bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity and Reliability of the Frontotemporal Dementia Rating Scale (FTD-FRS) for the Progression and Staging of Dementia in Brazilian Patients
Authors: Lima-Silva Thaís B. , Bahia Valéria S. , Cecchini Mário A. , Cassimiro Luciana , Guimarães Henrique C. , Gambogi Leandro B. , Caramelli Paulo , Balthazar Márcio , Damasceno Benito , Brucki Sônia M.D. , de Souza Leonardo C. , Nitrini Ricardo , Mioshi Eneida , Yassuda Mônica S. 
Published: February 2018

Introduction:
Few studies on instruments for staging frontotemporal dementia (FTD) have been conducted.

Objective:
The objective of this study was to analyze the factor structure, internal consistency, reliability, and convergent validity of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS).

Methods:
A total of 97 individuals aged 40 years and above with >2 years’ education took part in the study, 31 patients diagnosed with behavioral variant FTD (bvFTD), 8 patients with primary progressive aphasia, 28 with Alzheimer disease, 8 with mild cognitive impairment, and a control group of 22 healthy subjects. The FTD-FRS was completed by family members or caregivers, and Neurologists completed the 8-item Clinical Dementia Rating for Frontotemporal Lobar Degeneration (CDR-FTLD) scale (6 original domains plus Language and Behavior). The Alzheimer disease and FTD patients had equivalent disease severity level.

Results:
The internal consistency of the FTD-FRS, estimated by Cronbach α, was 0.975 whereas test-retest reliability was 0.977. Scree plot and exploratory factor (Varimax rotation) analyses revealed the existence of 4 factors, with eigenvalues >1, which together explained 77.13% of the total variance with values of 1.28 to 17.52. The domains of the Brazilian version of the FTD-FRS scale correlated with the domains of the CDR-FTLD.

Conclusions:
The present study is the first to document the factorial structure of the FTD-FRS and its convergent validity with the CDR-FTLD. These tools are key to determine dementia severity in FTD. The Brazilian FTD-FRS demonstrated adequate psychometric properties for use in Brazil. This instrument may contribute to disease staging in FTD and may help to document intervention-related changes.
Integrative studies of cultural evolution: crossing disciplinary boundaries to produce new insights
Authors: Kolodny Oren , Feldman Marcus W. , Creanza Nicole 
Published: February 2018

Culture evolves according to dynamics on multiple temporal scales, from individuals' minute-by-minute behaviour to millennia of cultural accumulation that give rise to population-level differences. These dynamics act on a range of entities—including behavioural sequences, ideas and artefacts as well as individuals, populations and whole species—and involve mechanisms at multiple levels, from neurons in brains to inter-population interactions. Studying such complex phenomena requires an integration of perspectives from a diverse array of fields, as well as bridging gaps between traditionally disparate areas of study. In this article, which also serves as an introduction to the current special issue, we highlight some specific respects in which the study of cultural evolution has benefited and should continue to benefit from an integrative approach. We showcase a number of pioneering studies of cultural evolution that bring together numerous disciplines. These studies illustrate the value of perspectives from different fields for understanding cultural evolution, such as cognitive science and neuroanatomy, behavioural ecology, population dynamics, and evolutionary genetics. They also underscore the importance of understanding cultural processes when interpreting research about human genetics, neuroscience, behaviour and evolution.This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
The evolution of the capacity for language: the ecological context and adaptive value of a process of cognitive hijacking
Authors: Kolodny Oren , Edelman Shimon 
Published: February 2018

Language plays a pivotal role in the evolution of human culture, yet the evolution of the capacity for language—uniquely within the hominin lineage—remains little understood. Bringing together insights from cognitive psychology, neuroscience, archaeology and behavioural ecology, we hypothesize that this singular occurrence was triggered by exaptation, or ‘hijacking’, of existing cognitive mechanisms related to sequential processing and motor execution. Observed coupling of the communication system with circuits related to complex action planning and control supports this proposition, but the prehistoric ecological contexts in which this coupling may have occurred and its adaptive value remain elusive. Evolutionary reasoning rules out most existing hypotheses regarding the ecological context of language evolution, which focus on ultimate explanations and ignore proximate mechanisms. Coupling of communication and motor systems, although possible in a short period on evolutionary timescales, required a multi-stepped adaptive process, involving multiple genes and gene networks. We suggest that the behavioural context that exerted the selective pressure to drive these sequential adaptations had to be one in which each of the systems undergoing coupling wasindependentlynecessary or highly beneficial, as well as frequent and recurring over evolutionary time. One such context could have been the teaching of tool production or tool use. In the present study, we propose the Cognitive Coupling hypothesis, which brings together these insights and outlines a unifying theory for the evolution of the capacity for language.This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Current and potential roles of archaeology in the development of cultural evolutionary theory
Authors: Garvey Raven 
Published: February 2018

