bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic profiling of soft tissue sarcomas with SWATH mass spectrometry
Authors: Milighetti Martina , Krasny Lukas , Lee Alex T.J. , McCarthy Frank , Morani Gabriele , Szecsei Cornelia , Chen Yingtong , Fisher Cyril , Judson Ian , Thway Khin , Maggie C.U. Cheang , Jones Robin L. , Huang Paul H. 
Published: June 2020

AbstractSoft tissue sarcomas (STS) are a group of rare and heterogeneous cancers. While large-scale genomic and epigenomic profiling of STS have been undertaken, proteomic analysis has thus far been limited. Here we utilise sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for proteomic profiling of formalin fixed paraffin embedded (FFPE) specimens from a cohort of STS patients (n=36) across four histological subtypes (leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma). We quantified 2951 proteins across all cases and show that there is a significant enrichment of gene sets associated with smooth muscle contraction in leiomyosarcoma, RNA splicing regulation in synovial sarcoma and leukocyte activation in undifferentiated pleomorphic sarcoma. We further identified a subgroup of STS cases (independent of histological subtype) that have a distinct expression profile in a panel of 133 proteins, with worse survival outcomes when compared to the rest of the cohort. Our study highlights the value of comprehensive proteomic characterisation as a means to identify histotype-specific STS profiles that describe key biological pathways of clinical and therapeutic relevance; as well as for discovering new prognostic biomarkers in this group of rare and difficult-to-treat diseases.
Optimal size of sample pooling for RNA pool testing: an avant-garde for scaling up SARS CoV 2 testing
Authors: Arvind Khodare , Abhishek Padhi , Ekta Gupta , Reshu Agarwal , Shantanu Dubey , Sarin SK 
Published: June 2020

AbstractIntroductionTimely diagnosis is essential for the containment of the disease and breaks in the chain of transmission of SARS-CoV-2. The present situation demands countries to scale up their testing and design innovative strategies to conserve diagnostic kits and reagents. The pooling of samples saves time, manpower, and most importantly diagnostic kits and reagents. In the present study, we tried to define the pool size that could be applied with acceptable confidence for testing.Material and methodsWe used repeatedly tested positive clinical sample elutes having different levels of SARS CoV 2 RNA and negative sample elutes to prepare seven series of 11 pools each, having pool sizes ranging from 2 to 48 samples to estimate the optimal pool size. Each pool had one positive sample elute in different compositions. All the pools were tested by SARS CoV 2 RT-qPCR.ResultsOut of the 77 pools, only 53 (68.8%) were found positive. The sensitivity of pools of 2 to 48 samples was decreased from 100% (95% CL; 98.4-100) to 41.41% (95% CL; 34.9-48.1). The maximum size of the pool with acceptable sensitivity (>95%) was found to be of 6 samples. For the pool size of 6 samples, the sensitivity was 97.8% and the efficiency of pooling was 0.38.ConclusionThe pooling of samples is a practical way for scaling up testing and ultimately containing the further spread of the COVID-19 pandemic.
When is SARS-CoV-2 in your shopping list?
Authors: Hernandez-Mejia Gustavo , Hernandez-Vargas Esteban A. 
Published: June 2020

ABSTRACTThe pandemic of coronavirus disease 2019 (COVID-19) has caused, by May 24th 2020, more than 5.3 million confirmed cases worldwide. The necessity of keeping open and accessible public commercial establishments such as supermarkets or pharmacies increases during the pandemic provided that distancing rules and crowd control are satisfied.Herein, using agent-based models, we explore the potential spread of the novel SARS-CoV-2 considering the case of a small size supermarket. For diverse distancing rules and number of simultaneous users (customers), we question flexible and limited movement policies, guiding the flow and interactions of users in place. Results indicate that a guided, limited in movement and well-organized policy combined with a distance rule of at least 1 m between users and a small number of them (15) may aid in the mitigation of potential new contagions in more than 90% compared to the usual policy of flexible movement with more users (30) which may reach up to 64% of mitigation of potential new infections under the same distancing conditions. This study may guide novel strategies for the mitigation of the current COVID-19 pandemic, at any stage, and prevention of future outbreaks of SARS-CoV-2 or related viruses.
COVID-19 Deaths: Which Explanatory Variables Matter the Most?
Authors: Riley Pete , Riley Allison , Turtle James , Ben-Nun Michal 
Published: June 2020

