Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced resistance to foliar fungal pathogens in carrot by application of elicitors

Treatment of greenhouse-grown carrot plants with salicylic acid (SA) (100 μM), chitosan (0.02%) and the nutrient-chelate product Alexin (1%) followed 10 h later by inoculation with the necrotrophic fungal pathogens Alternaria radicina and Botrytis cinerea significantly reduced disease development 10 days after inoculation (d.a.i.) compared with control plants sprayed with water. The most effective treatment was chitosan, followed by Alexin and SA. Additional sprays of elicitors resulted in significantly lower disease development 25 d.a.i. Treated plants had elevated transcript levels of pathogenesis-related protein 1 (PR1), chitinase, lipid transfer protein (LTP), chalcone synthase, nonexpressor of PR1 and pathogenesis-related protein 5 (PR5) genes compared with control plants when assayed 10―70 h after treatment. The activity of peroxidase, polyphenoloxidase, phenylalanine ammonia-lyase, chitinase, β-1,3-glucanase and lipoxygenase was significantly increased in elicitor-treated plants compared with control plants 12―72 h after treatment. Microscopic examination of treated leaves revealed reduced fungal growth and colonisation, 48 h after treatment, accompanied by fewer lesions at 120 h, compared with the control. Protein extracts from elicitor-treated plants reduced spore germination and germ tube elongation of the pathogens in vitro by 30―45%. Elicitor-treated plants accumulated higher amounts of total phenolics, 6-methoxymellin and H 2 O 2 compared with the control. Both chitosan and Alexin induced responses similar to that of SA, suggesting that these elicitors may activate the salicylate pathway, leading to induction of defence genes, enzymes, phytoalexin and phenolics, which collectively reduced fungal colonisation.
L1 adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to αvβ3 integrin

The L1 adhesion molecule is a member of the immunoglobulin (Ig) superfamily initially identified in the nervous system which contains six Ig‐like domains. Besides the known L1‐L1 homotypic interaction, L1 was recently shown to bind to very late antigen (VLA)‐5 in the mouse and αvβ3 in the human. The sixth Ig domain is critical for this function. We now demonstrate that human CD4+ peripheral blood T lymphocytes, monocytes and B lymphocytes, but not CD8+ T lymphocytes, express L1. When compared to the expression of CD31, another ligand for αvβ3 on T lymphocytes, only a small proportion of cells were CD31+L1+ double positive. L1 was also detected on the surface of human monocytic and lymphoid tumor lines and was shown to have a molecular mass of ∼220 kDa, similar to the molecule present on neuroblastoma cells. The function of the sixth Ig domain of human L1 as an integrin ligand was also investigated. Using an RGD‐containing peptide derived from the sixth Ig domain as well as a fusion protein of the sixth Ig domain of L1 and the Fc portion of human IgG1 (6.L1‐Fc), we demonstrated the binding of human MED‐B1 (αvβ3hi, α5β1lo) tumor cells and this binding was blocked by αv‐specific mAb. In contrast, human Nalm‐6 cells (αvβ3lo, α5β1hi) did not bind to the 6.L1‐Fc fusion protein. MED‐B1 cells could also be stained with the 6.L1‐Fc fusion protein. Our results suggest that human L1 binds predominantly to αvβ3 and that its presence on leukocytes could be important for adhesion and migration.
NITRO: Non-Intrusive Task Detection and Monitoring in Hard Real-Time Systems

With the increasing complexity of real-time systems, developers need advanced tools for detailed analysis. Existing tools usually come with a high configuration effort which prevents their usage or leads to configuration errors. Further problems are contributed by analysis techniques that may introduce software overhead, which changes the system's behavior. Another major issue is, that modern real-time systems make use of purchasable software components, so-called Intellectual Property (IP) blocks. Since not all information is accessible on these IP blocks, they can lead to the development of opaque real-time systems, which are then even harder to analyze. With NITRO we want to present a new methodology to tackle these problems. It enables developers to analyze hard real-time systems without requiring detailed knowledge of the system. NITRO is capable of detecting and monitoring the complete task set of a hard real-time operating system, without error-prone user configuration. Designers neither need to understand how the operating system is implemented, nor how to configure a tool. Moreover, NITRO works completely non-intrusive and is therefore superior to instrumentation based analysis techniques. We also show that non-intrusive monitoring does not require expensive tracing hardware.
Relationships between Habitat Characteristics and Fish Assemblages in Small Streams of Central Amazonia