Archaeology has much to contribute to the study of cultural evolution. Empirical data at archaeological timescales are uniquely well suited to tracking rates of cultural change, detecting phylogenetic signals among groups of artefacts, and recognizing long-run effects of distinct cultural transmission mechanisms. Nonetheless, these are still relatively infrequent subjects of archaeological analysis and archaeology's potential to help advance our understanding of cultural evolution has thus far been largely unrealized. Cultural evolutionary models developed in other fields have been used to interpret patterns identified in archaeological records, which in turn provides independent tests of these models' predictions, as demonstrated here through a study of late Prehistoric stone projectile points from the US Southwest. These tests may not be straightforward, though, because archaeological data are complex, often representing events aggregated over many years (or centuries or millennia), while processes thought to drive cultural evolution (e.g. biased learning) operate on much shorter timescales. To fulfil archaeology's potential, we should continue to develop models specifically tailored to archaeological circumstances, and explore ways to incorporate the rich contextual data produced by archaeological research.This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Copy number variants in clinical WGS: deployment and interpretation for rare and undiagnosed disease
Authors: Gross Andrew M , Ajay Subramanian S. , Rajan Vani , Brown Carolyn , Bluske Krista , Burns Nicole , Chawla Aditi , Coffey Alison J , Malhotra Alka , Scocchia Alicia , Thorpe Erin , Dzidic Natasa , Hovanes Karine , Sahoo Trilochan , Dolzhenko Egor , Lajoie Bryan , Khouzam Amirah , Chowdhury Shimul , Belmont John , Roller Eric , Ivakhno Sergii , Tanner Stephen , McEachern Julia , Hambuch Tina , Eberle Michael , Hagelstrom R Tanner , Bentley David R , Perry Denise L , Taft Ryan J 
Published: February 2018

AbstractPurposeCurrent diagnostic testing for genetic disorders involves serial use of specialized assays spanning multiple technologies. In principle, whole genome sequencing (WGS) has the potential to detect all genomic mutation types on a single platform and workflow. Here we sought to evaluate copy number variant (CNV) calling as part of a clinically accredited WGS test.MethodsUsing a depth-based copy number caller we performed analytical validation of CNV calling on a reference panel of 17 samples, compared the sensitivity of WGS-based variants to those from a clinical microarray, and set a bound on precision using orthogonal technologies. We developed a protocol for family-based analysis, annotation, filtering, visualization of WGS based CNV calls, and deployed this across a clinical cohort of 79 rare and undiagnosed cases.ResultsWe found that CNV calls from WGS are at least as sensitive as those from microarrays, while only creating a modest increase in the number of variants interpreted (~10 CNVs per case). We identified clinically significant CNVs in 15% of the first 79 cases analyzed. This pipeline also enabled identification of cases of uniparental disomy (UPD) and a 50% mosaic trisomy 14. Directed analysis of some CNVs enabled break-point level resolution of genomic rearrangements and phasing ofde-novoCNVs.ConclusionRobust identification of CNVs by WGS is possible within a clinical testing environment, and further developments will bring improvements in resolution of smaller and more complex CNVs.
Functional organization of motion and disparity sensitivity in human visual cortex
Authors: Kohler Peter J. , Meredith Wesley , Norcia Anthony M. 
Published: February 2018

AbstractVision with two eyes makes perception of weak visual contrast signals easier and, due to the lateral separation of the eyes, allows for the triangulation of depth relationships. While binocular summation of contrast signals affords the observer increased sensitivity, binocular summation of spatial cues related to changes in depth is associated with decreased sensitivity to the corresponding retinal image displacements. Perceptual models of contrast and motion-in-depth sensitivity have explained this divergence in sensitivity by proposing that probabilistic neural noise limits summing and differencing operations on small signals. Because these models do not scale well for highly suprathreshold visual signals typical of the natural environment, we approached the question of how dynamic binocular image differences are coded using direct neural measurements. Here we use Steady-State Visual Evoked Potentials in human participants to show that inter-ocular differences in retinal image motion that produce elevated perceptual thresholds generate strongly suppressed evoked response amplitudes compared to motion that is matched between the two eyes. This suppression is strongly dependent on the availability of well-defined spatial references in the image and is highly immature in 5-month-old infants. Because the suppression is of equal strength for horizontal and vertical directions of motion, it is not specific to the perception of motion in depth. Relational image cues play a critical role in early to intermediate perceptual processing stages, and these results suggest that a succession of spatial and inter-ocular differencing operations condition the visual signal representation, prior to the extraction of motion-in-depth.Significance StatementThe present work underscores the importance of relational spatial cues in both the motion and disparity domains for binocular visual coding. Relative motion and relative disparity cues not only support fine-grain displacement sensitivity but strongly influence suprathreshold responsiveness. Extraction of these cues supports a powerful binocular interaction within the motion pathway that is suppressive in nature and poorly developed in infants. This suppressive interaction is present for both horizontal and vertical directions of motion and is thus not specific to motion-in-depth, as previously believed, but is rather hypothesized to be a pre-processing step, with motion-in-depth being computed at a later or separate stage.
Allele-specific transcription factor binding as a benchmark for assessing variant impact predictors
Authors: Wagih Omar , Merico Daniele , Delong Andrew , Frey Brendan J 
Published: February 2018