SummaryAs Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spreads around the World, many questions about the disease are being answered; however, many more remain poorly understood. Although the situation is rapidly evolving, with datasets being continually corrected or updated, it is crucial to understand what factors may be driving transmission through different populations. While studies are beginning to highlight specific parameters that may be playing a role, few have attempted to thoroughly estimate the relative importance of these disparate variables that likely include: climate, population demographics, and imposed state interventions. In this report, we compiled a database of more than 28 potentially explanatory variables for each of the 50 U.S. states through early May 2020. Using a combination of traditional statistical and modern machine learning approaches, we identified those variables that were the most statistically significant, and, those that were the most important. These variables were chosen to be fiduciaries of a range of possible drivers for COVID-19 deaths in the USA. We found that population-weighted density (PWD), some “stay at home” metrics, monthly temperature and precipitation, race/ethnicity, and chronic low-respiratory death rate, were all statistically significant. Of these, PWD and mobility metrics dominated. This suggests that the biggest impact on COVID-19 deaths was, at least initially, a function of where you lived, and not what you did. However, clearly, increasing social distancing has the net effect of (at least temporarily) reducing the effective PWD. Our results strongly support the idea that the loosening of “lock-down” orders should be tailored to the local PWD. In contrast to these variables, while still statistically significant, race/ethnicity, health, and climate effects could only account for a few percent of the variability in deaths. Where associations were anticipated but were not found, we discuss how limitations in the parameters chosen may mask a contribution that might otherwise be present.
Structural and functional synaptic plasticity induced by convergent synapse loss requires co-innervation in the Drosophila neuromuscular circuit
Authors: Wang Yupu , Lobb-Rabe Meike , Ashley James , Carrillo Robert A. 
Published: June 2020

ABSTRACTThroughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each other’s structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs. An ideal model to address this question is theDrosophilalarval neuromuscular junction where each postsynaptic muscle cell receives inputs from two glutamatergic types of motor neurons (MNs), known as 1b and 1s MNs. Notably, each muscle is unique and receives input from a different combination of 1b and 1s motor neurons. We surveyed synapses on multiple muscles for this reason. Here, we identified a cell-specific promoter to ablate 1s MNs after innervation. Additionally, we genetically blocked 1s innervation. Then we measured 1b MN structural and functional responses using electrophysiology and microscopy. For all muscles, 1s MN ablation resulted in 1b MN synaptic expansion and increased basal neurotransmitter release. This demonstrates that 1b MNs can compensate for the loss of convergent inputs. However, only a subset of 1b MNs showed compensatory evoked activity, suggesting spontaneous and evoked plasticity are independently regulated. Finally, we usedDIP-αmutants that block 1s MN synaptic contacts; this eliminated robust 1b synaptic plasticity, raising the possibility that muscle co-innervation may define an activity “set point” that is referenced when subsequent synaptic perturbations occur. This model can be tested in more complex circuits to determine if co-innervation is fundamental for input-specific plasticity.SIGNIFICANCE STATEMENTIn complex neural circuits, multiple converging inputs contribute to the output of each target cell. Thus, each input must be regulated, but whether adjacent inputs contribute to this regulation is unclear. To examine input-specific synaptic plasticity in a structurally and functionally tractable system, we turn to theDrosophilaneuromuscular circuit. Each muscle is innervated by a unique pair of motor neurons. Removal of one neuron after innervation causes the adjacent neuron to increase synaptic outgrowth and functional output. However, this is not a general feature since each MN differentially compensates. Also, robust compensation requires co-innervation by both neurons. Understanding how neurons respond to perturbations in adjacent neurons will provide insight into nervous system plasticity in both healthy and diseased states.
Allelic Variation ofMYB10is the Major Force Controlling Natural Variation of Skin and Flesh Color in Strawberry (Fragariaspp.) fruit
Authors: Castillejo Cristina , Waurich Veronika , Wagner Henning , Ramos Rubén , Oiza Nicolás , Muñoz Pilar , Triviño Juan C. , Caruana Julie , Liu Zhongchi , Cobo Nicolás , Hardigan Michael A. , Knapp Steven J. , Vallarino José G. , Osorio Sonia , Martín-Pizarro Carmen , Posé David , Toivainen Tuomas , Hytönen Timo , Oh Youngjae , Barbey Christopher R. , Whitaker Vance M. , Lee Seonghee , Olbricht Klaus , Sánchez-Sevilla José F. , Amaya Iraida 
Published: June 2020

