A glucuronoxylomannan epitope exhibits serotype-specific accessibility and redistributes towards the capsule surface during Titanisation of the fungal pathogen Cryptococcus neoformans.

Disseminated infections with the fungal species Cryptococcus neoformans or, less frequently, C. gattii, are an important cause of mortality in immunocompromised individuals. Central to the virulence of both species is an elaborate polysaccharide capsule that consists predominantly of glucuronoxylomannan (GXM). Due to its abundance, GXM is an ideal target for host antibodies, and several monoclonal antibodies (mAbs) have previously been derived using purified GXM or whole capsular preparations as antigen. In addition to their application in the diagnosis of cryptococcosis, anti-GXM mAbs are invaluable tools for studying capsule structure. In this study, we report the production and characterisation of a novel anti-GXM mAb, Crp127, that unexpectedly reveals a role for GXM remodelling during the process of fungal Titanisation. We show that Crp127 recognises a GXM epitope in an O-acetylation dependent, but xylosylation-independent, manner. The epitope is differentially expressed by the four main serotypes of Cryptococcus neoformans and gattii, is heterogeneously expressed within clonal populations of C. gattii serotype B strains and is typically confined to the central region of the enlarged capsule. Uniquely, however, this epitope redistributes to the capsular surface in Titan cells, a recently characterised morphotype where haploid 5 μm cells convert to highly polyploid cells >10 μm with distinct but poorly understood capsular characteristics. Titans are produced in the host lung and critical for successful infection. Crp127 therefore advances our understanding of cryptococcal morphological change and may hold significant potential as a tool to differentially identify cryptococcal strains and subtypes

Spatial Dynamics Of Vertical And Horizontal Intergovernmental Collaboration

Although researchers have made progress in understanding motivations behind local government collaboration, there is little research that explores the spatial dynamics of such interactions. Does the idea of collaboration travel horizontally, passed from neighbor to neighbor, or is vertical leadership from state, county, or regional actors more important in influencing local governments’ decisions to share resources and functions? What factors influence local governments’ choices to collaborate with their neighbors versus a regional entity, county, or state government? In this article, we investigate the importance of vertical and horizontal influences when local governments decide to collaborate around land use planning. Using data from a survey of Michigan local government officials, we take a spatial statistical approach to answering this question. We find widespread evidence of collaboration at multiple scales, and observe patterns of both horizontal and vertical influence. We also find that contextual factors help to explain these patterns of collaboration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112248/1/juaf12139.pd

Investigating metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections: protocol for a laboratory-based cross-sectional study

Background: Fungal-bacterial cocolonization and coinfections pose an emerging challenge among patients suspected of having pulmonary tuberculosis (PTB); however, the underlying pathogenic mechanisms and microbiome interactions are poorly understood. Understanding how environmental microbes, such as fungi and bacteria, coevolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic pulmonary fungal coinfections. In this project, we propose to study the coexistence of fungal and bacterial microbial communities during chronic pulmonary diseases, with a keen interest in underpinning fungal etiological evolution and the predominating interactions that may exist between fungi and bacteria. Objective: This is a protocol for a study aimed at investigating the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections through determining and characterizing the burden, etiological profiles, microbial communities, and interactions established between fungi and bacteria as implicated among patients with presumptive PTB. Methods: This will be a laboratory-based cross-sectional study, with a sample size of 406 participants. From each participant, 2 sputa samples (one on-spot and one early morning) will be collected. These samples will then be analyzed for both fungal and bacterial etiology using conventional metabolic and molecular (intergenic transcribed spacer and 16S ribosomal DNA–based polymerase chain reaction) approaches. We will also attempt to design a genome-scale metabolic model for pulmonary microbial communities to analyze the composition of the entire microbiome (ie, fungi and bacteria) and investigate host-microbial interactions under different patient conditions. This analysis will be based on the interplays of genes (identified by metagenomics) and inferred from amplicon data and metabolites (identified by metabolomics) by analyzing the full data set and using specific computational tools. We will also collect baseline data, including demographic and clinical history, using a patient-reported questionnaire. Altogether, this approach will contribute to a diagnostic-based observational study. The primary outcome will be the overall fungal and bacterial diagnostic profile of the study participants. Other diagnostic factors associated with the etiological profile, such as incidence and prevalence, will also be analyzed using univariate and multivariate schemes. Odds ratios with 95% CIs will be presented with a statistical significance set at P<.05. Results: The study has been approved by the Mbarara University Research Ethic Committee (MUREC1/7-07/09/20) and the Uganda National Council of Science and Technology (HS1233ES). Following careful scrutiny, the protocol was designed to enable patient enrollment, which began in March 2022 at Mbarara University Teaching Hospital. Data collection is ongoing and is expected to be completed by August 2023, and manuscripts will be submitted for publication thereafter. Conclusions: Through this protocol, we will explore the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections among patients with presumptive PTB. Establishing key fungal-bacterial cross-kingdom synergistic relationships is crucial for instituting fungal bacterial coinfecting etiology. Trial Registration: ISRCTN Registry ISRCTN33572982; https://tinyurl.com/caa2nw69 International Registered Report Identifier (IRRID): DERR1-10.2196/48014 JMIR Res Protoc 2023;12:e48014 doi:10.2196/4801

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Animal health aspects of adaptation to climate change: beating the heat and parasites in a warming Europe

Weather patterns in northern European regions have changed noticeably over the past several decades, featuring warmer, wetter weather with more extreme events. The climate is projected to continue on this trajectory for the foreseeable future, even under the most modest warming scenarios. Such changes will have a significant impact on livestock farming, both directly through effects on the animals themselves, and indirectly through changing exposure to pests and pathogens. Adaptation options aimed at taking advantage of new opportunities and/or minimising the risks of negative impacts will, in themselves, have implications for animal health and welfare. In this review, we consider the potential consequences of future intensification of animal production, challenges associated with indoor and outdoor rearing of animals and aspects of animal transportation as key examples. We investigate the direct and indirect effects of climate change on the epidemiology of important livestock pathogens, with a particular focus on parasitic infections, and the likely animal health consequences associated with selected adaptation options. Finally, we attempt to identify key gaps in our knowledge and suggest future research priorities.</p

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM