bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic addiction to high 26S proteasome levels
Authors: Tsvetkov Peter , Adler Julia , Myers Nadav , Biran Assaf , Reuven Nina , Shaul Yosef 
Published: October 2017

AbstractProteasomes are large intracellular complexes responsible for the degradation of cellular proteins. The altered protein homeostasis of cancer cells results in increased dependency on proteasome function. There are several different proteasome complexes that may be assembled in cells, with the 20S catalytic core common to them all. 20S proteasomes can function in isolation, or as part of larger complexes (26S) with regulatory particles (RP) such as the 19S that is needed for the targeting and processing of ubiquitinated substrates. Proteasome inhibitors target the catalytic barrel (20S) and thus this inhibition does not allow the deconvolution of the distinct roles of 20S vs. 26S proteasomes in cancer progression. We examined the degree of dependency of cancer cells specifically to the level of the 26S proteasome complex. We found that oncogenic transformation of human and mouse immortalized cells with mutant Ras induced a strong increase in the translation of the 26S proteasome subunits, giving rise to high 26S complex levels. We show that depletion of a single subunit of the 19S RP was sufficient to significantly reduce the 26S proteasome level and lower the cellular 26S/20S ratio. We further demonstrate that the accumulated 26S proteasome was essential for the viability of the transformed cells. Moreover, the viability of 20 different cancer cell lines, but not normal human fibroblasts, was severely compromised upon specific 26S proteasome suppression regardless of their p53 status. Suppression of 26S activated the UPR and Caspase-3, which at least partially explains the cell-killing effect. Morphologically, suppression of the 26S proteasome resulted in cytoplasm shrinkage and nuclear deformation. Thus, the tumor cell-specific addiction to high 26S proteasome levels sets the stage for future strategies in cancer therapy.
The Bio::Phylo libraries for phylogenetic data analysis, version 2.0
Authors: Vos Rutger A. , Hettling Hannes 
Published: October 2017

AbstractMotivationPhylogenetic analysis is a broad and expanding field that requires versatile programming toolkits to manage the various data types, file formats, and needs for scalability, simulation, visualization, and data exploration.ResultsWe present version 2.0 of the Bio::Phylo libraries for phylogenetic data analysis. This new release represents a rewrite of the architecture, allowing for extensions that improve speed and persistence, as well as increased functionality in terms of analysis, data reading and writing, and visualization.AvailabilityThe package is released as open source software under the same terms as Perl itself and available from the comprehensive Perl archive network as well as directly from the source code repository.Contactrutger.vos@naturalis.nlSupplementary informationSupplementary data are available asdoi:10.5281/zenodo.1039210
Blue light is a universal tactic signal forEscherichia coli
Authors: Perlova Tatyana , Gruebele Martin , Chemla Yann R. 
Published: October 2017

AbstractBlue light has been shown to elicit a tumbling response inE. coli, a non-phototrophic bacterium. The exact mechanism of this phototactic response is still unknown, and its biological significance remains unclear. Here, we quantify phototaxis inE. coliby analyzing single-cell trajectories in populations of free-swimming bacteria before and after light exposure. Bacterial strains expressing only one type of chemoreceptor reveal that all fiveE. colireceptors - Aer, Tar, Tsr, Tap and Trg - are capable of mediating a response to light. In particular, light exposure elicits a running response in Tap-only strain, the opposite of the tumbling response observed for all other strains. Light therefore emerges as a universal stimulus for allE. colichemoreceptors. We also show that blue light exposure causes a reversible decrease in swimming velocity, a proxy for proton motive force. We hypothesize that rather than sensing light directly, chemoreceptors sense light-induced perturbations in proton motive force.ImportanceOur findings provide new insights on the mechanism ofE. coliphototaxis, showing that all five chemoreceptor types respond to light and that their interactions play an important role in cell behavior. Our results also open up new avenues for examining and manipulatingE. colitaxis. Since light is a universal stimulus, it may provide a way to quantify interactions between different types of receptors. Since light is easier to control spatially and temporally than chemicals, it may be used to study swimming behavior in complex environments. Since phototaxis can cause migration ofE. colibacteria in light gradients, light may be used to control bacterial density for studying density-dependent processes in bacteria.
Protective role of the vulture facial and gut microbiomes aid adaptation to scavenging
Authors: Mendoza M. Lisandra Zepeda , Graves Gary R. , Roggenbuck Michael , Vargas Karla Manzano , Hansen Lars Hestbjerg , Brunak Søren , Gilbert M. Thomas P. , Sicheritz-Pontén Thomas 
Published: October 2017

