bluuebunny/crossref_metadata_2025_split huggingface dataset:
A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples
Authors: Madan Taruna , Biswas Barnali , Varghese Praveen M. , Subedi Rambhadur , Pandit Hrishikesh , Idicula-Thomas Susan , Kundu Indra , Rooge Sheetalnath , Agarwal Reshu , Tripathi Dinesh M. , Kaur Savneet , Gupta Ekta , Gupta Sanjeev K. , Kishore Uday 
Published: December 2020

AbstractRationaleCOVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known.ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2.MethodsrfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR.Measurements and Main ResultsIn-silicointeraction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5μM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 μM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5μM rfhSP-D.ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replicationin-vitro.
Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particlesin vitro
Authors: Hsieh Miao-Hsi , beirag Nazar , Murugaiah Valarmathy , Chou Yu-Chi , Kuo Wen-Shuo , Kao Hui-Fan , Madan Taruna , Kishore Uday , Wang Jiu-Yao 
Published: December 2020

AbstractHuman SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows immune surveillance role against pulmonary pathogens. Higher levels of serum SP-D have been reported in patients with severe acute respiratory syndrome coronavirus-1 (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virusin vitro, in vivoandex vivomodels. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing Angiotensin Converting Enzyme 2. The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following rfhSP-D treatment (10 μg/ml). The results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merits pre-clinical studies in murine models.
SARS-CoV-2 spike protein interacts with and activates TLR4
Authors: Zhao Yingchi , Kuang Ming , Zhu Ling , Li Junhong , Jia Zijing , Guo Xuefei , Wang Xiangxi , You Fuping 
Published: December 2020

SummaryThe onset of sepsis is an important feature of COVID19 and a main cause of death. It is unknown how SARS-CoV-2 infection results in viral sepsis in human. We recently found that SARS-CoV-2 provoked an anti-bacterial like response and activation of TLR4 pathway at the very early stage of infection in animal models. This abnormal immune response led to emergency granulopoiesis and sepsis. However, the original trigger of TLR4 signaling by SARS-CoV-2 is unknown. We here identified that the trimeric spike protein of SARS-CoV-2 could bind to TLR4 directly and robustly activate downstream signaling in monocytes and neutrophils. Moreover, specific TLR4 or NFKB inhibitor, or knockout of MyD88 could significantly block IL-1B induction by spike protein. We thus reveal that spike protein of SARS-CoV-2 functions as a potent stimulus causing TLR4 activation and sepsis related abnormal responses.
A common genetic architecture enables the lossy compression of large CRISPR libraries
Authors: Zhao Boyang , Rao Yiyun , Gilbert Luke , Pritchard Justin 
Published: December 2020

AbstractThere are thousands of ubiquitously expressed mammalian genes, yet a genetic knockout can be lethal to one cell, and harmless to another. This context specificity confounds our understanding of genetics and cell biology. 2 large collections of pooled CRISPR screens offer an exciting opportunity to explore cell specificity. One explanation, synthetic lethality, occurs when a single “private” mutation creates a unique genetic dependency. However, by fitting thousands of machine learning models across millions of omic and CRISPR features, we discovered a “public” genetic architecture that is common across cell lines and explains more context specificity than synthetic lethality. This common architecture is built on CRISPR loss-of-function phenotypes that are surprisingly predictive of other loss-of-function phenotypes. Using these insights and inspired by thein silicolossy compression of images, we use machine learning to identify small “lossy compression” sets ofin vitroCRISPR constructs where reduced measurements produce genome-scale loss-of-function predictions.
Rapid local adaptation in both sexual and asexual invasive populations of monkeyflowers (Mimulus spp.)
Authors: Simón-Porcar Violeta I. , Silva Jose L. , Vallejo-Marín Mario 
Published: December 2020

