bluuebunny/crossref_metadata_2025_split huggingface dataset:
CNTN5−/+orEHMT2−/+iPSC-Derived Neurons from Individuals with Autism Develop Hyperactive Neuronal Networks
Authors: Deneault Eric , Faheem Muhammad , White Sean H. , Rodrigues Deivid C. , Sun Song , Wei Wei , Piekna Alina , Thompson Tadeo , Howe Jennifer L. , Chalil Leon , Kwan Vickie , Walker Susan , Pasceri Peter , Roth Frederick P. , Yuen Ryan K.C. , Singh Karun K. , Ellis James , Scherer Stephen W. 
Published: July 2018

AbstractInduced pluripotent stem cell (iPSC)-derived cortical neurons are increasingly used as a model to study developmental aspects of Autism Spectrum Disorder (ASD), which is clinically and genetically heterogeneous. To study the complex relationship of rare (penetrant) variant(s) and common (weaker) polygenic risk variant(s) to ASD, “isogenic” iPSC-derived neurons from probands and family-based controls, for modeling, is critical. We developed a standardized set of procedures, designed to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with ASD (14 ASD-affected individuals, 3 unaffected siblings, 8 unaffected parents). Heterozygousde novo(7 families; 16p11.2,NRXN1,DLGAP2,CAPRIN1,VIP,ANOS1,THRA) and rare-inherited (2 families;CNTN5,AGBL4) presumed-damaging variants were characterized in ASD risk genes/loci. In three additional families, functional candidates for ASD (SET), and combinations of putative etiologic variants (GLI3/KIF21AandEHMT2/UBE2Icombinations in separate families), were modeled. We used a large-scale multi-electrode array (MEA) as our primary high-throughput phenotyping assay, followed by patch clamp recordings. Our most compelling new results revealed a consistent spontaneous network hyperactivity in neurons deficient forCNTN5orEHMT2.Our biobank of iPSC-derived neurons and accompanying genomic data are available to accelerate ASD research.
Backward evolution from gene network dynamics
Authors: Belete Merzu Kebede , Charlebois Daniel A. , Balázsi Gábor 
Published: July 2018

AbstractGene expression is controlled by regulator genes that together with effector genes form gene regulatory networks. How mutation in the genes comprising gene regulatory networks influences cell population dynamics has not been adequately investigated. In this study, we develop mathematical models to study how a mutation in a regulator gene that reaches the effector gene with a time delay affects short-term and long-term population growth. Using theory and experiment, we find a paradoxical outcome of evolution where a mutation in a regulator gene leads to an interaction between gene regulatory network and population dynamics, causing in certain cases a permanent decrease in population fitness in a constant environment.Significance StatementThe properties of a cell are largely the products of its proteins, synthesized at rates depending on the regulation of protein coding genes. Single-cell measurements show that genetically identical cells can differ radically in their protein levels, partially due to the random production and degradation of proteins. It is currently unknown how mutants arise and spread in populations affected by such biological variability. We use computer simulations and evolution experiments to study how a mutant spreads in a population that carries a synthetic drug resistance gene network. Our results show for the first time a paradoxical outcome of evolution, where an initially beneficial mutation can interact with gene regulatory network dynamics and cause a permanent decrease in population fitness in the same environment.
The structural complexity of the Gammaproteobacteria flagellar motor is related to the type of its torque-generating stators
Authors: Kaplan Mohammed , Ghosal Debnath , Subramanian Poorna , Oikonomou Catherine M. , Kjær Andreas , Pirbadian Sahand , Ortega Davi R. , El-Naggar Mohamed Y. , Jensen Grant J. 
Published: July 2018

