluble E2 ubiquitin-conjugating enzyme UBE2G2. We further show that the CUE domain of AUP1 regulates polyubiquitylation and facilitates the interaction of AUP1 with the HRD1 complex and with dislocation substrates. AUP1 localizes both to the ER and to lipid droplets. The AUP1 expression level affects the abundance of cellular lipid droplets and as such represents the first protein with lipid droplet regulatory activity to be linked to ER quality control. These findings indicate a possible connection between ER protein quality control and lipid droplets.
Fluoroquinolone (FQ)-resistant Salmonella spp. were listed by the WHO in 2017 as priority pathogens for which new antibiotics were urgently needed. The overall global burden of Salmonella infections ...is high, but differs per region. Whereas typhoid fever is most prevalent in South and South-East Asia, non-typhoidal salmonellosis is prevalent across the globe and associated with a mild gastroenteritis. By contrast, invasive non-typhoidal Salmonella cause bloodstream infections associated with high mortality, particularly in sub-Saharan Africa. Most Salmonella strains from clinical sources are resistant to first-line antibiotics, with FQs now being the antibiotic of choice for treatment of invasive Salmonella infections. However, FQ resistance is increasingly being reported in Salmonella, and multiple molecular mechanisms are already described. Whole-genome sequencing (WGS) is becoming more frequently used to analyse bacterial genomes for antibiotic-resistance markers, and to understand the phylogeny of bacteria in relation to their antibiotic-resistance profiles. This mini-review provides an overview of FQ resistance in Salmonella, guided by WGS studies that demonstrate that WGS is a valuable tool for global surveillance.
PDF
