julilili42/papers huggingface dataset:
Decreased Na+/K+ ATPase Expression and Depolarized Cell Membrane in Neurons Differentiated from Chorea-Acanthocytosis Patients
2020-05-21

Abstract Loss of function mutations of the chorein-encoding gene VPS13A lead to chorea-acanthocytosis (ChAc), a neurodegenerative disorder with accelerated suicidal neuronal cell death, which could be reversed by lithium. Chorein upregulates the serum and glucocorticoid inducible kinase SGK1. Targets of SGK1 include the Na + /K + -ATPase, a pump required for cell survival. To explore whether chorein-deficiency affects Na + /K + pump capacity, cortical neurons were differentiated from iPSCs generated from fibroblasts of ChAc patients and healthy volunteers. Na + /K + pump capacity was estimated from K + -induced whole cell outward current (pump capacity). As a result, the pump capacity was completely abolished in the presence of Na + /K + pump-inhibitor ouabain (100 μM), was significantly smaller in ChAc neurons than in control neurons, and was significantly increased in ChAc neurons by lithium treatment (24 hours 2 mM). The effect of lithium was reversed by SGK1-inhibitor GSK650394 (24 h 10 μM). Transmembrane potential (V m ) was significantly less negative in ChAc neurons than in control neurons, and was significantly increased in ChAc neurons by lithium treatment (2 mM, 24 hours). The effect of lithium on V m was virtually abrogated by ouabain. Na + /K + α1-subunit transcript levels and protein abundance were significantly lower in ChAc neurons than in control neurons, an effect reversed by lithium treatment (2 mM, 24 hours). In conclusion, consequences of chorein deficiency in ChAc include impaired Na + /K + pump capacity.
Host-associated microbe PCR (hamPCR): accessing new biology through convenient measurement of both microbial load and community composition
2020-05-21

Abstract The ratio of microbial population size relative to the amount of host tissue, or “microbial load”, is a fundamental metric of colonization and infection, but it cannot be directly deduced from microbial amplicon data such as 16S rRNA gene counts. Because conventional methods to determine load, such as serial dilution plating or quantitative PCR, add substantial experimental burden, they are only rarely paired with amplicon sequencing. Alternatively, whole metagenome sequencing of DNA contributed by host and microbes both reveals microbial community composition and enables determination of microbial load, but host DNA typically greatly outweighs microbial DNA, severely limiting the cost-effectiveness and scalability of this approach. We introduce host-associated microbe PCR (hamPCR), a robust amplicon sequencing strategy to quantify microbial load and describe interkingdom microbial community composition in a single, cost-effective library. We demonstrate its accuracy and flexibility across multiple host and microbe systems, including nematodes and major crops. We further present a technique that can be used, prior to sequencing, to optimize the host representation in a batch of libraries without loss of information. Because of its simplicity, and the fact that it provides an experimental solution to the well-known statistical challenges provided by compositional data, hamPCR will become a transformative approach throughout culture-independent microbiology.
Video assisted thoracoscopic sympathectomy for intractable recurrent VT after minimal‐invasive LVAD implantation
2020-05-21

We believe video-assisted thoracoscopic sympathectomy might be a surgical treatment option in patients with intractable recurrent VTs after catheter ablation of VT reentrant substrate even after minimal-invasive LVAD implantation.
Uptalk interpretation as a function of listening experience
2020-05-21

The term "uptalk" describes utterance-final pitch rises that carry no sentence-structural information. Uptalk is usually dialectal or sociolectal, and Australian English (AusEng) is particularly known for this attribute. We ask here whether experience with an uptalk variety affects listeners' ability to categorise rising pitch contours on the basis of the timing and height of their onset and offset. Listeners were two groups of English-speakers (AusEng, and American English), and three groups of listeners with L2 English: one group with Mandarin as L1 and experience of listening to AusEng, one with German as L1 and experience of listening to AusEng, and one with German as L1 but no AusEng experience. They heard nouns (e.g. flower, piano) in the framework "Got a NOUN", each ending with a pitch rise artificially manipulated on three contrasts: low vs. high rise onset, low vs. high rise offset and early vs. late rise onset. Their task was to categorise the tokens as "question" or "statement", and we analysed the effect of the pitch contrasts on their judgements. Only the native AusEng listeners were able to use the pitch contrasts systematically in making these categorisations.
Blackboard as separation wall: classrooms, race and the contemporary crisis in Germany
2020-05-21

