julilili42/papers huggingface dataset:
“What Would a Microbe Say?”: Paving the Way toMultispecies Communication
2022-04-11

Microbiome research has shown that microbes sustain and significantly affect human and non-human existence. However, an antagonistic view of microbes still prevails, even on a linguistic level. In this paper, we use the approach of ecolinguistics to critique the term ‘invasion,’ which is frequently applied to describe microbe-human entanglements. Taking the example of Sonja Bäumel and Helen Blackwell’s BioArt project What WouldaMicrobe Say?, we demonstrate how even progressive non-anthropocentric perspectives of humanmicrobe interactions struggle with long-established language patterns. Yet, only respectfully conceived multispecies relationships allow for engaging in multispecies communication, which, in turn, makes it possible to perceive multispecies knowledge production. We argue that sensitivity to language is essential in order to reshape the perception of human-microbe relationships. Combining perspectives from medical and environmental humanities, we conclude our paper with a call for a microbial ethics that might allow for visions of how to live together with microbes in a respectful way.
Visualization of Biological Data - From Analysis to Communication (Dagstuhl Seminar 21401)
2022-04-11

Technological advancements in biology allow us to collect and generate a large quantity of data and pose a significant challenge to data interpretation and understanding. Addressing this challenge requires a blend of methodology from data visualization, bioinformatics, and biology. This methodology encompasses perception and design knowledge, algorithm design, techniques for analyzing and visualizing big data, statistical approaches, and specific domain knowledge for different application problems. In particular, it is essential to develop robust and integrative visualization methods combined with computational analytical techniques and approaches to communicate the outcomes visually. The purpose of Dagstuhl Seminar 21401, "Visualization of Biological Data - From Analysis to Communication," was to bring together researchers from various fields to discuss the state of the art, to debate means of advancing science in the field of visualization of biological data, and to foster the development of our international community.
Stone AgeYersinia pestisgenomes shed light on the early evolution, diversity, and ecology of plague
2022-04-12

Significance The bacterium Yersinia pestis has caused numerous historically documented outbreaks of plague and research using ancient DNA could demonstrate that it already affected human populations during the Neolithic. However, the pathogen’s genetic diversity, geographic spread, and transmission dynamics during this early period of Y. pestis evolution are largely unexplored. Here, we describe a set of ancient plague genomes up to 5,000 y old from across Eurasia. Our data demonstrate that two genetically distinct forms of Y. pestis evolved in parallel and were both distributed across vast geographic distances, potentially occupying different ecological niches. Interpreted within the archeological context, our results suggest that the spread of plague during this period was linked to increased human mobility and intensification of animal husbandry.
Noninvasive Physical Plasma as Innovative and Tissue-Preserving Therapy for Women Positive for Cervical Intraepithelial Neoplasia
2022-04-12

(1) Background: Cervical intraepithelial neoplasia (CIN) of long-term persistence or associated with individual treatment indications often requires highly invasive treatments. These are associated with risks of bleeding, infertility, and pregnancy complications. For low- and middle-income countries (LMICs), standard treatment procedures are difficult to implement and manage. We characterized the application of the highly energized gas “noninvasive physical plasma” (NIPP) for tissue devitalization and the treatment of CIN. (2) Methods: We report the establishment of a promising tissue devitalization procedure by NIPP application. The procedure was characterized at the in vitro, ex vivo and in vivo levels. We performed the first prospective, single-armed phase-IIb trial in 20 CIN1/2 patients (NCT03218436). (3) Results: NIPP-treated cervical cancer cells used as dysplastic in vitro model exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. Ex vivo and in vivo tissue assessments showed a highly noninvasive and tissue-preserving treatment procedure which induces transmucosal tissue devitalization. Twenty participants were treated with NIPP and attended a 24-week follow-up. Treatment success was achieved in 19 (95%) participants without postinterventional complications other than mild to moderate discomfort during application. (4) Conclusions: The results from this study preliminarily suggest that NIPP could be used for an effective and tissue-preserving treatment for CIN without the disadvantages of standard treatments. However, randomized controlled trials must confirm the efficacy and noninferiority of NIPP compared to standard treatments.
Maximal Speed for Macroscopic Particle Transport in the Bose-Hubbard Model
2022-04-12

The Lieb-Robinson bound asserts the existence of a maximal propagation speed for the quantum dynamics of lattice spin systems. Such general bounds are not available for most bosonic lattice gases due to their unbounded local interactions. Here we establish for the first time a general ballistic upper bound on macroscopic particle transport in the paradigmatic Bose-Hubbard model. The bound is the first to cover a broad class of initial states with positive density including Mott states, which resolves a longstanding open problem. It applies to Bose-Hubbard-type models on any lattice with not too long-ranged hopping. The proof is rigorous and rests on controlling the time evolution of a new kind of adiabatic spacetime localization observable via iterative differential inequalities.
Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5
2022-04-12

