Masaryk University

For millennia humans have interacted with a range of chemical substances that are an integral part of human history and culture. The chemical characteristics of the three similar-looking chemical species psilocybin, nicotine, and caffeine have remarkably different biological effects. The narratives of these chemical characters are compelling—their role traverses the unobservable submicroscopic world, influences our biological essence, and impacts societal values and scientific judgement. Visual storytelling through modern display technologies offers an educational method to communicate the nature and effect of these chemical actors. Biological information that transcends multi-directionally and constantly from submicroscopic through to macroscopic processes can be made accessible and meaningful to students and the public. In doing so, links are forged between scientific knowledge and the manner we view these chemical forms from a human and societal context. In attempting to capture these complexities, the aim of this chapter is to conceptualise and design a visual story to communicate the effect of psilocybin, nicotine, and caffeine on humans for public engagement. Whilst remarkably similar in chemical structure, these chemical species have dramatically different psychological and physiological effects on the human body. At the same time, human interaction with these substances is intertwined with historical associations, cultural norms, as well as perceived and enacted taboos.

Poales are one of the most species-rich, ecologically and economically important orders of plants and often characterise open habitats, enabled by unique suites of traits. We test six hypotheses regarding the evolution and assembly of Poales in open and closed habitats throughout the world and examine whether diversification patterns demonstrate parallel evolution. We sampled 42% of Poales species and obtained taxonomic and biogeographic data from the World Checklist of Vascular Plants database, which was combined with open/closed habitat data scored by taxonomic experts. A dated supertree of Poales was constructed. We integrated spatial phylogenetics with regionalisation analyses, historical biogeography and ancestral state estimations. Diversification in Poales and assembly of open and closed habitats result from dynamic evolutionary processes that vary across lineages, time and space, most prominently in tropical and southern latitudes. Our results reveal parallel and recurrent patterns of habitat and trait transitions in the species-rich families Poaceae and Cyperaceae. Smaller families display unique and often divergent evolutionary trajectories. The Poales have achieved global dominance via parallel evolution in open habitats, with notable, spatially and phylogenetically restricted divergences into strictly closed habitats.

Primates are an important source of infectious disease in humans. Strongyloidiasis affects an estimated 600 million people worldwide, with a global distribution and hotspots of infection in tropical and subtropical regions. Recently added to the list of neglected tropical diseases, global attention has been demanded in the drive for its control. Through a literature review of Strongyloides in humans and non-human primates (NHP), we analysed the most common identification methods and gaps in knowledge about this nematode genus. The rise of molecular-based methods for Strongyloides detection is evident in both humans and NHP and provides an opportunity to analyse all data available from primates. Dogs were also included as an important host species of Strongyloides and a potential bridge host between humans and NHP. This review highlights the lack of molecular data across all hosts—humans, NHP and dogs—with the latter highly underrepresented in the database. Despite the cosmopolitan nature of Strongyloides, there are still large gaps in our knowledge for certain species when considering transmission and pathogenicity. We suggest that a unified approach to Strongyloides detection be taken, with an optimized, repeatable molecular-based method to improve our understanding of this parasitic infection. This article is part of the Theo Murphy meeting issue ‘Strongyloides: omics to worm-free populations’.

