julilili42/papers huggingface dataset:
Antibody Response against SARS-CoV-2 and Seasonal Coronaviruses in Nonhospitalized COVID-19 Patients
2021-02-24

There is strong interest in the nature of the neutralizing antibody response against SARS-CoV-2 in infected individuals. For vaccine development, it is especially important which antibodies confer protection against SARS-CoV-2, if there is a phenomenon called antibody-dependent enhancement (ADE) of infection, and if there is cross-protection by antibodies directed against seasonal coronaviruses.
Land inequality and numeracy in Spain during the seventeenth and eighteenth century
2021-02-24

We assess the relationship between land inequality and human capital at the end of the early modern period, focusing on individual-level evidence from Spain. Our main finding is that land inequality had already had a significant negative effect on the formation of human capital there in the late-seventeenth and eighteenth centuries. We argue that this reflects the important role of a social structure based on farming families (as opposed to latifundia and day laborers) in the development of numeracy. This is consistent with earlier studies, which argued that farming households could (1) maintain a relatively favourable nutritional standard as a precondition for cognitive skills, (2) limit child labour and (3) encourage numeracy due to its demand by farming activities. Our results are robust, as they include several control variables and potential confounding variables.
Surgical management of choroid plexus papilloma of the cerebellopontine and cerebellomedullary angle: classification and strategy
2021-02-24

Abstract Choroid plexus papillomas (CPPs) are primary neuroectodermal neoplasms that usually arise in the fourth ventricle in adults. In this study, we present 12 patients with CPP arising from the cerebellopontine angle (CPP-CPA) and/or of the cerebellomedullary angle (CPP-CMA) that were treated in our department. Patients who underwent surgery for the treatment for CPP-CPA/CMA from January 2004 to March 2020 were identified by a computer search of their files from the Department of Neurosurgery, Tübingen. CPPs were classified according to their location into type 1 (tumor portion only in the CPA,), type 2 (tumor portions only in the CMA), and type 3 (tumor portions both in the CPA and CMA). Patients were evaluated for initial symptoms, previous therapies in other hospitals, extent of tumor resection, recurrence rate, and complications by reviewing patient documents. Of approximately 1500 CPA lesions, which were surgically treated in our department in the last 16 years, 12 patients (mean age 42 ± 19 years) were found to have CPP-CPA/CMA. Five were male, and seven were female patients. Gross total resection was achieved in nine cases, and a subtotal resection was attained in three cases. Tumor recurrence in the same location after the first surgery in our hospital was observed in 2 patients after 15 and 40 months of follow-up, and in another patient, distant metastases (C3/4 and L3 levels) were observed. Surgical removal of CPP is the treatment of choice, but additional therapeutic options may be necessary in case of remnant tumor portions, recurrence, or malignant transformation.
Distinct Synaptic Transfer Functions in Same-Type Photoreceptors
2021-02-24

SUMMARY Many sensory systems use ribbon-type synapses to transmit their signals to downstream circuits. The properties of this synaptic transfer fundamentally dictate which aspects in the original stimulus will be accentuated or suppressed, thereby partially defining the detection limits of the circuit. Accordingly, sensory neurons have evolved a wide variety of ribbon geometries and vesicle pool properties to best support their diverse functional requirements. However, the need for diverse synaptic functions does not only arise across neuron types, but also within . Here we show that UV-cones, a single type of photoreceptor of the larval zebrafish eye, exhibit striking differences in their synaptic ultrastructure and consequent calcium to glutamate transfer function depending on their location in the eye. We arrive at this conclusion by combining serial section electron microscopy and simultaneous “dual-colour” 2-photon imaging of calcium and glutamate signals from the same synapse in vivo . We further use the functional dataset to fit a cascade-like model of the ribbon synapse with different vesicle pool sizes, transfer rates and other synaptic properties. Exploiting recent developments in simulation-based inference, we obtain full posterior estimates for the parameters and compare these across different retinal regions. The model enables us to extrapolate to new stimuli and to systematically investigate different response behaviours of various ribbon configurations. We also provide an interactive, easy-to-use version of this model as an online tool. Overall, we show that already on the synaptic level of single neuron types there exist highly specialized mechanisms which are advantageous for the encoding of different visual features.
Special Issue: Phonological and phonetic variation in spoken morphology
2021-02-24

Abstract In recent years, more and more evidence is accumulating that there is a great deal of variation as a result of morphological complexity, both at the level of phonology and at the level of phonetics. Such findings challenge established linguistic models in which morphological information is lost in comprehension or production. The present Special Issue presents five studies that investigate the phenomenon in more detail, centered around the following questions: How do morphological relations affect articulatory and phonological properties of complex words? How do articulatory and phonological properties of complex words reflect their morphological relations? What do these two questions imply about theories that address morphological relatedness at the level of sounds?
<strong><b>Divergent Selection on Height and Cognitive Ability: Evidence from Both Genetic Distance (Fst) and Polygenic Scores </b></strong>
2021-02-24