AbstractBackgroundVultures have adapted the remarkable ability to feed on carcasses that may contain microorganisms that would be pathogenic to most other animals. The holobiont concept suggests that the genetic basis of such adaptation may not only lie within their genomes, but additionally in their associated microbes. To explore this, we generated shotgun DNA sequencing datasets of the facial and gut microbiomes from the black and turkey vultures. We characterizedi) the functional potential and taxonomic diversity of their microbiomes,ii) the potential pathogenic challenges they face, and iii) elements in the microbiome that could play a protective role to the vulture’s face and gut.ResultsWe found elements involved in diseases, such as periodontitis and pneumonia (more abundant in the face), and gas gangrene and food poisoning (more abundant in the gut). Interestingly, we found taxa and functions with potential for playing health beneficial roles, such as antilisterial bacteria in the gut, and genes for the production of antiparasites and antiinsectisides in the face. Based on the identified phages, we suggest that phages aid in the control, and possibly elimination as in phage therapy, of microbes reported as pathogenic to a variety of species. Interestingly, we also identifiedAdineta vagain the gut, an invertebrate that feeds on dead bacteria and protozoans, suggesting a defensive predatory mechanism. Finally, we suggest a colonization resistance role though biofilm formation played byFusobacteriaandClostridiain the gut.ConclusionsOur results highlight the importance of complementing genomic analyses with metagenomics in order to obtain a clearer understanding of the host-microbial alliance and show the importance of microbiome-mediated health protection for adaptation to extreme diets, such as scavenging.
Interplay between folding and binding modulates protein sequences, structures, functions and regulation
Authors: Mészáros Bálint , Dobson László , Fichó Erzsébet , Tusnády Gábor E. , Dosztányi Zsuzsanna , Simon István 
Published: October 2017

SummaryIntrinsically Disordered Proteins (IDPs) fulfill critical biological roles without having the potential to fold on their own. While lacking inherent structure, the majority of IDPs do reach a folded state via interaction with a protein partner, presenting a deep entanglement of the folding and binding process. Protein disorder has been recognized as a major determinant in several properties of proteins; yet the way the binding process is reflected in these features in general lacks this detail of description. Recent advances in database development enabled us to identify three basic scenarios of the interplay between folding and binding in unprecedented detail. These scenarios have fundamentally different properties in terms of protein sequence, structure, function and regulation, depending on the structural properties of the interacting partners. Strikingly, the existence of a binding partner and its structural properties influence all analyzed properties of proteins to the same extent as the divide between inherent order or disorder. The appreciation of this interplay between folding and binding is the basis for the successful charting of unknown territories in the protein interactome, the understanding of how different binding modes assemble regulatory networks, and the development of future pharmaceutical applications.
Pharaoh ant colonies dynamically regulate colony demography by culling young queen and male-destined larvae
Authors: Warner Michael R. , Lipponen Jessica , Linksvayer Timothy A. 
Published: October 2017

