Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre-gelation staining expansion microscopy for visualisation of the Plasmodium liver stage

Fluorescence and light microscopy are important tools in the history of natural science. However, the resolution of microscopes is limited by the diffraction of light. One possible method to circumvent this physical restriction is the recently developed expansion microscopy (ExM). By physically expanding the sample in a swellable hydrogel, biomolecules are separated in space allowing to image molecules that are otherwise difficult to study due to their size or complexity. Furthermore, the improved resolution is useful to study protein localization and interactions. However, the original ultrastructure ExM (U-ExM) protocol is very time-consuming, and some epitopes are lost during the process. In this study, we developed a shortened pre-gelation staining ExM (PS-ExM) protocol and tested it to investigate the Plasmodium liver stage. The protocol presented in this study allows expanding pre-stained samples, which results in shorter incubation times, better preservation of some epitopes, and the advantage that non-expanded controls can be performed alongside using the same staining protocol. The protocol applicability was accessed throughout the Plasmodium liver stage showing isotropic five-fold expansion. Furthermore, we used PS-ExM to visualize the association of lysosomes to the parasitophorous vacuole membrane (PVM) as an example of visualizing host-pathogen interaction. We are convinced that this new tool will be helpful for a deeper understanding of the biology of the Plasmodium liver stage.
Histopathological Domain Adaptation with Generative Adversarial Networks Bridging the Domain Gap Between Thyroid Cancer Histopathology Datasets

Deep learning techniques are increasingly being used to classify medical imaging data with high accuracy. Despite this, due to often limited training data, these models can lack sufficient generalizability to predict unseen test data, produced in a different domain, with comparable performance. This study focuses on thyroid histopathology image classification and investigates whether a Generative Adversarial Network (GAN), trained with just 156 patient samples, can produce high quality synthetic images to sufficiently augment training data and improve overall model generalizability. Utilizing a StyleGAN2-ADA approach, the generative network produced images with an FID score of 5.05, matching state-of-the-art GAN results in non-medical domains with comparable dataset sizes. Augmenting the training data with these GAN-generated images increased model generalizability significantly when tested on external data, improving overall accuracy and F1 scores by 36% and 42% respectively. Most importantly, this performance improvement was observed on minority class images, tumour subtypes which are known to suffer from high levels of inter-observer variability when classified by trained pathologists.
Fundamental equations linking methylation dynamics to maximum lifespan in mammals

Many studies have investigated the connection between the rate of change in diverse molecular markers and maximum lifespan across species. We describe a framework to address doubts that the rate of change in any biomarker displays a trivial inverse relation to lifespan. We leverage this framework on two comprehensive methylation datasets. The first connects the rate of change in blood methylation to the lifespan of 93 dog breeds. The second associates the rate of change in distinct chromatin states with the maximum lifespan of 125 mammalian species. We show how methylation levels in selected chromatin states shift with age across the lifespan. Our research reveals three significant outcomes: First, a reciprocal relationship exists between the rate of methylation change in bivalent promoter regions and maximum lifespan. Second, the association between age and average methylation within these bivalent promoter regions bears no relation to maximum lifespan. Third, the rate of methylation change in young animals is related to that in old animals. Our mathematical derivations draw connections between these findings. A substantial part of our mathematical framework for analyzing maximum lifespan can be applied to other molecular assessments as well. Overall, our study demonstrates that epigenetic aging rates in specific chromatin states exhibit an inverse relationship with maximum lifespan.
Holographie particle image velocimetry

Holography is truly the key to three dimensions in particle image velocimetry, i.e. the measurement of all spatial components of the velocity vector-and this over a deep measuring field. Sophisticated instruments have been designed that successfully tackle practical problems such as the low scattering efficiency of particles, the inferior depth resolution or the aberrations and distortions in the reconstruction. Furthermore, efficient strategies are introduced to interrogate the holographic storage and process the huge amount of data towards a final flow field representation. Recently, phase-sensitive metrology, familiar in many fields of experimental mechanics, has been examined for use in particle velocimetry. Suitable methods are holographic and speckle interferometry or the optical processing of data for three-dimensional correlation. While in these techniques the power of optics is unrivalled, the practical advantage of video and digital techniques over photographic recording is obvious. The electronic version of speckle interferometry (ESPI/DSPI) is a well-established method used in laser metrology and has received further exploitation for applications in flow analysis recently. Finally, the state-of-the-art of digital particle holography is reviewed to allow estimates of its future in experimental flow analysis.
Real Time In vivo Analysis of Pancreatic Beta-cell Autophagic Flux Reveals Impairment Before Onset of Autoimmune Diabetes