Tests of selection based on population differentiation were performed on two highly polygenic traits important for success and quality of life: body height and educational attainment (EA). Polygenic scores (PGS) of EA and height, computed across three public genomic databases revealed differences between populations (1000 Genomes, HGDP, gnomAD) that matched the average IQ and height of ethnic groups (r ~0.9). A moderately strong correlation between latitude and EA PGS (r= 0.67) implies the effect of climate (seasonality or winter temperature) on selection for cognitive ability. The effect of latitude was reduced (&amp;beta;= 0.28) but remained significant after adding the sub-continental group variable to the regression model.The global Fst index revealed population differentiation at height and EA loci, significantly deviating from random SNPs. Substantial Linkage Equilibrium (LD) Decay between YRI and CEU was found (r= 0.6) but there was no correlation between LD decay and population differences in polygenic scores for EA (r= 0.015, p= 0.45), and slight inflation of height PGS difference due to LD decay (r= -0.04, p= 0.0315). Selecting the SNPs most robust to LD decay (r&amp;gt;0.8) resulted in larger PGS gaps for EA, but smaller for height. Finally, it is shown that PGS differences are more sensitive to the significance of GWAS loci than Fst, reflecting the major limitations of Fst as an index of selection.
The production of less harmful and less toxic sparklers in an experiment for school students
2021-02-24

Abstract In this article, a new and simple way of producing sparklers is presented as a school experiment. These sparklers are more environmentally friendly and less health threatening than sparklers produced with existing preparation methods. The problem of conventional sparklers is the toxicity of barium nitrate, which is used as the oxidizer. The substitution of this oxidizer with strontium nitrate and also the reduction of the weight proportion makes the new mixture less dangerous and less toxic. Various tests for the categorization of high-energetic materials show that the newly developed sparklers are not classified as explosives. Furthermore, the tests demonstrate that the newly developed sparklers are not as dangerous as commercial sparklers. Due to their lower health risk, these new sparklers are well suited for use in school education. In addition, expenditure for this experiment is low and integrating it into the upper secondary level curriculum is easy. Sparklers are an impressive example of redox reactions from everyday life. The experiment is a best-practice application for chemistry education, incorporating current results of chemistry research.
GestaltMatcher: Overcoming the limits of rare disease matching using facial phenotypic descriptors
2021-02-24

<title>Abstract</title> The majority of monogenic disorders cause craniofacial abnormalities with characteristic facial morphology. These disorders can be diagnosed more efficiently with the support of computer-aided next-generation phenotyping tools, such as DeepGestalt. These tools have learned to associate facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this “supervised” approach means that diagnoses are only possible if they were part of the training set. To improve recognition of ultra-rare diseases, we created GestaltMatcher, which uses a deep convolutional neural network based on the DeepGestalt framework. We used photographs of 21,836 patients with 1,362 rare disorders to define a “Clinical Face Phenotype Space”. Distance between cases in the phenotype space defines syndromic similarity, allowing test patients to be matched to a molecular diagnosis even when the disorder was not included in the training set. Similarities among patients with previously unknown disease genes can also be detected. Therefore, in concert with mutation data, GestaltMatcher could accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism.
The Revised Self-monitoring Scale Detects Early Impairment of Social Cognition in Genetic Frontotemporal Dementia Within the GENFI Cohort
2021-02-24

<title>Abstract</title> BackgroundAlthough social cognitive dysfunction is a major feature of frontotemporal dementia (FTD) it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. MethodsWe used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the Genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 <italic>C9orf72</italic> expansion carriers, 193 <italic>GRN</italic> mutation carriers and 75 <italic>MAPT</italic> mutation carriers. All participants underwent the standardised GENFI clinical assessment including the ‘CDR® plus NACC FTLD’ scale and RSMS. The RSMS Total score and its two subscores, socioemotional expressiveness (EX score), and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis. ResultsThe RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the <italic>C9orf72</italic> (for the total score and both subscores), and <italic>GRN</italic> (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum. ConclusionsThe RSMS indexes socioemotional impairment at an early stage of genetic FTD, and may be a suitable outcome measure in forthcoming trials.
Interplay for change in equality, diversity and inclusion studies
2021-02-25

