Single-cell RNA sequencing profiling in a patient with discordant primary cutaneous B-cell and T-cell lymphoma reveals micromilieu-driven immune skewing.

BACKGROUND: Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood. OBJECTIVES: To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed and combined with T-cell and B-cell receptor sequencing. RESULTS: We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behaviour. CONCLUSIONS: These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.

Genome-scale phylogenies reveal relationships among Parastagonospora species infecting domesticated and wild grasses.

Several plant pathogenic Parastagonospora species have been identified infecting wheat and other cereals over the past 50 years. As new lineages were discovered, naming conventions grew unwieldy and the relationships with previously recognized species remained unclear. We used genome sequencing to clarify relationships among these species and provided new names for most of these species. Six of the nine described Parastagonospora species were recovered from wheat, with five of these species coming from Iran. Genome sequences revealed that three strains thought to be hybrids between P. nodorum and P. pseudonodorum were not actually hybrids, but rather represented rare gene introgressions between those species. Our data are consistent with the hypothesis that P. nodorum originated as a pathogen of wild grasses in the Fertile Crescent, then emerged as a wheat pathogen via host-tracking during the domestication of wheat in the same region. The discovery of a diverse array of Parastagonospora species infecting wheat in Iran suggests that new wheat pathogens could emerge from this region in the future. Citation: Croll D, Crous PW, Pereira D, et al. 2021. Genome-scale phylogenies reveal relationships among Parastagonospora species infecting domesticated and wild grasses. Persoonia 46: 116-128. https://doi.org/10.3767/persoonia.2021.46.04.

Analysis of anti-tumour necrosis factor-induced skin lesions reveals strong T helper 1 activation with some distinct immunological characteristics.

BACKGROUND: Psoriasiform and eczematous eruptions are the most common dermatological adverse reactions linked to anti-tumour necrosis factor (TNF)-α therapy. Yet, a detailed characterization of their immune phenotype is lacking. OBJECTIVES: To characterize anti-TNF-α-induced inflammatory skin lesions at a histopathological, cellular and molecular level, compared with psoriasis, eczema (atopic dermatitis) and healthy control skin. METHODS: Histopathological evaluation, gene expression (quantitative real-time polymerase chain reaction) and computer-assisted immunohistological studies (TissueFAXS) were performed on 19 skin biopsies from patients with inflammatory bowel disease (n = 17) and rheumatoid arthritis (n = 2) with new-onset inflammatory skin lesions during anti-TNF-α-therapy. RESULTS: Although most biopsies showed a psoriasiform and/or spongiotic (eczematous) histopathological architecture, these lesions were inconsistent with either psoriasis or eczema on a molecular level using an established chemokine (C-C motif) ligand 27/inducible nitric oxide synthase classifier. Despite some differences in immune skewing depending on the specific histopathological reaction pattern, all anti-TNF-α-induced lesions showed strong interferon (IFN)-γ activation, at higher levels than in psoriasis or eczema. IFN-γ was most likely produced by CD3/CD4/Tbet-positive T helper 1 lymphocytes. CONCLUSIONS: New-onset anti-TNF-α-induced eruptions previously classified as psoriasis or spongiotic dermatitis (eczema) exhibit a molecular profile that is different from either of these disorders.

Proteome analysis identifies L1CAM/CD171 and DPP4/CD26 as novel markers of human skin mast cells.

BACKGROUND: The function of skin mast cells has been well documented in IgE-mediated allergic reactions, whereas other mast cell functions are poorly defined. This study aimed at identifying novel mast cell proteins by proteome analysis of primary human skin mast cells. METHODS: The proteome of skin mast cells was compared to other cell types and analyzed using bioinformatics. The expression and function of two proteins hitherto not described in skin mast cells was investigated in isolated mast cells as well as in mast cells in situ. RESULTS: Within the mast cell proteome, we identified 49 highly expressed proteins previously not described in mast cells; 21 of these proteins were found to be selectively expressed in mast cells. Two proteins, the neural cell adhesion molecule L1 and dipeptidyl peptidase 4, were further studied. L1 was found to be highly expressed in mast cells in normal, psoriasis, and mastocytosis skin. Dipeptidyl peptidase 4 was found to be expressed in mast cells in normal, psoriasis, and mastocytosis skin as well as in bone marrow mast cells in patients with systemic mastocytosis. In normal skin, mast cells were identified as a major source of dipeptidyl peptidase 4 and we also found that skin mast cells and fibroblasts secrete an active form of this enzyme. CONCLUSIONS: In a systematic proteomics approach we identified two novel mast cell proteins potentially relevant to skin homeostasis: neural cell adhesion molecule L1 and dipeptidyl peptidase 4.

