bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal sensitivity of embryonic heart specification to FGFR signaling inDrosophila
Authors: Yadav V. , Tolwinski N. , Saunders T. E. 
Published: November 2020

ABSTRACTDevelopment of theDrosophilaembryonic mesoderm is controlled through both internal and external inputs to the mesoderm. One such factor is Heartless (Htl), a Fibroblast Growth Factor Receptor (FGFR) expressed in the mesoderm. Htl is involved in shaping the mesoderm at both early and later stages during embryogenesis. How Htl expression levels and timing of signaling affect mesoderm morphogenesis after spreading remains elusive. We have developed an optogenetic tool (Opto-htl) to control the activation of Htl signaling with precise spatiotemporal resolutionin vivo. We find that the embryo is most sensitive to Htl over-activation within a developmental window of ~4 hours ranging from late stage 10 until early stage 13, which corresponds to early stages of heart morphogenesis. Opto-htl restores heart cells inhtlmutants upon light activation, independent of its role in early mesoderm shaping events. We also successfully generated spatially distinct regions of Htl activity in the mesoderm using light-sheet microscopy. The developing tissue was unable to correct for the ensuing asymmetries in cell fate. Overall, Opto-htl is a powerful tool for studying spatiotemporal regulation of Htl signaling during embryogenesis.
Modelling species presence-only data with random forests
Authors: Valavi Roozbeh , Elith Jane , Lahoz-Monfort José J. , Guillera-Arroita Gurutzeta 
Published: November 2020

AbstractThe Random Forest (RF) algorithm is an ensemble of classification or regression trees, and is a widely used and high-performing machine learning technique. It is increasingly used for species distribution modelling (SDM). Many researchers use implementations of RF in the R programming language with default parameters to analyse species presence-only data together with background samples. However, there is good evidence that RF with default parameters does not perform well with such species “presence-background” data. This is often attributed to the typical disparity between the number of presence and background samples also known asclass imbalance, and several solutions have been proposed.Here, we first set the context: the background sample should be large enough to represent all environments in the region. We then aim to understand the drivers of poor performance of RF with presence-background data, and explain, test and evaluate suggested solutions. Using simulated and real species data, we compare performance of default RF with other weighting and sampling approaches.We show thatclass overlapis an important driver of poor performance, alongside class imbalance. The results demonstrate clear evidence of improvement in the performance of RFs when class imbalance is explicitly managed by sampling methods or when the overfitting commonly associated with overlapping classes is avoided by forcing shallow trees.Presence-background data is a particular version of class imbalance in which class overlap is highly likely and extreme imbalance exists. Without compromising the environmental representativeness of the sampled background, we show several approaches to fitting RF that ameliorate the effects of imbalance and overlap, and allow excellent predictive performance. Understanding the problems of RF in presence-background data allows new insights into how best to fit models, and should guide future efforts to best deal with such data.
The HIV-1 provirus excised by a single CRISPR/Cas9 RNA guide persists in the host cell and may be reactivated
Authors: Lai Michele , Maori Eyal , Quaranta Paola , Matteoli Giulia , Maggi Fabrizio , Sgarbanti Marco , Crucitta Stefania , Pacini Simone , Turriziani Ombretta , Freer Giulia , Antonelli Guido , Heeney Jonathan L. , Pistello Mauro 
Published: November 2020

AbstractGene editing may be used to cut out the human immunodeficiency virus type-1 (HIV-1) provirus from the host cell genome and eradicate infection. Here, using cells acutely or latently infected by HIV and treated with long terminal repeat-targeting CRISPR/Cas9, we show that the excised HIV provirus persists for a few weeks and, by means of HIV Integrase, rearranges in circular molecules. Circularization and integration restore proviral transcriptional activity that is enhanced in the presence of exogenous Tat and Rev or tumor necrosis factor-α, respectively, in acutely or latently infected cells. Although confirming that gene editing is a powerful tool to eradicate HIV infection, this work highlights that, to achieve this goal, the provirus has to be cleaved in several pieces and the infected cells treated with antiviral therapy before and after editing.
Resurgence of a perinatal attraction for animate objects via thyroid hormone T3
Authors: Lorenzi Elena , Lemaire Bastien S. , Versace Elisabetta , Matsushima Toshiya , Vallortigara Giorgio 
Published: November 2020

