bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human iPSC-derived astrocytes transplanted into the mouse brain display three morphological responses to amyloid-β plaques
Authors: Preman Pranav , TCW Julia , Calafate Sara , Snellinx An , Alfonso-Triguero Maria , Corthout Nikky , Munck Sebastian , Thal Dietmar Rudolf , Goate Alison M , De Strooper Bart , Arranz Amaia M 
Published: November 2020

ABSTRACTBackgroundIncreasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression.MethodsTo address these challenges, we established an approach to study human astroglia within the context of the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived glia progenitors into neonatal brains of immunodeficient mice.ResultsXenografted (hiPSC)-derived glia progenitors differentiate into astrocytes that integrate functionally within the mouse host brain and mature in a cell-autonomous way retaining human-specific morphologies, unique features and physiological properties. In Alzheimer’s chimeric brains, transplanted hiPSC-derived astrocytes respond to the presence of amyloid plaques with various morphological changes that seem independent of theAPOEallelic background.ConclusionIn sum, this chimeric model has great potential to analyze the role of patient-derived and genetically modified astroglia in Alzheimer’s disease.
Phylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota
Authors: Galindo Luis Javier , López-García Purificación , Torruella Guifré , Karpov Sergey , Moreira David 
Published: November 2020

AbstractCompared to multicellular fungi and unicellular yeasts, unicellular fungi with free-living flagellated stages (zoospores) remain poorly known and their phylogenetic position is often unresolved. Recently, rRNA gene phylogenetic analyses of two atypical parasitic fungi with amoeboid zoospores and long kinetosomes, the sanchytridsAmoeboradix gromoviandSanchytrium tribonematis, showed that they formed a monophyletic group without close affinity with known fungal clades. Here, we sequence single-cell genomes for both species to assess their phylogenetic position and evolution. Phylogenomic analyses using different protein datasets and a comprehensive taxon sampling result in an almost fully-resolved fungal tree, with Chytridiomycota as sister to all other fungi, and sanchytrids forming a well-supported, fast-evolving clade sister to Blastocladiomycota. Comparative genomic analyses across fungi and their allies (Holomycota) reveal an atypically reduced metabolic repertoire for sanchytrids. We infer three main independent flagellum losses from the distribution of over 60 flagellum-specific proteins across Holomycota. Based on sanchytrids’ phylogenetic position and unique traits, we propose the designation of a novel phylum, Sanchytriomycota. In addition, our results indicate that most of the hyphal morphogenesis gene repertoire of multicellular fungi had already evolved in early holomycotan lineages.
Parasitic flatworms infecting thorny skate,Amblyraja radiata:infection by the monogeneansAcanthocotyle verrilliandRajonchocotyle emarginatain Svalbard
Authors: Hermans Raquel , Vanhove Maarten P. M. , Ditrich Oleg , Tyml Tomáš , Gelnar Milan , Artois Tom , Kmentová Nikol 
Published: November 2020

AbstractParasite diversity above the Arctic circle remains understudied even for commercially valuable host taxa. Thorny skate,Amblyraja radiata,is a common bycatch species with a growing commercial value. Its natural range covers both sides of the North Atlantic including the Arctic zone. Svalbard is a Norwegian archipelago located on the northwest corner of the Barents Shelf which sustains a spectacular species diversity. So far, several monogenean species have been reported infecting thorny skate across the Atlantic Ocean. In the present study, we intend to fill in the knowledge gap on monogenean parasites infecting thorny skate in the northern part of its range and thus indirectly assess the connectivity between the thorny skate populations off the Svalbard coast and from previously studied locations. 46 monogenean individuals were recovered from 11 specimens of thorny skate. Following morphological and molecular assessment, two species of monogeneans,Acanthocotyle verrilliandRajonchocotyle emarginata,were identified. The results serve as the northernmost record for both parasite genera and the first record of monogenean species off Svalbard. Detailed morphometric evaluation revealed a relatively high level of morphological variation inA. verrillicompared to its congeners. Phylogenetic reconstruction placedA. verrilliin a well-supported clade withA. imo.Our study also suggests high diagnostic significance of sclerotised structures in the identification ofRajonchocotyle.Even though the occurrence of two directly transmitted parasite species supports the previously suggested long-distance migration ofA. radiata, future studies employing highly variable genetic markers are needed to assess the ongoing and historical migration patterns.HighlightsFirst record of monogenean species in SvalbardNorthernmost record for representatives of Acanthocotylidae and HexabothriidaeTransatlantic occurrence of parasites supports connectivity of thorny skate populations
Ribonucleotide reductase, a novel target for gonorrhea
Authors: Narasimhan J. , Letinski S. , Jung S. , Gerasyuto A. , Wang J. , Arnold M. , Chen G. , Hedrick J. , Dumble M. , Ravichandran K. , Levitz T. S. , Chang C. , Drennan C. L. , Stubbe J. , Karp G. , Branstrom A. 
Published: November 2020

