bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Interaction of Child Abuse and rs1360780 of the FKBP5 Gene is Associated with Amygdala Resting-State Functional Connectivity in Young Adults
Authors: Wesarg Christiane , Veer Ilya M. , Oei Nicole Y. L. , Daedelow Laura S. , Lett Tristram A. , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L.W. , Quinlan Erin Burke , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Brühl Rüdiger , Martinot Jean-Luc , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Poustka Luise , Hohmann Sarah , Fröhner Juliane H. , Smolka Michael N. , Whelan Robert , Schumann Gunter , Heinz Andreas , Walter Henrik ,   IMAGEN Consortium
Published: November 2020

AbstractExtensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase risk for psychopathology.
Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
Authors: Cagigi Alberto , Yu Meng , Österberg Björn , Svensson Julia , Falck-Jones Sara , Vangeti Sindhu , Åhlberg Eric , Azizmohammadi Lida , Warnqvist Anna , Falck-Jones Ryan , Gubisch Pia C , Ödemis Mert , Ghafoor Farangies , Eisele Mona , Lenart Klara , Bell Max , Johansson Niclas , Albert Jan , Sälde Jörgen , Pettie Deleah , Murphy Michael , Carter Lauren , King Neil P , Ols Sebastian , Normark Johan , Ahlm Clas , Forsell Mattias , Färnert Anna , Loré Karin , Smed-Sörensen Anna 
Published: November 2020

AbstractUnderstanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights on the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity; from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared to naïve individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, while systemic IgG levels were durable for up to 8 months, airway IgG and IgA had declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naïve individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccination also for previously infected individuals to obtain optimal mucosal protection.
Social responsibility is the crucial factor in adopting early vaccination plans
Authors: Georgiou Harris V. 
Published: November 2020

Early vaccination of the general population is a very crucial aspect in the successful mitigation of highly infectious diseases, as it is the case of the SARS-CoV-2 pandemic. The perception of possible side-effects from early batches of vaccines, presumably under-tested, is often a hindering factor for people not in high-risk categories to optin for early vaccination. In this work, early vaccination is formulated under a game-theoretic view with preference ranking and expectation maximization, in order to explore the constraints and conditions under which individuals are keen to opt-in for getting vaccinated. Although simple preference ranking leads to purely non-cooperative / non-altruistic Nash equilibrium, stable cooperative strategies can emerge under simple constraints on the payoffs, specifically the individual cost from possible side-effects versus the collective gain for the community (‘herd’) when endorsing vaccination by default.Significance StatementIf the collective gain from community-scale vaccination is deemed even marginally greater than each individual’s cost of possible side-effects, then the best strategy is to ‘cooperate’, i.e., every individual to opt-in for getting vaccinated.This condition is independent from the probabilities of getting infected, with or without vaccination, and it is sufficient to lead to a stable cooperative Nash equilibrium.In any lethal infectious disease like SARS-CoV-2 and less-than-lethal possible side-effects from the vaccine, for anyone that is susceptible plus one more in his/her own close environment, vaccination is the optimal strategy for all.
The Epidemiologic Transition Theory and Evidence for Cancer Transitions in the US, Select European Nations, and Japan
Authors: Gersten Omer , Barbieri Magali 
Published: November 2020

AbstractDespite cancer being a leading cause of death worldwide, scant research has been carried out on the existence of “cancer transitions,” the idea that as nations develop, they move from a situation where infectious related cancers are prominent, to one where non-infectious related cancers dominate. We use annual cause-of-death data to produce death rates for common types of cancer in select high-income countries. We find that cancer mortality patterns parallel the epidemiologic transition, which states that as countries advance, they move from a regime where infectious diseases are most common to one where non-infectious disease are most common. An implication is that the epidemiologic transition theory as originally formulated continues to be relevant despite some researchers arguing that we need additional stages beyond the original three.
ExaminingFouquieria splendensin an environmental and ecological context: Effect of topography and interspecific neighbors on ocotillo morphology and distribution
Authors: Bernat Anastasia , So Tang Acacia Tsz , Steenson Allegra , Larsen Eric 
Published: November 2020