AbstractThe success of social insect colonies is dependent upon efficient and dynamic allocation of resources to alternate queen and worker castes. The developmental and molecular mechanisms regulating the caste fate of individual larvae in response to environmental cues have been the focus of intense study. However, the mechanisms regulating colony-level resource allocation into alternate castes (i.e. caste allocation ratios) are less well studied. Here, we systematically manipulate colony demography to elucidate the social regulatory mechanisms of caste allocation in the antMonomorium pharaonis. We find that differences in caste allocation result from differences in timing and efficiency of culling of very young reproductive-destined larvae, which are always present in colonies. Based on our results, we develop a conceptual model depicting how colonies integrate numerous individual-level caste determination decisions to regulate colony-level caste allocation. We propose that adult workers make decisions about culling larvae based on the ratio of the number of workers to the number of eggs contained in colonies, likely signalled by pheromone present on eggs. This strategy is a bet-hedging strategy which enables the dynamic alteration of colony demography in response to internal and external conditions. The strategy is likely key to the ability ofM. pharaonisand similar ants to thrive in disturbed habitats and to become widespread invasive species.Significance StatementThe defining feature of social insect societies is the presence of alternate queen (reproductive) and worker (non-reproductive) castes of individuals. The fitness of social insect colonies is dependent upon efficient allocation of resources to alternate castes, particularly in the case of highly polygynous (multi-queen) societies. However, the mechanisms by which such societies regulate caste allocation are largely unknown. In this study, we show that colonies manipulate their production of queens (and also males) versus workers according to the present density of eggs in the colony, which serves as a reliable indicator of queens’ fertility. Provided egg density is high, colonies kill queen-and male-destined larvae; when egg density falls, colonies begin to rear queens and males. This flexible resource allocation strategy is key to the ability of highly polygynous species to thrive in marginal (often human-associated) habitats.
A longitudinal model of human neuronal differentiation for functional investigation of schizophrenia polygenic risk
Authors: Ori Anil P.S. , Bot Merel H.M. , Molenhuis Remco T. , Olde Loohuis Loes M. , Ophoff Roel A. 
Published: October 2017

AbstractThere is a pressing need for in vitro experimental systems that allow for interrogation of polygenic psychiatric disease risk to study the underlying biological mechanisms. We developed an analytical framework that integrates genome-wide disease risk from GWAS with longitudinal in vitro gene expression profiles of human neuronal differentiation. We demonstrate that the cumulative impact of risk loci of specific psychiatric disorders is significantly associated with genes that are differentially expressed across neuronal differentiation. We find significant evidence for schizophrenia, which is driven by a longitudinal synaptic gene cluster that is upregulated during differentiation. Our findings reveal that in vitro neuronal differentiation can be used to translate the polygenic architecture of schizophrenia to biologically relevant pathways that can be modeled in an experimental system. Overall, this work emphasizes the use of longitudinal in vitro transcriptomic signatures as a cellular readout and the application to the genetics of complex traits.
Everything community? Destructive processes in communities of crowdsourcing competitions
Authors: Faullant Rita , Dolfus Guido 
Published: October 2017

PurposeVirtual crowdsourcing initiatives, and in particular crowdsourcing competitions, have become a promising means of harnessing users’ creativity to help corporate innovation. To date, research has tended to focus on the outcome of the competition, i.e. on the creative solution. There is, however, a lack of understanding in such crowdsourcing environments of the creative process itself and the influence of social interaction on the platform during this process. The paper aims to discuss these issues.Design/methodology/approachThe authors conducted a series of qualitative interviews with participants from a major European crowdsourcing platform. The platform acts as an intermediary between companies and firms, and has launched more than 370 idea competitions.FindingsThe results suggest that there are not only positive interactions going on between participants. Below the surface, there also appear destructive processes provoked by the fierce competition among the contestants for prizes and a position in the Top Innovator lists. Such destructive behavior includes bullying of successful contestants, excessive use of like-functions among befriended contestants, and mutual donation of prize money among in-group members.Practical implicationsNegative social interaction among contestants of crowdsourcing communities can potentially threaten the platform provider’s business model. Managers of crowdsourcing platforms should engage in the development of strong social norms explicitly disapproving destructive behavior.Originality/valueThis study is the first to investigate in detail the phase of idea generation on crowdsourcing platforms, and the nature and impact of social interactions among contestants.
Financial Flexibility and Manager–Shareholder Conflict: Evidence from REITs
Authors: Riddiough Timothy , Steiner Eva 
Published: October 2017