Nonlesional atopic dermatitis skin shares similar T-cell clones with lesional tissues.

BACKGROUND: Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and nonlesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to nonlesional skin remains unclear. METHODS: We performed high-throughput deep sequencing of the ß-TCR repertoire in 29 lesional and 19 nonlesional AD biopsies, compared to six healthy control and six cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts. RESULTS: While greater T-cell infiltrates were observed in lesional vs nonlesional AD, TCR repertoire diversity was similar in lesional and nonlesional tissues, and absolute numbers of unique T-cell clones correlated with respective T-cell counts. Most (87%) top expanded lesional T-cell clones were shared with nonlesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and nonlesional AD showed a highly polyclonal TCR pattern, without evidence of oligoclonal expansion, or a preferred usage of certain V-ß genes in AD skin. Size of the overall T-cell infiltrate, but not the level of clonality, correlated with mRNA levels of key inflammatory mediators (e.g., IL-13, CCL17, IL23p19, CXCL10). CONCLUSION: While AD harbors a highly polyclonal T-cell receptor repertoire, and despite the lack of information on TCR antigen specificity, the sharing of top abundant clones between lesional and nonlesional skin, and their persistence after months of therapy, points to the continuous presence of potentially pathogenic skin resident memory T cells well beyond clinically inflamed lesions.

Oscillatory phase modulates the timing of neuronal activations and resulting behavior.

Human behavioral response timing is highly variable from trial to trial. While it is generally understood that behavioral variability must be due to trial-by-trial variations in brain function, it is still largely unknown which physiological mechanisms govern the timing of neural activity as it travels through networks of neuronal populations, and how variations in the timing of neural activity relate to variations in the timing of behavior. In our study, we submitted recordings from the cortical surface to novel analytic techniques to chart the trajectory of neuronal population activity across the human cortex in single trials, and found joint modulation of the timing of this activity and of consequent behavior by neuronal oscillations in the alpha band (8-12Hz). Specifically, we established that the onset of population activity tends to occur during the trough of oscillatory activity, and that deviations from this preferred relationship are related to changes in the timing of population activity and the speed of the resulting behavioral response. These results indicate that neuronal activity incurs variable delays as it propagates across neuronal populations, and that the duration of each delay is a function of the instantaneous phase of oscillatory activity. We conclude that the results presented in this paper are supportive of a general model for variability in the effective speed of information transmission in the human brain and for variability in the timing of human behavior.

Alpha power indexes task-related networks on large and small scales: A multimodal ECoG study in humans and a non-human primate.

Performing different tasks, such as generating motor movements or processing sensory input, requires the recruitment of specific networks of neuronal populations. Previous studies suggested that power variations in the alpha band (8-12Hz) may implement such recruitment of task-specific populations by increasing cortical excitability in task-related areas while inhibiting population-level cortical activity in task-unrelated areas (Klimesch et al., 2007; Jensen and Mazaheri, 2010). However, the precise temporal and spatial relationships between the modulatory function implemented by alpha oscillations and population-level cortical activity remained undefined. Furthermore, while several studies suggested that alpha power indexes task-related populations across large and spatially separated cortical areas, it was largely unclear whether alpha power also differentially indexes smaller networks of task-related neuronal populations. Here we addressed these questions by investigating the temporal and spatial relationships of electrocorticographic (ECoG) power modulations in the alpha band and in the broadband gamma range (70-170Hz, indexing population-level activity) during auditory and motor tasks in five human subjects and one macaque monkey. In line with previous research, our results confirm that broadband gamma power accurately tracks task-related behavior and that alpha power decreases in task-related areas. More importantly, they demonstrate that alpha power suppression lags population-level activity in auditory areas during the auditory task, but precedes it in motor areas during the motor task. This suppression of alpha power in task-related areas was accompanied by an increase in areas not related to the task. In addition, we show for the first time that these differential modulations of alpha power could be observed not only across widely distributed systems (e.g., motor vs. auditory system), but also within the auditory system. Specifically, alpha power was suppressed in the locations within the auditory system that most robustly responded to particular sound stimuli. Altogether, our results provide experimental evidence for a mechanism that preferentially recruits task-related neuronal populations by increasing cortical excitability in task-related cortical areas and decreasing cortical excitability in task-unrelated areas. This mechanism is implemented by variations in alpha power and is common to humans and the non-human primate under study. These results contribute to an increasingly refined understanding of the mechanisms underlying the selection of the specific neuronal populations required for task execution.