This article suggests that racism, construed as a reified and artificial dichotomization of social bodies into acutely hypostatized and opposed identities, can best be understood by placing it within a larger global context of exploitative hierarchies which racism retrospectively legitimizes. The loss of the global perspective and the obscured knowledge of global networks of toxic causalities allow the broader context of racism to remain invisible, thus condemning local anti-racist activism to mitigated success. The article suggests that the classroom as a vital site of education of citizens tends to be isolated from the world; racism can be combatted in the classroom by opening its walls up to the larger global context in which education is a significant factor. A pedagogical practice of interrogative critical assemblages may facilitate the reconstruction of invisible global networks, which in turn may enable us to better understand the workings of micro-racisms within a larger context of global macro-racism.
Oomycete small RNAs bind to the plant RNA-induced silencing complex for virulence
2020-05-22

The exchange of small RNAs (sRNAs) between hosts and pathogens can lead to gene silencing in the recipient organism, a mechanism termed cross-kingdom RNAi (ck-RNAi). While fungal sRNAs promoting virulence are established, the significance of ck-RNAi in distinct plant pathogens is not clear. Here, we describe that sRNAs of the pathogen Hyaloperonospora arabidopsidis, which represents the kingdom of oomycetes and is phylogenetically distant from fungi, employ the host plant’s Argonaute (AGO)/RNA-induced silencing complex for virulence. To demonstrate H. arabidopsidis sRNA (HpasRNA) functionality in ck-RNAi, we designed a novel CRISPR endoribonuclease Csy4/GUS reporter that enabled in situ visualization of HpasRNA-induced target suppression in Arabidopsis. The significant role of HpasRNAs together with AtAGO1 in virulence was revealed in plant atago1 mutants and by transgenic Arabidopsis expressing a short-tandem-target-mimic to block HpasRNAs, that both exhibited enhanced resistance. HpasRNA-targeted plant genes contributed to host immunity, as Arabidopsis gene knockout mutants displayed quantitatively enhanced susceptibility.
Retracted: Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease
2020-05-22

Retraction: Heinzel, S. et al., Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease, Annals of Neurology 2020, 88(2), 320‐331 ( https://onlinelibrary.wiley.com/doi/10.1002/ana.25788 ). The above article, published online on May 22, 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief Clifford B. Saper, MD, PhD, and Wiley Periodicals LLC. The retraction has been agreed due to an unintentional extensive misuse of the term “physical activity” instead of “physical inactivity” throughout the paper. The errors have been corrected for clarity and republished here: https://doi.org/10.1002/ana.26128 .
Higgs-pair production via gluon fusion at hadron colliders: NLO QCD corrections
2020-05-22

Higgs-pair production via gluon fusion is the dominant production mechanism of Higgs-boson pairs at hadron colliders. In this work, we present details of our numerical determination of the full next-to-leading-order (NLO) QCD corrections to the leading top-quark loops. Since gluon fusion is a loop-induced process at leading order, the NLO calculation requires the calculation of massive two-loop diagrams with up to four different mass/energy scales involved. With the current methods, this can only be done numerically, if no approximations are used. We discuss the setup and details of our numerical integration. This will be followed by a phenomenological analysis of the NLO corrections and their impact on the total cross section and the invariant Higgs-pair mass distribution. The last part of our work will be devoted to the determination of the residual theoretical uncertainties with special emphasis on the uncertainties originating from the scheme and scale dependence of the (virtual) top mass. The impact of the trilinear Higgs-coupling variation on the total cross section will be discussed.
Dams and protected areas: Quantifying the spatial and temporal extent of global dam construction within protected areas
2020-05-22

Abstract Protected areas (PAs) are an essential tool for freshwater biodiversity conservation. Given past and expected future global increases in dams and impacts of dams on freshwater ecosystems, we document the number of dams existing or planned within PAs, their history, and the extent of PA downgrading, downsizing, and degazettement (PADDD) proximally caused by dams. Globally, at least 1,249 large dams are located within PAs; two‐thirds (907) were built before PA establishment. Additionally, 14% of planned geolocated hydropower dams (509 dams) are located within PAs. PADDD events have also legalized dam construction within existing PAs. Environmental safeguards should preclude development of dams within or adjacent to PAs and prioritize dams within PAs for possible removal and restoration.
The Prognostic Value of Quantitative Bone SPECT/CT Before 223Ra Treatment in Metastatic Castration-Resistant Prostate Cancer
2020-05-22

