bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomagnetic Sequential Ultrafiltration (iSUF) Platform for Enrichment and Purification of Extracellular Vesicles from Biofluids
Authors: Zhang Jingjing , Nguyen Luong TH , Hickey Richard , Walters Nicole , Wang Xinyu , Kwak Kwang Joo , Lee L. James , Palmer Andre F. , Reátegui Eduardo 
Published: May 2020

AbstractExtracellular vesicles (EVs) derived from tumor cells have the potential to provide a much-needed source of non-invasive molecular biomarkers for liquid biopsies. However, current methods for EV isolation have limited specificity towards tumor-derived EVs that limit their clinical use. Here, we present an approach called immunomagnetic sequential ultrafiltration (iSUF) that consists of sequential stages of purification and enrichment of EVs (nonspecifically and specifically) in approximately 2 h. In iSUF, EVs present in different volumes of biofluids (0.5 mL to 100 mL) can be significantly enriched (up to 1000 times), with up to 99 % removal of contaminating proteins (e.g., albumin). The EV recovery rate by iSUF for cell culture media (CCM), serum, and urine corresponded to 98.0% ± 3.6%, 96.0% ± 2.0% and 94.0% ± 1.9%, respectively (p > 0.05). The final step of iSUF enables the separation of tumor-specific EVs by incorporating immunomagnetic beads specific to a target subpopulation of EVs. Serum from a small cohort of clinical samples from metastatic breast cancer (BC) patients and healthy donors were processed by the iSUF platform and the isolated EVs from patients showed significantly higher expression levels of BC biomarkers (i.e., HER2, CD24, and miR21).
A mechanistic model of the neural entropy increase elicited by psychedelic drugs
Authors: Herzog Rubén , Mediano Pedro A.M. , Rosas Fernando E. , Carhart-Harris Robin , Perl Yonatan Sanz , Tagliazucchi Enzo , Cofre Rodrigo 
Published: May 2020

ABSTRACTPsychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, encoding both acute alterations in consciousness and mediating long-term effects. However, no clear mechanistic explanation for this ‘entropic’ phenomenon has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experimentsin vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.
Characterizing the genetic basis of copper toxicity inDrosophilareveals a complex pattern of allelic, regulatory, and behavioral variation
Authors: Everman Elizabeth R. , Cloud-Richardson Kristen M. , Macdonald Stuart J. 
Published: May 2020

AbstractA range of heavy metals are required for normal cell function and homeostasis. Equally, the anthropogenic release of heavy metals into soil and water sources presents a pervasive health threat. Copper is one such metal; it functions as a critical enzymatic cofactor, but at high concentrations is toxic, and can lead to the production of reactive oxygen species. Using a combination of quantitative trait locus (QTL) mapping and RNA sequencing in theDrosophilaSynthetic Population Resource (DSPR), we demonstrate that resistance to the toxic effects of ingested copper inD. melanogasteris genetically complex, and influenced by allelic and expression variation at multiple loci. Additionally, we find that copper resistance is impacted by variation in behavioral avoidance of copper and may be subject to life-stage specific regulation. Multiple genes with known copper-specific functions, as well as genes that are involved in the regulation of other heavy metals were identified as potential candidates to contribute to variation in adult copper resistance. We demonstrate that nine of 16 candidates tested by RNAi knockdown influence adult copper resistance, a number of which may have pleiotropic effects since they have previously been shown to impact the response to other metals. Our work provides new understanding of the genetic complexity of copper resistance, highlighting the diverse mechanisms through which copper pollution can negatively impact organisms. Additionally, we further support the similarities between copper metabolism and that of other essential and nonessential heavy metals.
Self-organization of cortical areas in the development and evolution of neocortex: a network growth model
Authors: Imam Nabil , Finlay Barbara 
Published: May 2020

AbstractWhile the mechanisms generating the topographic organization of primary sensory areas in the neocortex are well-studied, what generates secondary cortical areas is virtually unknown. Using physical parameters representing primary and secondary visual areas as they vary from monkey to mouse, we derived a growth model to explore if characteristic features of secondary areas could be produced from correlated activity patterns arising from V1 alone. We found that V1 seeded variable numbers of secondary areas based on activity-driven wiring and wiring density limits within the cortical surface. These secondary areas exhibited the typical mirror-reversal of map topography on cortical area boundaries and progressive reduction of the area and spatial resolution of each new map on the caudorostral axis. Activity-based map formation may be the basic mechanism that establishes the matrix of topographically-organized cortical areas available for later computational specialization.
Evolutionary and homeostatic changes in morphology of visual dendrites of Mauthner cells inAstyanaxblind cavefish
Authors: Tanvir Zainab , Rivera Daihana , Severi Kristen E. , Haspel Gal , Soares Daphne 
Published: May 2020