AbstractThe bacterial flagellar motor is a cell-envelope-embedded macromolecular machine that functions as a propeller to move the cell. Rather than being an invariant machine, the flagellar motor exhibits significant variability between species, allowing bacteria to adapt to, and thrive in, a wide range of environments. For instance, different torque-generating stator modules allow motors to operate in conditions with different pH and sodium concentrations and some motors are adapted to drive motility in high-viscosity environments. How such diversity evolved is unknown. Here we use electron cryo-tomography to determine thein situmacromolecular structures of the flagellar motors of three Gammaproteobacteria species:Legionella pneumophila,Pseudomonas aeruginosa, andShewanella oneidensisMR-1, providing the first views of intact motors with dual stator systems. Complementing our imaging with bioinformatics analysis, we find a correlation between the stator system of the motor and its structural complexity. Motors with a single H+-driven stator system have only the core P- and L-rings in their periplasm; those with dual H+-driven stator systems have an extra component elaborating their P-ring; and motors with Na+- (or dual Na+-H+)- driven stator systems have additional rings surrounding both their P- and L-rings. Our results suggest an evolution of structural complexity that may have enabled pathogenic bacteria likeL. pneumophilaandP. aeruginosato colonize higher-viscosity environments in animal hosts.
Structural Determinants of the Interactions Between Influenza A Virus Matrix Protein M1 and Lipid Membranes
Authors: Höfer C.T. , Di Lella S. , Dahmani I. , Jungnick N. , Bordag N. , Bobone S. , Huang Q. , Keller S. , Herrmann A. , Chiantia S. 
Published: July 2018

ABSTRACTInfluenza A virus is a pathogen responsible for severe seasonal epidemics threatening human and animal populations every year. One of the ten proteins encoded by the viral genome, the matrix protein M1, is abundantly produced in infected cells and plays a structural role in determining the morphology of the virus. During assembly of new viral particles, M1 is recruited to the host cell membrane where it associates with lipids and other viral proteins. The structure of M1 is only partially known. In particular, structural details of M1 interactions with the cellular plasma membrane as well as M1–protein interactions and multimerization have not been clarified, yet.In this work, we employed a set of complementary experimental and theoretical tools to tackle these issues. Using raster image correlation, surface plasmon resonance and circular dichroism spectroscopies, we quantified membrane association and oligomerization of full-length M1 and of different genetically engineered M1 constructs (i.e., N- and C-terminally truncated constructs and a mutant of the polybasic region, residues 95-105). Furthermore, we report novel information on structural changes in M1 occurring upon binding to membranes. Our experimental results are corroborated by an all-atom model of the full-length M1 protein bound to a negatively charged lipid bilayer.
Asymmetric effective connectivity between primate anterior cingulate and lateral prefrontal cortex revealed by electrical microstimulation
Authors: Nácher Verónica , Hassani Seyed Alireza , Womelsdorf Thilo 
Published: July 2018

AbstractThe anterior cingulate cortex (ACC) and lateral prefrontal cortex (IPFC) of the non-human primate show neural firing correlations and synchronize at theta and beta frequencies during the monitoring and shifting of attention. These functional interactions might be based on synaptic connectivity that is equally efficacious in both directions, but it might be that there are systematic asymmetries in connectivity consistent with reports of more effective inhibition within the ACC than IPFC, or with a preponderance of ACC projections synapsing onto inhibitory neurons in the IPFC. Here, we tested effective ACC-IPFC connectivity in awake monkeys and report systematic asymmetries in the temporal patterning and latencies of effective connectivity as measured using electrical microstimulation. We found that ACC stimulation triggered evoked fields (EFPs) were more likely to be multiphasic in the IPFC than in the reverse direction, with a large proportion of connections showing 2-4 inflection points resembling resonance in the 20-30 Hz beta frequency range. Stimulation of ACC → IPFC resulted, on average, in shorter-latency EFPs than IPFC → ACC. Overall, latencies and connectivity strength varied more than two-fold depending on the precise anterior-to-posterior location of the connections. These findings reveal systematic asymmetries in effective connectivity between ACC and IPFC in the awake non-human primate and document the spatial and temporal patchiness of effective synaptic connections. We speculate that measuring effective connectivity profiles will be essential for understanding how local synaptic efficacy and synaptic connectivity translates into functional neuronal interactions to support adaptive behaviors.
Facile real time detection of membrane colocalization of RAS superfamily GTPase proteins in living cells
Authors: Li Yao-Cheng , Wang Luke , Hayes Tikvah K. , Sutton Margie N. , Bast Robert C. , McCormick Frank , Der Channing J. , Wahl Geoffrey M. 
Published: July 2018

