bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociation of dorso-lateral and dorso-medial prefrontal cortex contributions to familiarity and recollective processes in primates
Authors: Wu Zhemeng , Kavanova Martina , Hickman Lydia , Lin Fiona , Boschin Erica , Galeazzi Juan M. , Verhagen Lennart , Buckley Mark J. 
Published: January 2020

AbstractAccording to dual-process theories, recognition memory draws upon both familiarity and recollection. It remains unclear how primate prefrontal cortex (PFC) contributes to familiarity and recollection processes but frequency-specific neuronal activities are considered to play a key role. Here, non-human primate (NHP) electrophysiological local field potential (LFP) recordings first showed that a specific subregion of macaque PFC (i.e., dorsolateral PFC, dlPFC) was implicated in task performance at a specific frequency (i.e., increased beta power in the 10-15 Hz range observed in correct versus error trials) in a specific phase of a recognition memory task (i.e., during sample presentation). Then, to assess generalization to humans and causality we targeted left human dlPFC (BA 9/46) as well as left dorsomedial prefrontal cortex (BA 8/9) for comparison, and also vertex as a control, with transcranial magnetic stimulation at a frequency in the middle of the low-beta range observed in NHP (i.e. 12.5 Hz) and compared that to non-frequency-specific stimulation, and also to a no-stimulation control, during occasional sample presentations within a similar task. Hence we investigated hypotheses about the causal importance for human memory of a location-specific, frequency-specific, and task-epoch-specific intervention derived directly from the NHP electrophysiological observations. Using a dual-process signal detection (DPSD) model based on analysing receiver operating characteristics (ROC) curves, we showed beta-frequency TMS caused decreased recollection when targeted to human dlPFC, but enhanced familiarity when targeted to dorsomedial prefrontal cortex. Non-frequency-specific patterns of stimulation to all sites, and beta-frequency stimulation to vertex, were all without behavioural effect. This study provides causal evidence that PFC-mediated contributions to object recognition memory are modulated by beta-frequency activity; more broadly it provides translational evidence bridging NHPs and humans by emphasizing functional roles of beta-frequency activity in homologous brain regions in recognition memory.Highlightslow beta power in NHP dlPFC during stimulus encoding was related to behaviourhuman rTMS study used parameters derived from NHP observations to test causalitylow beta rTMS to human dlPFC, but not dmPFC, impairs recollectionlow beta rTMS to human dmPFC, but not dlPFC, enhances familiarityprovides cross-species validation of prefrontal beta power to primate recognition
A hybrid spectral library combining DIA-MS data and a targeted virtual library substantially deepens the proteome coverage
Authors: Lou Ronghui , Tang Pan , Ding Kang , Li Shanshan , Tian Cuiping , Li Yunxia , Zhao Suwen , Zhang Yaoyang , Shui Wenqing 
Published: January 2020

AbstractData-independent acquisition mass spectrometry (DIA-MS) is a rapidly evolving technique that enables relatively deep proteomic profiling with superior quantification reproducibility. DIA data mining predominantly relies on a spectral library of sufficient proteome coverage that, in most cases, is built on data-dependent acquisition-based analysis of the same sample. To expand the proteome coverage for a pre-determined protein family, we report herein on the construction of a hybrid spectral library that supplements a DIA experiment-derived library with a protein family-targeted virtual library predicted by deep learning. Leveraging this DIA hybrid library substantially deepens the coverage of three transmembrane protein families (G protein coupled receptors; ion channels; and transporters) in mouse brain tissues with increases in protein identification of 37-87%, and peptide identification of 58-161%. Moreover, of the 412 novel GPCR peptides exclusively identified with the DIA hybrid library strategy, 53.6% were validated as present in mouse brain tissues based on orthogonal experimental measurement.
Estrogen attenuates the growth of human papillomavirus positive epithelial cells
Authors: Bristol Molly L. , James Claire D. , Wang Xu , Fontan Christian T. , Morgan Iain M. 
Published: January 2020

