Non-invasive markers of liver fibrosis: adjuncts or alternatives to liver biopsy?

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care

First hospital outbreak of the globally emerging Candida auris in a European hospital

Background: Candida auris is a globally emerging multidrug resistant fungal pathogen causing nosocomial transmission. We report an ongoing outbreak of C. auris in a London cardio-thoracic center between April 2015 and July 2016. This is the first report of C. auris in Europe and the largest outbreak so far. We describe the identification, investigation and implementation of control measures. Methods: Data on C. auris case demographics, environmental screening, implementation of infection prevention/control measures, and antifungal susceptibility of patient isolates were prospectively recorded then analysed retrospectively. Speciation of C. auris was performed by MALDI-TOF and typing of outbreak isolates performed by amplified fragment length polymorphism (AFLP). Results: This report describes an ongoing outbreak of 50 C. auris cases over the first 16 month (April 2015 to July 2016) within a single Hospital Trust in London. A total of 44 % (n = 22/50) patients developed possible or proven C. auris infection with a candidaemia rate of 18 % (n = 9/50). Environmental sampling showed persistent presence of the yeast around bed space areas. Implementation of strict infection and prevention control measures included: isolation of cases and their contacts, wearing of personal protective clothing by health care workers, screening of patients on affected wards, skin decontamination with chlorhexidine, environmental cleaning with chorine based reagents and hydrogen peroxide vapour. Genotyping with AFLP demonstrated that C. auris isolates from the same geographic region clustered. Conclusion: This ongoing outbreak with genotypically closely related C. auris highlights the importance of appropriate species identification and rapid detection of cases in order to contain hospital acquired transmission

Adaptive planning for resilient urban water systems under an uncertain future

Water planners are familiar with some form of variability in climate and demand. However, the uncertainty associated with the frequency and magnitude of the variations, coupled with broader performance expectations, means that long term deterministic planning needs to give way to a new approach. The structured adaptive planning process proposed in this paper aims to meet those objectives and accommodate the uncertainty in the future by developing a portfolio of measures that are both flexible to gradual changes in trends and robust to sudden shocks. A step-by-step process of the planning framework is presented. This is followed by a case study of the inputs and results based on its implementation by the Melbourne water businesses

Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil.

Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this "uncultivated majority" remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages.IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism

The Influence of pH on Zinc Lability and Toxicity to a Tropical Freshwater Microalga.

Increased focus on the development and application of bioavailability-based metal water quality guideline values requires increased understanding of the influence of water chemistry on metal bioavailability and toxicity. Development of empirical models, such as multiple linear regression models, requires the assessment of the influence of individual water quality parameters as toxicity-modifying factors. The present study investigated the effect of pH on the lability and toxicity of zinc (Zn) to a tropical green microalga (Chlorella sp.). Zinc speciation and lability were explored using the Windermere Humic Aqueous Model (WHAM7), ultrafiltration, and diffusive gradients in thin films (DGT). Zinc toxicity increased significantly with increasing pH from 6.7 to 8.3, with 50% growth inhibition effect concentrations decreasing from 185 to 53 µg l-1 across the pH range. Linear relationships between DGT-labile Zn and dissolved Zn did not vary across the tested pH range, nor did the linear relationship between dissolved (<0.45 µm) and ultrafiltered (<3 kDa) Zn. Our findings show that Zn toxicity to this freshwater alga is altered as a function of pH across environmentally realistic pH ranges and that these toxicity changes could not be explained by Zn speciation and lability as measured by DGT and WHAM7. Environ Toxicol Chem 2021;40:2836-2845. © 2021 SETAC