ABSTRACTAnthocyanins are the principal color-producing compounds synthesized in developing fruits of strawberry (Fragariaspp.). Substantial natural variation in color have been observed in fruits of diploid and octoploid accessions, resulting from distinct accumulation and distribution of anthocyanins in fruits. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among whichMYB10has been shown as the main activator in strawberry fruit. Here, we show thatMYB10mutations cause most of the anthocyanin variation observed in diploid woodland strawberry(F. vesca)and octoploid cultivated strawberry (F. ×ananassa). Using a mapping-by-sequencing approach, we identified agypsy-transposon insertion inMYB10that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruitedF. vescaecotype. Two additional loss-of-functionMYB10mutations were identified among geographically diverse white-fruitedF. vescaecotypes. Genetic and transcriptomic analyses in octoploidFragaria spp.revealed thatFaMYB10-2,one of threeMYB10homoeologs identified, residing in theF. iinumae-derivedsubgenome, regulates the biosynthesis of anthocyanins in developing fruit. Furthermore, independent mutations inMYB10-2are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon(FaEnSpm-2)insertion in theMYB10-2promoter of red-fleshed accessions that was associated with enhanced expression and anthocyanin accumulation. Our findings suggest that putative cis regulatory elements provided byFaEnSpm-2are required for high and ectopicMYB10-2expression and induction of anthocyanin biosynthesis in fruit flesh. We developedMYB10-2(sub-genome) specific DNA markers for marker-assisted selection that accurately predicted anthocyanin phenotypes in octoploid segregating populations.
Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Authors: Zhou Daming , Duyvesteyn Helen ME , Chen Cheng-Pin , Huang Chung-Guei , Chen Ting-Hua , Shih Shin-Ru , Lin Yi-Chun , Cheng Chien-Yu , Cheng Shu-Hsing , Huang Yhu-Chering , Lin Tzou-Yien , Ma Che , Huo Jiandong , Carrique Loic , Malinauskas Tomas , Ruza Reinis R , Shah Pranav NM , Tan Tiong Kit , Rijal Pramila , Donat Robert F. , Godwin Kerry , Buttigieg Karen , Tree Julia , Radecke Julika , Paterson Neil G , Supasa Piyasa , Mongkolsapaya Juthathip , Screaton Gavin R , Carroll Miles W. , Jaramillo Javier G. , Knight Michael , James William , Owens Raymond J , Naismith James H. , Townsend Alain , Fry Elizabeth E , Zhao Yuguang , Ren Jingshan , Stuart David I , Huang Kuan-Ying A. 
Published: June 2020

AbstractThe COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KDof 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Å crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19.
Spike–frequency adaptation is modulated by interacting currents in an Hodgkin-Huxley-type model: Role of the Na,K–ATPase
Authors: Jolivet Renaud Blaise , Magistretti Pierre J. 
Published: June 2020