The catabolic pathway of autophagy is critical for pancreatic beta-cell function and is defective in established type 1 diabetes (T1D). However, it is unclear when and how this critical cell process becomes defective during diabetes pathogenesis. To study the nature of autophagy dysfunction in the context of autoimmune diabetes, we utilized intravital microscopy to study autophagic flux in vivo in real time. We generated a custom AAV8- packaged mCherry-eGFP-LC3B biosensor driven by the insulin promoter for beta-cell-selective expression. For real time autophagic flux evaluation, fluorescent signal from eGFP and mCherry fluorophores was correlated in space and time to follow the process of autophagosome-lysosome fusion. We observed autophagic flux defects in the beta-cells of non-obese diabetic (NOD) mouse model of T1D prior to hyperglycemia onset that were less apparent in mice without a functional immune system. We also evaluated autophagic flux in human donor islets that were transplanted under the kidney capsule of immune incompetent mice. Collectively, we provide the first evaluation of autophagic flux in vivo in 4D and demonstrate that autophagy defects precede hyperglycemia in NOD mice suggesting a potential causative role for these defects in beta-cell demise during T1D pathogenesis.
Ethnopharmacological disease classification and bioprospecting: the diversity of plant drugs used to treat cancer

Cancer is a highly-diverse disease and as the second-leading cause of death worldwide is a focus of drug discovery research. Natural products have been shown to be a useful source of novel molecules for the treatment of cancer. It is likely there are many plants with undiscovered molecules of therapeutic value, however identifying new leads from among the vast diversity of plants is very challenging. Traditional knowledge might inform bioprospecting by predicting lineages of plants rich in therapeutically useful molecules. Here, we characterise the phylogenetic diversity of plants used traditionally to manage cancer. We demonstrate the independent and repeated targeting of specific lineages of plants by different peoples in different parts of the world. That the same lineages are used to treat different cancers is suggestive of independent discovery of therapeutic value. However, the lineages we report here as rich in plants used traditionally to treat cancer coincide with those for other ethnobotanical applications, and contain few plants with proven anti-cancer activity. It is likely that the traditional knowledge recorded and explored here is shaped by selection of plants conferring milder effects for treating wider symptoms, such as tiredness or nausea, rather than for halting tumour growth. Accurate prediction of useful plant lineages for cancer management requires more nuanced information than is commonly provided in ethnobotanical records.
Influence of visual information on sniffing behavior in a routinely trichromatic primate

Most catarrhine primates are considered to be strongly visually oriented, obtaining information about conspecifics and their environment from a diversity of visual cues. Other sensory modalities may provide information that is redundant and/or complimentary to visual cues. When cues from multiple sensory modalities are available, these may reinforce or suppress each other, as shown in several taxa ranging from insects to humans. Here, we tested how the presence and ambiguity of visual information affects the use of olfactory cues when exploring food and non-food items in semi-free ranging Barbary macaques at Affenberg Salem, Germany. We presented monkeys with pipes containing food (peanuts, popcorn), non-food (stones, feces) or no items in transparent or opaque containers, and assessed whether animals looked, sniffed and/or grabbed into the pipes depending on visibility of the contents (experiment 1). Visual information had no robust effect on sniffing probability, but it did affect sniffing behavior with respect to the timing of olfactory inspections (i.e. whether sniffing occurred first). Both visual and olfactory information affected, whether or not monkeys attempted to retrieve the items from the pipes. Furthermore, we manipulated the visual appearance of familiar food items (popcorn) with food colorant (experiment 2), which resulted in substantially increased olfactory inspections compared to unmanipulated popcorn. Taken together, reliance on the olfactory sense was modulated by the available visual information, emphasizing the interplay between different sensory modalities for obtaining information about the environment.
High-throughput phenotyping of single nucleotide variants by linking transcriptomes to genotypes in single cells

CRISPR screens with single-cell transcriptomic readouts are a valuable tool to understand the effect of genetic perturbations, but are currently limited because genotypes are inferred from the guide RNA identity. We have developed a technique that couples single-cell genotyping to transcriptomics of the same cells to enable screening for the effects of single nucleotide variants. Analysis of variants tiling across the JAK1 gene demonstrates the importance of determining the precise genetic perturbation and classifies missense variants into three functional categories.
Endogenous pathology in tauopathy mice progresses via brain networks