AbstractBackground and AimsTraditionally, local adaptation has been seen as the outcome of a long evolutionary history, particularly in sexual lineages. In contrast, phenotypic plasticity has been thought to be most important during the initial stages of population establishment and in asexual species. We evaluated the roles of adaptive evolution and phenotypic plasticity in the invasive success of two closely related species of invasive monkeyflowers (Mimulus) in the United Kingdom (UK) that have contrasting reproductive strategies:M. guttatuscombines sexual (seeds) and asexual (clonal growth) reproduction whileM. × robertsiiis entirely asexual.MethodsWe compared the clonality (number of stolons), floral and vegetative phenotype, and phenotypic plasticity of native (M. guttatus) and invasive (M. guttatusandM. ×robertsii) populations grown in controlled environment chambers under the environmental conditions at each latitudinal extreme of the UK. The goal was to discern the roles of temperature and photoperiod on the expression of phenotypic traits. Next, we tested the existence of local adaptation in the two species within the invasive range with a reciprocal transplant experiment at two field sites in the latitudinal extremes of the UK, and analysed which phenotypic traits underlie potential local fitness advantage in each species.Key ResultsPopulations ofM. guttatusin the UK showed local adaptation through sexual function (fruit production), whileM. ×robertsiishowed local adaptation via asexual function (stolon production). Phenotypic selection analyses revealed that different traits are associated with fitness in each species. Invasive and native populations ofM. guttatushad similar phenotypic plasticity and clonality.M. ×robertsiipresents greater plasticity and clonality than nativeM. guttatus, but most populations have restricted clonality under the warm conditions of the south of UK.ConclusionsOur study provides experimental evidence of local adaptation in a strictly asexual invasive species with high clonality and phenotypic plasticity. This indicates that even asexual taxa can rapidly (< 200 years) adapt to novel environmental conditions in which alternative strategies may not ensure the persistence of populations.
Sleep leads to system-wide neural changes independent of allo- and egocentric spatial training in humans and rats
Authors: Samanta Anumita , van Rongen Laurens S , Rossato Janine I. , Jacobse Justin , Schoenfeld Robby , Genzel Lisa 
Published: December 2020

AbstractSleep is important for memory consolidation, especially the process of systems consolidation should occur during sleep. While a significant amount of research has been done in regards to the effect of sleep on behavior and certain mechanisms during sleep, until now evidence is lacking that sleep leads to consolidation across the system. Here, we investigated the role of sleep in consolidation of spatial memory in the watermaze in both rats and humans using allocentric and egocentric based training. Combining behavior with immediate early gene expression analysis in rodents and functional MR imaging in humans, elucidated similar behavioral and neural effects in both species. Rats and humans showed a benefit of sleep on behavior. Interestingly, sleep led to systems-wide retrieval network in both species in both training conditions. Thus, we provide cross-species evidence for memory consolidation on the system-level occurring during sleep.Significance StatementProcesses occurring during sleep such as memory reactivations are proposed to lead to consolidation from the initial hippocampal memory representation to long-lasting cortical representations, this is known as systems consolidation. By combining behavioral measurements in the watermaze with immediate early gene expression analysis in rats and function magnetic resonance imaging in humans, we could show a benefit of sleep on behavioral memory performance. And, sleep lead to systems-wide changes in the retrieval network. These results are the first direct evidence supporting the role of sleep for systems-wide memory consolidation in both rats and humans.
Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE
Authors: Chaudhary P , Marracci GH , Calkins E , Pocius E , Bensen AL , Scanlan TS , Emery B , Bourdette DN 
Published: December 2020

AbstractWe have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4mg/kg), Sob (5mg/kg) or Sob-AM2 (5mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis.HighlightsThyroid hormone, the thyromimetic Sob and its CNS penetrating prodrug, Sob-AM2, reduce disease severity, reduce myelin and axonal degeneration and protect oligodendrocytes in EAE.The benefits of Sob and Sob-AM2 may be via direct protective effects on oligodendrocytes and reduction in activity of microglia/macrophages.
The novel chaperone protein SRCP1 reduces insoluble SOD1 proteinin vivowithout extending ALS mouse lifespan
Authors: Luecke Ian W. , Lin Gloria , Santarriaga Stephanie , Scaglione K. Matthew , Ebert Allison D. 
Published: December 2020