AbstractFouquieria splendensis a stem-succulent native to the Chihuahuan, Mojave, and Sonoran Deserts that spans Mexico and the American Southwest. It is well-known for its variable morphology, the underlying reason for which remains incompletely understood. Here, we attempt to quantify the effect of topographic and interspecific factors onF. splendensmorphology and distribution. To this end, we measured 27 ocotillos located in the Organ Pipe Cactus National Monument within the Sonoran Desert during June of 2019. We also quantified the spatial distribution of interspecific neighbors relative toF. splendenswithin two topographically different sites: a bajada gradient and a plain. Using ocotillo morphology, the distances to the nearest neighbors of ocotillos, and hydrographic data extracted from the National Hydrography Dataset, we demonstrate 1) the effect of major interspecific neighbors, i.e. shrubs and cacti, on ocotillo morphology; 2) the effect of elevation on intraspecific spacing as individuals compete for limited space; and 3) a trade-off between height and number of branches. This placesF. splendensmorphology in its larger environmental and ecological context, highlighting the importance of individual traits and associated trade-offs among traits affected by topography and interspecific neighbors. By examining the ocotillo in a multi-species community and diverse landscape, this study provides empirical insight into a wider range of factors contributing to the variation inF. splendensmorphology and spacing.
Cryptic promoter activation occurs by at least two different mechanisms in theArabidopsisgenome
Authors: Kudo Hisayuki , Matsuo Mitsuhiro , Satoh Soichirou , Hachisu Rei , Nakamura Masayuki , Yamamoto Yoshiharu Y , Hata Takayuki , Kimura Hiroshi , Matsui Minami , Obokata Junichi 
Published: November 2020

ABSTRACTIn gene-trap screening of plant genomes, promoterless reporter constructs are often expressed without trapping of annotated gene promoters. The molecular basis of this phenomenon, which has been interpreted as the trapping of cryptic promoters, is poorly understood. In this study, usingArabidopsisgene-trap lines in which a firefly luciferase (LUC) open reading frame (ORF) was expressed from intergenic regions, we found that cryptic promoter activation occurs by at least two different mechanisms: one is the capturing of pre-existing promoter-like chromatin marked by H3K4me3 and H2A.Z, and the other is the entirely new formation of promoter chromatin near the 5’ end of the insertedLUCORF. To discriminate between these, we denoted the former mechanism as “cryptic promoter capturing”, and the latter one as “promoterde novoorigination”. The latter finding raises a question as to how insertedLUCORF sequence is involved in this phenomenon. To examine this, we performed a model experiment with chimericLUCgenes in transgenic plants. UsingArabidopsis psaH1promoter–LUCconstructs, we found that the functional core promoter region, where transcription start sites (TSS) occur, cannot simply be determined by the upstream nor core promoter sequences; rather, its positioning proximal to the insertedLUCORF sequence was more critical. This result suggests that the insertion of theLUCORF sequence alters the local distribution of the TSS in the plant genome. The possible impact of the two types of cryptic promoter activation mechanisms on plant genome evolution and endosymbiotic gene transfer is discussed.
Streamlined Magnetic Resonance Fingerprinting: Fast Whole-brain Coverage with Deep-learning Based Parameter Estimation
Authors: Khajehim Mahdi , Christen Thomas , Tam Fred , Graham Simon J. 
Published: November 2020

AbstractMagnetic resonance fingerprinting (MRF) is a novel quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current bottlenecks exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. The aim of this study is to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework that is based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1+correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm3and 1.7×1.7×3 mm3, and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R=1-1.04, R2>0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R2>0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4±0.4%, 3.6±0.3% and 6.0±0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation.
Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos
Authors: Furno Elena Lo , Busseau Isabelle , Lorenzi Claudio , Saghira Cima , Danzi Matt C , Zuchner Stephan , Maiorano Domenico 
Published: November 2020

AbstractIn early embryogenesis of fast cleaving embryos DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient implying the possible generation of mutations. We have analyzed mutagenesis inXenopus laevisandDrosophila melanogasterearly embryos. We report the occurrence of a high mutation rate inXenopusand show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastodermDrosophilaembryo resulted in reduction of both the hatching rate and Single Nucleotide Variations on specific chromosome regions in adult flies. Altogether, these findings indicate that during very earlyXenopusandDrosophilaembryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.
Plant genome response to incoming coding sequences: stochastic transcriptional activation independent of integration loci
Authors: Satoh Soichirou , Hata Takayuki , Takada Naoto , Tachikawa Makoto , Matsuo Mitsuhiro , Kushnir Sergei , Obokata Junichi 
Published: November 2020