AbstractAntibiotic resistantNeisseria gonorrhoeae (Ng)are an emerging public health threat due to increasing numbers of multidrug resistant (MDR) organisms. We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum of activity againstNgincluding MDR isolates. By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). Activity studies and negative stain electron microscopy of theNgIa RNR suggest that these inhibitors potentiate conversion of its active α2β2state to an inactive α4β4similar to states first identified with theEscherichia coli (Ec)Ia RNR. Resistance mutations inNgmap to theN-terminal, ATP cone domain of its α subunit and disrupt the interaction with the β subunit required to form the specific quaternary inhibited state. Oral administration of PTC-672 reducesNginfection in a mouse model and may have therapeutic potential for treatment ofNgthat is resistant to current drugs.
Elucidating the neuroanatomical correlates of social connectedness, sleep quality and psychological distress in early adolescence
Authors: Jamieson Daniel , McLoughlin Larisa T , Beaudequin Denise A , Shan Zack , Boyes Amanda , Schwenn Paul , Lagopoulos Jim , Hermens Daniel F 
Published: November 2020

AbstractBackgroundAdolescence is an important period for developing one’s sense of self. Social connectedness has been linked to a sense of self which in turn has links to resilience in mental disorders. Adolescence is also a period of increased risk of chronic sleep deprivation during a time of ongoing white matter (WM) maturation. The complex relationship between these variables and their relationship with the onset on mental disorders during adolescence remains largely unexplored.MethodsN= 64 participants aged 12 years (M= 12.6) completed the Pittsburgh Sleep Quality Index (PSQI), Social connectedness scale (SCS) and a diffusion weighted Magnetic Resonance Imaging (MRI) scan to investigate the relationship of these variables to predict psychological distress via the Kessler psychological distress scale (K10) in early adolescents. Multiple regression analysis was used with K10 entered as the dependent variable and SCS, PSQI, and values of white matter integrity as the predictor variables.ResultsResults showed that while all four variables collectively accounted for a significant proportion of the variance in K10 (41.1%), SCS and PSQI were the only predictors that accounted for a significant proportion of variance uniquely.ConclusionsThese findings suggest interventions aimed at increasing levels of social connectedness and sleep quality during adolescence may reduce psychological distress. Future longitudinal reporting of this combination of variables is suggested.
Stress-sensitive inference of task controllability
Authors: Ligneul Romain , Mainen Zachary , Ly Verena , Cools Roshan 
Published: November 2020

AbstractEstimating the controllability of the environment enables agents to better predict upcoming events and decide when to engage controlled action selection. How does the human brain estimate controllability? Trial-by-trial analysis of choices, decision times, and neural activity in an explore-and-predict task demonstrate that humans solve this problem by comparing the predictions of an “actor” model with those of a reduced “spectator” model of their environment. Neural BOLD responses within striatal and medial prefrontal areas tracked the instantaneous difference in the prediction errors generated by these two statistical learning models. BOLD activity in the posterior cingulate, temporoparietal, and prefrontal cortices covaried with changes in estimated controllability. Exposure to inescapable stressors biased controllability estimates downward and increased reliance on the spectator model in an anxiety-dependent fashion. Taken together, these findings provide a mechanistic account of controllability inference and its distortion by stress exposure.
On-site rapid molecular testing, mobile sampling teams and eHealth to support primary care physicians during the COVID-19 pandemic
Authors: Cheung N.N. , Boers S.A. , deh Kiani S. Kiani , Jansen R.W. , Mook-Kanamori D.O. , Janssens L. , Feltkamp M.C.W. , Kroes A.C.M , Mourik B.C. 
Published: November 2020