AbstractHuman papillomaviruses (HPVs) are small, double-stranded DNA viruses that are significant risk factors in the development of cancer, and HPV accounts for approximately 5% of all worldwide cancers. Recent studies using data from The Cancer Genome Atlas (TCGA) have demonstrated that elevated levels of estrogen receptor alpha (ERα) are associated with improved survival in oropharyngeal cancers, and these elevated receptor levels were linked with human papillomavirus positive cancers (HPV+cancers). There has been a dramatic increase in HPV-related head and neck squamous cell carcinomas (HPV+HNSCCs) over the last two decades and therapeutic options for this ongoing health crisis are a priority; currently there are no anti-viral therapeutics available for combating HPV+cancers. During our own TGCA studies on head and neck cancer we had also discovered the overexpression of ERα in HPV+cancers. Here we demonstrate that 17β-estradiol (estrogen) attenuates the growth/cell viability of HPV+cancersin vitro, but not HPV negative cancer cells. In addition, N/Tert-1 cells (foreskin keratinocytes immortalized with hTERT) containing HPV16 have elevated levels of ERα and growth sensitivity following estrogen treatment when compared with parental N/Tert-1. Finally, we demonstrate that there are potentially two mechanisms contributing to the attenuation of HPV+ cell growth following estrogen treatment. First, estrogen represses the viral transcriptional long control region (LCR) downregulating early gene expression, including E6/E7. Second, expression of E6 and E7 by themselves sensitizes cells to estrogen. Overall our results support the recent proposal that estrogen could be exploited therapeutically for the treatment of HPV positive oral cancers.ImportanceHuman papillomaviruses cause around 5% of all human cancers, yet there are no specific anti-viral therapeutic approaches available for combating these cancers. These cancers are currently treated with standard chemo-radiation therapy (CRT). Specific anti-viral reagents are desperately required, particularly for HPV+HNSCC whose incidence is increasing and for which there are no diagnostic tools available for combating this disease. Using data from The Cancer Genome Atlas (TCGA) ourselves and others determined that the estrogen receptor α (ERα) is overexpressed in HPV+HNSCC, and that elevated levels are associated with an improved disease outcome. This has led to the proposal that estrogen treatment could be a novel therapeutic approach for combating HPV+cancers. Here we demonstrate that estrogen attenuates the growth of HPV+epithelial cells using multiple mechanisms, supporting the idea that estrogen has potential as a therapeutic agent for the treatment of HPV+HNSCC.
Risk prediction with office and ambulatory blood pressure using artificial intelligence
Authors: Guimarães Pedro , Keller Andreas , Böhm Michael , Lauder Lucas , Ayala José L. , Banegas José R. , de la Sierra Alejandro , Vinyoles Ernest , Gorostidi Manuel , Segura Julián , Ruiz-Hurtado Gema , Ruilope Luis M. , Mahfoud Felix 
Published: January 2020

AbstractBackgroundTo develop and validate a novel, machine learning-derived model for prediction of cardiovascular (CV) mortality risk using office (OBP) and ambulatory blood pressure (ABP), to compare its performance with existing risk scores, and to assess the possibility of predicting ABP phenotypes (i.e. white-coat, ambulatory and masked hypertension) utilizing clinical variables.MethodsUsing data from 63,910 patients enrolled in the Spanish ABP monitoring registry, machine-learning approaches (logistic regression, support vector machine, gradient boosted decision trees, and deep neural networks) and stepwise forward feature selection were used for the classification of the data.ResultsOver a median follow-up of 4.7 years, 3,808 deaths occurred from which 1,295 were from CV causes. The performance for all tested classifiers increased while adding up to 10 features and converged thereafter. For the prediction of CV mortality, deep neural networks yielded the highest clinical performance. The novel mortality prediction models using OBP (CV-MortalityOBP) and ABP (CV-MortalityABP) outperformed all other risk scores. The area under the curve (AUC) achieved by the novel approach, using OBP variables only, was already significantly higher when compared with the AUC of Framingham score (0.685 vs 0.659, p = 1.97×10−22), the SCORE (0.679 vs 0.613, p = 6.21×10−22), and ASCVD (0.722 vs 0.639, p = 8.03×10−30) risk score. However, prediction of CV mortality with ABP instead of OBP data led to a significant increase in AUC (0.781 vs 0.752, p = 1.73×10−42), accuracy, balanced accuracy and sensitivity. The sensitivity and specificity for detection of ambulatory, masked, and white-coat hypertension ranged between 0.653-0.661 and 0.573-0.651, respectively.ConclusionWe developed a novel risk calculator for CV death using artificial intelligence based on a large cohort of patients included in the Spanish ABP monitoring registry. The receiver operating characteristic curves for CV-MortalityOBP and CV-MortalityABP with deep neural networks models outperformed all other risk metrics. Prediction of CV mortality using ABP data led to a significant increase in performance metrics. The prediction of ambulatory phenotypes using clinical characteristics, including OBP, was limited.
Retrospective evaluation of a filtering trabeculotomy in comparison to conventional trabeculectomy byexact matching
Authors: Strzalkowska A. , Strzalkowski P. , Al Yousef Y. , Hillenkamp J. , Grehn F. , Loewen N. A. 
Published: January 2020