AbstractMauthner cells are the largest neurons in the hindbrain of teleost fish and most amphibians. Each cell has two major dendrites thought to receive segregated streams of sensory input: the lateral dendrite receives mechanosensory input while the ventral dendrite receives visual input. These inputs, which mediate escape responses to sudden stimuli, may be modulated by the availability of sensory information to the animal. To understand the impact of the absence of visual information on the morphologies of Mauthner cells during development and evolutionary time scales, we examinedAstyanax mexicanus. This species of tetra is found in two morphs: a seeing surface fish and a blind cavefish. We compared the structure of Mauthner cells in surface fish raised under daily light conditions, surface fish that raised in constant darkness, and two independent lineages of cave populations. The length of ventral dendrites of Mauthner cells in dark-raised surface larvae were longer and more branched, while in both cave morphs the ventral dendrites were smaller or absent. The absence of visual input in surface fish with normal eye development leads to a homeostatic increase in dendrite size, whereas over evolution, the absence of light led to the loss of eyes and a phylogenetic reduction in dendrite size. Consequently, homeostatic mechanisms are under natural selection that provide adaptation to constant darkness.
Prediction of LncRNA Encoded Small Peptides in Glioma and The Oligomer Channel Functional Analysis Using in Silico Approaches
Authors: Cao Yipeng , Yang Rui , Lee Imshik , Zhang Wenwen , Sun Jiana , Wang Wei 
Published: May 2020

AbstractGlioma is lethal malignant brain cancers, many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating glioma proliferation, migration, apoptosis and differentiation. Recently, new studies have suggested that some long noncoding RNAs (lncRNAs) containing small open reading frames (smORFs), can encode small peptides and form oligomers for water or ion regulation. However, because these peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatic methods and softwares to identify and evaluate lncRNAs in gliomas that may encode small transmembrane peptides. Combining ab initio homology modeling, molecular dynamics simulations and energetic calculations, we constructed a predictive model and predicted the oligomer channel activity of peptides by identifying the lncRNA ORFs.We found that one key hub lncRNA, DLEU1, which contains two smORFs (ORF1 and ORF8) could encode small peptides that form pentameric channels. The mechanics of water and ion (Na + and Cl-) transport through this pentameric channel were simulated. The potential of mean force (PMF) of the H2O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 neither permeating ions nor water.This work provides new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer. Additionally, it provides a theoretical basis for drug development.
BACPHLIP: Predicting bacteriophage lifestyle from conserved protein domains
Authors: Hockenberry Adam J. , Wilke Claus O. 
Published: May 2020

ABSTRACTBacteriophages are broadly classified into two distinct lifestyles: temperate and virulent. Temperate phages are capable of a latent phase of infection within a host cell (lysogenic cycle), whereas virulent phages directly replicate and lyse host cells upon infection (lytic cycle). Accurate lifestyle identification is critical for determining the role of individual phage species within ecosystems and their effect on host evolution. Here, we present BACPHLIP, a BACterioPHage LIfestyle Predictor. BACPHLIP detects the presence of a set of conserved protein domains within an input genome and uses this data to predict lifestyle via a Random Forest classifier that was trained on a dataset of 634 phage genomes. On an independent test set of 423 phages, BACPHLIP has an accuracy of 98%, greatly exceeding that of the previously existing tools (79%). BACPHLIP is freely available on GitHub (https://github.com/adamhockenberry/bacphlip) and the code used to build and test the classifier is provided in a separate repository (https://github.com/adamhockenberry/bacphlip-model-dev) for users wishing to interrogate and re-train the underlying classification model.
Location Invariant Animal Recognition Using Mixed Source Datasets and Deep Learning
Authors: Shepley Andrew , Falzon Greg , Meek Paul , Kwan Paul 
Published: May 2020