AbstractProtein misfolding and aggregation are shared features of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and protein quality control disruption contributes to neuronal toxicity. Therefore, reducing protein aggregation could hold therapeutic potential. We previously identified a novel chaperone protein, serine-rich chaperone protein 1 (SRCP1), that effectively prevents protein aggregation in cell culture and zebrafish models of Huntington’s disease. Here we tested whether this benefit extends to aggregated proteins found in ALS. We used viral-mediated expression of SRCP1 inin vitroandin vivomodels of ALS. We found that SRCP1 reduced insoluble SOD1 protein levels in HEK293T cells overexpressing either the A4V or G93R mutant SOD1. However, the reduction of insoluble protein was not observed in either mutant C9orf72 or SOD1 ALS iPSC-derived motor neurons infected with a lentivirus expressing SRCP1. SOD1 G93A ALS mice injected with AAV-SRCP1 showed a small but significant reduction in insoluble and soluble SOD1 in both the brain and spinal cord, but SRCP1 expression did not improve mouse survival. These data indicate that SRCP1 likely reduces insoluble protein burden in a protein and/or context-dependent manner indicating a need for additional insight into SRCP1 function and therapeutic potential.
Analysis of six-decadal seed mass and emergence records in mast species shows little inter-annual variability
Authors: Liu Yang , El-Kassaby Yousry A. 
Published: December 2020

AbstractPatterns of crop production in mast species do not track crop-year climate, but instead are regulated by climate cues in prior-years. Whether the pattern of year-to-year seed mass variation is coupled in time with mast seeding, maintaining seed mass-number trade-offs, and coherently driven by similar climate cues as other seed traits (e.g. seed germination) remains unknown. Using ca. 6,000 long-term seed inventory data over the years 1955-2015 in conifers, this retrospective study revealed the temporal patterns of mast species’ seed mass and its associated trait, seed germination. To pinpoint their ecological drivers, pairwise correlation analysis was performed between each trait and seasonal climates in crop year and four prior-years. Using climate variables key to each trait, regression models were constructed to project trait values. Findings showed minor seed mass variation among years, which rejects the generality of seed mass-number trade-offs in many plant species. This result reasonably arises as the economies of scale (compensating benefits) theory are often used to account for mast seeding but not for seed mass. Moreover, final germination fraction also varied little over time, but exhibited an increasing tendency. In addition, we found that temperature-based climate variables drive seed mass, number, and germination variation, but these variables in different seasons of crop year or prior-years did not have equal influences on trait variability. Finally, regression models showed that the number of frost-free days and evapotranspiration are crucial to the three traits and climate in autumn is a critical season, followed by summer and winter. This study holds considerable promise for explaining reproductive strategies of taxonomic groups with mast seeding characteristics in allocating reproductive resources to different life-history traits using ecological signals.
Stabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1
Authors: Dang Mei , Li Yifan , Song Jianxing 
Published: December 2020

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RRM domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including ALS, FTD, AD and MSP. Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: 1) very unexpectedly, upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. 2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity higher to the tethered than isolated forms. 3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1-RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.
Metaproteomics boosted up by untargeted data-independent acquisition data analysis framework
Authors: Pietilä Sami , Suomi Tomi , Elo Laura L. 
Published: December 2020

AbstractMass spectrometry based metaproteomics is a relatively new field of research that provides the ability to characterize the functionality of microbiota. Recently, we were the first to demonstrate the applicability of data-independent acquisition (DIA) mass spectrometry to the analysis of complex metaproteomic samples. This allowed us to circumvent many of the drawbacks of the conventionally used data-dependent acquisition (DDA) mass spectrometry, mainly the limited reproducibility when analyzing samples with complex microbial composition. However, the previous method still required additional DDA data on the samples to assist the DIA analysis. Here, we introduce, for the first time, a DIA metaproteomics approach that does not require any DDA data, but instead replaces a spectral library generated from DDA data with a pseudospectral library generated directly from the metaproteomics DIA samples. We demonstrate that using the new DIA-only approach, we can achieve higher peptide yields than with the DDA-assisted approach, while the amount of required mass spectrometry data is reduced to a single DIA run per sample. The new DIA-only metaproteomics approach is implemented as open-source software packageDIAtools 2.0, which is freely available from DockerHub.
Heat transfer hybrid nanofluid (1-Butanol/MoS2–Fe3O4) through a wavy porous cavity and its optimization
Authors: Hosseinzadeh Kh. , Montazer Elham , Shafii Mohammad Behshad , Ganji D.D. 
Published: December 2020

Purpose
The purpose of this paper is to investigate natural convection in a porous wavy-walled enclosure that is including a cylinder cavity in the middle of it and filled with a hybrid nanofluid contains 1-Butanol as the base fluid and MoS2–Fe3O4 hybrid nanoparticles.