AbstractUsing equity Real Estate Investment Trust data, we show empirically that the use of unsecured debt, which contains standardized covenants that place limits on total leverage and the use of secured debt, is associated with lower leverage outcomes. We then show that firm value is sensitive to leverage levels, where lower leverage is associated with higher firm value. In the presence of weak managerial governance, our results suggest that unsecured debt covenants function as a managerial commitment device that preserves the firm's debt capacity to enhance financial flexibility.
Changing Racial/Ethnic Disparities in Heavy Drinking Trajectories Through Young Adulthood: A Comparative Cohort Study
Authors: Williams Edwina , Mulia Nina , Karriker‐Jaffe Katherine J. , Lui Camillia K. 
Published: October 2017

BackgroundThere is evidence of racial/ethnic differences in the age at which young adults age out of heavy drinking. Some studies have found Black and Hispanic drinkers engage in more frequent heavy drinking than White people beyond adulthood. Yet, the alcohol‐related disparities literature has produced contradictory findings on whether an age‐crossover effect is evident among racial/ethnic groups; that is, whether racial/ethnic minorities' drinking levels or trajectories are lower than White people at young ages but later exceed (or crossover) those of White people. This study extends this scant literature by assessing whether racial/ethnic differences in heavy drinking have changed over time (possibly accounting for mixed findings from prior research); and tests for an age‐crossover effect in heavy drinking using longitudinal data from 2 cohorts born 20 years apart.MethodsData are from the 1979 (n = 10,963) and 1997 (n = 8,852) cohorts of the National Longitudinal Survey of Youth (NLSY). Generalized estimating equations were used to model trajectories of heavy drinking frequency from ages 17 to 31. Racial/ethnic differences were determined using sex‐stratified models and 3‐way interactions of race/ethnicity with age, age‐squared, and cohort.ResultsRacial/ethnic differences in heavy drinking trajectories have changed over time in men and women. In the older NLSY cohort, Hispanic men and Black women surpassed White men's and women's heavy drinking frequency by age 31. This crossover was absent in the younger cohort, where trajectories of all racial–sex groups converged by age 31. Normative trajectories have changed in Hispanics and White people of both sexes, with a delay in age of peak frequency, and greater levels of heavy drinking in the younger cohort of women.ConclusionsChanges in heavy drinking trajectories over time suggest the need for targeted interventions during young adulthood. While disparities in young adult heavy drinking were no longer apparent in the more recent birth cohort, continued monitoring is important.
Dynamic intra‐epidermal bodies (IEBs) in koi epidermis
Authors: DePasquale Joseph A. 
Published: October 2017

AbstractKoi scale epidermis contains large intra‐epidermal bodies (IEBs). IEBs are dynamic and circular structures that form in low frequency within the epidermis. During formation, an IEB pulls down the microridge‐laden surface layer, which takes on a creased or wrinkled appearance. After the IEB constricts, the microridge layer unfolds to its original state. The newly described IEBs are distinctly different from the recently reported apical rings which are situated on the surface of individual epidermal cells. While apical rings are directly exposed to the external environment where sampling can occur, IEBs appear to reflect intra‐epidermal events such as sequestering of dead cell remnants.
Predictive value of α‐amylase in tracheal aspirates for ventilator‐associated pneumonia in elderly patients
Authors: Qu Ge‐Ping , Fang Xiang‐Qun , Xu Ya‐Ping , Shi Min , Wang Yang , Gong Mei‐Liang , Fang Hao‐Ming 
Published: October 2017