AbstractHorizontal gene transfer can occur between phylogenetically distant organisms, such as prokaryotes and eukaryotes. In these cases, how do the translocated genes acquire transcriptional competency in the alien eukaryotic genome? According to the conventional view, specific loci of the eukaryotic genome are thought to provide transcriptional competency to the incoming coding sequences. To examine this possibility, we randomly introduced the promoterless luciferase (LUC)-coding sequences into the genome ofArabidopsis thalianacultured cells and performed a genome-wide “transgene location vs. expression” scan. We mapped 4,504 promoterlessLUCinserts on theA. thalianachromosomes, and found that about 30% of them were transcribed. Only a small portion of them were explained by the conventional transcriptional fusions with the annotated genes, and the remainder occurred in a quite different manner; (1) they occurred all over the chromosomal regions, (2) independently of the insertion sites relative to the annotated gene loci, inherent transcribed regions, or heterochromatic regions, and (3) with one magnitude lower transcriptional level than the conventional transcriptional fusions. This type of transcriptional activation occurred at about 30% of the inserts, raising a question as to what this 30% means. We tested two hypotheses: the activation occurred at 30% of the entire chromosomal regions, or stochastically at 30% of each insertion event. Our experimental analysis indicates that the latter model could explain this transcriptional activation, a new type of plant genome response to the incoming coding sequences. We discuss the possible mechanisms and evolutionary roles of this phenomenon in the plant genome.
Orbitofrontal-hypothalamic projections are disrupted in hypermetabolic murine ALS model and human patients
Authors: Bayer David , Antonucci Stefano , Müller Hans-Peter , Dupuis Luc , Boeckers Tobias , Ludolph Albert , Kassubek Jan , Roselli Francesco 
Published: November 2020

AbstractIncreased catabolism is a new clinical manifestation of Amyotrophic Lateral Sclerosis. A dysfunction of lateral hypothalamus may drive hypermetabolism in ALS; however, Its causes and anatomical substrates are unknown. We hypothesize that disruption cortico-hypothalamic circuits may impair energy homeostasis in ALS. We used rAAV2 for large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik to quantify projections from the forebrain to the latera hypothalamus of the SOD1(G93A) ALS mouse model as well as of the FusΔNLSALS mouse model. Expanded projections from agranular Insula, ventrolateral orbitofrontal and secondary motor cortex to lateral hypothalamus were found in two independent cohorts of the hypermetabolic SOD1(G93A) ALS model. The non-hypermetabolic FusΔNLSALS mouse model display a loss of projections from motor cortex but no change in projections from insula and orbitofronal cortex. 3T DTI-MRI data on 83 ALS patients and 65 controls confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS patients. Converging murine and human data demonstrate the selective disruption of hypothalamic inputs in ALS as a factor contributing to the origin of hypermetabolism.Significance statementWe provide a circuit perspective of the recently identified and medically relevant hyper-metabolic phenotype of Amyotrophic Lateral Sclerosis. We demonstrate the selective involvement of orbitofrontal, insular and motor cortex projections to hypothalamus in murine ALS models and in human patients. The enhanced pipeline for large-scale registration, segmentation projections mapping, the identification of new circuits target of neurodegeneration, and the relevance of these circuits in metabolic disturbances make this work relevant not only for the investigation of ALS but also for other neurodegenerative disease as well as for all conditions characterized by systemic energy imbalances.
The non-adrenergic imidazoline-1 receptor protein Nischarin is a key regulator of astrocyte glutamate uptake
Authors: Gupta Swati , Bazargani Narges , Drew James , Modi Souvik , Marie Hélène , Attwell David , Kittler Josef T. 
Published: November 2020

