bluuebunny/crossref_metadata_2025_split huggingface dataset:
Context-dependent modulation of aggressiveness of pediatric tumors by individual oncogenic RAS isoforms
Authors: Bauer Julia , Cuvelier Nicole , Ragab Nada , Simon-Keller Katja , Nitzki Frauke , Geyer Natalie , Botermann Dominik S. , Elmer Dominik P. , Rosenberger Albert , Rando Thomas A. , Biressi Stefano , Fagin James A. , Saur Dieter , Dullin Christian , Schildhaus Hans-Ulrich , Schulz-Schaeffer Walter , Aberger Fritz , Uhmann Anja , Hahn Heidi 
Published: June 2021

AbstractA prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS, KRAS, or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh-driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse.
A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma
Authors: Maiques Oscar , Fanshawe Bruce , Crosas-Molist Eva , Rodriguez-Hernandez Irene , Volpe Alessia , Cantelli Gaia , Boehme Lena , Orgaz Jose L. , Mardakheh Faraz K. , Sanz-Moreno Victoria , Fruhwirth Gilbert O. 
Published: June 2021

AbstractBackgroundMetastasis is a hallmark of cancer and responsible for most cancer deaths. Migrastatics were defined as drugs interfering with all modes of cancer cell invasion and thus cancers’ ability to metastasise. First anti-metastatic treatments have recently been approved.MethodsWe used bioinformatic analyses of publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D cell morphology analysis and mass spectrometric analysis of RhoA binding partners), developed a new traceable spontaneously metastasising murine melanoma model for in vivo validation, and employed histology (haematoxylin/eosin and phospho-myosin II staining) to confirm drug action in harvested tumour tissues.ResultsUnbiased and targeted bioinformatic analyses identified the Rho kinase (ROCK)-myosin II pathway and its various components as potentially relevant targets in melanoma. In vitro validation demonstrated redundancy of several RhoGEFs upstream of RhoA and confirmed ROCK as a druggable target downstream of RhoA. The anti-metastatic effects of two ROCK inhibitors were demonstrated through in vivo melanoma metastasis tracking and inhibitor effects also confirmed ex vivo by digital pathology.ConclusionsWe proposed a migrastatic drug development pipeline. As part of the pipeline, we provide a new traceable spontaneous melanoma metastasis model for in vivo quantification of metastasis and anti-metastatic effects by non-invasive imaging.
Divide-and-conquer: machine-learning integrates mammalian and viral traits with network features to predict virus-mammal associations
Authors: Wardeh Maya , Blagrove Marcus S. C. , Sharkey Kieran J. , Baylis Matthew 
Published: June 2021

AbstractOur knowledge of viral host ranges remains limited. Completing this picture by identifying unknown hosts of known viruses is an important research aim that can help identify and mitigate zoonotic and animal-disease risks, such as spill-over from animal reservoirs into human populations. To address this knowledge-gap we apply a divide-and-conquer approach which separates viral, mammalian and network features into three unique perspectives, each predicting associations independently to enhance predictive power. Our approach predicts over 20,000 unknown associations between known viruses and susceptible mammalian species, suggesting that current knowledge underestimates the number of associations in wild and semi-domesticated mammals by a factor of 4.3, and the average potential mammalian host-range of viruses by a factor of 3.2. In particular, our results highlight a significant knowledge gap in the wild reservoirs of important zoonotic and domesticated mammals’ viruses: specifically, lyssaviruses, bornaviruses and rotaviruses.
Impact of an accelerated melting of Greenland on malaria distribution over Africa
Authors: Chemison Alizée , Ramstein Gilles , Tompkins Adrian M. , Defrance Dimitri , Camus Guigone , Charra Margaux , Caminade Cyril 
Published: June 2021