Neurodegenerative tauopathies are hypothesized to propagate via brain networks. This is uncertain because we have lacked precise network resolution of pathology. We therefore developed whole-brain staining methods with anti-p-tau nanobodies and imaged in 3D PS19 tauopathy mice, which have pan-neuronal expression of full-length human tau containing the P301S mutation. We analyzed patterns of p-tau deposition across established brain networks at multiple ages, testing the relationship between structural connectivity and patterns of progressive pathology. We identified core regions with early tau deposition, and used network propagation modeling to determine the link between tau pathology and connectivity strength. We discovered a bias towards retrograde network-based propagation of tau. This novel approach establishes a fundamental role for brain networks in tau propagation, with implications for human disease. One-Sentence Summary Novel whole brain imaging of p-tau deposition reveals retrograde-dominant network propagation in a tauopathy mouse model.
sncRNAP: Prediction and profiling of full sncRNA repertoires from sRNAseq data

Motivation Non-coding RNAs (ncRNAs), which include long non-coding RNAs (lncRNAs) and small non-coding RNAs (sncRNAs), have been shown to play essential roles in various biological processes. Over the past few years, a group of sncRNA identification tools have been developed but none has shown the capacity to fully profile and accurately identify those that are differentially expressed in control vs treated samples. Therefore, a tool that fully profiles and identifies differentially expressed sncRNAs in group comparisons is required. Results We developed sncRNAP, a Nextflow pipeline for the profiling and identification of differentially abundant sncRNAs from sRNAseq datasets. sncRNAP primary use case is the comparison of multiple small RNA-seq datasets belonging to two conditions such as the comparison of treatment (T) and control (C) cohorts. sncRNAP can be used to analyze human, mouse, and rat datasets. The pipeline carries out all the steps required to assess raw sequencing data, performs differential gene expression (DE) analysis, profiles sncRNAs in each sample, and outputs TXT, PDF, CSV, and interactive HTML files for the quality score and the top identified sncRNA candidates. We verified sncRNAP on publicly available sRNAseq datasets in chronic hepatitis-infected liver tissue and pancreatic ductal adenocarcinoma (PDAC) datasets. Our results support the identification of Val[C/A]AC in hepatitis patients and miR135b in PDAC as potential disease biomarkers. Furthermore, we applied sncRNAP on mouse samples from control and Opa1 mouse mutants and identified AspGTC, ValAAC, SerTGA, and AspGTC as the top DE tsRNAs. In addition, sncRNAP identified mmu-miR-136-5p, mmu-miR-10b-5p, mmu-miR-351-5p, and mmu-miR-6390 as the top DE miRNA candidates.
Regulation of hippocampal mossy fiber-CA3 synapse function by a 1 Bcl11b/C1ql2/Nrxn3(25b+) pathway

1 2 The transcription factor Bcl11b has been linked to neurodevelopmental and neuropsychiatric disorders 3 associated with synaptic dysfunction. Bcl11b is highly expressed in dentate gyrus granule neurons and 4 is required for the structural and functional integrity of mossy fiber-CA3 synapses. The underlying 5 molecular mechanisms, however, remained unclear. We show that the synaptic organizer molecule 6 C1ql2 is a direct functional target of Bcl11b that regulates synaptic vesicle recruitment and long-term 7 potentiation at mossy fiber-CA3 synapses in vivo and in vitro . Furthermore, we demonstrate C1ql2 to 8 exert its functions through direct interaction with a specific splice variant of neurexin-3, Nrxn3(25b+). 9 Interruption of C1ql2-Nrxn3(25b+) interaction by expression of a non-binding C1ql2 mutant or by 10 deletion of Nrxn3 in the dentate gyrus granule neurons recapitulates major parts of the Bcl11b as well 11 as C1ql2 mutant phenotype, and interferes with C1ql2 targeting to the synapse. Together, this study 12 identifies a novel C1ql2-Nrxn3(25b+)-dependent signaling pathway through which Bcl11b controls 13 mossy fiber-CA3 synapse function. Thus, our findings contribute to the mechanistic understanding of 14 neurodevelopmental disorders accompanied by synaptic dysfunction. 15
Thalamic contributions to psychosis susceptibility: Evidence from co‐activation patterns accounting for intra‐seed spatial variability (μCAPs)

The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro-co-activation patterns (μCAPs) by employing this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting-state functional MRI and a data-driven iterative process resulting in the identification of six whole-brain μCAPs with specific activity patterns within the thalamus. Unlike conventional methods, μCAPs extract dynamic spatial patterns that reveal partially overlapping and non-mutually exclusive functional subparts. Thus, the μCAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a μCAP showing co-activation of the mediodorsal thalamus with brain-wide cortical regions was significantly less frequent in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, the activity within the auditory-visual cortex and their respective geniculate nuclei were expressed in two different μCAPs. One of these auditory-visual μCAPs co-activated with salience areas, while the other co-activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo-auditory-thalamus to the DMN+visuo-auditory-thalamus μCAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio-visual cortex in 22q11.2DS in the context of dynamic functional connectivity as specific hyper-occurrence of these circuits with the task negative brain networks.
Vocal-visual combinations in wild chimpanzees