AbstractA time-consuming challenge faced by camera trap practitioners all over the world is the extraction of meaningful data from images to inform ecological management. The primary methods of image processing used by practitioners includes manual analysis and citizen science. An increasingly popular alternative is automated image classification software. However, most automated solutions are not sufficiently robust to be deployed on a large scale. Key challenges include limited access to images for each species and lack of location invariance when transferring models between sites. This prevents optimal use of ecological data and results in significant expenditure of time and resources to annotate and retrain deep learning models.In this study, we aimed to (a) assess the value of publicly available non-iconic FlickR images in the training of deep learning models for camera trap object detection, (b) develop an out-of-the-box location invariant automated camera trap image processing solution for ecologist using deep transfer learning and (c) explore the use of small subsets of camera trap images in optimisation of a FlickR trained deep learning model for high precision ecological object detection.We collected and annotated a dataset of images of “pigs” (Sus scrofaandPhacochoerus africanus)from the consumer image sharing website FlickR. These images were used to achieve transfer learning using a RetinaNet model in the task of object detection. We compared the performance of this model to the performance of models trained on combinations of camera trap images obtained from five different projects, each characterised by 5 different geographical regions. Furthermore, we explored optimisation of the FlickR model via infusion of small subsets of camera trap images to increase robustness in difficult images.In most cases, the mean Average Precision (mAP) of the FlickR trained model when tested on out of sample camera trap sites (67.21-91.92%) was significantly higher than the mAP achieved by models trained on only one geographical location (4.42-90.8%) and rivalled the mAP of models trained on mixed camera trap datasets (68.96-92.75%). The infusion of camera trap images into the FlickR training further improved AP by 5.10-22.32% to 83.60-97.02%.Ecology researchers can use FlickR images in the training of automated deep learning solutions for camera trap image processing to significantly reduce time and resource expenditure by allowing the development of location invariant, highly robust out-of-the-box solutions. This would allow AI technologies to be deployed on a large scale in ecological applications.
Gene Editing Reveals Obligate and Modulatory Components of the CO2Receptor Complex in the Malaria Vector Mosquito,Anopheles coluzzii
Authors: Liu Feng , Ye Zi , Baker Adam , Sun Huahua , Zwiebel Laurence J. 
Published: May 2020

AbstractThe sensitivity to volatile carbon dioxide (CO2) produced by humans and other animals is a critical component in the host preference behaviors of the malaria vector mosquitoAnopheles coluzzii. The molecular receptors responsible for the ability to sense CO2are encoded by three putative gustatory receptor (Gr) genes (Gr22,23,24) which are expressed in a distinctive array of sensory neurons housed in maxillary palp capitate peg sensilla ofAn. coluzzii. Despite the identification of these components and subsequent studies, there is a paucity of understanding regarding the respective roles of these three GRs in the mosquito’s CO2transduction process. To address this, we have used CRISPR/Cas9-based gene editing techniques combined within vivoelectrophysiological recordings to directly examine the role ofGr22,23,24in detecting CO2inAn. coluzzii. These studies reveal that bothGr23andGr24are absolutely required to maintainin vivoCO2sensitivity while, in contrast,Gr22knock out mutants are still able to respond to CO2stimuli albeit with significantly weaker sensitivity. Our data supports a model in whichGr22plays a modulatory role to enhance the functionality ofGr23/24complexes that are responsible for CO2sensitivity of mosquitoes.
STING deficiency-associated aberrant CXCL10 expression contributes to pathogenesis of arthritogenic alphaviruses
Authors: Lin Tao , Geng Tingting , Harrison Andrew , Yang Duomeng , Vella Anthony T. , Fikrig Erol , Wang Penghua 
Published: May 2020

AbstractArthritogenic alphaviruses such as Chikungunya virus and O’nyong nyong virus cause acute and chronic crippling arthralgia associated with inflammatory immune responses. However, the physiological functions of individual immune signaling pathways in the pathogenesis of alphaviral arthritis remain poorly understood. Here we report that a deficiency in the stimulator-of-interferon-genes (STING) led to enhanced viral loads, exacerbated inflammation and selectively elevated expression of CXCL10, a chemoattractant for monocytes/macrophages/T cells, in mouse feet.Cxcl10-/-mice had the same viremia as wild-type animals, but fewer immune infiltrates and lower viral loads in footpads at the peak of arthritic disease (6-8 days post infection). Macrophages constituted the largest immune cell population in footpads following infection, which were significantly reduced inCxcl10-/-mice. The viral RNA loads in neutrophils and macrophages were reduced inCxcl10-/-compared to wild-type mice. In summary, our results demonstrate that STING signaling represses, while CXCL10 signaling promotes, pathogenesis of alphaviral disease.
Integrin αvβ8 on T cells is responsible for suppression of anti-tumor immunity in multiple syngeneic models and is a promising target for tumor immunotherapy
Authors: Dodagatta-Marri Eswari , Ma Hsiao-Yen , Liang Benjia , Li John , Meyer Dominique S. , Sun Kai-Hui , Ren Xin , Zivak Bahar , Rosenblum Michael D. , Headley Mark B. , Pinzas Lauren , Reed Nilgun I. , Del Cid Joselyn S. , Adoumie Maeva , Hann Byron C. , Yang Sharon , Giddabasappa Anand , Noorbehesht Kavon , Yang Bing , Dal Porto Joseph , Tsukui Tatsuya , Niessen Kyle , Atakilit Amha , Akhurst Rosemary J. , Sheppard Dean 
Published: May 2020