Abstract Flagellin, the protein unit of the bacterial flagellum, stimulates the innate immune receptor Toll-like receptor (TLR)5 following pattern recognition, or evades TLR5 through lack of recognition. This binary response fails to explain the weak agonism of flagellins from commensal bacteria, raising the question of how TLR5 response is tuned. Here, we describe a novel class of flagellin-TLR5 interaction, termed silent recognition. Silent flagellins are weak agonists despite high affinity binding to TLR5. This dynamic response is tuned by TLR5-flagellin interaction distal to the site of pattern recognition. Silent flagellins are produced primarily by the abundant gut bacteria Lachnospiraceae and are enriched in non-Western populations. These findings provide a mechanism for the innate immune system to tolerate commensal-derived flagellins. One-Sentence Summary TLR5 sensitively recognizes, but responds weakly to, flagellins from gut commensal bacteria.
Target Hopping from Protein Kinases to PXR: Identification of Small-Molecule Protein Kinase Inhibitors as Selective Modulators of Pregnane X Receptor from TüKIC Library
2022-04-12

Small-molecule protein kinase inhibitors are used for the treatment of cancer, but off-target effects hinder their clinical use. Especially off-target activation of the pregnane X receptor (PXR) has to be considered, as it not only governs drug metabolism and elimination, but also can promote tumor growth and cancer drug resistance. Consequently, PXR antagonism has been proposed for improving cancer drug therapy. Here we aimed to identify small-molecule kinase inhibitors of the Tübingen Kinase Inhibitor Collection (TüKIC) compound library that would act also as PXR antagonists. By a combination of in silico screen and confirmatory cellular reporter gene assays, we identified four novel PXR antagonists and a structurally related agonist with a common phenylaminobenzosuberone scaffold. Further characterization using biochemical ligand binding and cellular protein interaction assays classified the novel compounds as mixed competitive/noncompetitive, passive antagonists, which bind PXR directly and disrupt its interaction with coregulatory proteins. Expression analysis of prototypical PXR target genes ABCB1 and CYP3A4 in LS174T colorectal cancer cells and HepaRG hepatocytes revealed novel antagonists as selective receptor modulators, which showed gene- and tissue-specific effects. These results demonstrate the possibility of dual PXR and protein kinase inhibitors, which might represent added value in cancer therapy.
The at-issue status of ideophones in German: An experimental approach
2022-04-12

Formal linguistics generally assumes that form-meaning relations in spoken language are arbitrary and not iconic. Ideophones, such as the English splish-splash have been considered exceptions to this rule of arbitrariness. Recently, however, researchers have begun to examine iconicity in spoken language more closely. Following work which established the default not- at-issue status of iconic co-speech gestures, here we discuss the crosslinguistic evidence for the (not-)at-issueness of ideophones and the factors that may have an influence upon this. We also present what we believe to be the first experimental work on the at-issue status of ideophones, conducted with German speakers. Although German may not be a prototypical ideophonic language, we argue that German ideophones follow crosslinguistic patterns in terms of at-issueness and provide initial evidence for the not-at-issue status of sentence- medial adverbial ideophones in German. This evidence comes from sentence-context matching tasks, where the mismatch effect was significantly larger for sentences containing standard adverbials than those containing sentence-medial adverbial ideophones. We presume that speaker judgements concerning how well target sentences match discourse contexts should be more impaired by mismatches induced by material relevant to the Question Under Discussion (QUD), i.e. at-issue material, than those induced by material irrelevant to the QUD, i.e. not-at- issue material. We thus argue that speakers’ ratings indicate that sentence-medial adverbial ideophones in German are not at-issue. This paper suggests a starting point for investigating the pragmatic status of ideophones crosslinguistically and also allows for comparison to previous research on other iconic enrichments, in particular gestures. This then has implications for our understanding of the at-issue status of iconic enrichments and how these enrichments interact with each other.
Right hemispheric white matter hyperintensities improve the prediction of spatial neglect severity in acute stroke
2022-04-12