AbstractObjectiveThis study aims to investigate the correlation between α‐amylase in tracheal aspirates and risk factors of aspiration, as well as ventilator‐associated pneumonia (VAP), in elderly patients undergoing mechanical ventilation and explore the clinical value of α‐amylase for predicting VAP.MethodsTracheal aspirates were collected from elderly patients within 2 weeks after tracheal intubation in mechanical ventilation, and α‐amylase was detected. Patients were grouped according to the presence of VAP. The correlation between α‐amylase and risk factors of aspiration before intubation, as well as VAP, were analyzed.ResultsThe sample of this study comprised 147 patients. The average age of these patients was 86.9 years. The incidence of VAP was 21% during the study period. Tracheal aspirate α‐amylase level increased with the increase in the number of risk factors for aspiration before intubation, α‐amylase level was significantly higher in the VAP group than in the non‐VAP group, the area under the receiver operating characteristic curve (ROC) of the diagnostic value of α‐amylase for VAP was 0.813 (95% CI: 0.721‐0.896), threshold value was 4,681.5 U/L, sensitivity was 0.801 and specificity was 0.793. Logistic multivariate analysis revealed the following risk factors for VAP: a number of risk factors before intubation of ≥3, a Glasgow score of <8 points, the absence of continuous aspiration of subglottic secretion and a tracheal aspirate α‐amylase level of >4681.5 U/L.ConclusionTracheal aspirate α‐amylase can serve as a biomarker for predicting VAP in elderly patients undergoing mechanical ventilation.
Folliculotropic mycosis fungoides presenting with a solitary lesion: Clinicopathological features and long‐term follow‐up data in a series of 9 cases
Authors: van Santen Suzanne , Jansen Patty M. , Vermeer Maarten H. , Willemze Rein 
Published: October 2017

BackgroundFolliculotropic mycosis fungoides (FMF) is a distinct variant of mycosis fungoides, which in rare cases may present with a solitary lesion. Reported cases describe an excellent prognosis, but follow up was generally short. Herein, clinicopathologic characteristics, long‐term follow‐up data of 9 patients with solitary FMF are presented and differential diagnosis is discussed.MethodsFrom a cohort of 203 patients with FMF, 9 cases with solitary FMF were selected. Clinical data and histological sections obtained at diagnosis and during follow up were reviewed.ResultsSkin lesions, in all patients located on the head, went into complete remission after treatment with radiotherapy (6 cases) or topical steroids (1 case) or regressed spontaneously (2 cases). After a median follow up of 89 months (range 51‐203 months), 5 patients were still in complete remission, 2 patients had developed multiple skin relapses, while 2 patients had progressed to extracutaneous and fatal disease. Histologically, all patients showed marked folliculotropism, associated with syringotropism (4 cases) and/or follicular mucinosis (5 cases). Large‐cell transformation was observed at presentation (2 cases) and during follow‐up (3 cases).ConclusionsLong‐term follow‐up data indicate that patients with solitary FMF do not always have an indolent clinical course and therefore require long‐term follow up.
High calcium enhances the expression of double‐stranded RNA sensors and antiviral activity in epidermal keratinocytes
Authors: Yamamura Yuriko , Morizane Shin , Yamamoto Takenobu , Wada Jun , Iwatsuki Keiji 
Published: October 2017

AbstractDouble‐stranded RNA (dsRNA) sensors including TLR3, MDA5 and RIG‐I are expressed in epidermal keratinocytes and play an important immunological role by enhancing various innate and adaptive immune responses. Although the role of elevated extracellular calcium concentration in keratinocyte differentiation is well understood, the effect of high calcium on dsRNA sensors is not well studied. We investigated alterations in dsRNA sensor expression and antiviral activity induced by a high extracellular concentration of calcium in epidermal keratinocytes. Normal human epidermal keratinocytes (NHEKs) were stimulated with high calcium and/or synthetic dsRNA, poly (I:C). TLR3, IFIH1 (MDA5) and DDX58 (RIG‐I) expression were measured via qPCR, and IFN‐β and human beta‐defensin 2 (HBD2) levels were measured using ELISA. TLR3 localization was evaluated with immunocytofluorescence. Antiviral activity was quantified with virus plaque assays using herpes simplex virus type 1 (HSV‐1). High calcium significantly upregulated mRNA expression of TLR3, IFIH1 and DDX58 in NHEKs. In addition, high calcium significantly enhanced poly (I:C)‐induced anti‐HSV‐1 activity in NHEKs. The antiviral molecule HBD2 but not IFN‐β induction by poly (I:C) was enhanced by high calcium. Our findings indicate that high levels of extracellular calcium enhance the expression of dsRNA sensors and augment antiviral activity in epidermal keratinocytes.