bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile microscopy and telemedicine platform assisted by deep learning for quantification ofTrichuris trichiurainfection
Authors: Dacal Elena , Bermejo-Peláez David , Lin Lin , Álamo Elisa , Cuadrado Daniel , Martínez Álvaro , Mousa Adriana , Postigo María , Soto Alicia , Sukosd Endre , Vladimirov Alexander , Mwandawiro Charles , Gichuki Paul , Williams Nana Aba , Muñoz José , Kepha Stella , Luengo-Oroz Miguel 
Published: January 2021

AbstractSoil-transmitted helminths (STH) are the most prevalent pathogens among the group of neglected tropical diseases (NTDs). Kato-Katz technique is the diagnosis method recommended by WHO and although is generally more sensitive than other microscopic methods in high transmission settings, it often presents a decreased sensitivity in low transmission settings and it is labour intensive. Digitizing the samples could provide a solution which allows to store the samples in a digital database and perform remote analysis. Artificial intelligence methods based on digitized samples can support diagnostics efforts by support diagnostics efforts by performing an automatic and objective quantification of disease infection.In this work, we propose an end-to-end pipeline for microscopy image digitization and automatic analysis of digitized images of soil-transmitted helminths. Our solution includes (1) a digitalization system based on a mobile app that digitizes the microscope samples using a low-cost 3D-printed microscope adapter, (2) a telemedicine platform for remote analysis and labelling and (3) novel deep learning algorithms for automatic assessment and quantification of parasitological infection of STH.This work has been evaluated by comparing the STH quantification using both a manual remote analysis based on the digitized images and the AI-assisted quantification against the reference method based on conventional microscopy. The deep learning algorithm has been trained and tested on 41 slides of stool samples containing 949 eggs from 6 different subjects using a cross-validation strategy obtaining a mean precision of 98,44% and mean recall of 80,94%. The results also proved the potential of generalization capability of the method at identifying different types of helminth eggs.In conclusion, this work has presented a comprehensive pipeline using smartphone-based microscopy integrated with a telemedicine platform for automatic image analysis and quantification of STH infection using artificial intelligence models.
Fibrillar Aβ causes profound microglial metabolic perturbations in a novel APP knock-in mouse model
Authors: Xia Dan , Lianoglou Steve , Sandmann Thomas , Calvert Meredith , Suh Jung H. , Thomsen Elliot , Dugas Jason , Pizzo Michelle E. , DeVos Sarah L. , Earr Timothy K. , Lin Chia-Ching , Davis Sonnet , Ha Connie , Nguyen Hoang , Chau Roni , Yulyaningsih Ernie , Solanoy Hilda , Masoud Shababa T. , Liang Richard , Lin Karin , Thorne Robert G. , Garceau Dylan , Whitesell Jennifer D. , Sasner Michael , Harris Julie A. , Scearce-Levie Kimberly , Lewcock Joseph W. , Di Paolo Gilbert , Sanchez Pascal E. 
Published: January 2021

AbstractMicroglial dysfunction is believed to play a pathogenic role in Alzheimer’s disease (AD). Here, we characterize the amyloid-β related pathology and microglial responses in an engineered APP knock-in mouse model of familial AD. This model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered glial responses and neurodegeneration. Leveraging multi-omics approaches, we found lipid accumulation and an exacerbated disease-associated transcriptomic response in methoxy-X04-positive, phagocytic microglia. Together, these findings highlight the potential of this novel, open-access mouse model to investigate AD pathogenesis and demonstrate that fibrillar Aβ triggers lipid dysregulation and immuno-metabolic perturbations in phagocytic microglia.HighlightsNovel open-access APP KI mouse model shows salient AD pathological featuresDeep phenotyping of sorted microglia reveals profound lipidomic perturbations in line with Alois Alzheimer’s original descriptions of glial adipose inclusionsImmunometabolic perturbations are exacerbated in microglia accumulating fibrillar Aβ
The neuroprotective effects of Sonic hedgehog pathway agonist SAG in a rat model of neonatal stroke
Authors: Nguyen Vien , Chavali Manideep , Larpthaveesarp Amara , Kodali Srikirti , Gonzalez Ginez , Franklin Robin J.M. , Rowitch David H. , Gonzalez Fernando 
Published: January 2021