Radiolabeled bisphosphonates such as <sup>99m</sup>Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (<sup>99m</sup>Tc-DPD) typically show intense uptake in skeletal metastases from metastatic castration-resistant prostate cancer (mCRPC). Extensive bone involvement is regarded as a risk factor for mCRPC patients treated with <sup>223</sup>Ra-dichloride (<sup>223</sup>Ra). The aim of this study was to quantify <sup>99m</sup>Tc-DPD uptake by means of SPECT/CT before <sup>223</sup>Ra and compare the results with the feasibility of treatment and overall survival (OS). <b>Methods:</b> Sixty consecutive mCRPC patients were prospectively included in this study. SPECT/CT of the central skeleton covering the skull to the mid-femoral level was performed before the first cycle of <sup>223</sup>Ra. The bone compartment was defined by means of low-dose CT. Emission data were corrected for scatter, attenuation, and decay supplemented by resolution recovery using dedicated software. The Kaplan-Meier estimator, <i>U</i> test, and Cox regression analysis were used for statistics. <b>Results:</b> Total <sup>99m</sup>Tc-DPD uptake of the central skeleton varied between 11% and 56% of injected dose (%ID) or between 1.8 and 10.5 %ID/1,000 mL of bone volume (%ID/L). SUV<sub>mean</sub> ranged from 1.9 to 7.4, whereas the SUV<sub>max</sub> range was 18-248. Patients unable to complete <sup>223</sup>Ra treatment because of progression and/or cytopenia (<i>n</i> = 23) showed significantly higher uptake (31.9 vs. 25.4 %ID and 6.0 vs. 4.7 %ID/L; <i>P</i> < 0.02). OS after <sup>223</sup>Ra (median, 15.2 mo) was reduced to 7.3 mo in cases of skeletal uptake that was 26 %ID or higher, as compared with 30.8 mo if lower than 26 %ID (<i>P</i> = 0.008). Similar results were obtained for %ID/L and SUV<sub>mean</sub> SUV<sub>max</sub> did not correlate with survival. %ID/L was identified as an independent prognostic factor for OS (hazard ratio, 1.381 per unit), along with number of previous treatment lines. <b>Conclusion:</b> Quantitative SPECT/CT of bone scans performed at baseline is prognostic for survival in mCRPC patients treated with <sup>223</sup>Ra.
Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia
2020-05-22

Background and purpose The differentiation of Alzheimer’s disease (AD) dementia from vascular dementia (VaD) and mixed‐type dementia (mixed dementia) requires stepwise analysis and usually occurs late in the disease process. Early diagnosis and therapy monitoring would benefit greatly from the identification of biomarkers of neurodegeneration, especially blood biomarkers. To this end, the aim of the present pilot study was to investigate differences in the distribution of peripheral T‐cell populations in patients with AD compared to VaD and mixed dementia. Methods Flow cytometry was performed on blood samples from 11 patients with AD, six with VaD and six with mixed dementia, as well as 17 healthy control subjects (HCs). CD4+ and CD8+ T cells were typed for expression of CD45, CD27, CD28, CD25, FoxP3, CCR4 and CCR6; the other leukocytes were also assessed. Functionally, immune cell uptake of the β‐amyloid (Aβ) toxic fragment (Aβ 1–42 ) was also evaluated. Results A higher proportion of CD4+CD28− memory T cells and a reciprocal reduction of CD4+CD28+CD27+ naïve T lymphocytes was detected in all patient groups relative to controls. Significantly fewer CD4+CD25+FoxP3 regulatory T cells were present in patients with VaD, and significantly more CCR6+ and CCR4+ CD4+ T cells in those with AD. Higher CCR6+ T‐cell frequencies were also present in patients with mixed dementia, potentially due to the inflammation and immune cell chemoattraction triggered by Aβ. Conclusions The present study was a comprehensive investigation comparing different kinds of dementia, revealing differentially expressed peripheral markers that are potentially useful for early AD, VaD and mixed dementia diagnoses, and that would assist in proper treatments for these disparate diseases. Validation is now required.
Corticothalamic feedback sculpts visual spatial integration in mouse thalamus
2020-05-22