AbstractStudies about the impact of future climate change on diseases have mostly focused on standard Representative Concentration Pathway climate change scenarios. These scenarios do not account for the non-linear dynamics of the climate system. A rapid ice-sheet melting could occur, impacting climate and consequently societies. Here, we investigate the additional impact of a rapid ice-sheet melting of Greenland on climate and malaria transmission in Africa using several malaria models driven by Institute Pierre Simon Laplace climate simulations. Results reveal that our melting scenario could moderate the simulated increase in malaria risk over East Africa, due to cooling and drying effects, cause a largest decrease in malaria transmission risk over West Africa and drive malaria emergence in southern Africa associated with a significant southward shift of the African rain-belt. We argue that the effect of such ice-sheet melting should be investigated further in future public health and agriculture climate change risk assessments.
Barrel cortex plasticity after photothrombotic stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits
Authors: Zeiger William A. , Marosi Máté , Saggi Satvir , Noble Natalie , Samad Isa , Portera-Cailliau Carlos 
Published: June 2021

AbstractRecovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. However, definitive longitudinal evidence of neurons changing their response selectivity after stroke is lacking. We sought to directly test whether such functional “remapping” occurs within mouse primary somatosensory cortex after a stroke that destroys the C1 barrel. Using in vivo calcium imaging to longitudinally record sensory-evoked activity under light anesthesia, we did not find any increase in the number of C1 whisker-responsive neurons in the adjacent, spared D3 barrel after stroke. To promote plasticity after stroke, we also plucked all whiskers except C1 (forced use therapy). This led to an increase in the reliability of sensory-evoked responses in C1 whisker-responsive neurons but did not increase the number of C1 whisker-responsive neurons in spared surround barrels over baseline levels. Our results argue against remapping of functionality after barrel cortex stroke, but support a circuit-based mechanism for how rehabilitation may improve recovery.
Scalable, highly stable Si-based metal-insulator-semiconductor photoanodes for water oxidation fabricated using thin-film reactions and electrodeposition
Authors: Lee Soonil , Ji Li , De Palma Alex C. , Yu Edward T. 
Published: June 2021

AbstractMetal-insulator-semiconductor (MIS) structures are widely used in Si-based solar water-splitting photoelectrodes to protect the Si layer from corrosion. Typically, there is a tradeoff between efficiency and stability when optimizing insulator thickness. Moreover, lithographic patterning is often required for fabricating MIS photoelectrodes. In this study, we demonstrate improved Si-based MIS photoanodes with thick insulating layers fabricated using thin-film reactions to create localized conduction paths through the insulator and electrodeposition to form metal catalyst islands. These fabrication approaches are low-cost and highly scalable, and yield MIS photoanodes with low onset potential, high saturation current density, and excellent stability. By combining this approach with a p+n-Si buried junction, further improved oxygen evolution reaction (OER) performance is achieved with an onset potential of 0.7 V versus reversible hydrogen electrode (RHE) and saturation current density of 32 mA/cm2 under simulated AM1.5G illumination. Moreover, in stability testing in 1 M KOH aqueous solution, a constant photocurrent density of ~22 mA/cm2 is maintained at 1.3 V versus RHE for 7 days.
LEAFY COTYLEDON1 expression in the endosperm enables embryo maturation in Arabidopsis
Authors: Song Jingpu , Xie Xin , Chen Chen , Shu Jie , Thapa Raj K. , Nguyen Vi , Bian Shaomin , Kohalmi Susanne E. , Marsolais Frédéric , Zou Jitao , Cui Yuhai 
Published: June 2021