ABSTRACTObjectiveNeonatal stroke affects 1 in 2800 live births and is a major cause of neurological injury. The Sonic Hedgehog (Shh) signaling pathway is critical for central nervous system (CNS) development and has neuroprotective and reparative effects in different CNS injury models. Previous studies have demonstrated beneficial effects of small molecule Shh-Smoothened-agonist (SAG) against neonatal cerebellar injury and it improves Down syndrome-related brain structural deficits in mice. Here, we investigated SAG neuroprotection in rat models of neonatal ischemia-reperfusion (stroke) and adult focal white matter injury.MethodsWe used transient middle cerebral artery occlusion at P10 and ethidium bromide injection in adult rats to induce damage. Following surgery and SAG or vehicle treatment we analyzed tissue loss, cell proliferation and fate, and behavioral outcome.ResultsWe report that a single dose of SAG administered following neonatal stroke preserved brain volume, reduced inflammation, enhanced oligodendrocyte progenitor cell (OPC) and EC proliferation, and resulted in long-term cognitive improvement. Single-dose SAG also promoted proliferation of OPCs following focal demyelination in the adult rat.ConclusionThese findings indicate benefit of one-time SAG treatment post-insult in reducing brain injury and improving behavioral outcome after experimental neonatal stroke.
Ectopic FVIII expression and misfolding in hepatocytes as a cause for hepatocellular carcinoma
Authors: Kapelanski-Lamoureux Audrey , Chen Zhouji , Gao Zu-Hua , Deng Ruishu , Lazaris Anthoula , Lebeaupin Cynthia , Giles Lisa , Malhotra Jyoti , Yong Jing , Zou Chenhui , de Jong Ype P. , Metrakos Peter , Herzog Roland W. , Kaufman Randal J. 
Published: January 2021

AbstractHemophilia A gene therapy targets hepatocytes to express B domain deleted-(BDD) clotting factor VIII (FVIII) to permit viral encapsidation. Since BDD is prone to misfolding in the endoplasmic reticulum (ER) and ER protein misfolding in hepatocytes followed by high fat diet (HFD) can cause hepatocellular carcinoma (HCC), we studied how FVIII misfolding impacts HCC development using hepatocyte DNA delivery to express three proteins from the same parental vector: 1) well-folded cytosolic dihydrofolate reductase (DHFR); 2) BDD-FVIII, which is prone to misfolding in the ER; and 3) N6-FVIII which folds more efficiently than BDD-FVIII. One week after DNA delivery, when FVIII expression was undetectable, mice were fed HFD for 65 weeks. Remarkably, all mice that received BDD-FVIII vector developed liver tumors, whereas only 58% of mice that received N6 and no mice that received DHFR vector developed liver tumors, suggesting that the degree of protein misfolding in the ER increases predisposition to HCC in the context of a HFD and in the absence of viral transduction. Our findings raise concerns of ectopic BDD-FVIII expression in hepatocytes in the clinic, which poses risks independent of viral vector integration. Limited expression per hepatocyte and/or use of proteins that avoid misfolding may enhance safety.Graphical abstract
Development of larvae of the Australian blowfly,Calliphora augur(Diptera: Calliphoridae), at constant temperatures
Authors: Day Donnah M. , Butterworth Nathan J. , Tagat Anirudh , Markowsky Gregory , Wallman James F. 
Published: January 2021

AbstractCalliphora augur(Diptera: Calliphoridae) is a common carrion-breeding blowfly of forensic, medical and agricultural importance in eastern Australia. Despite this, detailed information on the developmental biology ofC. auguris lacking. Here, we present the first comprehensive study on the development of all three larval instars ofC. augur, fed on sheep’s liver, at constant temperatures of 15, 20, 25, 30 and 35°C. We provide thermal summation models describing instar duration, as well as 95% prediction intervals for larval length at each constant temperature, enabling the age of larvae ofC. augurto be estimated from their developmental stage and their average length. These data provide a basis for the application of this species to forensic investigations.
Breeding seasonality generates reproductive trade-offs in a long-lived mammal
Authors: Dezeure Jules , Baniel Alice , Carter Alecia J. , Cowlishaw Guy , Godelle Bernard , Huchard Elise 
Published: January 2021