ABSTRACT En route from retina to cortex, visual information passes through the dorsolateral geniculate nucleus of the thalamus (dLGN), where extensive corticothalamic (CT) feedback has been suggested to modulate spatial processing. How this modulation arises from direct excitatory and indirect inhibitory CT feedback pathways remains enigmatic. Here we show that in awake mice, retinotopically organized cortical feedback sharpens receptive fields (RFs) and increases surround suppression in the dLGN. Guided by a network model indicating that widespread inhibitory CT feedback is necessary to reproduce these effects, we targeted the visual sector of the thalamic reticular nucleus (visTRN) for recordings. We found that visTRN neurons have large receptive fields, show little surround suppression, and exhibit strong feedback-dependent responses to large stimuli. These features make them an ideal candidate for mediating feedback-enhanced surround suppression in the dLGN. We conclude that cortical feedback sculpts spatial integration in dLGN, likely via recruitment of neurons in visTRN.
Eye-Catching Microbes—Polyphasic Analysis of the Microbiota on Microscope Oculars Verifies Their Role as Fomites
2020-05-22

Microscopes are used in virtually every biological and medical laboratory. Previous cultivation-based studies have suggested that direct contact with microscope eyepieces increases the risk of eye infections. To obtain a deeper insight into the microbiota on oculars, we analysed 10 recently used university microscopes. Their left oculars were used for a cultivation-based approach, while the right oculars served for massive gene sequencing. After cleaning with isopropyl alcohol, the oculars were re-sampled and analysed again. All oculars were found to be contaminated with bacteria, with a maximum load of 1.7 × 103 CFU cm−2. MALDI Biotyping revealed mainly Cutibacterium (68%), Staphylococcus (14%) and Brevibacterium (10%), with the most abundant species being Cutibacterium acnes (13%) and Staphylococcus capitis (6%). Cleaning reduced the microbial load by up to 2 log scales. Within 10 uncleaned and 5 cleaned samples, 1480 ASVs were assigned to 10 phyla and 262 genera. The dominant genera before cleaning were Cutibacterium (78%), Paracoccus (13%), Pseudomonas (2%) and Acinetobacter (1%). The bacteriota composition on the cleaned oculars was similar; however, it probably largely represented dead bacteria. In summary, used oculars were significantly contaminated with skin and environmental bacteria, including potential pathogens. Regular cleaning is highly recommended to prevent eye and skin infections.
Christliches Influencing auf YouTube als ‚doing emotion‘
2020-05-22

This article is about Christian Influencing on Youtube and the ‘emotional practices’ they contain. The phenomenon Christian Influencing will be explained and discussed in view of the ‘doing emotion’ approach by Monique Scheer. This is followed by an exemplary analysis of two videos from Christian Influencer LiMarie. The analysis shows that practices generate certain emotions that can be grouped into three themes: ‘Doing Intimacy‘, ‘Undoing Complexity‘ and ‘Doing Christian Lifestyle‘. Through the doing emotion approach it’s possible to decipher how these influencers create a stage of craving for simple truths and burning enthusiasm for being a Christian. The article addresses the need to be sensitized about how influencing functions and the impact it has.
The EORTC-DeCOG nomogram adequately predicts outcomes of patients with sentinel node–positive melanoma without the need for completion lymph node dissection
2020-05-23

The EORTC-DeCOG nomogram provides an adequate prognostic tool for patients with SN-positive melanoma, without the need for CLND. It showed consistent results across validation. The nomogram could be used for patient counselling and might aid in adjuvant therapy decision-making.
MAT2A as Key Regulator and Therapeutic Target in MLLr Leukemogenesis
2020-05-24