SummaryFor inexperienced brains, some stimuli are more attractive than others. Human neonates and newly-hatched chicks preferentially orient towards face-like stimuli, biological motion, and objects changing speed. In chicks, this enhances exposure to social partners, and subsequent attachment trough filial imprinting. Early preferences are not steady. The preference for stimuli changing speed fades away after three days in chicks. To understand the physiological mechanisms underlying these transient responses, we tested whether the early preferences for objects changing speed can be promoted by thyroid hormone 3,5,3’-triiodothyronine (T3). This hormone determines the start of imprinting’s sensitive period. We found that the preference for objects changing speed can be re-established in female chicks treated with T3. Moreover, day-one chicks treated with an inhibitor of endogenous T3did not show any preference. These results suggest that the time windows of early predispositions and of high plasticity are controlled by the same molecular mechanisms.
Hexarelin exerts neuroprotective and antioxidant effects against hydrogen peroxide-induced toxicity through the modulation of MAPK and PI3K/Akt patways in Neuro-2A cells
Authors: Meanti Ramona , Rizzi Laura , Bresciani Elena , Molteni Laura , Locatelli Vittorio , Coco Silvia , Omeljaniuk Robert J. , Torsello Antonio 
Published: November 2020

AbstractHexarelin, a synthetic hexapeptide, protects cardiac and skeletal muscles by inhibiting apoptosis, bothin vitroandin vivo. Moreover, evidence suggests that hexarelin could have important neuroprotective bioactivity.Oxidative stress and the generation of free radicals has been implicated in the etiologies of several neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and multiple sclerosis. In addition to direct oxidative stress, exogenous hydrogen peroxide (H2O2) can penetrate biological membranes and enhance the formation of other reactive oxygen species.The aim of this study was to examine the inhibitory influence of hexarelin on H2O2-induced apoptosis in Neuro-2A cells, a mouse neuroblastoma cell line. Our results indicate that H2O2reduced the viability of Neuro-2A cells in a dose-related fashion. Furthermore, H2O2induced significant changes in the morphology of Neuro-2A cells, reflected in the formation of apoptotic cell bodies, and an increase of nitric oxide (NO) production. Hexarelin effectively antagonized H2O2oxidative damage to Neuro-2A cells as indicated by improved cell viability, normal morphology and reduced nitrite (NO2−) release. Hexarelin treatment of Neuro-2A cells also reduced mRNA levels of caspases−3 and −7 and those of the pro-apoptotic molecule Bax; by contrast, hexarelin treatment increased anti-apoptotic Bcl-2 mRNA levels. Hexarelin also reduced MAPKs phosphorylation induced by H2O2and concurrently increased p-Akt protein expression.In conclusion, our results identify several neuroprotective and anti-apoptotic effects of hexarelin. These properties suggest that further investigation of hexarelin as a neuroprotective agent in an investigational and therapeutic context are merited.
BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models
Authors: Liu Guo-yi , Wu Yan , Kong Fan-yi , Ma Shu , Fu Li-yan , Geng Jia 
Published: November 2020

AbstractMultiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Previous studies have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2 neurons marker, GFAP astrocytes marker, and MBP oligodendrocytes marker expression to evaluate whether BMSCs can differentiate. The effect of BMSCs transplantation on inflammatory cell invasion and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining. Inflammatory factors expression was detected by ELISA and RT-qPCR. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro. In addition, BMSCs transplant improved the survival rate and weight, and reduced neurological function scores and disease incidence of EAE mice. Moreover, BMSCs transplant alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the expression levels of pro-inflammatory factors TNF-α, IL-1β and IFN-γ, and up-regulated the expression levels of anti-inflammatory factors IL-10 and TGF-β. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.
Social transmission of egg rejection in a cuckoo host
Authors: Yang Canchao , Feeney William E 
Published: November 2020