AbstractPurposeTo compare 2-year results of a filtering trabeculotomy (FTO) to conventional trabeculectomy (TE) in open-angle glaucoma by exact matching.Methods110 patients received an FTO and 86 a TE. FTO avoided the need for an iridectomy due to a preserved trabeculo-Descemet window anterior to the scleral flap. TE employed a trabecular block excision and iridectomy. Mitomycin C was used in both. FTO and TE were exact-matched by baseline intraocular pressure (IOP) and the number of glaucoma medications. Complete and qualified success (IOP ≤18 mmHg and IOP reduction ≥ 30%, with or without medication) were primary endpoints. IOP, visual acuity (BCVA), complications and intervention were secondary endpoints.Results44 FTO were exact-matched to 44 TE. The IOP baseline in both groups was 22.5±4.7 mmHg on 3±0.9 medications. At 24 months, complete success was reached by 59% in FTO and 66% in TE and qualified success by 59% in FTO and 71% in TE. In FTO, IOP was reduced to 12.4±4.3 mmHg at 12 months and 13.1±4.1 mmHg at 24 months. In TE, IOP was 11.3±2.2 mmHg at 12 months and 12.0±3.5 mmHg at 24 months. Medications could be reduced at 24 months to 0.6±1.3 in FTO and 0.2±0.5 in TE. There were no significant differences between the two groups in IOP, medications, complications or interventions at any point.ConclusionModifying aqueous flow through a limited trabeculotomy in FTO yielded clinical outcomes similar to traditional TE but allowed to avoid an iridectomy.
The impact and implications of vehicle collisions on the endangered and endemic Zanzibar red colobus (Piliocolobus kirkii)
Authors: Olgun Harry , Mohammed Mzee Khamis , Mzee Abbas Juma , Green M. E. Landry , Davenport Tim R. B. , Georgiev Alexander V. 
Published: January 2020

AbstractRoads can affect wildlife in a variety of negative ways. Studies of road ecology have mostly concentrated in the northern hemisphere despite the potentially greater impact on biodiversity that roads may have in tropical habitats. Here, we examine a 4-year opportunistic dataset (January 2016 – December 2019) on mammalian roadkill observed along a road intersecting Jozani-Chwaka Bay National Park, Unguja, Zanzibar. In particular, we assess the impact of collisions on the population of an endangered and endemic primate, the Zanzibar red colobus (Piliocolobus kirkii). Primates accounted for the majority of roadkill. Monthly rainfall variation was not associated with roadkill frequency for mammals and specifically for the Zanzibar red colobus. No single age-sex class of colobus was found dead more often than expected given their availability in the local population. The exact effect of roadkill on colobus populations in habitats fragmented by roads is unknown given the lack of accurate, long-term life history data for this species. However, the frequency of kills documented in this study suggests further mitigation measures may be important. Our data show that mortality from collisions with vehicles in some groups of colobus are comparable to rates of mortality experienced by other primate populations from natural predation. Unlike natural predators, however, vehicles are not ‘selective’ in their targeting of ‘prey’. The long-term implications of such a ‘predation regime’ on this species remain to be established.
The Deep(er) Roots of Eukaryotes and Akaryotes
Authors: Harish Ajith , Morrison David A. 
Published: January 2020

AbstractLocating the root-node of the “tree of life” (ToL) is one of the hardest problems in phylogenetics1. The root-node or the universal common ancestor (UCA) divides the descendants into organismal domains2. Two notable variants of the two-domains ToL (2D-ToL) have gained support recently3,4, though, Williams and colleagues (W&C)4claim that one is better supported than the other. Here, we argue that important aspects of estimating evolutionary relatedness and assessing phylogenetic signal in empirical data were overlooked4. We focus on phylogenetic character reconstructions necessary to describe the UCA or its closest descendants in the absence of reliable fossils. It is well-known that different character-types present different perspectives on evolutionary history that relate to different phylogenetic depths5–7. Which of the 2D-ToL2,4hypotheses is better supported depends on which kind of molecular features – protein-domains or their component amino-acids – are better for resolving the common ancestors (CA) at the roots of clades. In practice, this involves reconstructing character compositions of the ancestral nodes all the way back to the UCA2,3.
The fungal collaboration gradient dominates the root economics space in plants
Authors: Bergmann Joana , Weigelt Alexandra , van der Plas Fons , Laughlin Daniel C. , Kuyper Thom W. , Guerrero-Ramirez Nathaly , Valverde-Barrantes Oscar J. , Bruelheide Helge , Freschet Grégoire T. , Iversen Colleen M. , Kattge Jens , McCormack M. Luke , Meier Ina C. , Rillig Matthias C. , Roumet Catherine , Semchenko Marina , Sweeney Christopher J. , van Ruijven Jasper , York Larry M. , Mommer Liesje 
Published: January 2020