Abstract Small streams with acidic, nutrient-poor waters form a dense hydrological system in Central Amazonia. However, little is known about the fish assemblages that occur in these systems. We investigated the relationships among stream size, substrate, and other physical-chemical factors and fish distributions. Fish assemblages and stream characteristics were sampled in 50-m long sections of streams at 38 sites distributed throughout the 100-km2 florestal reserve. Forty-nine species were encountered. The mean richness was similar among sites; however, community composition was correlated with physical and chemical characteristics of the streams. The mean number of species per site (X̄ = 9) was low in relation to the total number of species recorded from the reserve (49) and in relation to the ichthyofauna that has been recorded from small forest streams near the study area. This contrasts with studies in temperate zones where strong patterns of species addition along the river continuum were found, resulting in prominent species richness gradients. The high between-site turnover in species composition and the strong habitat specificity indicate that it will be necessary to create a network of reserves to efficiently conserve the fish fauna of small forest streams in Central Amazonia. Na Amazônia Central, pequenos riachos de águas ácidas e pobres em nutrientes constituem uma densa rede hidrica. Contudo, pouco é conhecido sobre a riqueza e abundância de sua ictiofauna. Para determinar a composição ictiofaunistica existente, bem como determinar a relação entre o tamanho dos igarapés, substratos presentes nos leitos, e fatores fisico-quimicos e a estrutura da comunidade, nós amostramos trechos de 50-m em 38 locais distribuidos em uma reserva de 100-km2. A riqueza média foi semelhante entre os sitios de amostragem. No entanto, a composição de espécies foi relacionada com caracteristicas fisicas e quimicas dos riachos. O número médio de espécies por local (X̄ = 9) foi pequeno em relação ao número total de espécies encontrado na reserva (49) e em relação à ictiofauna que foi encontrada em pequenos riachos próximos à área de estudo. Isto contrasta com estudos realizados em zonas temperadas, onde um padrão muito forte de adição de espécies ao longo das bacias foi encontrado, resultando em um gradiente acentuado de riqueza de espécies. A alta troca na composição de espécies entre locais, e a alta especificidade de hábitat, indica que seria necessário criar uma rede de reservas para conservar eficientemente a ictiofauna de pequenos riachos na região.
Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis

Sepsis is a serious syndrome characterised by a dysregulated systemic inflammatory response. Here we have analysed the role and the therapeutic potential of Granzyme A (GzmA) in the pathogenesis of peritoneal sepsis using the Cecal Ligation and Puncture (CLP) polymicrobial sepsis model and samples from humans undergoing abdominal sepsis. Elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen indicating that GzmA has no role in bacterial control. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFα. Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis, and suggest that it could be targeted for treatment of this severe pathology.
SARS-CoV-2-specific T cells exhibit phenotypic features reflecting robust helper function, lack of terminal differentiation, and high proliferative potential

Convalescing COVID-19 patients mount robust T cell responses against SARS-CoV-2, suggesting an important role for T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from nine individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells, and predominantly Tcm with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly Temra cells in a state of less terminal differentiation than most Temra cells. Subsets of SARS-CoV-2-specific T cells express CD127, can homeostatically proliferate, and can persist for over two months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection, and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19.
Multiplexed imaging of human tuberculosis granulomas uncovers immunoregulatory features conserved across tissue and blood

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that is distinctly characterized by granuloma formation within infected tissues. Granulomas are dynamic and organized immune cell aggregates that limit dissemination, but can also hinder bacterial clearance. Consequently, outcome in TB is influenced by how granuloma structure and composition shift the balance between these two functions. To date, our understanding of what factors drive granuloma function in humans is limited. With this in mind, we used Multiplexed Ion Beam Imaging by Time-of-Flight (MIBI-TOF) to profile 37 proteins in tissues from thirteen patients with active TB disease from the U.S. and South Africa. With this dataset, we constructed a comprehensive tissue atlas where the lineage, functional state, and spatial distribution of 19 unique cell subsets were mapped onto eight phenotypically-distinct granuloma microenvironments. This work revealed an immunosuppressed microenvironment specific to TB granulomas with spatially coordinated co-expression of IDO1 and PD-L1 by myeloid cells and proliferating regulatory T cells. Interestingly, this microenvironment lacked markers consistent with T-cell activation, supporting a myeloid-mediated mechanism of immune suppression. We observed similar trends in gene expression of immunoregulatory proteins in a confirmatory transcriptomic analysis of peripheral blood collected from over 1500 individuals with latent or active TB infection and healthy controls across 29 cohorts spanning 14 countries. Notably, PD-L1 gene expression was found to correlate with TB progression and treatment response, supporting its potential use as a blood-based biomarker. Taken together, this study serves as a framework for leveraging independent cohorts and complementary methodologies to understand how local and systemic immune responses are linked in human health and disease.
Genetic screen to saturate guard cell signaling network reveals a role of GDP-L-fucose metabolism in stomatal closure