Abstract White matter hyperintensities (WMH) are frequently observed in brain scans of elderly people. They are associated with an increased risk of stroke, cognitive decline, and dementia. However, it is unknown yet if measures of WMH provide information that improve the understanding of poststroke outcome compared to only state-of-the-art stereotaxic structural lesion data. We implemented high-dimensional machine learning models, based on support vector regression (SVR), to predict the severity of spatial neglect in 103 acute right hemispheric stroke patients. We found that (1) the additional information of right hemispheric voxel-based topographic WMH extent indeed yielded an improvement in predicting acute neglect severity (compared to the voxel-based stroke lesion map alone). (2) Periventricular WMH appeared more relevant for prediction than deep subcortical WMH. (3) Among different WMH measures, voxel-based maps as measures of topographic extent allowed more accurate predictions compared to the use of traditional ordinally assessed visual rating scales (Fazekas scale, Cardiovascular Health Study scale). In summary, topographic WMH appears to be a valuable clinical imaging biomarker for predicting the severity of cognitive deficits and bears great potential for rehabilitation guidance of acute stroke patients.
Identification of three new inhibitor classes against Plasmodium falciparum
2022-04-12

In this study, we identified three novel compound classes with potent activity against Plasmodium falciparum, the most dangerous human malarial parasite. Resistance of this pathogen to known drugs is increasing and compounds with different modes of action are urgently needed. One promising drug target is the enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXPS) of the methylerythritol 4-phosphate (MEP) pathway for which we have previously identified three active compound classes against Mycobacterium tuberculosis. The close structural similarities in the active sites of the DXPS enzymes of P. falciparum and M. tuberculosis prompted investigation of its antiparasitic action, displaying good cell-based activity for all classes. Through structure-activity relationship studies we increased their antimalarial potency, and two classes also show good metabolic stability and low toxicity against human liver cells. The most active compound 1 inhibits the growth of blood-stage P. falciparum with an IC50 of 600 nM. The results from three different methods for target validation of compound 1 suggest intracellular polypharmacy. Similarity-based searches revealed two other possible target enzymes for this compound, which were further analyzed by docking calculations. All inhibitor classes are active against chloroquine resistant strains, confirming a new mode of action.
The impact of rehabilitation sport on breast-cancer related lymphedema and quality of life
2022-04-12

Abstract Purpose Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP), on HRQoL and BCRL in breast cancer survivors (BCS). Methods Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70) the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ-C30) were evaluated to understand the differences in HRQoL. Results The paddle group started with a higher HRQoL compared to in the control group. Most interesting, whether the affected or unaffected arm, whether before or after training - the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group the physical health was constant over the season, while the physical health of the control group decreased significantly over time. Conclusion PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy and seems to have a positive effect on the quality of life.
Monitoring extracellular ion and metabolite dynamics with recombinant nanobody-fused biosensors
2022-04-12

ABSTRACT The tumor microenvironment (TME) consists of different cell types that secrete proteins and also control the extracellular concentration of ions and metabolites. Changes in these intra-tumoral analytes and conditions, including K + , glucose, and pH, have been described to alter the metabolic activity of cancer cells, promote tumor cell growth, and impair anti-tumor immunity. However, the mechanisms regulating ion and metabolite levels and their effects on certain characteristics of the TME are still poorly understood. Therefore, accurate determination and visualization of analyte or state changes in real time within the TME is desired. In this study, we genetically combined FRET-based fluorescent biosensors with nanobodies (Nbs) and used them for targeted visualization and monitoring of extracellular changes in K + , pH, and glucose on cell surfaces. We demonstrated that these recombinant biosensors quantitatively visualize extracellular K + alterations on multiple cancer and non-cancer cell lines and primary neurons. By implementing a HER2 specific Nb, we generated K + and pH sensors, which retain their functionality and specifically stained HER2 positive breast cancer cells. Based on the successful technical development of several Nb-biosensor combinations, we anticipate that this approach can be easily extended to design other targeted biosensors. Such versatile probes will open new possibilities for the reliable study of extracellular analytes in advanced 3D cell models or even in vivo systems.
Immunosenescence and Altered Vaccine Efficiency in Older Subjects: A Myth Difficult to Change
2022-04-13

Organismal ageing is associated with many physiological changes, including differences in the immune system of most animals. These differences are often considered to be a key cause of age-associated diseases as well as decreased vaccine responses in humans. The most often cited vaccine failure is seasonal influenza, but, while it is usually the case that the efficiency of this vaccine is lower in older than younger adults, this is not always true, and the reasons for the differential responses are manifold. Undoubtedly, changes in the innate and adaptive immune response with ageing are associated with failure to respond to the influenza vaccine, but the cause is unclear. Moreover, recent advances in vaccine formulations and adjuvants, as well as in our understanding of immune changes with ageing, have contributed to the development of vaccines, such as those against herpes zoster and SARS-CoV-2, that can protect against serious disease in older adults just as well as in younger people. In the present article, we discuss the reasons why it is a myth that vaccines inevitably protect less well in older individuals, and that vaccines represent one of the most powerful means to protect the health and ensure the quality of life of older adults.
The Radical Unacceptability Hypothesis: Accounting for Unacceptability without Universal Constraints
2022-04-13