AbstractMembers of the RAS family of GTPases (KRAS4A, KRAS4B, HRAS, and NRAS) are the most frequently mutated oncogenes in human cancers. The CAAX motif in the C-terminal hypervariable region (HVR-CAAX domain) contains the cysteine residue that is critical for protein prenylation that enables RAS protein membrane localization, homodimer/oligomer formation, and activation of effector signaling and oncogenic activity. However, it remains unclear if RAS can interact with other prenylated proteins, and if so, how this impacts RAS function. Here we use a newly developed quantifiable Recombinase enhanced Bimolecular Luciferase Complementation strategy (ReBiL2.0) to investigate some of the requirements for RAS superfamily small GTPase protein interactions, and whether this requires cell membrane localization. ReBiL enables such analyses to be done at physiologic expression levels in living cells. Our results confirm that the C-terminal prenylated HVR-CAAX domain is sufficient to direct KRAS and heterologous proteins to colocalize in the cell membrane. We discovered that KRAS also colocalizes with a subset of small GTPase superfamily members including RAC1, RAC2 and DIRAS3 in a prenylation-dependent manner. KRAS colocalization or co-clustering with heterologous proteins can impact KRAS downstream signaling. ReBiL2.0 thus provides a rapid, simple and straightforward method to identify and characterize the colocalization of membrane-associated proteins and to discover agonists and antagonists thereof.
Bullous pemphigoid with hyperkeratosis and palmoplantar keratoderma: Three cases
Authors: Fania Luca , Didona Dario , Pacifico Valeria , Mariotti Feliciana , De Luca Naomi , Abeni Damiano , Mazzanti Cinzia , Di Zenzo Giovanni , Didona Biagio 
Published: July 2018

AbstractThe clinical features of bullous pemphigoid are extremely polymorphous. Several atypical forms of bullous pemphigoid have been described, and the diagnosis critically relies on immunopathological findings. We describe three bullous pemphigoid patients characterized by palmoplantar keratoderma, diffused hyperkeratotic cutaneous lesions and extremely high levels of immunoglobulin E serum. The diagnosis of bullous pemphigoid should be taken into account in patients presenting diffused hyperkeratotic cutaneous lesions and palmoplantar keratoderma, even in the absence of blisters. Alteration of the keratinization process, that could occur in patients with genetic mutations in desmosomal and hemidesmosomal genes, may also be due to circulating autoantibodies against hemidesmosomal proteins in these bullous pemphigoid patients.
Contribution of local rarity and climatic suitability to local extinction and colonization varies with species traits
Authors: White Hannah J. , Montgomery Ian W. , Lennon Jack J. 
Published: July 2018

AbstractChanges in species distributions through local extinction and colonization events are a major consequence of climate change. The mechanisms underlying these processes, however, are yet to be fully understood.We investigate the effects of climatic suitability and local rarity on local extinction and colonization of British birds. We test the hypothesis that local extinction and colonization on decadal scales are driven by both climatic suitability and the prevalence of the species within an area and that the balance between these two is affected by species traits.We use spatially explicit conditional autoregressive models to determine the effect size of local rarity and climatic suitability (extracted from climate envelope models) on local extinction and colonization events. We then use phylogenetically constrained, generalized least‐square models to estimate the association of extinction and colonization predictors with body mass, clutch size and national range of each species.Both local rarity and climatic suitability of an area contributed to local extinctions and colonizations, but the importance of these predictors varied between species. This interspecific variation was explained, in part, by species traits, in particular national range, which influenced the importance of local rarity and climatic suitability to both local extinction and colonization.These results further our knowledge of the mechanisms underlying changes in species occupancy due to climate change. This can inform predictive models as well as contribute to more focussed avian conservation efforts.
Covalent Whey Protein–Rosmarinic Acid Interactions: A Comparison of Alkaline and Enzymatic Modifications on Physicochemical, Antioxidative, and Antibacterial Properties
Authors: Ali Mostafa , Keppler Julia K. , Coenye Tom , Schwarz Karin 
Published: July 2018