AbstractThe endosperm provides nutrients and growth regulators to the embryo during seed development. LEAFY COTYLEDON1 (LEC1) has long been known to be essential for embryo maturation. LEC1 is expressed in both the embryo and the endosperm; however, the functional relevance of the endosperm-expressed LEC1 for seed development is unclear. Here, we provide genetic and transgenic evidence demonstrating that endosperm-expressed LEC1 is necessary and sufficient for embryo maturation. We show that endosperm-synthesized LEC1 is capable of orchestrating full seed maturation in the absence of embryo-expressed LEC1. Inversely, without LEC1 expression in the endosperm, embryo development arrests even in the presence of functional LEC1 alleles in the embryo. We further reveal that LEC1 expression in the endosperm begins at the zygote stage and the LEC1 protein is then trafficked to the embryo to activate processes of seed maturation. Our findings thus establish a key role for endosperm in regulating embryo development.
Catalytic asymmetric nucleophilic fluorination using BF3·Et2O as fluorine source and activating reagent
Authors: Zhu Weiwei , Zhen Xiang , Wu Jingyuan , Cheng Yaping , An Junkai , Ma Xingyu , Liu Jikun , Qin Yuji , Zhu Hao , Xue Jijun , Jiang Xianxing 
Published: June 2021

AbstractFluorination using chiral catalytic methods could result in a direct access to asymmetric fluorine chemistry. However, challenges in catalytic asymmetric fluorinations, especially the longstanding stereochemical challenges existed in BF3·Et2O-based fluorinations, have not yet been addressed. Here we report the catalytic asymmetric nucleophilic fluorination using BF3·Et2O as the fluorine reagent in the presence of chiral iodine catalyst. Various chiral fluorinated oxazine products were obtained with good to excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >20:1 dr). Control experiments (the desired fluoro-oxazines could not be obtained when Py·HF or Et3N·3HF were employed as the fluorine source) indicated that BF3·Et2O acted not only as a fluorine reagent but also as the activating reagent for activation of iodosylbenzene.
Population genomics of apricots unravels domestication history and adaptive events
Authors: Groppi Alexis , Liu Shuo , Cornille Amandine , Decroocq Stéphane , Bui Quynh Trang , Tricon David , Cruaud Corinne , Arribat Sandrine , Belser Caroline , Marande William , Salse Jérôme , Huneau Cécile , Rodde Nathalie , Rhalloussi Wassim , Cauet Stéphane , Istace Benjamin , Denis Erwan , Carrère Sébastien , Audergon Jean-Marc , Roch Guillaume , Lambert Patrick , Zhebentyayeva Tetyana , Liu Wei-Sheng , Bouchez Olivier , Lopez-Roques Céline , Serre Rémy-Félix , Debuchy Robert , Tran Joseph , Wincker Patrick , Chen Xilong , Pétriacq Pierre , Barre Aurélien , Nikolski Macha , Aury Jean-Marc , Abbott Albert Glenn , Giraud Tatiana , Decroocq Véronique 
Published: June 2021

AbstractAmong crop fruit trees, the apricot (Prunus armeniaca) provides an excellent model to study divergence and adaptation processes. Here, we obtain nearly 600 Armeniaca apricot genomes and four high-quality assemblies anchored on genetic maps. Chinese and European apricots form two differentiated gene pools with high genetic diversity, resulting from independent domestication events from distinct wild Central Asian populations, and with subsequent gene flow. A relatively low proportion of the genome is affected by selection. Different genomic regions show footprints of selection in European and Chinese cultivated apricots, despite convergent phenotypic traits, with predicted functions in both groups involved in the perennial life cycle, fruit quality and disease resistance. Selection footprints appear more abundant in European apricots, with a hotspot on chromosome 4, while admixture is more pervasive in Chinese cultivated apricots. Our study provides clues to the biology of selected traits and targets for fruit tree research and breeding.
GFAP and desmin expression in lymphatic tissues leads to difficulties in distinguishing between glial and stromal cells
Authors: Günther Hauke Simon , Henne Stephan , Oehlmann Jasmin , Urban Julia , Pleizier Desiree , Renevier Niclas , Lohr Christian , Wülfing Clemens 
Published: June 2021