In equality, diversity and inclusion studies, there is often an underlying assumption that research will advance equality and inclusion. Yet scholars increasingly point to a gap between theory and practice to achieve change. While paradigmatic differences in how change is framed may in part account for this gap, we argue that ‘action knowledges’ drawn from different paradigms are both important and ‘commensurable’ once a change agenda is adopted. Placing these in tension, we develop an interplay requiring scholars to engage differences in both ontology and ideology to ‘see’ the change knowledge in other paradigms. A ‘fifth knowledge’ for research to combat inequality and contribute to more equitable organizations can result from engaging with the dynamic tensions identified in our analysis.
Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19
2021-02-25

Abstract Background Accumulating evidence indicates toward an association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and procoagulatory state in blood. Thromboelastographic investigations are useful point-of-care devices to assess coagulation and fibrinolysis. Objectives We investigated the hypothesis that the procoagulatory state in COVID-19 patients is associated with impaired fibrinolysis system. Methods Altogether, 29 COVID-19 patients admitted to normal wards or to the intensive care unit (ICU) were included in this descriptive study. Whole blood samples were investigated by thromboelastography to assess coagulation and fibrinolysis. Additionally, standard routine coagulation testing and immunoassays for factors of fibrinolysis as plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), plasminogen activity and α2-antiplasmin (A2AP) were performed. Results A significantly increased lysis resistance and a significantly longer time of lysis after adding tissue plasminogen activator were observed in blood samples from ICU COVID-19 patients compared with healthy controls (maximal lysis: 3.25 ± 0.56 vs. 6.20 ± 0.89%, p = 0.0127; lysis time: 365.7 ± 44.6 vs. 193.2 ± 16.3 seconds, p = 0.0014). PAI-1 activity was significantly higher in plasma samples of ICU COVID-19 patients (PAI-1: 4.92 ± 0.91 vs. 1.28 ± 0.33 U/mL, p = 0.001). A positive correlation between the activity of PAI-1 and lysis time of the formed clot (r = 0.70, p = 0.0006) was observed. Conclusion Our data suggest that severe SARS-CoV-2 infection is associated with impaired fibrinolytic activity in blood, where fibrinolytic inhibitors are elevated leading to an increased resistance to clot lysis. Thromboelastography could offer a tool to investigate the contribution of the fibrinolytic status to the procoagulatory condition in COVID-19.
Targeting the NLRP3 Inflammasome via BTK
2021-02-25

The NLRP3 inflammasome represents a critical inflammatory machinery driving pathology in many acute (e. g., myocardial infarction or stroke) and chronic (Alzheimer's disease, atherosclerosis) human disorders linked to the activity of IL-1 cytokines. Although the therapeutic potential of NLRP3 is undisputed, currently no clinically approved therapies exist to target the NLRP3 inflammasome directly. The recent discovery of BTK as a direct and positive regulator of the NLRP3 inflammasome has, however, raised the intriguing possibility of targeting the NLRP3 inflammasome via existing or future BTK inhibitors. Here, I review the mechanistic basis for this notion and discuss the molecular and cellular role of BTK in the inflammasome process. Specific attention will be given to cell-type dependent characteristics and differences that may be relevant for targeting approaches. Furthermore, I review recent (pre-)clinical evidence for effects of BTK inhibitors on NLRP3 activity and highlight and discuss open questions and future research directions. Collectively, the concept of targeting BTK to target NLRP3-dependent inflammation will be explored comprehensively at the molecular, cellular and therapeutic levels.
Human β-Defensin 2 Mutations Are Associated With Asthma and Atopy in Children and Its Application Prevents Atopic Asthma in a Mouse Model
2021-02-25

Asthma and allergies are complex, chronic inflammatory diseases in which genetic and environmental factors are crucial. Protection against asthma and allergy development in the context of farming environment is established by early animal contact, unpasteurized milk consumption and gut microbiota maturation. The human β-defensin 2 (hBD-2) is a host defense peptide present almost exclusively in epithelial tissues, with pronounced immunomodulatory properties, which has recently been shown to ameliorate asthma and IBD in animal models. We hypothesized that adequate hBD-2 secretion plays a role in the protection against asthma and allergy development and that genetic variations in the complex gene locus coding for hBD-2 may be a risk factor for developing these diseases, if as a consequence, hBD-2 is insufficiently produced. We used MALDI-TOF MS genotyping, sequencing and a RFLP assay to study the genetic variation including mutations, polymorphisms and copy number variations in the locus harboring both genes coding for hBD-2 ( DEFB4A and DEFB4B) . We administered hBD-2 orally in a mouse model of house dust mite (HDM)-asthma before allergy challenge to explore its prophylactic potential, thereby mimicking a protective farm effect. Despite the high complexity of the region harboring DEFB4A and DEFB4B we identified numerous genetic variants to be associated with asthma and allergy in the GABRIELA Ulm population of 1,238 children living in rural areas, including rare mutations, polymorphisms and a lack of the DEFB4A . Furthermore, we found that prophylactic oral administration of hBD-2 significantly curbed lung resistance and pulmonary inflammation in our HDM mouse model. These data indicate that inadequate genetic capacity for hBD-2 is associated with increased asthma and allergy risk while adequate and early hBD-2 administration (in a mouse model) prevents atopic asthma. This suggests that hBD-2 could be involved in the protective farm effect and may be an excellent candidate to confer protection against asthma development.
Unshielded bent folded‐end dipole 9.4 T human head transceiver array decoupled using modified passive dipoles
2021-02-25