AbstractSocial learning can enable the rapid dissemination of behaviors throughout a population. Rejection of foreign eggs is a key defense in hosts of avian brood parasites; however, whether social cues can inform whether a host rejects an egg remains unknown. Here, we aimed to determine whether access to social information can influence egg rejection behavior in semi-colonial barn swallows (Hirundo rustica). By manipulating the social information available from a neighboring nest, we found that swallows that had access to social information (i.e. neighbor recently rejected an egg) were more likely to reject a foreign egg compared to those that did not have access to social information (i.e. neighbor did not reject an egg). This result provides the first empirical evidence that egg rejection behavior can solely be informed by social information, and in doing so highlights the dynamic nature of defenses that hosts can deploy against brood parasitism.
Incredible internal strains within a biogenic single crystal viewed by X-ray diffraction tomography
Authors: Seknazi Eva , Zaslansky Paul , Katsman Alex , Villanova Julie , Pokroy Boaz 
Published: November 2020

AbstractThe dorsal arm plates (DAPs) of theOphiocoma Wendtiibrittle star are highly functional single crystalline biominerals whose optimized structure and nanostructure enable them to fullfill mechanical and optical functions in the organism. Here, a large DAP bulk piece is characterized by means of synchrotron X-ray Diffraction Tomography (XRDT). This non-destructive crystallographic characterization revealed an astounding feature: the presence of very high compressive strains which relax when the mineral is cracked or grinded into a powder. Thus, previous destructive characterization techniques did not allow their detection. We attribute the compressive strains to the previously identified high-Mg calcite particles, which are coherently included and thereby compress the low-Mg calcite matrix. The measured slice contained both the bulk DAP sample as well as DAP powder. The data generated by the bulk piece could be separated from those by the powder, and the latter was used to calibrate and interprete the former. This study reveals yet another awe-inspiring feature of a biogenic structure, highlights the importance of non-destructive crystallographic characterization for biominerals, and exemplifies the potential of XRDT use in studying a single crystalline material, as well as the advantage of complementary measurement of bulk and powder for data calibration and interpretation.
Solving the sex ratio scandal inMelittobiawasps
Authors: Abe Jun , Iritani Ryosuke , Tsuchida Koji , Kamimura Yoshitaka , West Stuart A. 
Published: November 2020

AbstractThe scandalous sex ratio behaviour ofMelittobiawasps has long posed one of the greatest problems for the field of sex allocation. In contrast to the predictions of theory, and the behaviour of numerous other organisms, laboratory experiments have found thatMelittobiafemales do not produce less female-biased offspring sex ratios when more females lay eggs on a patch. We resolve this scandal, by showing that, in nature, females ofM. australicahave sophisticated sex ratio behaviour, where their strategy also depends upon whether they have dispersed from the patch where they emerged. When females have not dispersed, they will be laying eggs with close relatives, which keeps local mate competition high, even with multiple females, and so they are selected to produce consistently female-biased sex ratios. Laboratory experiments mimic these conditions. In contrast, when females disperse, they will be interacting with non-relatives, and so they adjust their sex ratio depending upon the number of females laying eggs. Consequently, females appear to use dispersal status as an indirect cue of relatedness, and whether they should adjust their sex ratio in response to the number of females laying eggs on the patch.
CAMP: a Convolutional Attention-based Neural Network for Multifaceted Peptide-protein Interaction Prediction
Authors: Lei Yipin , Li Shuya , Liu Ziyi , Wan Fangping , Tian Tingzhong , Li Shao , Zhao Dan , Zeng Jianyang 
Published: November 2020