Guard cells regulate plant gas exchange by controlling the aperture of stomatal pores. The process of stomatal closure involves a multi-input signaling network that governs the activity of ion channels, which in turn regulate guard cell turgor pressure and volume. Here we describe a forward genetic screen to identify novel components involved in stomatal movements. Through an ozone-sensitivity approach combined with whole-rosette gas exchange analysis, 130 mutants of established stomatal regulators and 76 novel mutants impaired in stomatal closure were identified. One of the novel mutants was mapped to MURUS1 (MUR1), the first enzyme in de novo GDP-L-fucose biosynthesis. Defects in synthesis or import of GDP-L-Fuc into the Golgi apparatus resulted in impaired stomatal closure to multiple stimuli. Stomatal phenotypes observed in mur1 were independent from the canonical guard cell signaling and instead could be related to altered mechanical properties of guard cell walls. Impaired fucosylation of xyloglucan, N-linked glycans and arabinogalactan proteins did not explain the aberrant function of mur1 stomata, however our data suggest that the stomatal phenotypes observed in mur1 can at least partially be attributed to defective dimerization of rhamnogalactouronan-II. In addition to providing the genetic framework for future studies on guard cell signaling, our work emphasizes the impact of fucose metabolism on stomatal movement.
Timecourse and convergence of abstract and concrete knowledge in the anterior temporal lobe

How is conceptual knowledge organized and retrieved by the brain? Recent evidence points to the anterior temporal lobe (ATL) as a crucial semantic hub integrating both abstract and concrete conceptual features according to a dorsal-to-medial gradient. It is however unclear when this conceptual gradient emerges and how semantic information reaches the ATL during conceptual retrieval. Here we used a multiple regression approach to magnetoencephalography signals of spoken words, combined with dimensionality reduction in concrete and abstract semantic feature spaces. Results showed that the dorsal-to-medial abstract-to-concrete ATL gradient emerges only in late stages of word processing: Abstract and concrete semantic information are initially encoded in posterior temporal regions and travel along separate cortical pathways eventually converging in the ATL. The present finding sheds light on the neural dynamics of conceptual processing that shape the organization of knowledge in the anterior temporal lobe.
The Impact of Restriction-Modification Systems on Mating in Haloferax volcanii

Halobacteria have been observed to be highly recombinogenic, frequently exchanging genetic material. Several barriers to mating in the Halobacteria have been examined, such as CRISPR-Cas, glycosylation, and archaeosortases, but these are low barriers that do not drastically reduce the recombination frequency. Another potential barrier could be restriction-modification (RM) systems, which cleave DNA that is not properly methylated, thus limiting the exchange of genetic material between cells which do not have compatible RM systems. In order to examine the role of RM systems on limiting recombination in the Halobacteria, the impact of RM systems on cell-to-cell mating in Haloferax volcanii, a well-characterized method of genetic exchange and recombination in a halobacterial species, was examined. Strains which possessed all naturally-occurring RM system genes in H. volcanii (RM+) and strains without these RM systems (ΔRM) were mated together to compare the efficiency of gene transfer between RM-compatible strains and RM-incompatible strains. The results indicated that mating RM-incompatible strains together resulted in a decrease in gene transfer efficiency compared to mating RM-compatible strains together, suggesting that RM systems limit mating in H. volcanii, but do not act as absolute barriers to recombination. Therefore, RM systems are low barriers to recombination in the Halobacteria, with RM-incompatible strains exchanging genetic material at a lower frequency than those with compatible RM systems, similar to other low recombination barriers in the Halobacteria.
Proximity Labeling-assisted Identification of Endogenous Kinase Substrates

Mass spectrometry-based phosphoproteomics can identify more than 10,000 phosphorylated sites in a single experiment. But, despite the fact that enormous phosphosite information has been accumulated in public repositories, protein kinase-substrate relationships remain largely unknown. Here, we describe a method to identify endogenous substrates of kinases by means of proximity labeling. We used a proximity-dependent biotin identification approach, called BioID, in combination with kinase-perturbed phosphoproteomics profiling and phosphorylation sequence motifs derived from in vitro kinase assay to find molecules that interact with a target kinase, that show altered phosphorylation in response to kinase perturbation, and that are directly phosphorylated by the kinase in vitro; i.e., endogenous kinase substrates. Application of this methodology to casein kinase 2 (CK2) and protein kinase A (PKA) identified 33 and 52 putative substrates, respectively. We also show that known cancer-associated missense mutations near phosphosites of substrates affect phosphorylation by CK2 or PKA, and thus might alter downstream signaling in cancer cells bearing these mutations. This study extends our knowledge of kinase-substrate networks by proposing a new large-scale approach to identify endogenous substrates of kinases.
Measuring Neuronal Signals with Microelectrode Arrays: A Finite Element Analysis