AbstractRecently, we found many immune cells including antigen presenting cells neurally hard wired in the T-cell zone of most lymphoid organs like amongst others, lymph nodes in rats, mice and humans. Single immune cells were reached by single neurites and enclosed with a dense neural meshwork. As it is well known that axons are always accompanied by glial cells, we were able to identify Schwann cells in the hilum, medullary and capsule region, like expected. Unexpected was the result, that we found oligodendrocyte-like cells in these regions, myelinating more than one axon. Likewise important was the finding, that one of the standard glial markers used, a polyclonal GFAP antibody equally bound to desmin and therefore marked nearly all stromal cells in cortical, paracortical and medullary cord regions. More detailed analysis showed that these results also appeared in many other non-lymphoid organs. Therefore, polyclonal GFAP antibodies are only conditionally usable for immunohistochemical analysis in peripheral tissues outside the central nervous system. It remains to be elucidated, if the binding of the GFAP antibody to desmin has its reason in a special desmin variant that can give stromal cells glial character.
Simultaneous multi-nuclide imaging via double-photon coincidence method with parallel hole collimators
Authors: Uenomachi Mizuki , Shimazoe Kenji , Ogane Kenichiro , Takahashi Hiroyuki 
Published: June 2021

AbstractMulti-tracer imaging can provide useful information in the definitive diagnosis and research of medical, biological, and pharmaceutical sciences. Single-photon emission computed tomography (SPECT) is one of the nuclear medicine imaging modalities widely used for diagnosis or medical research and has a multi-tracer imaging capability. One of the drawbacks of multi-tracer imaging is crosstalk from other gamma rays, which affects the reconstructed image. Scattering correction methods, such as the dual- and triple-energy window methods, are used for conventional SPECT imaging to reduce the background caused by the crosstalk. This study proposes another crosstalk reduction method. Some nuclides emit two or more gamma rays through intermediate levels. Thus, detecting these gamma rays with the coincidence method allows us to distinguish a true gamma ray signal and a background signal. The nuclide position can be estimated at the intersection of two gamma rays using collimators. We demonstrate herein simultaneous 111In and 177Lu imaging via the double-photon coincidence method using GAGG detectors and parallel hole collimators. The double-photon coincidence method greatly reduces the background caused by other gamma rays and offers higher-quality images than does conventional imaging.
Determinants of moult haulout phenology and duration in southern elephant seals
Authors: de Kock Leandri , Oosthuizen W. Chris , Beltran Roxanne S. , Bester Marthán N. , de Bruyn P. J. Nico 
Published: June 2021

AbstractPhenological shifts are among the most obvious biological responses to environmental change, yet documented responses for Southern Ocean marine mammals are extremely rare. Marine mammals can respond to environmental changes through phenological flexibility of their life-history events such as breeding and moulting. Southern elephant seals (Mirounga leonina) undergo an obligatory annual moult which involves the rapid shedding of epidermal skin and hair while seals fast ashore. We quantified the timing (phenology) and duration (the time from arrival ashore to departure) of the moult haulout of 4612 female elephant seals at Marion Island over 32 years. Using linear mixed-effects models, we investigated age, breeding state and environmental drivers of moult timing and haulout duration. We found no clear evidence for a temporal shift in moult phenology or its duration. Annual variation in moult arrival date and haulout duration was small relative to age and breeding effects, which explained more than 90% of the variance in moult arrival date and 25% in moult haulout duration. All environmental covariates we tested explained minimal variation in the data. Female elephant seals moulted progressively later as juveniles, but adults age 4 and older had similar moult start dates that depended on the breeding state of the female. In contrast, moult haulout duration was not constant with age among adults, but instead became shorter with increasing age. Moulting is energetically expensive and differences in the moult haulout duration are possibly due to individual variation in body mass and associated metabolizable energy reserves, although other drivers (e.g. hormones) may also be present. Individual-based data on moult arrival dates and haulout duration can be used as auxiliary data in demographic modelling and may be useful proxies of other important biological parameters such as body condition and breeding history.
Implication of problematic substance use in poststroke depression: an hospital-based study
Authors: Rabat Yolaine , Sibon Igor , Berthoz Sylvie 
Published: June 2021