AbstractThe covalent interactions between whey protein isolate (WPI) and rosmarinic acid (RosA) at two different conditions, alkaline (pH 9) and enzymatic (in the presence of tyrosinase, PPO), at room temperature with free atmospheric air were studied. The conjugates formed between WPI and RosA were characterized in terms of their physicochemical and functional properties. The changes in protein structure were analyzed by intrinsic fluorescence and binding of 8‐anilino‐1‐naphthalenesulfonic acid. The findings show that the covalent interactions caused a decrease in free amino and thiol groups and tryptophan content at both conditions. The decrease at enzymatic conditions was lower than at alkaline conditions. In addition, modified WPI at alkaline conditions exhibited higher antioxidative capacity compared to the modification at enzymatic conditions. However, WPI modified at enzymatic condition showed mild antimicrobial activity against Staphylococcus aureus LMG 10147 and MU50 compared to WPI modified at alkaline conditions and unmodified WPI (control). The modified WPI can be used as multifunctional ingredient into various food products with an additional health promoting effect of the bound phenolic compounds.
Risk factors for intracranial hemorrhage during vitamin K antagonist therapy in patients with nonvalvular atrial fibrillation: A case‐control study
Authors: Zanella Luca , Zoppellaro Giacomo , Marigo Lucia , Denas Gentian , Padayattil Jose Seena , Pengo Vittorio 
Published: July 2018

SummaryBackgroundIntracranial hemorrhage (ICH) is the most fearful side effect of oral anticoagulant therapy. It is still unclear which risk factor is involved in ICH during vitamin K antagonists (VKAs) treatment and if commonly used bleeding risk scores are able to predict ICH.PurposeSearch for individual risk factors and bleeding risk scores (HAS‐BLED, ATRIA and ORBIT) associated with ICHs in patients with atrial fibrillation treated with VKAs.MethodsThis is a retrospective case‐control study in a single Thrombosis Center. During a 7‐year period, patients with nonvalvular atrial fibrillation (NVAF) who developed ICH during VKAs were identified as cases. Four control patients matched for gender, age and length of VKAs were assigned to each case. The association between considered risk factors and ICHs was evaluated using a linear logistic regression method and expressed as odds ratio. Receiver operator characteristic (ROC) curves to assess the predictive ability of bleeding risk scores HAS‐BLED, ATRIA and ORBIT were also evaluated.ResultsFifty‐one cases of ICH, most of whom were 80 years of age or older (72.5%), were retrieved from the Thrombosis Center's database. Compared to 204 controls, no individual risk factors were associated with ICH. Poor ability to predict ICH was also found using ROC curves (C‐statistic for HAS‐BLED, ATRIA, and ORBIT were 0.55, 0.53 and 0.54, respectively).ConclusionsICHs during VKA therapy preferentially occur in very elderly patients. The risk of ICH is not predicted by the commonly used risk scores.
Say‐on‐pay judgements: the two‐strikes rule and the pay‐performance link
Authors: Liang Yimeng , Moroney Robyn , Rankin Michaela 
Published: July 2018

AbstractWe undertake an experiment to explore shareholder voting behaviour when the pay‐performance link is weak or strong; and when there has (has not) been a first strike in the preceding year. We find shareholders are more supportive of a remuneration package evidencing a strong pay‐performance link than a weak link. Further, shareholders are less supportive of a remuneration package when there has been a first strike in the preceding year than when there has not been a first strike. Importantly, we find that a first strike reduces the effect of the pay‐performance link on voting intentions.
Return windows and the value relevance of earnings
Authors: He Wen , Tan Hwee Cheng , Wong Leon 
Published: July 2018