AbstractPlant economics run on carbon and nutrients instead of money. Leaf strategies aboveground span an economic spectrum from ‘live fast and die young’ to ‘slow and steady’, but the economy defined by root strategies belowground remains unclear. Here we take a holistic view of the belowground economy, and show that root-mycorrhizal collaboration can short circuit a one-dimensional economic spectrum, providing an entire space of economic possibilities. Root trait data from 1,781 species across the globe confirm a classical fast-slow ‘conservation’ gradient but show that most variation is explained by an orthogonal ‘collaboration’ gradient, ranging from ‘do-it-yourself’ resource uptake to ‘outsourcing’ of resource uptake to mycorrhizal fungi. This broadened ‘root economics space’ provides a solid foundation for predictive understanding of belowground responses to changing environmental conditions.One Sentence SummaryCollaboration broadens the ‘root economics space’ ranging from ‘do-it-yourself’ resource acquisition to ‘outsourcing’ to mycorrhizal partners.
Genetic population structure constrains local adaptation in sticklebacks
Authors: Kemppainen Petri , Li Zitong , Rastas Pasi , Löytynoja Ari , Fang Bohao , Yang Jing , Guo Baocheng , Shikano Takahito , Merilä Juha 
Published: January 2020

AbstractRepeated and independent adaptation to specific environmental conditions from standing genetic variation is common. However, if genetic variation is limited, the evolution of similar locally adapted traits may be restricted to genetically different and potentially less optimal solutions or prevented from happening altogether. Using a quantitative trait locus (QTL) mapping approach, we identified the genomic regions responsible for the repeated pelvic reduction (PR) in three crosses between nine-spined stickleback populations expressing full and reduced pelvic structures. In one cross, PR mapped to linkage group 7 (LG7) containing the genePitx1, known to control pelvic reduction also in the three-spined stickleback. In the two other crosses, PR was polygenic and attributed to ten novel QTL, of which 90% were unique to specific crosses. When screening the genomes from 27 different populations for deletions in thePitx1regulatory element, these were only found in the population in which PR mapped to LG7, even though the morphological data indicated large effect QTL for PR in several other populations as well. Consistent with the available theory and simulations parameterised on empirical data, we hypothesise that the observed variability in genetic architecture of PR is due to heterogeneity in the spatial distribution of standing genetic variation caused by >2x stronger population structuring among freshwater populations and >10x stronger genetic isolation by distance in the sea in nine-spined sticklebacks as compared to three-spined sticklebacks.
Invertebrate Community Associated with the Asexual Generation ofBassettia pallidaAshmead (Hymenoptera: Cynipidae)
Authors: Weinersmith Kelly L. , Forbes Andrew A. , Ward Anna K.G. , Brandão-Dias Pedro F. P. , Zhang Y. Miles , Egan Scott P. 
Published: January 2020