AbstractThe αvβ8 integrin is a key activator of transforming growth factor β (TGF β), which has been shown to inhibit anti-tumor immunity. Previous work has suggested that αvβ8 on tumor cells could modulate tumor growth and responses to immune checkpoint blockade. We now show that a potent blocking monoclonal antibody against αvβ8 (ADWA-11) causes growth suppression or complete regression in syngeneic models of squamous cell carcinoma (CCK168), mammary cancer (EMT-6), colon cancer (CT26), and prostate cancer (TRAMPC2), especially when it is combined with other immunomodulators (anti-PD-1, anti-CTLA-4 or 4-1BB) or radiotherapy. αvβ8 is expressed on tumor cells in some of these models, but tumor cell expression of αvβ8 is not essential for the beneficial effects of ADWA-11 therapy. αvβ8 is consistently expressed at highest levels on CD4+CD25+ T cells within tumors, and specific deletion ofItgb8from T cells is as effective as ADWA-11 in suppressing tumor growth. Treatment with ADWA-11 increases expression of a suite of genes in tumor infiltrating CD8+ T cells that are normally inhibited by TGFβ and are involved in tumor cell killing, including Granzyme B and Interferon-γ. These findings solidify αvβ8 integrin as a promising target for cancer immunotherapy, even for tumors that do not express this integrin.
A simple method for gene expression in endo- and ectodermal cells in mouse embryos before neural tube closure
Authors: Kishi Yusuke , Maeda Yurie , Kuwayama Naohiro , Gotoh Yukiko 
Published: May 2020

AbstractThe lack of a widely accessible method for expressing genes of interest in wild-type embryos is the fundamental obstacle in understanding genetic regulation during embryonic development. In particular, only a few methods are available for introducing gene expression vectors into cells prior to neural tube closure, a period for the drastic development of many tissues. In this study, we present a simple technique for transferring vectors into the endo- and ectodermal cells of mouse embryos at E7.0 or E8.0 via in utero injection, without any specialized equipment. Using this technique, introduction of retroviruses can facilitate the labeling of cells in various tissues, including the brain, spinal cord, epidermis, and digestive and respiratory organs. As such, this technique can aid in analyzing the roles of genes of interest during endo- and ectodermal development prior to neural tube closure.
Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption
Authors: Umansky Carla , Morellato Agustín , Scheidegger Marco , Rieckher Matthias , Martinefski Manuela R. , Fernandez Gabriela A. , Kolesnikova Ksenia , Vesting Anna J. , Karakasilioti Ismene , Reingruber Hernán , Wei Yan , He Rongqiao , Bollini Mariela , Monge María Eugenia , Schumacher Björn , Pontel Lucas B. 
Published: May 2020

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify theADH5-ortholog gene inCaenorhabditis elegansand show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthyBRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.
Transparency in butterflies and moths: structural diversity, optical properties and ecological relevance
Authors: Gomez D. , Pinna C. , Pairraire J. , Arias M. , Barbut J. , Pomerantz A. , Noûs C. , Daney de Marcillac W. , Berthier S. , Patel N. , Andraud C. , Elias M. 
Published: May 2020

ABSTRACTIn water, transparency seems an ideal concealment strategy, as testified by the variety of transparent aquatic organisms. By contrast, transparency is nearly absent on land, with the exception of insect wings, and knowledge is scarce about its functions and evolution, with fragmentary studies and no comparative perspective. Lepidoptera (butterflies and moths) represent an outstanding group to investigate transparency on land, as species typically harbour opaque wings covered with coloured scales, a key multifunctional innovation. Yet, many Lepidoptera species have evolved partially or fully transparent wings. At the interface between physics and biology, the present study investigates transparency in 123 Lepidopteran species (from 31 families) for its structural basis, optical properties and biological relevance in relation to thermoregulation and vision. Our results establish that transparency has likely evolved multiple times independently. Efficiency at transmitting light is largely determined by clearwing microstructure (scale shape, insertion, colouration, dimensions and density) and macrostructure (clearwing area, species size or wing area). Microstructural traits – density, dimensions – are tightly linked in their evolution, with different constraints according to scale shape, insertion, and colouration. Transparency appears highly relevant for vision, especially for camouflage, with size-dependent and activity-rhythm dependent variations. Links between transparency and latitude are consistent with an ecological relevance of transparency in thermoregulation, and not so for protection against UV radiation. Altogether, our results shed new light on the physical and ecological processes driving the evolution of transparency on land and underline that transparency is a more complex than previously thought colouration strategy.