AbstractSpike–frequency adaptation is a prominent feature of spiking neurons. Using a Hodgkin–Huxley–type model, we studied adaptation originating from the Na,K–ATPase electrogenic pump and its evolution in presence of a medium–duration calcium–dependent potassium channel. We found that the Na,K–ATPase induces spike–frequency adaptation with a time constant of up to a few seconds and interacts with the calcium–dependent potassium current through the output frequency, yielding a very typical pattern of instantaneous frequencies. Because channels responsible for spike–frequency adaptation can interact with each other, our results suggest that their meaningful time courses and parameters can be difficult to measure experimentally. To circumvent this problem, we developed a simple phenomenological model that captures the interaction between currents and allows the direct evaluation of the underlying biophysical parameters directly from the frequency vs. current curves. Finally, we found that for weak stimulations, the pump induces phasic spiking and linearly converts the stimulus amplitude in a finite number of spikes acting like an inhibitory spike–counter. Our results point to the importance of considering interacting currents involved in spike–frequency adaptation collectively rather than as isolated elements and underscore the importance of sodium as a messenger for long–term signal integration in neurons. Within this context, we propose that the Na,K–ATPase plays an important role and show how to recover relevant biological parameters from adapting channels using simple electrophysiological measurements.
Quantitative genetic architecture of adaptive phenology traits in the deciduous tree,Populus trichocarpa(Torr. & Gray)
Authors: Richards Thomas J , Karacic Almir , Apuli Rami-Petteri , Weih Martin , Ingvarsson Pär K. , Rönnberg-Wästljung Ann Christin 
Published: June 2020

ABSTRACTIn a warming climate, the ability to accurately predict and track shifting environmental conditions will be fundamental for plant survival. Environmental cues define the transitions between growth and dormancy as plants synchronise development with favourable environmental conditions, however these cues are predicted to change under future climate projections which may have profound impacts on tree survival and growth. Here, we use a quantitative genetic approach to estimate the genetic basis of spring and autumn phenology inPopulus trichocarpato determine this species capacity for climate adaptation. We measured bud burst, leaf coloration, and leaf senescence traits across two years (2017-2018) and combine these observations with measures of lifetime growth to determine how genetic correlations between phenology and growth may facilitate or constrain adaptation. Timing of transitions differed between years, although we found strong cross year genetic correlations in all traits, suggesting that genotypes respond in consistent ways to seasonal cues. Spring and autumn phenology were correlated with lifetime growth, where genotypes that burst leaves early and shed them late had the highest lifetime growth. We also identified substantial heritable variation in the timing of all phenological transitions (h2= 0.5-0.8) and in lifetime growth (h2= 0.8). The combination of abundant additive variation and favourable genetic correlations in phenology traits suggests that cultivated varieties ofP. trichocarpahave the capability to create populations which may adapt their phenology to climatic changes without negative impacts on growth.
Enlarged Ingroup Effect: How a Shared Culture Shapes In-Group Perception
Authors: Rigo Paola , Ragunath Bindiya L. , Bornstein Marc H. , Esposito Gianluca 
Published: June 2020

ABSTRACTIncreasing levels of migration and constant redefinition of a ‘sense of belonging’ characterize modern societies. Thus, social perception of people from different ethnicities as in-group or out-group members is influenced by a shared culture that might go beyond ethnicity. Using functional magnetic resonance imaging, we aim to study how sharing a common culture changes the social perceptions of in-groups and out-groups. We presented same- and different-race faces to young adults living in an integrated multicultural society. Same- and different-race faces were primed by images of environmental context that promotes identification with the participants’ ethnicity or a common shared culture.We found that same and different-race faces recruit similar brain networks only when associated with an environmental context, which promoted identification with a common shared culture. These results support a possible emergent phenomenon in multicultural societies that we call enlarged multi-ethnic in-group effect, which may form the basis of a potential new way to categorize oneself and others in terms of membership.
Neurotransmitter Classification from Electron Microscopy Images at Synaptic Sites in Drosophila Melanogaster
Authors: Eckstein Nils , Bates Alexander Shakeel , Champion Andrew , Du Michelle , Yin Yijie , Schlegel Philipp , Lu Alicia Kun-Yang , Rymer Thomson , Finley-May Samantha , Paterson Tyler , Parekh Ruchi , Dorkenwald Sven , Matsliah Arie , Yu Szi-Chieh , McKellar Claire , Sterling Amy , Eichler Katharina , Costa Marta , Seung Sebastian , Murthy Mala , Hartenstein Volker , Jefferis Gregory S.X.E. , Funke Jan 
Published: June 2020