Design/methodology/approach
The domain of interest is bounded by constant temperature horizontal corrugated surfaces and isothermal vertical flat surfaces. The numerical outputs are explained in the type of isotherms, streamline and average Nusselt number with variations of the Rayleigh number, Hartmann number, nanoparticle shape factor and porosity of the porous medium. For solving the governing equations, the finite element method has been used.

Findings
The results show that Nuave is proportional to Rayleigh and nanoparticle shape factor directly as well as it has an inverse relation with Hartmann and porosity. The obtained results reveal that the shape factor parameter has a significant effect on the heat transfer performance, which shows a 55.44% contribution on the average Nusselt number.

Originality/value
As a novelty, to maximize the heat transfer performance in a corrugated walls enclosure, the optimal parameters have intended by using the response surface and Taguchi methods. Additionally, an accurate correlation for the average Nusselt number is developed with sensibly great precision.
Determinants of inpatient satisfaction: evidence from Switzerland
Authors: Tobler Stephan , Stummer Harald 
Published: December 2020

PurposeA common way to handle quality problems and increasing costs of modern health care systems is more transparency through public reporting. Thereby, patient satisfaction is seen as one main reported outcome. Previous studies proposed several associated factors. Only a few of them included organizational determinants with potential to inform the health care provider's management. Therefore, the aim of this study was to investigate the influence of organizational contingency factors on patient satisfaction.Design/methodology/approachAs a case, Switzerland's inpatient rehabilitation sector was used. Therein, a cross-sectional study of public released secondary data with an exploratory multiple linear regression (MLR) modeling approach was conducted.FindingsFive significant influencing factors on patient satisfaction were found. They declared 42.2% of the variance in satisfaction on provider level. The organizations' supplementary insured patients, staff payment, outpatients, extracantonal patients and permanent resident population revealed significant correlations with patient satisfaction.Research limitations/implicationsDrawing on publicly available cross-sectional data, statistically no causality can be proved. However, integration of routine data and organization theory can be useful for further studies.Practical implicationsRegarding inpatient satisfaction, improvement levers for providers' managers are as follow: first, service provision should be customized to patients' needs, expectations and context; second, employees' salary should be adequate to prevent dissatisfaction; third, the main business should be prioritized to avoid frittering.Originality/valueFormer studies regarding public reporting are often atheoretical and rarely used organizational variables as determinants for relevant outcomes. Therefore, uniformed data are useful.
Consumer reactions to unsustainable luxury: a cross-country analysis
Authors: Amatulli Cesare , De Angelis Matteo , Pino Giovanni , Jain Sheetal 
Published: December 2020

PurposeThis paper investigates why and when messages regarding unsustainable luxury products lead to negative word-of-mouth (NWOM) through a focus on the role of guilt, need to warn others and consumers' cultural orientation.Design/methodology/approachThree experiments test whether messages describing unsustainable versus sustainable luxury manufacturing processes elicit guilt and a need to warn others and whether and how the need to warn others affects consumers' NWOM depending on their cultural orientation.FindingsConsumers experience guilt in response to messages emphasizing the unsustainable (vs sustainable) nature of luxury products. In turn, guilt triggers a need to warn other consumers, which leads to NWOM about the luxury company. Furthermore, the results suggest that two dimensions of Hofstede's model of national culture – namely individualism/collectivism and masculinity/femininity – moderate the effect of the need to warn others on NWOM.Practical implicationsLuxury managers should design appropriate strategies to cope with consumers' different reactions to information regarding luxury brands' unsustainability. Managers should be aware that the risk of NWOM diffusion may be higher in countries characterized by a collectivistic and feminine orientation rather than an individualistic and masculine orientation.Originality/valueConsumer reaction to unsustainable luxury, especially across different cultural groups, is a neglected area of investigation. This work contributes to this novel area of research by investigating NWOM stemming from unsustainable luxury manufacturing practices in different cultural contexts.