AbstractResearch on the value relevance of annual earnings commonly accumulate stock returns over a 12‐month period starting from the fourth month of the fiscal year, resulting in a mismatch between the return window and the earnings period (i.e. the fiscal year). By comparing this return window with alternative windows, we show that the mismatch produces a downward bias in the estimated R2 from the regression of stock returns on earnings, especially for firms that announce earnings early. Our results also show that both profits and losses are more value relevant when announced earlier, supporting regulatory calls for timely disclosure.
Negative effects of an invasive grass, but not of native grasses, on plant species richness along a cover gradient
Authors: Dresseno André L. P. , Guido Anaclara , Balogianni Vasiliki , Overbeck Gerhard E. 
Published: July 2018

AbstractImpacts of invasive plants on plant communities are not universal, and effects may differ depending on the life form of the invading species. At three sites in the Brazilian Pampa region, we assessed the effects of invasion by Eragrostis plana Nees, considered to be the most problematic invasive plant in South Brazilian grasslands, on local plant communities. Specifically, we evaluated effects on species richness, community evenness and richness of principal functional groups along an invasion gradient. Based on plant community data, we also evaluated the effects of dominant native species on the same plant community features, thus being able to assess the relative impacts of an invasive species compared to abundant native species. Eragrostis plana invasion reduced total plant richness, with some distinct effects regarding plant functional groups, and differently from other coexisting native species that did not show the same effects even when of high abundance. Grasses were the most affected plant group when E. plana cover increased, consistent with the limiting similarity hypothesis. Overall, our results indicate clear negative effects of this invasive plant on the grassland communities. Comparing the effects of an invasive species to those of coexisting natives is crucial for disentangling the real impact of an invader. Our results demonstrate that effects are consequence of species identity, and not only of high abundances.
Interactive effects of local and landscape factors on farmland carabids
Authors: Fusser Moritz S. , Holland John M. , Jeanneret Philippe , Pfister Sonja C. , Entling Martin H. , Schirmel Jens 
Published: July 2018

AbstractAs a result of migration and spillover from noncrop habitats, predacious insects in agricultural fields respond locally to adjacent field margins and on a larger spatial scale to habitats in the surrounding landscape. However, the relative importance of local and landscape effects and their possible interactions have rarely been studied.
We studied carabids in 18 pumpkin fields bordered by different field margins, along a gradient from simple to structural rich landscapes. Carabids were caught in pitfall traps along transects from the adjoining semi‐natural habitat towards the field centre.
Although estimated species richness generally increased towards the field edges, carabid abundance increased towards adjacent woody margins and other crop fields. By contrast, abundance decreased towards adjacent herbaceous margins. Estimated carabid species richness in organically managed fields increased with increasing landscape heterogeneity, whereas this effect was absent in conventional fields. However, estimated species richness did not differ between organic and conventional fields.
The differential response of carabid abundance to distance from the field edge in accordance with the type of field margin may explain the variability of patterns reported in the literature. The results of the present study show that both local and landscape parameters must be taken into account to promote carabids as natural enemies of crop pests.
Narcissism and Political Orientations
Authors: Hatemi Peter K. , Fazekas Zoltán 
Published: July 2018

AbstractThe connections between narcissism and political orientations have been theorized by scholars and increasingly evoked by political parties, politicians, public intellectuals, and the media. Yet surprisingly little research has been undertaken to empirically asses the veracity of these claims. We address this lacuna by identifying the relationship between narcissism, political ideologies, and partisanship in a nationally representative sample taken days before the 2016 U.S. presidential election. Overall, we find those on the left and right are equally narcissistic. However, liberals and conservatives differ in which dimensions drive their narcissism. Specifically, we find that the entitlement facet of narcissism is uniformly related to more conservative positions, whereas exhibitionism is related to more liberal values, including political party identification. Narcissism, as a complex multidimensional construct, has an important role in understanding political ideology.