Pyricularia graminis-tritici, a new Pyricularia species causing wheat blast.

Pyricularia oryzae is a species complex that causes blast disease on more than 50 species of poaceous plants. Pyricularia oryzae has a worldwide distribution as a rice pathogen and in the last 30 years emerged as an important wheat pathogen in southern Brazil. We conducted phylogenetic analyses using 10 housekeeping loci for 128 isolates of P. oryzae sampled from sympatric populations of wheat, rice, and grasses growing in or near wheat fields. Phylogenetic analyses grouped the isolates into three major clades. Clade 1 comprised isolates associated only with rice and corresponds to the previously described rice blast pathogen P. oryzae pathotype Oryza (PoO). Clade 2 comprised isolates associated almost exclusively with wheat and corresponds to the previously described wheat blast pathogen P. oryzae pathotype Triticum (PoT). Clade 3 contained isolates obtained from wheat as well as other Poaceae hosts. We found that Clade 3 is distinct from P. oryzae and represents a new species, Pyricularia graminis-tritici (Pgt). No morphological differences were observed among these species, but a distinctive pathogenicity spectrum was observed. Pgt and PoT were pathogenic and highly aggressive on Triticum aestivum (wheat), Hordeum vulgare (barley), Urochloa brizantha (signal grass), and Avena sativa (oats). PoO was highly virulent on the original rice host (Oryza sativa), and also on wheat, barley, and oats, but not on signal grass. We conclude that blast disease on wheat and its associated Poaceae hosts in Brazil is caused by multiple Pyricularia species. Pyricularia graminis-tritici was recently found causing wheat blast in Bangladesh. This indicates that P. graminis-tritici represents a serious threat to wheat cultivation globally.

Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours.

PURPOSE: Somatostatin-based radiopeptide treatment is generally performed using the ß-emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. METHODS: In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y-DOTA]-TOC or [(177)Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. RESULTS: Overall, 910 patients underwent 1,804 cycles of [(90)Y-DOTA]-TOC and 141 patients underwent 259 cycles of [(177)Lu-DOTA]-TOC. The median survival after [(177)Lu-DOTA]-TOC and after [(90)Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95% confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [(177)Lu-DOTA]-TOC over [(90)Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [(177)Lu-DOTA]-TOC treatment (1.4 vs 10.1%, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8%, p = 0.32). CONCLUSION: The present results revealed no difference in median overall survival after [(177)Lu-DOTA]-TOC and [(90)Y-DOTA]-TOC. Furthermore, [(177)Lu-DOTA]-TOC was less haematotoxic than [(90)Y-DOTA]-TOC.

QoI Resistance and Mitochondrial Genetic Structure of Zymoseptoria tritici in Morocco.

In total, 230 single-conidial isolates of the fungal wheat pathogen Zymoseptoria tritici (formerly Septoria tritici, teleomorph: Mycosphaerella graminicola) were sampled in Morocco in 2008 and 2010 to assess resistance against quinone outside inhibitors (QoIs), a widely used group of fungicides in wheat pest management. All 134 isolates sampled in 2008 were QoI sensitive. In contrast, 9 of the 96 isolates from the 2010 collection were resistant, suggesting a recent emergence of the resistance. Mitochondrial (mt)DNA-sequence analyses identified four haplotypes among the resistant isolates. Wright's F statistics (FST) analyses from mtDNA sequences revealed a shallow population structure of Z. tritici within Morocco and a substantial asymmetric gene flow from Europe into Morocco. A phylogenetic reconstruction including Moroccan and European isolates clustered the haplotypes regardless of their geographic origin. The four Moroccan QoI-resistant mitochondrial haplotypes clustered in two distinct clades in the tree topology, suggesting at least two independent origins of the resistance. This study reported, for the first time, the occurrence of QoI-resistant genotypes of Z. tritici in Morocco. Our findings are consistent with the hypothesis that QoI resistance emerged very recently through parallel genetic adaptation in Morocco, although gene flow from Europe cannot be excluded.