Monoclonal gammopathies are a group of blood diseases characterized by presence of abnormal immunoglobulins in peripheral blood and/or urine of patients. Multiple myeloma and plasma cell leukemia are monoclonal gammopathies with unclear etiology, caused by malignant transformation of bone marrow plasma cells. Mass spectrometry with matrix-assisted laser desorption/ ionization and time-of-flight detection is commonly used for investigation of the peptidome and small proteome of blood plasma with high accuracy, robustness, and cost-effectivity. In addition, mass spectrometry coupled with advanced statistics can be used for molecular profiling, classification, and diagnosis of liquid biopsies and tissue specimens in various malignancies. Despite the fact there have been fully optimized protocols for mass spectrometry of normal blood plasma available for decades, in monoclonal gammopathy patients, the massive alterations of biophysical and biochemical parameters of peripheral blood plasma often limit the mass spectrometry measurements. In this paper, we present a new two-step extraction protocol and demonstrated the enhanced resolution and intensity (>50×) of mass spectra obtained from extracts of peripheral blood plasma from monoclonal gammopathy patients. When coupled with advanced statistics and machine learning, the mass spectra profiles enabled the direct identification, classification, and discrimination of multiple myeloma and plasma cell leukemia patients with high accuracy and precision. A model based on PLS-DA achieved the best performance with 71.5% accuracy (95% confidence interval, CI = 57.1−83.3%) when the 10× repeated 5-fold CV was performed. In summary, the two-step extraction protocol improved the analysis of monoclonal gammopathy peripheral blood plasma samples by mass spectrometry and provided a tool for addressing the complex molecular etiology of monoclonal gammopathies.

Svalbard has experienced a dramatic increase in air temperature and glacier retreat since the end of the Little Ice Age. In many cases, this retreat has resulted in glaciers transitioning from being marine-terminating to land-terminating. Nordenskiöldbreen is an excellent contemporary example of this transition. A set of historical observations of glacier front positions was used to assess Nordenskiöldbreen's retreat rate and we found that the southern portion of the glacier front retreated by ∼3500 m, since records began in 1896. The general retreat rate corresponds well with the air temperature trend during most of the 20th century. However, the average retreat rate has slowed since the 1990s despite increasing air temperatures. We show that this discrepancy between air temperature and retreat rate marks the transition from marine-terminating towards a land-terminating glacier, as the glacier's bedrock topography started to play an essential role in the glacier margin geometry, ice flow and retreat dynamics.

Measurable residual disease (MRD) monitoring in childhood acute myeloid leukemia (AML) is used to assess response to treatment and for early detection of imminent relapse. In childhood AML, MRD is typically evaluated using flow cytometry, or by quantitative detection of leukemia-specific aberrations at the mRNA level. Both methods, however, have significant limitations. Recently, we demonstrated the feasibility of MRD monitoring in selected subgroups of AML at the genomic DNA (gDNA) level. To evaluate the potential of gDNA-based MRD monitoring across all AML subtypes, we conducted a comprehensive analysis involving 133 consecutively diagnosed children. Integrating next-generation sequencing into the diagnostic process, we identified (presumed) primary genetic aberrations suitable as MRD targets in 97% of patients. We developed patient-specific quantification assays and monitored MRD in 122 children. The gDNA-based MRD monitoring via quantification of primary aberrations with a sensitivity of at least 10⁻⁴ was possible in 86% of patients; via quantification with sensitivity of 5 × 10⁻⁴, of secondary aberrations, or at the mRNA level in an additional 8%. Importantly, gDNA-based MRD exhibited independent prognostic value at early time-points in patients stratified to intermediate-/high-risk treatment arms. Our study demonstrates the broad applicability, feasibility, and clinical significance of gDNA-based MRD monitoring in childhood AML.

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate β-catenin–dependent (canonical) or –independent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells.

Mass spectral libraries have proven to be essential for mass spectrum annotation, both for library matching and training new machine learning algorithms. A key step in training machine learning models is having high-quality training data. Public libraries of mass spectrometry data that are open to user submission often suffer from limited metadata curation and harmonization. The resulting variability in data quality makes training of machine learning models challenging. Here we present a library cleaning pipeline designed for cleaning tandem mass spectrometry library data. The pipeline is designed with ease of use, flexibility and reproducibility as leading principles.