Human communication is strikingly multi-modal, relying on vocal utterances combined with visual gestures, facial expressions and more. Recent efforts to describe multi-modal signal production in our ape relatives have shed important light on the evolutionary trajectory of this core hallmark of human language. However, whilst promising, a systematic quantification of primate signal production which filters out random combinations produced across modalities is currently lacking. Here, through recording the communicative behaviour of wild chimpanzees from the Kibale forest, Uganda we address this issue and generate the first repertoire of non-random combined vocal and visual components. Using collocation analysis, we identify more than 100 vocal-visual combinations which occur more frequently than expected by chance. We also probe how multi-modal production varies in the population, finding no differences between individuals as a function of age, sex or rank. The number of visual components exhibited alongside vocalizations was, however, associated with vocalization type and duration. We demonstrate that chimpanzees produce a vast array of combined vocal and visual components, exhibiting a hitherto underappreciated level of combinatorial complexity. We conclude that a multi-modal approach is crucial to accurately representing the communicative abilities of non-human primates.
Prototyping an End-User User Interface for the Solid Application Interoperability Specification Under GDPR

This paper describes prototyping of the draft Solid application interoperability specification (INTEROP). We developed and evaluated a dynamic user interface (UI) for the new Solid application access request and authorization extended with the Data Privacy Vocabulary. Solid places responsibility on users to control their data. INTEROP adds new declarative access controls. Solid applications to date have provided few policy interfaces with high usability. GDPR controls on usage are rarely addressed. Implementation identified specification and Semantic Web tool issues and also in the understandability of declarative policies, a key concern under GDPR or data ethics best practices. The prototype was evaluated in a usability and task accuracy experiment, where the UI enabled users to create access and usage control policies with an accuracy of between 72 and 37%. Overall, the UI had a poor usability rating, with a median SUS (system usability scale) score of 37.67. Experimental participants were classified according to the Westin privacy scale to investigate the impact of user attitudes to privacy on the results. The paper discusses the findings of the study and their consequences for future data sovereignty access request and authorization UI designs.
LegalHTML: A Representation Language for Legal Acts

The Publications Office (OP) of European Union (EU) expressed the need to simplify the Official Journal production workflow, which required different formats and, consequently, document instances at different stages of the process. We met this need by developing LegalHTML, which unifies the formal, structural and semantic representation of legal acts, as well allowing for diverse typographic requirements for publication. This streamlines the production workflow and publication/fruition of content as well, since a single document instance is first drafted and then incrementally enriched. LegalHTML consists of an extension of HTML for the structural representation of legal acts (e.g., articles, paragraphs, items, and references), while a supplementary ontology enables the annotation (using RDFa) of domain references (e.g., signatories, people and their role in organizations, the scope of the document). LegalHTML also supports the consolidation of an act and its subsequent changes into a single document using a tree-based representation. Finally, we implemented a CSS stylesheet for the default rendering of the model and a JavaScript file imbuing documents with an API that supports TOC generation, footnote cross-references and point-in-time visualization of legal acts.
On Torsion-Free Groups of Finite Rank

This paper deals with two conditions which, when stated, appear similar, but when applied to finitely generated solvable groups have very different effect. We first establish the notation before stating these conditions and their implications. If H is a subgroup of a group G, let denote the set We say G has the isolator property if is a subgroup for all H ≦ G. Groups possessing the isolator property were discussed in [2]. If we define the relation ∼ on the set of subgroups of a given group G by the rule H ∼ K if and only if , then ∼ is an equivalence relation and every equivalence class has a maximal element which may not be unique. If , we call H an isolated subgroup of G.
Correction of sky glint above water surface based on polarized principle

The specular reflected light above water surface,including sun-glint and sky-glint,is one of the key factors that affect remote sensing of water color.This paper aims to correct the sun-glint and sky-glint effects in measurements of upward radiance from water surface based on the polarized principle and the multi-angle polarized remote sensing.A polarization filter was placed in front of the sensor of ASD field spectrometer to obtain the polarized characteristics of water surface spectrum in various conditions.By contrast with the spectral obtained under different incident geometry and polarized conditions,the experimental results show that the reflected light can be corrected completely with an incident zenith angle of 53 degree(Brewster's angle) and zero polarized angle.And most of the reflected light can be corrected with a random incident angle and zero polarized angle.In conclusion,the reflected light can be reduced obviously or even removed completely based on the polarized principle,which provide important value to improve the accuracy of water color remote sensing.