ABSTRACTThe evolutionary benefits of reproductive seasonality are usually measured by a single fitness component, namely offspring survival to nutritional independence (Bronson, 2009). Yet different fitness components may be maximised by dissimilar birth timings. This may generate fitness trade-offs that could be critical to understanding variation in reproductive timing across individuals, populations and species. Here, we use long-term demographic and behavioural data from wild chacma baboons (Papio ursinus) living in a seasonal environment to test the adaptive significance of seasonal variation in birth frequencies. Like humans, baboons are eclectic omnivores, give birth every 1-3 years to a single offspring that develops slowly, and typically breed year-round. We identify two distinct optimal birth timings in the annual cycle, located 4-months apart, which maximize offspring survival or minimize maternal interbirth intervals (IBIs), by respectively matching the annual food peak with late or early weaning. Observed births are the most frequent between these optima, supporting an adaptive trade-off between current and future reproduction. Furthermore, infants born closer to the optimal timing favouring maternal IBIs (instead of offspring survival) throw more tantrums, a typical manifestation of mother-offspring conflict (Maestripieri, 2002). Maternal trade-offs over birth timing, which extend into mother-offspring conflict after birth, may commonly occur in long-lived species where development from birth to independence spans multiple seasons. Such trade-offs may substantially weaken the benefits of seasonal reproduction, and our findings therefore open new avenues to understanding the evolution of breeding phenology in long-lived animals, including humans.SIGNIFICANCE STATEMENTWhy some species breed seasonally and others do not remain unclear. The fitness consequences of birth timing have traditionally been measured on offspring survival, ignoring other fitness components. We investigated the effects of birth timing on two fitness components in wild baboons, who breed year-round despite living in a seasonal savannah. Birth timing generates a trade-off between offspring survival and future maternal reproductive pace, meaning that mothers cannot maximize both. When birth timing favours maternal reproductive pace (instead of offspring survival), behavioural manifestations of mother-offspring conflict around weaning are intense. These results open new avenues to understand the evolution of reproductive timings in long-lived animals including humans, where such reproductive trade-offs may commonly weaken the intensity of reproductive seasonality.
Architecture of the Neuro-Glia-Vascular System
Authors: Zisis Eleftherios , Keller Daniel , Kanari Lida , Arnaudon Alexis , Gevaert Michael , Delemontex Thomas , Coste Benoît , Foni Alessandro , Abdellah Marwan , Calì Corrado , Hess Kathryn , Magistretti Pierre Julius , Schürmann Felix , Markram Henry 
Published: January 2021

AbstractAstrocytes connect the vasculature to neurons and mediate the supply of nutrients and biochemicals. They also remove metabolites from the neurons and extracellular environment. They are involved in a growing number of physiological and pathophysiological processes. Understanding the biophysical, physiological, and molecular interactions in this neuro-glia-vascular ensemble (NGV) and how they support brain function is severely restricted by the lack of detailed cytoarchitecture. To address this problem, we used data from multiple sources to create a data-driven digital reconstruction of the NGV at micrometer anatomical resolution. We reconstructed 0.2 mm3of rat somatosensory cortical tissue with approximately 16000 morphologically detailed neurons, its microvasculature, and approximately 2500 morphologically detailed protoplasmic astrocytes. The consistency of the reconstruction with a wide array of experimental measurements allows novel predictions of the numbers and locations of astrocytes and astrocytic processes that support different types of neurons. This allows anatomical reconstruction of the spatial microdomains of astrocytes and their overlapping regions. The number and locations of end-feet connecting each astrocyte to the vasculature can be determined as well as the extent to which they cover the microvasculature. The structural analysis of the NGV circuit showed that astrocytic shape and numbers are constrained by vasculature’s spatial occupancy and their functional role to form NGV connections. The digital reconstruction of the NGV is a resource that will enable a better understanding of the anatomical principles and geometric constraints which govern how astrocytes support brain function.Table of contentsMain pointsThe Blue Brain Project digitally reconstructs a part of neocortical Neuro-Glia-Vascular organizationInterdependencies and topological methods allow dense in silico reconstruction from sparse experimental dataThe polarized role of protoplasmic astrocytes constrains their shapes and numbersTable of contents image
In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration
Authors: Pronobis Mira I. , Zheng Susan , Singh Sumeet P. , Poss Kenneth D. 
Published: January 2021