Matching logic (ML) is a formalism for specifying and reasoning about mathematical structures by means of patterns and pattern matching. Previously, it has been used to capture a number of other logics, e.g., separation logic with recursive definitions and linear temporal logic. ML has also been formalized in the Coq Proof Assistant, and the soundness of its Hilbert-style proof system has been mechanized. However, using a Hilbert-style system for interactive reasoning is challenging—even more so in ML, which lacks a general deduction theorem. Therefore, we propose a single-conclusion sequent calculus for ML that is more amenable to interactive proving. Based on this sequent calculus, we implement a proof mode for interactive reasoning in ML, which significantly simplifies the construction of ML proofs in Coq. The proof mode is a mechanism for displaying intermediate proof states and an extensible set of proof tactics that implement the rules of the sequent calculus. We evaluate our proof mode on a collection of examples, showing a substantial improvement in proof script size and readability.

Attack trees are a graphical formalism for security assessment. They are particularly valued for their explainability and high accessibility without security or formal methods expertise. They can be used, for instance, to quantify the global insecurity of a system arising from the unreliability of its parts, graphically explain security bottlenecks, or identify additional vulnerabilities through their systematic decomposition. However, in most cases, the main hindrance in the practical deployment is the need for a domain expert to construct the tree manually or using further models. This paper demonstrates how to learn attack trees from logs, i.e., sets of traces, typically stored abundantly in many application domains. To this end, we design a genetic algorithm and apply it to classes of trees with different expressive power. Our experiments on real data show that comparably simple yet highly accurate trees can be learned efficiently, even from small data sets.

Stress variations in the Earth's crust need to be understood in both the spatial and temporal domains to address a number of pressing societal issues. In this paper, precise three dimensional records of fault kinematic behaviour obtained by mechanical extensometers are used to investigate changes in stress states along major faults in the Eastern Alps. The monitored faults are fractures with evident Upper Quaternary displacement and are directly attributed to their master tectonic structures. The results demonstrate that activity at the submillimetric scale is highly episodic; periods of repose are punctuated by conspicuous reactivation events affecting one or more of the displacement components. An original approach named the SMB2018 method is used to define the stress state associated with each fault reactivation event. The outputs evidence significant short term changes in the local stress regime. The directions of the principal normal stresses calculated from these reactivation events present generally similar patterns for both compressional and extensional stress states. Consequently, submillimetric fault activity cannot be controlled by a rotating stress field; such shifts can only be caused by a change in the magnitude of the individual principal normal stresses so that the maximum compression changes to the minimum and vice versa.

Common variable immunodeficiency disorder (CVID) is the most common form of primary antibody immunodeficiency. Due to low antibody levels, CVID patients receive intravenous or subcutaneous immunoglobulin replacement therapy as treatment. CVID is associated with the chronic activation of granulocytes, including an increased percentage of low‐density neutrophils (LDNs). In this study, we examined changes in the percentage of LDNs and the expression of their surface markers in 25 patients with CVID and 27 healthy donors (HD) after in vitro stimulation of whole blood using IVIg. An oxidative burst assay was used to assess the functionality of LDNs. CVID patients had increased both relative and absolute LDN counts with a higher proportion of mLDNs compared to iLDNs, distinguished based on the expression of CD10 and CD16. Immature LDNs in the CVID and HD groups had significantly reduced oxidative burst capacity compared to mature LDNs. Interestingly we observed reduced oxidative burst capacity, reduced expression of CD10 after stimulation of WB, and higher expression of PD‐L1 in mature LDNs in CVID patients compared to HD cells. Our data indicate that that the functional characteristics of LDNs are closely linked to their developmental stage. The observed reduction in oxidative burst capacity in mLDNs in CVID patients could contribute to an increased susceptibility to recurrent bacterial infections among CVID patients.

Introduction The I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021. Aim We aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period). Methods In both networks, 46 hospitals (13 countries) follow a similar test-negative case–control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition. Results We included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29–54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51–66) after addition of one booster dose. The VE was 85% (95% CI: 78–89), 70% (95% CI: 61–77) and 36% (95% CI: 17–51) for those with onset 14–59 days, 60–119 days and 120–179 days after booster vaccination, respectively. Conclusions Our results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.