Epigenetic dysregulation plays a pivotal role in mixed-lineage leukemia (MLL) pathogenesis, therefore serving as a suitable therapeutic target. S-adenosylmethionine (SAM) is the universal methyl donor in human cells and is synthesized by methionine adenosyltransferase 2A (MAT2A), which is deregulated in different cancer types. Here, we used our human CRISPR/Cas9-MLL-rearranged (CRISPR/Cas9-MLLr) leukemia model, faithfully mimicking MLLr patients’ pathology with indefinite growth potential in vitro, to evaluate the unknown role of MAT2A. Comparable to publicly available patient data, we detected MAT2A to be significantly overexpressed in our CRISPR/Cas9-MLLr model compared to healthy controls. By using non-MLLr and MLLr cell lines and our model, we detected an MLLr-specific enhanced response to PF-9366, a new MAT2A inhibitor, and small interfering (si) RNA-mediated knockdown of MAT2A, by alteration of the proliferation, viability, differentiation, apoptosis, cell cycling, and histone methylation. Moreover, the combinational treatment of PF-9366 with chemotherapy or targeted therapies against the SAM-dependent methyltransferases, disruptor of telomeric silencing 1 like (DOT1L) and protein arginine methyltransferase 5 (PRMT5), revealed even more pronounced effects. In summary, we uncovered MAT2A as a key regulator in MLL leukemogenesis and its inhibition led to significant anti-leukemic effects. Therefore, our study paves the avenue for clinical application of PF-9366 to improve the treatment of poor prognosis MLLr leukemia.
A gifted SNARC? Directional spatial–numerical associations in gifted children with high-level math skills do not differ from controls
2020-05-24

Abstract The SNARC (Spatial-Numerical Association of Response Codes) effect (i.e., a tendency to associate small/large magnitude numbers with the left/right hand side) is prevalent across the whole lifespan. Because the ability to relate numbers to space has been viewed as a cornerstone in the development of mathematical skills, the relationship between the SNARC effect and math skills has been frequently examined. The results remain largely inconsistent. Studies testing groups of people with very low or very high skill levels in math sometimes found relationships between SNARC and math skills. So far, however, studies testing such extreme math skills level groups were mostly investigating the SNARC effect in individuals revealing math difficulties. Groups with above average math skills remain understudied, especially in regard to children. Here, we investigate the SNARC effect in gifted children, as compared to normally developing children (overall n = 165). Frequentist and Bayesian analysis suggested that the groups did not differ from each other in the SNARC effect. These results are the first to provide evidence for the SNARC effect in a relatively large sample of gifted (and mathematically highly skilled) children. In sum, our study provides another piece of evidence for no direct link between the SNARC effect and mathematical ability in childhood.
Application of Atomic Force Microscopy to Detect Early Osteoarthritis
2020-05-24

Biomechanical properties of cells and tissues not only regulate their shape and function but are also crucial for maintaining their vitality. Changes in elasticity can propagate or trigger the onset of major diseases like cancer or osteoarthritis (OA). Atomic force microscopy (AFM) has emerged as a strong tool to qualitatively and quantitatively characterize the biomechanical properties of specific biological target structures on a microscopic scale, measuring forces in a range from as small as the piconewton to the micronewton. Biomechanical properties are of special importance in musculoskeletal tissues, which are subjected to high levels of strain. OA as a degenerative disease of the cartilage results in the disruption of the pericellular matrix (PCM) and the spatial rearrangement of the chondrocytes embedded in their extracellular matrix (ECM). Disruption in PCM and ECM has been associated with changes in the biomechanical properties of cartilage. In the present study we used AFM to quantify these changes in relation to the specific spatial pattern changes of the chondrocytes. With each pattern change, significant changes in elasticity were observed for both the PCM and ECM. Measuring the local elasticity thus allows for drawing direct conclusions about the degree of local tissue degeneration in OA.
Stress in the USSR. On the Dissemination of Health Knowledge in the Soviet Public Sphere, 1960s–1991 Jan Arend
2020-05-24

When and where does “stress” – a psychological and bodily condition associated with the pressure to perform – become a social concern? Previous historical research has situated the topic in the West, linking it to what is understood to be a Western type of capitalism and / or neoliberalism. This article departs from this line of research by demonstrating the broad dissemination of the topic of stress in the Soviet public sphere since the mid-1960s. Based on an examination of three of the most widely read Soviet state newspapers, the article shows how the notion of stress was conveyed to the Soviet public and thereby sheds light on the circulation of knowledge related to health in the period of late socialism. Stress, although the concept originally came to the Soviet context through a process of knowledge transfer from the West, had a life of its own in the Soviet Union. By analyzing how the concept of stress was adapted to a state socialist context, the article points to previously underexplored cross-bloc similarities with regard to perceptions of emotions and the body.