AbstractStrategies have not been available until recently to uncover interacting protein networks specific to key cell types, their subcellular compartments, and their major regulators during complexin vivoevents. Here we apply BioID2 proximity labeling to capture protein networks acting within cardiomyocytes during a key model of innate heart regeneration in zebrafish. Transgenic zebrafish expressing a promiscuous BirA2 localized to the entire myocardial cell or membrane compartment were generated, each identifying unique proteomes in adult cardiomyocytes that became altered during regeneration. BioID2 profiling for interactors with ErbB2, a co-receptor for the cardiomyocyte mitogen Nrg1, implicated Rho A as a target of ErbB2 signaling in cardiomyocytes. Blockade of Rho A during heart regeneration, or during cardiogenic stimulation by the mitogenic influences Nrg1, Vegfaa or Vitamin D, disrupted muscle creation. Our findings reveal proximity labeling as a useful resource to interrogate cell proteomes and signaling networks during tissue regeneration in zebrafish.
COVID-19 Knowledge, Attitudes, and Practices of United Arab Emirates Medical and Health Sciences Students: A Cross Sectional Study
Authors: Baniyas Noura , Sheek-Hussein Mohamud , Al Kaabi Nouf , Al Shamsi Maitha , Al Neyadi Maitha , Al Khoori Rauda , Ajab Suad , Abid Muhammad , Grivna Michael , Abu Zidan Fikri M. 
Published: January 2021

AbstractCOVID-19 pandemic is the largest unprecedented viral pandemic of the 21st century. We aimed to study the COVID-19 knowledge, attitudes, and practices (KAP) among medical and health sciences students in the United Arab Emirates (UAE). We performed a cross-sectional study between 2nd June and 19th August 2020. The survey was developed using online Survey Monkey. The link was distributed via UAE University to all students and via WhatsApp© groups. The self-administered questionnaire was conducted in English and comprised of two parts: socio-demographic characteristics and KAP towards COVID-19. A total of 712 responses to the questionnaire were collected. 90% (n=695) were under-graduate, while 10% (n=81) were post-graduate students. Majority (87%, n=647) stated that they obtained COVID-19 information from multiple reliable sources. They were highly knowledgeable about COVID-19 pandemic but 76% (n=539) did not recognize its routes of transmission. 63% (n=431) were worried of getting COVID-19, while 92% (n=633)) were worried that a family member could get infected with the virus. 97% (n=655) took precautions when accepting home deliveries, 94% (n=637) had been washing their hands more frequently, and 95% (n=643) had been wearing face masks. In conclusion, participants showed high levels of knowledge and awareness about COVID-19. They were worried about getting infected themselves or their family members, and had good practices against COVID-19.
Metabolic regulation of ILC2 differentiation into ILC1-like cells duringMycobacterium tuberculosisinfection
Authors: Corral Dan , Charton Alison , Krauss Maria Z , Blanquart Eve , Levillain Florence , Lefrançais Emma , Sneperger Tamara , Girard Jean-Philippe , Eberl Gérard , Poquet Yannick , Guéry Jean-Charles , Arguello Rafael J , Hepworth Matthew R , Neyrolles Olivier , Hudrisier Denis 
Published: January 2021

AbstractTissue-resident innate lymphoid cells (ILCs) regulate tissue homeostasis, protect against pathogens at mucosal surfaces and are key players at the interface of innate and adaptive immunity. How ILCs adapt their phenotype and function to environmental cues within tissues remains to be fully understood. Here, we show thatMycobacterium tuberculosisinfection alters the phenotype and function of immature lung ILC2 toward a protective interferon-γ-producing ILC1-like population. This differentiation is controlled by type 1 cytokines and is associated with a glycolytic program involving the transcription factor HIF1α. Collectively, our data reveal how tissue-resident ILCs adapt to type 1 inflammation toward a pathogen tailored immune response.
VISUAL network analysis reveals the role of BEH3 as a stabilizer in the secondary vascular development in Arabidopsis
Authors: Furuya Tomoyuki , Saito Masato , Uchimura Haruka , Satake Akiko , Nosaki Shohei , Miyakawa Takuya , Shimadzu Shunji , Yamori Wataru , Tanokura Masaru , Fukuda Hiroo , Kondo Yuki 
Published: January 2021