AbstractObjectivesWe evaluated the effects of on-site rapid molecular testing at a drive-through sampling facility, deployment of mobile sampling teams and implementation of an online eHealth platform as supportive measures for general practitioners (GPs) during the COVID-19 pandemic.MethodsAn eHealth platform was developed that allowed GPs to either refer patients to a drive-through sampling facility or to request a home visit by a sampling team. Nasopharyngeal swab samples from patients marked as urgent (n=333) were tested immediately on-site using a GeneXpert System. Non-urgent samples (n=1,460) were sent once a day to a university hospital laboratory for routine testing. Time stamps starting from referral to the moment of test report sent were recorded to calculate the turnaround time.ResultsThe eHealth platform was rapidly adopted and used by a total of 517 GPs to test 1,793 patients in a period of 13 weeks. On-site rapid molecular testing reduced the median turnaround time to 03h:41m compared to 29h:15m for routine testing. Positive SARS-CoV-2 test results were identified amongst 84/1,477 (5.7%) and 33/316 (10.4%) patients sampled at the drive-through or at home, respectively. In the age category of >80 years, 80.4% of patients were tested by a mobile sampling team.ConclusionsThe combination of rapid molecular testing and eHealth reduced the time between referral and results sent back to the GP to less than four hours. In addition, mobile sampling teams helped in reaching non-mobile, elderly patient populations with a higher prevalence of COVID-19.
Breast cancer dormancy is associated with a 4NG1 state and not senescence
Authors: Prunier Chloé , Alay Ania , van Dijk Michiel , Ammerlaan Kelly L. , van Gelderen Sharon , Marvin Dieuwke L. , Teunisse Amina , Slieker Roderick C. , Szuhai Karoly , Jochemsen A.G. , Solé Xavier , Dijke Peter ten , Ritsma Laila 
Published: November 2020

ABSTRACTReactivation of dormant cancer cells can lead to cancer relapse, metastasis and patient death. Dormancy is a non-proliferative state and is linked to late relapse and death. No targeted therapy is currently available to eliminate dormant cells, highlighting the need for a deeper understanding and reliable models. Here, we thoroughly characterize the dormant D2.OR and proliferative D2A1 breast cancer cell line modelsin vivoandin vitro, and assess if there is overlap between a dormant and a senescent phenotype. We show that D2.OR but not D2A1 cells become dormant in the liver of an immunocompetent model.In vitro, we show that D2.OR cells are polyploid ER+/Her2+cells, and in response to a 3D environment are growth arrested in G1, of which a subpopulation resides in a 4NG1 state. The dormancy state is reversible, and not associated with a senescence phenotype. This will aid future research on breast cancer dormancy.
Antibiotic resistance profiles and population structure of disease-associatedStaphylococcus aureusinfecting patients in Fort Portal Regional Referral Hospital, Western Uganda
Authors: Ackers-Johnson G. , Kibombo D. , Kusiima B. , Nsubuga M.L. , Kigozi E. , Kajumbula H.M. , Kateete D.P. , Walwema R. , Ackers H.L. , Goodhead I.B. , Birtles R.J. , James C.E. 
Published: November 2020

AbstractTackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41Staphylococcus aureusisolates (2017-2019). AST revealed 73% (30/41) of isolates were resistant to one or more antibiotics and 29% (12/41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistantS. aureus(MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24% carriage ofermgenes suggests potential for rapid development of resistance. We inferred a population structure for theS. aureusisolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitiveS. aureus(MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton-Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulatingS. aureusand their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.
Inactivation of mitochondrial Complex I stimulates chloroplast ATPase in Physcomitrella (Physcomitrium patens)
Authors: Mellon Marco , Storti Mattia , Vives Antoni Mateu Vera , Kramer David M. , Alboresi Alessandro , Morosinotto Tomas 
Published: November 2020

AbstractWhile light is the ultimate source of energy for photosynthetic organisms, mitochondrial respiration is still fundamental for supporting metabolism demand during the night or in heterotrophic tissues. Respiration is also important for the metabolism of photosynthetically active cells, acting as a sink for excess reduced molecules and source of substrates for anabolic pathways. In this work, we isolated Physcomitrella (Physcomitrium patens) plants with altered respiration by inactivating Complex I of the mitochondrial electron transport chain by independent targeting of two essential subunits. Results show that the inactivation of Complex I causes a strong growth impairment even in fully autotrophic conditions in tissues where all cells are photosynthetically active. Complex I mutants show major alterations in the stoichiometry of respiratory complexes while the composition of photosynthetic apparatus was substantially unaffected. Complex I mutants showed altered photosynthesis with higher yields of both Photosystems I and II. These are the consequence of a higher chloroplast ATPase activity that also caused a smaller ΔpH formation across thylakoid membranes as well as decreased photosynthetic control on cytochromeb6f, possibly to compensate for a deficit in ATP supply relative to demand in Complex I mutants. These results demonstrate that alteration of respiratory activity directly impacts photosynthesis inP. patensand that metabolic interaction between organelles is essential in their ability to use light energy for growth.
Lethal and sublethal effects of synthetic and bio-insecticides onTrichogramma brassicaeparasitizingTuta absoluta
Authors: Nozad-Bonab Zahra , Hejazi Mir Jalil , Iranipour Shahzad , Arzanlou Mehdi , Biondi Antonio 
Published: November 2020