Objective Measuring neuronal cell activity using microelectrode arrays reveals a great variety of derived signal shapes within extracellular recordings. However, possible mechanisms responsible for this variety have not yet been entirely determined, which might hamper any subsequent analysis of the recorded neuronal data. For an investigation of this issue, we propose a computational model based on the finite element method describing the electrical coupling between an electrically active neuron and an extracellular recording electrode in detail. This allows for a systematic study of possible parameters that may play an essential role in defining or altering the shape of the measured electrode potential. Our results indicate that neuronal geometry and neurite structure, as well as the actual pathways of input potentials that evoke action potential generation, have a significant impact on the shape of the resulting extracellular electrode recording and explain most of the known signal shape variety.
Differentiation of ciliated human midbrain-derived LUHMES neurons

Many human cell types are ciliated, including neural progenitors and differentiated neurons. Ciliopathies are characterized by defective cilia and comprise various disease states, including brain phenotypes, where the underlying biological pathways are largely unknown. Our understanding of neuronal cilia is rudimentary and an easy-to-maintain, ciliated human neuronal cell model is missing. LUHMES is a ciliated neuronal cell line derived from human fetal mesencephalon. LUHMES cells can easily be maintained and differentiated into mature, functional neurons within one week. They have a single primary cilium as proliferating progenitor cells and as post-mitotic, differentiating neurons. These developmental stages are completely separable within one day of culture condition change. The Sonic Hedgehog (SHH) signaling pathway is active in differentiating LUHMES neurons. RNA-seq time course analyses reveal molecular pathways and gene-regulatory networks critical for ciliogenesis and axon outgrowth at the interface between progenitor cell proliferation, polarization and neuronal differentiation. Gene expression dynamics of cultured LUHMES neurons faithfully mimic the corresponding in vivo dynamics of human fetal midbrain. In LUHMES, neuronal cilia biology can be investigated along a complete timeline: from proliferation through differentiation to mature neurons. Summary Statement With LUHMES, a ciliated human neuronal cell model, the underlying “neurobiology” of cilia and ciliopathies can be investigated along a complete time line: from proliferation through differentiation to mature neurons.
Grazer control of nitrogen fixation: phytoplankton taxonomic composition and ecosystem functioning

By differentially manipulating external nutrient inputs and grazer assemblages (through the presence or absence of fish that fed preferentially on daphniids) in replicate experimental ponds, we explored the potential for grazers to affect phytoplankton composition, particularly the abundance of N-fixing cyanobacteria, the concentration of fixed N, and the extent to which these effects were influenced by nutrient loading. Results indicate marked effects of both grazing and nutrient loading on phytoplankton abundance and composition, N-fixing cyanobacteria presence and N-fixing heterocyst density. When we manipulated N:P using two different N loading regimes at high P loading, grazer and N:P loading effects on cyanobacteria were similar in magnitude. In contrast when N:P loading was kept high while P loading was varied, grazer effects on cyanobacteria were small relative to nutrient loading effects. Aggregate grazer effects appeared to result exclusively from direct removal of cyanobacteria by grazing. Indirect alteration of available N:P by zooplankton was minor in magnitude compared with external and internal nutrient loading. Ecological interactions that structure zooplankton assemblages, such as fish predation, can have substantial cascading effects not only on primary producer biomass, but also on phytoplankton taxonomic composition and ecosystem functioning.
Dispersal evolution diminishes the negative density dependence in dispersal

In many organisms, dispersal varies with the local population density. Such patterns of density-dependent dispersal (DDD) are expected to shape the dynamics, spatial spread and invasiveness of populations. Despite their ecological importance, empirical evidence for the evolution of DDD patterns remains extremely scarce. This is especially relevant because rapid evolution of dispersal traits has now been empirically confirmed in several taxa. Changes in DDD of dispersing populations could help clarify not only the role of DDD in dispersal evolution, but also the possible pattern of subsequent range expansion. Here, we investigate the relationship between dispersal evolution and DDD using a long-term experimental evolution study on Drosophila melanogaster. We compared the DDD patterns of four dispersal-selected populations and their non-selected controls. The control populations showed negative DDD, which was stronger in females than in males. In contrast, the dispersal-selected populations showed density-independent dispersal, where neither males nor females exhibited DDD. We compare our results with previous evolutionary predictions that focused largely on positive DDD, and highlight how the direction of evolutionary change depends on the initial DDD pattern of a population. Finally, we discuss the implications of DDD evolution for spatial ecology and evolution.