AbstractDuring secondary growth in plants, vascular stem cells located in the cambium continuously undergo self-renewal and differentiation throughout the lifetime. Recent cell-sorting technique enables to uncover transcriptional regulatory framework for cambial cells. However, the mechanisms underlying the robust control of vascular stem cells have not been understood yet. By coexpression network analysis using multiple transcriptome datasets of an ectopic vascular cell transdifferentiation system using Arabidopsis cotyledons, VISUAL, we newly identified a cambium-specific gene module from an alternative approach. The cambium gene list included a transcription factor BES1/BZR1 homolog 3 (BEH3), whose homolog BES1 is known to control vascular stem cell maintenance negatively. Interestingly, the vascular size of thebeh3mutants showed a large variation, implying the role of BEH3 as a stabilizer. BEH3 almost lost the transcriptional repressor activity and functioned antagonistically with other BES/BZR members via competitive binding to the same motif BRRE. Indeed, mathematical modeling suggests that the competitive relationship among BES/BZRs leads to the robust regulation of vascular stem cells.
Mechanosensitive remodeling of the bacterial flagellar motor is independent of direction of rotation
Authors: Wadhwa Navish , Tu Yuhai , Berg Howard C. 
Published: January 2021

Motility is critical for the survival and dispersal of bacteria, and it plays an important role during infection. How bacteria regulate motility is thus a question of broad interest. Regulation of bacterial motility by chemical stimuli is well studied, but recent work has added a new dimension to the problem of motility control. The bidirectional flagellar motor of the bacteriumEscherichia colirecruits or releases torque-generating units (stator units) in response to changes in load. Here, we show that this mechanosensitive remodeling of the flagellar motor is independent of direction of rotation. Remodeling rate constants in clockwise rotating motors and in counterclockwise rotating motors, measured previously, fall on the same curve if plotted against torque. Increased torque decreases the off rate of stator units from the motor, thereby increasing the number of active stator units at steady state. A simple mathematical model based on observed dynamics provides quantitative insight into the underlying molecular interactions. The torque-dependent remodeling mechanism represents a robust strategy to quickly regulate output (torque) in response to changes in demand (load).SignificanceMacromolecular machines carry out most of the biological functions in living organisms. Despite their significance, we do not yet understand the rules that govern the self-assembly of large multi-protein complexes. The bacterial flagellar motor tunes the assembly of its torque-generating stator complex with changes in external load. Here, we report that clockwise and counterclockwise rotating motors have identical remodeling response to changes in the external load, suggesting a purely mechanical mechanism for this regulation. Autonomous control of self-assembly may be a general strategy for tuning the functional output of protein complexes. The flagellar motor is a prime example of a macromolecular machine in which the functional regulation of assembly can be rigorously studied.
Identification and characterization of a G-quadruplex structure in the pre-core promoter region of hepatitis B virus
Authors: Meier-Stephenson Vanessa , Badmalia Maulik D , Mrozowich Tyler , Lau Keith CK , Schultz Sarah K , Gemmill Darren L , Osiowy Carla , van Marle Guido , Coffin Carla S , Patel Trushar R 
Published: January 2021

ABSTRACTWorldwide, ∼250 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of cirrhosis and hepatocellular carcinoma. The HBV persists as covalently closed circular DNA (cccDNA), which acts as the template for all HBV mRNA transcripts. Nucleos(t)ide analogs do not directly target the HBV cccDNA and cannot eradicate the HBV. We have discovered a unique structural motif, a G-quadruplex in HBV’s pre-core promoter region that is conserved amongst nearly all genotypes, and is central to critical steps in the viral life-cycle including the production of pre-genomic RNA, core and polymerase proteins, and encapsidation. Thus, an increased understanding of the HBV pre-core may lead to the development of novel anti-HBV cccDNA targets. We utilized biophysical methods to characterize the presence of the G-quadruplex, employed assays using a known quadruplex- binding protein (DHX36) to pull-down HBV cccDNA, and compared HBV infection in HepG2 cells transfected with wild-type and mutant HBV plasmids. This study provides insights into the presence of a G-quadruplex in the HBV pre-core promoter region essential for HBV replication. The evaluation of this critical host-protein interaction site in the HBV cccDNA may ultimately facilitate the development of novel anti-HBV therapeutics against the resilient cccDNA template.