RepSeq-A database of amino acid repeats present in lower eukaryotic pathogens

BACKGROUND Amino acid repeat-containing proteins have a broad range of functions and their identification is of relevance to many experimental biologists. In human-infective protozoan parasites (such as the Kinetoplastid and Plasmodium species), they are implicated in immune evasion and have been shown to influence virulence and pathogenicity. RepSeq http://repseq.gugbe.com is a new database of amino acid repeat-containing proteins found in lower eukaryotic pathogens. The RepSeq database is accessed via a web-based application which also provides links to related online tools and databases for further analyses. RESULTS The RepSeq algorithm typically identifies more than 98% of repeat-containing proteins and is capable of identifying both perfect and mismatch repeats. The proportion of proteins that contain repeat elements varies greatly between different families and even species (3 - 35% of the total protein content). The most common motif type is the Sequence Repeat Region (SRR) - a repeated motif containing multiple different amino acid types. Proteins containing Single Amino Acid Repeats (SAARs) and Di-Peptide Repeats (DPRs) typically account for 0.5 - 1.0% of the total protein number. Notable exceptions are P. falciparum and D. discoideum, in which 33.67% and 34.28% respectively of the predicted proteomes consist of repeat-containing proteins. These numbers are due to large insertions of low complexity single and multi-codon repeat regions. CONCLUSION The RepSeq database provides a repository for repeat-containing proteins found in parasitic protozoa. The database allows for both individual and cross-species proteome analyses and also allows users to upload sequences of interest for analysis by the RepSeq algorithm. Identification of repeat-containing proteins provides researchers with a defined subset of proteins which can be analysed by expression profiling and functional characterisation, thereby facilitating study of pathogenicity and virulence factors in the parasitic protozoa. While primarily designed for kinetoplastid work, the RepSeq algorithm and database retain full functionality when used to analyse other species

Improving the ORR Performance by Enhancing the Pt Oxidation Resistance

Proton exchange membrane fuel cells require oxygen reduction catalysts with high activity and stability. Pt based alloy materials are most widely applied ORR catalyst due to its high intrinsic activity, but usually suffer from rapid deactivation as a result of particle agglomeration, detachment, Ostwald ripening and/or Pt dissolution. Here we investigate the degradation of the PdPt alloys via in situ X-ray absorption fine structure, Δμ analysis, identical location-electron microscopy and DFT calculations. We conclude that the origin of high activity and stability of the PdPt catalyst stems from the oxidation resistance of metallic Pt, forming mainly surface adsorbed O species at high potentials. Two stage degradation process are observed, showing an evolution of dynamic surface dependent ORR performance along with the deactivation process. The careful design of Pt alloy structure leads to controlled surface oxygen behaviours. This opens a new way to increase the lifespan of fuel cells and improve the Pt utilization efficiency

Precisely visit the performance modulation of functionalized separator in Li-S batteries via consecutive multiscale analysis

Despite progress of functionalized separator in preventing the shuttle effect and promoting the sulfur utilization, the precise and non-destructive investigation of structure-function-performance associativity remains limited so far in Li-S batteries. Here, we build consecutive multiscale analysis via combining X-ray absorption fine structure (XAFS) and X-ray computational tomography (CT) techniques to precisely visit the structure-function-performance relationship. XAFS measurement offers the atomic scale changes in the chemical structure and environment. Moreover, a non-destructive technique of X-ray CT proves the functionalized separator role for microscopic scale, which is powerful chaining to bridge the chemical structures of the materials with the overall performance modulation of cells. Benefiting from this consecutive multiscale analysis, we report that the uniform doping of Sr2+ into the perovskite LaMnO3-δ material changes the Mn oxidation states and conductivity (chemical structure), leading to effective lithium polysulfide trapping and accelerated sulfur redox (separator function), and resulting in outstanding cell performance

Ultrastructural and functional fate of recycled vesicles in hippocampal synapses

Efficient recycling of synaptic vesicles is thought to be critical for sustained information transfer at central terminals. However, the specific contribution that retrieved vesicles make to future transmission events remains unclear. Here we exploit fluorescence and time-stamped electron microscopy to track the functional and positional fate of vesicles endocytosed after readily releasable pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles are recovered near the active zone but subsequently take up random positions in the cluster, without preferential bias for future use. These vesicles non-selectively queue, advancing towards the release site with further stimulation in an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved recently in the stimulus train persist nearer the active zone and exhibit more privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate based on nanoscale position and timing rules, providing new insights into the origins of future pool constitution