AbstractPeptide-protein interactions (PepPIs) are involved in various fundamental cellular functions and their identification is crucial for designing efficacious peptide therapeutics. To facilitate the peptide drug discovery process, a number of computational methods have been developed to predict peptide-protein interactions. However, most of the existing prediction approaches heavily depend on high-resolution structure data. Although several deep-learning-based frameworks have been proposed to predict compound-protein interactions or protein-protein interactions, few of them are particularly designed to specifically predict peptide-protein interactions. In this paper, We present a sequence-basedConvolutionalAttention-based neural network forMultifaceted prediction ofPeptide-protein interactions, calledCAMP, including predicting binary peptide-protein interactions and corresponding binding residues in the peptides. We also construct a benchmark dataset containing high-quality peptide-protein interaction pairs with the corresponding peptide binding residues for model training and evaluation. CAMP incorporates convolution neural network architectures and attention mechanism to fully exploit informative sequence-based features, including secondary structures, physicochemical properties, intrinsic disorder features and position-specific scoring matrix of the protein. Systematical evaluation of our benchmark dataset demonstrates that CAMP outperforms the state-of-the-art baseline methods on binary peptide-protein interaction prediction. In addition, CAMP can successfully identify the binding residues involved non-covalent interactions for peptides. These results indicate that CAMP can serve as a useful tool in peptide-protein interaction prediction and peptide binding site identification, which can thus greatly facilitate the peptide drug discovery process. The source code of CAMP can be found inhttps://github.com/twopin/CAMP.
LOXL2 Mediates Airway Smooth Muscle Cell Matrix Stiffness and Drives Asthmatic Airway Remodelling
Authors: Ramis Jopeth , Middlewick Robert , Pappalardo Francesco , Cairns Jennifer T. , Stewart Iain D. , John Alison E. , Naveed Shams-un Nisa , Krishnan Ramaswamy , Miller Suzanne , Shaw Dominick E. , Brightling Christopher E. , Buttery Lee , Rose Felicity , Jenkins Gisli , Johnson Simon R. , Tatler Amanda L 
Published: November 2020

AbstractAirway smooth muscle cells (ASM) are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyper-responsiveness, and airway remodelling. Extracellular matrix (ECM) can influence tissue remodelling pathways, however, to date no study has investigated the effect of ASM ECM stiffness and crosslinking on the development of asthmatic airway remodelling. We hypothesised that TGFβ activation by ASM is influenced by ECM in asthma and sought to investigate the mechanisms involved.This study combines in vitro and in vivo approaches: human ASM cells were used in vitro to investigate basal TGFβ activation and expression of ECM crosslinking enzymes. Human bronchial biopsies from asthmatic and non-asthmatic donors were used to confirm LOXL2 expression ASM. A chronic ovalbumin model of asthma was used to study the effect of LOXL2 inhibition on airway remodelling.We found that ASM cells from asthmatics activated more TGFβ basally than non-asthmatic controls and that diseased cell-derived ECM influences levels of TGFβ activated. Our data demonstrate that the ECM crosslinking enzyme LOXL2 is increased in asthmatic ASM cells and in bronchial biopsies. Crucially, we show that LOXL2 inhibition reduces ECM stiffness and TGFβ activation in vitro, and can reduce subepithelial collagen deposition and ASM thickness, two features of airway remodelling, in an ovalbumin mouse model of asthma.These data are the first to highlight a role for LOXL2 in the development of asthmatic airway remodelling and suggest that LOXL2 inhibition warrants further investigation as a potential therapy to reduce remodelling of the airways in severe asthma.
Self-organization and culture of Mesenchymal Stromal Cell spheroids in acoustic levitation
Authors: Jeger-Madiot Nathan , Arakelian Lousineh , Setterblad Niclas , Bruneval Patrick , Hoyos Mauricio , Larghero Jérôme , Aider Jean-Luc 
Published: November 2020