Purpose To develop an unshielded dipole transceiver array for human head imaging at 9.4 Tesla and to improve decoupling of adjacent dipole elements, a novel array design with modified passive dipole antennas was developed, evaluated, and tested. Methods The new array consisted of 8 bent folded‐end dipole elements placed in a single row and surrounding the head. Adjacent elements of RF transceiver arrays are usually decoupled by introducing circuits electrically connected to elements. These methods are difficult to use for dipole arrays because of the distant location of the adjacent antennas. A recently developed decoupling technique using passive dipoles is simple and does not require any electrical connection. However, common parallel passive dipoles can produce destructive interference with the RF field of the array itself. To minimize this interference, we placed the passive dipoles perpendicularly to the active dipoles and positioned them at the ends of the array. We also evaluated the effect of different passive dipoles on the array transmit performance. Finally, we optimized the array transmit performance by varying the length of the dipole folded portion. Results By rotating the passive dipoles 90o and moving them toward the ends of the array, we minimized the destructive interference to an acceptable level without compromising decoupling and the transmit efficiency. Conclusion While keeping the benefits of the passive dipole decoupling method, the new modified dipoles produce substantially less destructive interference with the RF field of the array than the common design. The constructed transceiver array demonstrated good decoupling and whole‐brain coverage.
The plant immune receptors NRG1.1 and ADR1 are calcium influx channels
2021-02-25

Abstract Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. RPW8 domain-containing “helper” NLRs (RNLs) are required by many “sensor” NLRs. Our crystal structure of the RNL N REQUIREMENT GENE 1.1 (NRG1.1) N-terminal signaling domain resembled that of the resting state plant resistosome-forming HOPZ-ACTIVATED RESISTANCE 1 (ZAR1) and the animal MIXED-LINEAGE KINASE-LIKE (MLKL) cation channel. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta and conferred cytoplasmic Ca 2+ influx in plant and human HeLa cells. NRG1.1-dependent Ca 2+ influx and cell death were sensitive to Ca 2+ channel blockers. Ca 2+ influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another RNL, required conserved negatively charged N-terminal residues. Thus, RNLs apparently form influx channels to directly regulate cytoplasmic [Ca 2+ ] and consequent cell death. One Sentence Summary A specific class of plant immune receptors function as calcium-permeable channels upon activation to induce cell death.
A freeze-and-thaw-induced fragment of the microtubule-associated protein tau in rat brain extracts: implications for the biochemical assessment of neurotoxicity
2021-02-25

Abstract Tau is a microtubule-associated protein (MAP) responsible for controlling the stabilization of microtubules in neurons. Tau function is regulated by phosphorylation. However, in some neurological diseases Tau becomes aberrantly hyperphosphorylated, which contributes to the pathogenesis of neurological diseases, known as tauopathies. Western blotting (WB) has been widely employed to determine Tau levels in neurological disease models. However, Tau quantification by WB should be interpreted with care, as this approach has been recognized as prone to produce artifactual results if not properly performed. In the present study, our goal was to evaluate the influence of a freeze-and-thaw cycle, a common procedure preceding WB, to the integrity of Tau in brain homogenates from rats, 3xTg-AD mice and human samples. Homogenates were prepared in ice-cold RIPA buffer supplemented with protease/phosphatase inhibitors. Immediately after centrifugation, an aliquot of the extracts was analyzed via WB to quantify total and phosphorylated Tau levels. The remaining aliquots of the same extracts were stored for at least 2 weeks at either −20 or −80°C and then subjected to WB. Extracts from rodent brains submitted to freeze-and-thaw presented a ∼25 kDa fragment immunoreactive to anti-Tau antibodies. An in-gel digestion followed by mass spectrometry (MS) analysis in excised bands revealed this ∼25 kDa species corresponds to a Tau fragment. Freeze-and-thaw-induced Tau proteolysis was detected even when extracts were stored at −80°C. This phenomenon was not observed in human samples at any storage condition tested. Based on these findings, we strongly recommend the use of fresh extracts of brain samples in molecular analysis of Tau levels in rodents.