SummaryAstrocytic GLT-1 is the main glutamate transporter involved in glutamate buffering in the brain, pivotal for glutamate removal at excitatory synapses to terminate neurotransmission and for preventing excitotoxicity. We show here that the surface expression and function of GLT-1 can be rapidly modulated through the interaction of its N-terminus with the nonadrenergic imidazoline-1 receptor protein, Nischarin. The phox domain of Nischarin is critical for interaction and internalization of surface GLT-1. Using live super-resolution imaging, we found that glutamate accelerated Nischarin-GLT-1 internalization into endosomal structures. The surface GLT-1 level increased in Nischarin knockout astrocytes, and this correlated with a significant increase in transporter uptake current. Furthermore, Nischarin knockout in astrocytes is neuroprotective against glutamate excitotoxicity. These data provide new molecular insights into regulation of GLT-1 surface level and function and suggest novel drug targets for the treatment of neurological disorders.HighlightsThe phox domain of Nischarin interacts with the N-terminal tail of the main astrocyte glutamate transporter, GLT-1.Nischarin promotes internalization of GLT-1 to endosomes.Glutamate modulates GLT-1 surface levels via regulation of the Nischarin-GLT-1 interaction.Genetic loss of Nischarin significantly increases GLT-1 surface expression, resulting in increased glutamate transport currents and enhanced neuroprotection.
Stool serology: development of a non-invasive immunological method for the detection of Enterovirus-specific antibodies in Congo gorilla faeces
Authors: Sereme Youssouf , Zarza Sandra Madariaga , Medkour Hacène , Amona Inestin , Fenollar Florence , Akiana Jean , Mezouar Soraya , Orain Nicolas , Vitte Joana , Davoust Bernard , Raoult Didier , Mediannikov Oleg 
Published: November 2020

AbstractThe incidence of poliovirus has significantly reduced by as much as 99.9% globally. Alongside this, however, vaccine-associated paralytic poliomyelitis has emerged. Recently, a new recombinant virus (Enterovirus C/Poliovirus) was identified in humans working as eco-guards and in gorillas in Democratic Republic of Congo, including one gorilla with polio-like sequelae. A strain of this recombinant virus (Ibou002) was also isolated from gorilla faeces. In order to assess the potential role of poliovirus infection, we have developed and optimised a protocol, based on the lyophilisation and solubilisation of small volumes of stool extracts, to detect specific antibodies. First, total immunoglobulins was detected in the concentrated stool extracts. Specific antibodies were then detected in 4/16 gorilla samples and 2/3 human samples by western blot using both the polio vaccine antigen and the Ibou002 antigen and by ELISA using the polio vaccine antigen. Humoral responses were greater with the Ibou002 antigen. We therefore suggest that this recombinant virus could lead to a polio-like disease in the endangered western lowland gorilla. The development of a non-invasive method to detect microorganism-specific immunoglobulins from faecal samples opens up new perspectives for the exploration of humoral responses of pathogens in animals and a greater understanding of zoonotic infectious diseases.
A phage satellite tunes inducing phage gene expression using a domesticated endonuclease to balance inhibition and virion hijacking
Authors: Netter Zoe , Boyd Caroline M. , Silvas Tania V. , Seed Kimberley D. 
Published: November 2020

AbstractBacteria persist under constant threat of predation by bacterial viruses (phages). Bacteria-phage conflicts result in evolutionary arms races often driven by mobile genetic elements (MGEs). One such MGE, a phage satellite in Vibrio cholerae called PLE, provides specific and robust defense against a pervasive lytic phage, ICP1. The interplay between PLE and ICP1 has revealed strategies for molecular parasitism allowing PLE to hijack ICP1 processes in order to mobilize. Here, we describe the mechanism of PLE-mediated transcriptional manipulation of ICP1 structural gene transcription. PLE encodes a novel DNA binding protein, CapR, that represses ICP1’s capsid morphogenesis operon. Although CapR is sufficient for the degree of capsid repression achieved by PLE, its activity does not hinder the ICP1 lifecycle. We explore the consequences of repression of this operon, demonstrating that more stringent repression achieved through CRISPRi restricts both ICP1 and PLE. We also discover that PLE transduces in modified ICP1-like particles. Examination of CapR homologs led to the identification of a suite of ICP1-encoded homing endonucleases, providing a putative origin for the satellite-encoded repressor. This work unveils a facet of the delicate balance of satellite-mediated inhibition aimed at blocking phage production while successfully mobilizing in a phage-derived particle.