Revisiting Mt Fuji's groundwater origins with helium, vanadium and environmental DNA tracers.

Known locally as the water mountain, for millennia Japan's iconic Mt Fuji has provided safe drinking water to millions of people via a vast network of groundwater and freshwater springs. Groundwater, which is recharged at high elevations, flows down Fuji's flanks within three basaltic aquifers, ultimately forming countless pristine freshwater springs among Fuji's foothills. Here we challenge the current conceptual model of Fuji being a simple system of laminar groundwater flow with little to no vertical exchange between its three aquifers. This model contrasts strongly with Fuji's extreme tectonic instability due to its unique location on top of the only known continental trench-trench-trench triple junction, its complex geology and its unusual microbial spring water communities. On the basis of a unique combination of microbial environmental DNA, vanadium and helium tracers, we provide evidence for prevailing deep circulation and a previously unknown deep groundwater contribution to Fuji's freshwater springs. The most substantial deep groundwater upwelling has been found along Japan's most tectonically active region, the Fujikawa-kako Fault Zone. Our findings broaden the hydrogeological understanding of Fuji and demonstrate the vast potential of combining environmental DNA, on-site noble gas and trace element analyses for groundwater science.

Migration patterns and changes in population biology associated with the worldwide spread of the oilseed rape pathogen Leptosphaeria maculans.

Pathogen introductions into novel areas can lead to the emergence of new fungal diseases of plants. Understanding the origin, introduction pathways, possible changes in reproductive system and population size of fungal pathogens is essential in devising an integrated strategy for the control of these diseases. We used minisatellite markers to infer the worldwide invasion history of the fungal plant pathogen Leptosphaeria maculans, which causes stem canker (blackleg) of oilseed and vegetable brassicas. Clustering analyses partitioned genotypes into distinct populations corresponding to major geographic regions, along with two differentiated populations in Western Canada. Comparison of invasion scenarios using Approximate Bayesian Computation suggested an origin of the pathogen in the USA, the region where epidemics were first recorded, and independent introductions from there over the last few decades into Eastern Canada (Ontario), Europe and Australia. The population in Western Canada appeared to be founded from a source in Ontario and the population in Chile resulted from an admixture between multiple sources. A bottleneck was inferred for the introduction into Western Canada but not into Europe, Ontario or Australia. Clonality appeared high in Western Canada, possibly because environmental conditions there were less conducive to sexual reproduction. Leptosphaeria maculans is a model invasive pathogen with contrasting features in different regions: shallow population structure, high genetic variability and regular sexual recombination in some regions, by comparison with reduced genetic variability, high rates of asexual multiplication, strong population structure or admixture in others.

[Posterior percutaneous arthrodesis under CT guidance after surgical anterior arthrodesis: a new technique]. / Arthrodèse percutanée postérieure sous guidage scanner en complément de l'arthrodèse antérieure chirurgicale: une nouvelle technique.

Transfacet screws may be useful for stabilizing segments reconstructed with bone graft or cages, the role of supplementary posterior fixation, particularly minimally invasive techniques such as transfacetar percutaneous screws is relevant. To benefit from a mechanical fixation after anterior arthrodesis without the inconveniences of the open classical posterior surgical intervention, we have developed a new procedure performed under local anesthesia and CT guidance and based on the intra-articular application of screws. This study was designed to demonstrate the feasibility of using a CT-scan to perform posterior arthrodesis of the spine under local anesthesia.

Cross-sphere modelling to evaluate impacts of climate and land management changes on groundwater resources.