AbstractHigh-resolution electron microscopy of nervous systems enables the reconstruction of connectomes. A key piece of missing information from connectomes is the synaptic sign. We show that forD. melanogaster, artificial neural networks can predict the transmitter type released at synapses from electron micrographs and thus add putative signs to connections. Our network discriminates between six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) with an average accuracy of 87%/94% for synapses/entire neurons. We developed an explainability method to reveal which features our network is using and found significant ultrastructural differences between the classical transmitters. We predict transmitters in two connectomes and characterize morphological and connection properties of tens of thousands of neurons classed by predicted transmitter expression. We find that hemilineages inD. melanogasterlargely express only one fastacting transmitter among their neurons. Furthermore, we show that neurons with different transmitters may differ in features like polarization and projection targets.
Ethylene-triggered subcellular trafficking of CTR1 enhances the response to ethylene gas
Authors: Lee Han Yong , Seo Dong Hye , Park Hye Lin , Bakshi Arkadipta , Park Chanung , Kieber Joseph J. , Binder Brad M. , Yoon Gyeong Mee 
Published: June 2020

SummaryEthylene gas controls plant growth and stress responses. Ethylene-exposed dark-grown seedlings exhibit dramatic growth reduction, yet the seedlings rapidly return to the basal growth rate when ethylene gas is removed. However, the underlying mechanism governing this reversible acclimation of dark-grown seedlings to ethylene remains enigmatic. Here, we report that ethylene triggers the translocation of the Raf-like protein kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1), a negative regulator of ethylene signaling, from the endoplasmic reticulum to the nucleus. Nuclear-localized CTR1 stabilizes the ETHYLENE-INSENSITIVE3 (EIN3) transcription factor via interaction with the EIN3-BINDING F-box (EBF) proteins, thus enhancing the ethylene response and delaying growth recovery. These findings uncover a mechanism of the ethylene signaling pathway that links the spatiotemporal dynamics of cellular signaling components to organismal responses.
Temporal hierarchy of intrinsic neural timescales converges with spatial core-periphery organization
Authors: Golesorkhi Mehrshad , Gomez-Pilar Javier , Tumati Shankar , Fraser Maia , Northoff Georg 
Published: June 2020

AbstractThe human cortex exhibits intrinsic neural timescales that shape a temporal hierarchy. Whether this temporal hierarchy follows the spatial hierarchy of its topography namely the core-periphery organization remains an open issue. Using Magnetoencephalography data, we investigate intrinsic neural timescales during rest and task states; we measure the autocorrelation window in short (ACW-50) and, introducing a novel variant, long (ACW-0) windows. We demonstrate longer ACW-50 and ACW-0 in networks located at the core compared to those at the periphery with rest and task states showing a high ACW correlation. Calculating rest-task differences, i.e., subtracting the shared core-periphery organization, reveals task-specific ACW changes in distinct networks. Finally, employing kernel density estimation, machine learning, and simulation, we demonstrate that ACW-0 exhibits better prediction in classifying a region’s time window as core or periphery. Overall, our findings provide fundamental insight into how the human cortex’s temporal hierarchy converges with its spatial core-periphery hierarchy.