AbstractThe prevalence of clinically defined problematic substance use among stroke patients is overlooked and its association with post-stroke depression (PSD) is unknown. Our aims were to: (1) estimate the proportion of stroke patients with a problematic substance use as defined by clinical screening scales; (2) determine the proportion of PSD at three months of follow-up; (3) explore if the baseline severity in substance use and its evolution are independent predictors of PSD. A cohort of first-ever non-severe stroke adult patients was screened at baseline and three months post-stroke using recommended cut-off scores of standardized scales for tobacco, alcohol and cannabis abuse. PSD was defined using the Center of Epidemiological Studies Depression scale score. Out of the 244 eligible patients, 74 (30.3%) presented a problematic substance use, including 21 (8.6%) polydrug abusers. Among these patients, the prevalence of PSD was 50.8%, including 29.5% of severe depression. The severity of tobacco dependence at baseline was found to double the risk (OR 1.59, 95% CI 1.05–2.43) of presenting a PSD, independently of previously reported risk factors. We found no significant evidence for an effect of the evolution in substance use at follow-up. Addictive disorders are part of the critical unmet needs that should be addressed in the management of PSD.
Mesna ameliorates acute lung injury induced by intestinal ischemia–reperfusion in rats
Authors: Abd El-Baset Samia Adel , Abd El-haleem Manal R. , Abdul-Maksoud Rehab S. , Kattaia Asmaa A. A. 
Published: June 2021

AbstractThe lung is severely affected by intestinal ischemia–reperfusion (I–R) injury. Mesna, a thiol compound, possess anti-inflammatory and antioxidant properties. We aimed in the present work to explore the potential beneficial effects of Mesna on the acute lung damage mediated by intestinal I–R in a rat model. Forty male adult albino rats were randomly separated into; control, intestinal I–R, Mesna I and Mesna II groups. Mesna was administered by intraperitoneal injection at a dose of 100 mg/kg, 60 min before ischemia (Mesna I) and after reperfusion (Mesna II). Arterial blood gases and total proteins in bronchoalveolar lavage (BAL) were measured. Lung tissue homogenates were utilized for biochemical assays of proinflammatory cytokines and oxidative stress markers. Lung specimens were managed for examination by light and electron microscopy. Our results revealed that Mesna attenuated the histopathological changes and apoptosis of the lung following intestinal I–R. Mesna also recovered systemic oxygenation. Mesna suppressed neutrophil infiltration (as endorsed by the reduction in MPO level), reduced ICAM-1 mRNA expression, inhibited NF-κB pathway and reduced the proinflammatory cytokines (TNF-α, IL-1β and IL-6) in the lung tissues. Mesna maintained the antioxidant profile as evidenced by the elevation of the tissue GPx and SOD and down-regulation of HSP70 immune-expressions. Accordingly, Mesna treatment can be a promising way to counteract remote injury of the lung resulted from intestinal I–R.
The paradox of second-order homophily in networks
Authors: Evtushenko Anna , Kleinberg Jon 
Published: June 2021

AbstractHomophily—the tendency of nodes to connect to others of the same type—is a central issue in the study of networks. Here we take a local view of homophily, defining notions of first-order homophily of a node (its individual tendency to link to similar others) and second-order homophily of a node (the aggregate first-order homophily of its neighbors). Through this view, we find a surprising result for homophily values that applies with only minimal assumptions on the graph topology. It can be phrased most simply as “in a graph of red and blue nodes, red friends of red nodes are on average more homophilous than red friends of blue nodes”. This gap in averages defies simple intuitive explanations, applies to globally heterophilous and homophilous networks and is reminiscent of but structually distinct from the Friendship Paradox. The existence of this gap suggests intrinsic biases in homophily measurements between groups, and hence is relevant to empirical studies of homophily in networks.