Climate change affects both water resources and agricultural production. With rising temperatures and decreasing summer precipitation, it is expected that agricultural production will be increasingly limited by drought. Where surface- or groundwater resources are available for irrigation, an increase in water withdrawals for irrigation is to be expected. Therefore, quantitative approaches are required to anticipate and manage the expected conflicts related to increased water abstraction for irrigation. This project aims to investigate how agricultural production, water demand for irrigation, runoff and groundwater dynamics are affected by future climate change and how climate change impacts combined with changes in agricultural water use affect groundwater dynamics. To answer these research questions, a comprehensive, loosely coupled model approach was developed, combining models from three disciplines: an agricultural plant growth model, a hydrological model and a hydrogeological model. The model coupling was implemented and tested for an agricultural area located in Switzerland in which groundwater plays a significant role in providing irrigation water. Our suggested modelling approach can be easily adapted to other areas. The model results show that yield changes are driven by drought limitations and rising temperatures. However, an increase in yield may be realized with an increase in irrigation. Simulation results show that the water requirement for irrigation without climate protection (RCP8.5) could increase by 40% by the end of the century with an unchanged growing season and by up to 80% with varietal adaptations. With climate change mitigation (RCP2.6) the increase in water demand for irrigation would be limited to 7%. The increase in irrigation (+12 mm) and the summer decrease in recharge rates (~20 mm/month) with decreasing summer precipitation causes a lowering of groundwater levels (40 mm) in the area in the late summer and autumn. This impact may be accentuated by an intensification of irrigation and reduced by extensification.

Habitat-specific population structure in native western flower thrips Frankliniella occidentalis (Insecta, Thysanoptera).

Invasions by pest organisms are among the main challenges for sustainable crop protection. They pose a serious threat to crop production by introducing a highly unpredictable element to existing crop protection strategies. The western flower thrips Frankliniella occidentalis (Insecta, Thysanoptera) managed to invade ornamental greenhouses worldwide within < 25 years. To shed light on possible genetic and/or ecological factors that may have been responsible for this invasion success, we studied the population genetic structure of western flower thrips in its native range in western North America. Analysis of nucleotide sequence variation and variation at microsatellite loci revealed the existence of two habitat-specific phylogenetic lineages (ecotypes) with allopatric distribution. One lineage is associated with hot/dry climates, the second lineage is restricted to cool/moist climates. We speculate that the ecological niche segregation found in this study may be among the key factors determining the invasion potential of western flower thrips.

4-Nonylphenol in sewage sludge: accumulation of toxic metabolites from nonionic surfactants.

Anaerobically treated sewage sludge was found to contain extraordinarily high concentrations of 4-nonylphenol, a metabolite derived from nonionic surfactants of the nonylphenol polyethoxylate type. Concentrations in activated sewage sludge, in mixed primary and secondary sludge, and in aerobically stabilized sludge were substantially lower, suggesting that the formation of 4-nonylphenol is favored under mesophilic anaerobic conditions. Because 4-nonylphenol may be highly toxic to aquatic life, further research is needed on the fate of 4-nonylphenol after sludge is disposed of in the environment.

[Postoperative chest: normal imaging features]. / Imagerie du thorax post-opératoire: les aspects normaux.

Chest radiographs and CT are especially useful for the follow-up of patients after lung resection. The purpose of this paper is to illustrate normal postsurgical imaging findings that differ according to the type of surgery (pneumonectomy, lobectomy, segmentectomy and wedge resection). Anatomic changes induced by surgery affect the remaining lung, pleura and chest wall, mediastinum and diaphragm. After pneumonectomy, there is accumulation of fluid in the post pneumonectomy space, progressive chest retraction with mediastinal shift toward the operated side and elevation of the ipsilateral hemidiaphragm. After lobectomy, there is hyperexpansion of the remaining lung, mediastinal shift and intercostal space narrowing. Theses findings are different according to the delay after surgery. Knowledge of the variable imaging features is necessary to detect complications and to provide appropriate follow-up of the primary disease.

Brain-computer interfaces (BCIs): detection instead of classification.

Many studies over the past two decades have shown that people can use brain signals to convey their intent to a computer through brain-computer interfaces (BCIs). These devices operate by recording signals from the brain and translating these signals into device commands. They can be used by people who are severely paralyzed to communicate without any use of muscle activity. One of the major impediments in translating this novel technology into clinical applications is the current requirement for preliminary analyses to identify the brain signal features best suited for communication. This paper introduces and validates signal detection, which does not require such analysis procedures, as a new concept in BCI signal processing. This detection concept is realized with Gaussian mixture models (GMMs) that are used to model resting brain activity so that any change in relevant brain signals can be detected. It is implemented in a package called SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection). The results indicate that SIGFRIED produces results that are within the range of those achieved using a common analysis strategy that requires preliminary identification of signal features. They indicate that such laborious analysis procedures could be replaced by merely recording brain signals during rest. In summary, this paper demonstrates how SIGFRIED could be used to overcome one of the present impediments to translation of laboratory BCI demonstrations into clinically practical applications.