AbstractCynipid gall wasps play an important role in structuring oak invertebrate communities. Wasps in the Cynipini tribe typically lay their eggs in oaks (QuercusL.), and induce the formation of a “gall”, which is a tumor-like growth of plant material that surrounds the developing wasp. As the wasp develops, the cynipid and its gall are attacked by a diverse community of natural enemies, including parasitoids, hyperparasitoids, and inquilines. Determining what structures these species-rich natural enemy communities across cynipid gall wasp species is a major question in gall wasp biology. Additionally, gall wasps are ecosystem engineers, as the abandoned gall is used by other invertebrates. The gall-associated insect communities residing on live oaks (Quercus geminataSmall andQ. virginianaMill.) are emerging as a model system for answering ecological and evolutionary questions ranging from community ecology to the evolution of new species. Documenting the invertebrates associated with cynipids in this system will expand our understanding of the mechanisms influencing eco-evolutionary processes, record underexplored axes of biodiversity, and facilitate future work. Here, we present the community of natural enemies and other associates of the asexual generation of the crypt gall wasp,Bassettia pallidaAshmead. We compare the composition of this community to communities recently documented from two other cynipid gall wasps specializing on live oaks along the U.S. Gulf coast,Disholcaspis quercusvirensAshmead andBelonocnema treataeMayr.B. pallidaand their crypts support a diverse arthropod community, including over 25 parasitoids, inquilines, and other associated invertebrates spanning 5 orders and 16 families.
Late Holocene land vertebrate fauna from Cueva de los Nesofontes, Western Cuba: stratigraphy, last appearance dates, diversity and paleoecology
Authors: Orihuela Johanset , Pérez Orozco Leonel , Álvarez Licourt Jorge L. , Viera Muñoz Ricardo A. , Santana Barani Candido 
Published: January 2020

ABSTRACTHere we report a Late Holocene fossil-rich cave deposit from Cueva de los Nesofontes, Mayabeque Province, Cuba. The deposit’s formation and its fauna were studied through a multidisciplinary approach that included stable isotope analyses, radiocarbon chronology, stratigraphy, sedimentology, and taphonomy. Thousands of microvertebrate skeletal remains were recovered, representing a diverse land vertebrate fauna that included threatened and extinct species. The deposit is characterized by profuseNesophontesremains due to raptor predation. Previously unreported last appearance dates are provided for the extinct island-shrewNesophontes major, the batsArtibeus anthonyiandPhyllops vetus. Radiocarbon (14C AMS) age estimates between ∼1960 rcyr BP and the present were recovered. The presence of locally extinct species, including the endemic parakeetPsittacara eups, the flickerColaptescf.auratus/fernandinae, and the lipotyphlanSolenodon cubanussuggests that these species had broader distributions in the near past. Isotope analyses and faunal composition indicate the previous presence of diverse habitats, including palm grove savannas and mixed woodlands. Isotopes also provide insight into the habitat and coexistence of the extinct batArtibeus anthonyiand extantA. jamaicensis, the diet ofNesophontes major, and local paleoenvironmental conditions. Oxygen isotopes reveal an excursion suggestive of drier/colder local conditions between 660 and 770 AD. Our research further expands the understanding of Cuban Quaternary extinction episodes and provides data on the distribution and paleoecology of extinct taxa. It supports the conclusion that many Cuban extinct species survived well into the pre-Columbian late Holocene and retained wide distribution ranges until human colonization.
Multiplexed Single-cell Metabolic Profiles Organize the Spectrum of Cytotoxic Human T Cells
Authors: Hartmann Felix J. , Mrdjen Dunja , McCaffrey Erin , Glass David R. , Greenwald Noah F. , Bharadwaj Anusha , Khair Zumana , Baranski Alex , Baskar Reema , Angelo Michael , Bendall Sean C. 
Published: January 2020

SummaryCellular metabolism regulates immune cell activation, differentiation and effector functions to the extent that its perturbation can augment immune responses. However, the analytical technologies available to study cellular metabolism lack single-cell resolution, obscuring metabolic heterogeneity and its connection to immune phenotype and function. To that end, we utilized high-dimensional, antibody-based technologies to simultaneously quantify the single-cell metabolic regulome in combination with phenotypic identity. Mass cytometry (CyTOF)-based application of this approach to early human T cell activation enabled the comprehensive reconstruction of the coordinated metabolic remodeling of naïve CD8+T cells and aligned with conventional bulk assays for glycolysis and oxidative phosphorylation. Extending this analysis to a variety of tissue-resident immune cells revealed tissue-restricted metabolic states of human cytotoxic T cells, including metabolically repressed subsets that expressed CD39 and PD1 and that were enriched in colorectal carcinoma versus healthy adjacent tissue. Finally, combining this approach with multiplexed ion beam imaging by time-of-flight (MIBI-TOF) demonstrated the existence of spatially enriched metabolic neighborhoods, independent of cell identity and additionally revealed exclusion of metabolically repressed cytotoxic T cell states from the tumor-immune boundary in human colorectal carcinoma. Overall, we provide an approach that permits the robust approximation of metabolic states in individual cells along with multimodal analysis of cell identity and functional characteristics that can be applied to human clinical samples to study cellular metabolism how it may be perturbed to affect immunological outcomes.