AbstractThe invasive tomato leaf miner (TLM),Tuta absoluta(Meyrick) is an invasive pest on tomatoes worldwide. The main control measure against the pest has been chemical insecticides, but the pest developed resistance to many chemical classes. So alternative methods, such as biological control agents, alone or combined to chemical compounds must be evaluated to validate their synergistic actions. In this study, both lethal (concentration-mortality response) and sublethal effects of three synthetic insecticides, the bioinsecticide spinosad, as well as the entomopathogenic fungusMetarhizium anisopliae(Metschnikoff) Sorokin were studied onTrichogramma brassicaeBezdenko withinT. absolutaeggs. To assess the sublethal effects, the lethal concentration 25% (LC25) of chlorantraniliprole, spinosad, abamectin and indoxacarb and LC50value ofM. anisopliaewas sprayed on eggs and then offered at three time intervals to the parasitoids. Fertility and other life table parameters of the individuals emerged from treated eggs were estimated. The results showed that indoxacarb showed the highest deleterious sublethal effects onT. brassicae. On the other hand,M. anisopliaewas the safest treatment to combine toTrichogrammawith no significant effect on some parameters. The lowest LC50value forT.brassicaewas obtained for chlorantraniliprole followed by spinosad. Synergistic effect was observed whenM. anisopliaeandT. brassicaeused together. Hence, this will be a promising integration againstT. absoluta.
A novel stem cell type at the basal side of the subventricular zone maintains adult neurogenesis
Authors: Baur Katja , Abdullah Yomn , Mandl Claudia , Hölzl-Wenig Gabriele , Shi Yan , Edelkraut Udo , Khatri Priti , Hagenston Anna M. , Irmler Martin , Beckers Johannes , Ciccolini Francesca 
Published: November 2020

AbstractAccording to the current consensus, neural stem cells (NSCs) apically contacting the lateral ventricle generate differentiated progenitors by rare asymmetric divisions or by relocating to the basal side of the ventricular-subventricular zone V-SVZ. Both processes will then ultimately lead to the generation of adult-born olfactory bulb (OB) interneurons. In contrast to this view, we here found that adult-born OB interneurons largely derive from an additional NSC type resident in the basal V-SVZ. Despite being both capable of self-renewal and long-term quiescence, apical and basal NSCs differ in Nestin expression, primary cilia extension and frequency of cell division. The expression of Notch-related genes also differed between the two NSC groups and Notch-activation was greatest in apical NSCs. Apical downregulation of Notch-effector Hes1 decreased Notch activation while increasing proliferation across the niche and neurogenesis from apical NSCs. Underscoring their different roles in neurogenesis, lactation-dependent increase in neurogenesis was paralleled by extra activation of basal but not apical NSCs. Thus, basal NSCs support OB neurogenesis whereas apical NSCs impart Notch-mediated lateral inhibition across the V-SVZ.
Arena3Dweb: Interactive 3D visualization of multilayered networks
Authors: Karatzas Evangelos , Baltoumas Fotis A. , Panayiotou Nikolaos A. , Schneider Reinhard , Pavlopoulos Georgios A. 
Published: November 2020

ABSTRACTEfficient integration and visualization of heterogeneous biomedical information in a single view is a key challenge. In this study, we present Arena3Dweb, the first, fully interactive and dependency-free, web application which allows the visualization of multilayered graphs in 3D space. With Arena3Dweb, users can integrate multiple networks in a single view along with their intra- and inter-layer connections. For clearer and more informative views, users can choose between a plethora of layout algorithms and apply them on a set of selected layers either individually or in combination. Users can align networks and highlight node topological features, whereas each layer as well as the whole scene can be translated, rotated and scaled in 3D space. User-selected edge colors can be used to highlight important paths, while node positioning, coloring and resizing can be adjusted on-the-fly. In its current version, Arena3Dwebsupports weighted and unweighted undirected graphs and is written in R, Shiny and JavaScript. We demonstrate the functionality of Arena3Dwebusing two different use-case scenarios; one regarding drug repurposing for SARS-CoV-2 and one related to GPCR signaling pathways implicated in melanoma. Arena3Dwebis available athttp://bib.fleming.gr:3838/Arena3D.