The Radical Unacceptability Hypothesis (RUH) has been proposed as a way of explaining the unacceptability of extraction from islands and frozen structures. This hypothesis explicitly assumes a distinction between unacceptability due to violations of local well-formedness conditions—conditions on constituency, constituent order, and morphological form—and unacceptability due to extra-grammatical factors. We explore the RUH with respect to classical islands, and extend it to a broader range of phenomena, including freezing, A′ chain interactions, zero-relative clauses, topic islands, weak crossover, extraction from subjects and parasitic gaps, and sensitivity to information structure. The picture that emerges is consistent with the RUH, and suggests more generally that the unacceptability of extraction from otherwise well-formed configurations reflects non-syntactic factors, not principles of grammar.
5S Ribosomal DNA of Genus Solanum: Molecular Organization, Evolution, and Taxonomy
2022-04-13

The Solanum genus, being one of the largest among high plants, is distributed worldwide and comprises about 1,200 species. The genus includes numerous agronomically important species such as Solanum tuberosum (potato), Solanum lycopersicum (tomato), and Solanum melongena (eggplant) as well as medical and ornamental plants. The huge Solanum genus is a convenient model for research in the field of molecular evolution and structural and functional genomics. Clear knowledge of evolutionary relationships in the Solanum genus is required to increase the effectiveness of breeding programs, but the phylogeny of the genus is still not fully understood. The rapidly evolving intergenic spacer region (IGS) of 5S rDNA has been successfully used for inferring interspecific relationships in several groups of angiosperms. Here, combining cloning and sequencing with bioinformatic analysis of genomic data available in the SRA database, we evaluate the molecular organization and diversity of IGS for 184 accessions, representing 137 species of the Solanum genus. It was found that the main mechanisms of IGS molecular evolution was step-wise accumulation of single base substitution or short indels, and that long indels and multiple base substitutions, which arose repeatedly during evolution, were mostly not conserved and eliminated. The reason for this negative selection seems to be association between indels/multiple base substitutions and pseudogenization of 5S rDNA. Comparison of IGS sequences allowed us to reconstruct the phylogeny of the Solanum genus. The obtained dendrograms are mainly congruent with published data: same major and minor clades were found. However, relationships between these clades and position of some species ( S. cochoae, S. clivorum, S. macrocarpon , and S. spirale ) were different from those of previous results and require further clarification. Our results show that 5S IGS represents a convenient molecular marker for phylogenetic studies on the Solanum genus. In particular, the simultaneous presence of several structural variants of rDNA in the genome enables the detection of reticular evolution, especially in the largest and economically most important sect. Petota . The origin of several polyploid species should be reconsidered.
Combined electrophysiological and morphological phenotypes in patients with genetic generalized epilepsy and their healthy siblings
2022-04-13

Abstract Objective Genetic generalized epilepsy (GGE) is characterized by aberrant neuronal dynamics and subtle structural alterations. We evaluated whether a combination of magnetic and electrical neuronal signals and cortical thickness would provide complementary information about network pathology in GGE. We also investigated whether these imaging phenotypes were present in healthy siblings of the patients to test for genetic influence. Methods In this cross‐sectional study, we analyzed 5 min of resting state data acquired using electroencephalography (EEG) and magnetoencephalography (MEG) in patients, their siblings, and controls, matched for age and sex. We computed source‐reconstructed power and connectivity in six frequency bands (1–40 Hz) and cortical thickness (derived from magnetic resonance imaging). Group differences were assessed using permutation analysis of linear models for each modality separately and jointly for all modalities using a nonparametric combination. Results Patients with GGE ( n = 23) had higher power than controls ( n = 35) in all frequencies, with a more posterior focus in MEG than EEG. Connectivity was also increased, particularly in frontotemporal and central regions in theta (strongest in EEG) and low beta frequencies (strongest in MEG), which was eminent in the joint EEG/MEG analysis. EEG showed weaker connectivity differences in higher frequencies, possibly related to drug effects. The inclusion of cortical thickness reinforced group differences in connectivity and power. Siblings ( n = 18) had functional and structural patterns intermediate between those of patients and controls. Significance EEG detected increased connectivity and power in GGE similar to MEG, but with different spectral sensitivity, highlighting the importance of theta and beta oscillations. Cortical thickness reductions in GGE corresponded to functional imaging patterns. Our multimodal approach extends the understanding of the resting state in GGE and points to genetic underpinnings of the imaging markers studied, providing new insights into the causes and consequences of epilepsy.