AbstractIn recent years, 3D cell culture models such as spheroid or organoid technologies have known important developments. Many studies have shown that 3D cultures exhibit better biomimetic properties compared to 2D cultures. These properties are important forin-vitromodeling systems, as well as forin-vivocell therapies and tissue engineering approaches. A reliable use of 3D cellular models still requires standardized protocols with well-controlled and reproducible parameters. To address this challenge, a robust and scaffold-free approach is proposed, which relies on multi-trap acoustic levitation. This technology is successfully applied to Mesenchymal Stromal Cells (MSCs) maintained in acoustic levitation over a 24-hour period. During the culture, MSCs spontaneously self-organized from cell sheets to cell spheroids with a characteristic time of about ten hours. Each acoustofluidic chip could contain up to 30 spheroids in acoustic levitation and four chips could be ran in parallel, leading to the production of 120 spheroids per experiment. Various biological characterizations showed that the cells inside the spheroids were viable, maintained the expression of their cell surface markers and had a higher differentiation capacity compared to standard 2D culture conditions. These results open the path to long-time cell culture in acoustic levitation of cell sheets or spheroids for any type of cells.
SeqStain using fluorescent-DNA conjugated antibodies allows efficient, multiplexed, spatialomic profiling of human and murine tissues
Authors: Rajagopalan Anugraha , Venkatesh Ishwarya , Aslam Rabail , Kirchenbuechler David , Khanna Shreyaa , Cimbaluk David , Gupta Vineet 
Published: November 2020

ABSTRACTSpatial organization of molecules and cells in complex tissue microenvironments provides essential cues during healthy growth and in disease. Novel techniques are needed for elucidation of their spatial relationships and architecture. Although a few multiplex immunofluorescence based techniques have been developed for visualization of the spatial relationships of various molecules in cells and tissues, there remains a significant need for newer methods that are rapid, easy to adapt and are gentle during the cyclic steps of fluorescence staining and de-staining. Here, we describe a novel, multiplex immunofluorescence imaging method, termed SeqStain, that uses fluorescent-DNA labelled antibodies for immunofluorescence staining of cells and tissues, and nuclease treatment for de-staining that allows selective enzymatic removal of the fluorescent signal. SeqStain can be used with primary antibodies, secondary antibodies and antibody fragments, such as Fabs, to efficiently analyse complex cells and tissues in multiple rounds of staining and de-staining. Additionally, incorporation of specific endonuclease restriction sites in antibody labels allows for selective removal of fluorescent signals, while retaining other signals that can serve as marks for subsequent analyses. The application of SeqStain on human kidney tissue provided spatialomic profile of the organization of >25 markers in the kidney, highlighting it as a versatile, easy to use and gentle new technique for spatialomic analyses of complex microenvironments.
Rapid evolution and horizontal gene transfer in the genome of a male-killingWolbachia
Authors: Hill Tom , Unckless Robert L. , Perlmutter Jessamyn I. 
Published: November 2020

AbstractWolbachiaare widespread bacterial endosymbionts that infect a large proportion of insect species. While some strains of this bacteria do not cause observable host phenotypes, many strains ofWolbachiahave some striking effects on their hosts. In some cases, these symbionts manipulate host reproduction to increase the fitness of infected, transmitting females. Here we examine the genome and population genomics of a male-killingWolbachiastrain,wInn, that infectsDrosophila innubilamushroom-feeding flies. We comparedwInn to other closely-relatedWolbachiagenomes to understand the evolutionary dynamics of specific genes. ThewInn genome is similar in overall gene content towMel, but also contains many unique genes and repetitive elements that indicate distinct gene transfers betweenwInn and non-Drosophilahosts. We also find that genes in theWolbachiaprophage and Octomom regions are particularly rapidly evolving, including those putatively or empirically confirmed to be involved in host pathogenicity. Of the genes that rapidly evolve, many also show evidence of recent horizontal transfer amongWolbachiasymbiont genomes, suggesting frequent movement of rapidly evolving regions among individuals. These dynamics of rapid evolution and horizontal gene transfer across the genomes of severalWolbachiastrains and divergent host species may be important underlying factors inWolbachia’s global success as a symbiont.