ABSTRACTGenetic variation has long been known to alter transcription factor binding sites, resulting in sometimes major phenotypic consequences. While the performance for current binding site predictors is well characterised, little is known on how these models perform at predicting impact of variants. We collected and curated over 132,000 potential allele-specific binding (ASB) ChIP-seq variants across 101 transcription factors (TFs). We then assessed the accuracy of TF binding models from five different methods on these high-confidence measurements, finding that deep learning methods were best performing yet still have room for improvement. Importantly, machine learning methods were consistently better than the venerable position weight matrix (PWM). Finally, predictions for certain TFs were consistently poor, and our investigation supports efforts to use features beyond sequence, such as methylation, DNA shape, and post-translational modifications. We submit that ASB data is a valuable benchmark for variant impact on TF binding.
Generative adversarial networks as a tool to recover structural information from cryo-electron microscopy data
Authors: Su Min , Zhang Hantian , Schawinski Kevin , Zhang Ce , Cianfrocco Michael A. 
Published: February 2018

ABSTRACTCryo-electron microscopy (cryo-EM) is a powerful structural biology technique capable of determining atomic-resolution structures of biological macromolecules. Despite this ability, the low signal-to-noise ratio of cryo-EM data continues to remain a hurdle for assessing raw cryo-EM micrographs and subsequent image analysis. To help address this problem, we have performed proof-of-principle studies with generative adversarial networks, a form of artificial intelligence, to denoise individual particles. This approach effectively recovers global structural information for both synthetic and real cryo-EM data, facilitating per-particle assessment from noisy raw images. Our results suggest that generative adversarial networks may be able to provide an approach to denoise raw cryo-EM images to facilitate particle selection and raw particle interpretation for single particle and tomography cryo-EM data.
Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs
Authors: Ibn-Salem Jonas , Andrade-Navarro Miguel A. 
Published: February 2018

AbstractWe present a computational method to gain knowledge of the three-dimensional structure of the genome from ChIP-seq datasets. While not designed to detect contacts, the ChIP-seq protocol cross-links proteins with each other and with DNA. Consequently, genomic regions that interact with the protein binding-site via chromatin looping are coimmunoprecipitated and sequenced. This produces minor ChIP-seq signals around CTCF motif pairs at loop anchor regions. Together with genomic sequence features, these signals predict whether loop anchors interact or not. Our method, Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs (7C), is available as an R/Bioconductor package: http://bioconductor.org/packages/sevenC
Fatherhood alters gene expression within the MPOA
Authors: Seelke Adele M. H. , Bond Jessica M. , Simmons Trent C. , Joshi Nikhil , Settles Matthew L. , Stolzenberg Danielle , Rhemtulla Mijke , Bales Karen L. 
Published: February 2018

AbstractFemale parenting is obligate in mammals, but fathering behavior among mammals is rare. Only 3–5% of mammalian species exhibit biparental care, including humans, and mechanisms of fathering behavior remain sparsely studied. However, in species where it does exist, paternal care is often crucial to the survivorship of offspring. The present study is the first to identify new gene targets linked to the experience of fathering behavior in a biparental species using RNA sequencing. In order to determine the pattern of gene expression within the medial preoptic area that is specifically associated with fathering behavior, we identified differentially expressed genes in male prairie voles (Microtus ochrogaster)that experienced one of three social conditions: virgin males, pair bonded males, and males with fathering experience. Differentially expressed genes from each comparison (i.e., Virgin vs Paired, Virgin vs Fathers, and Paired vs Fathers) were evaluated using the Gene Ontology enrichment analysis, and Kegg pathways analysis to reveal metabolic pathways associated with specific differentially expressed genes. Using these tools, we identified a group of genes that are differentially expressed in voles with different amounts of social experience. These genes are involved in a variety of processes, with particular enrichment in genes associated with immune function, metabolism, synaptic plasticity, and the remodeling of dendritic spines. The identification of these genes and processes will lead to novel insights into the biological basis of fathering behavior.
Improved pathway reconstruction from RNA interference screens by exploiting off-target effects
Authors: Srivatsa Sumana , Kuipers Jack , Schmich Fabian , Eicher Simone , Emmenlauer Mario , Dehio Christoph , Beerenwinkel Niko 
Published: February 2018

AbstractPathway reconstruction has proven to be an indispensable tool for analyzing the molecular mechanisms of signal transduction underlying cell function. Nested effects models (NEMs) are a class of probabilistic graphical models designed to reconstruct signalling pathways from high-dimensional observations resulting from perturbation experiments, such as RNA interference (RNAi). NEMs assume that the short interfering RNAs (siRNAs) designed to knockdown specific genes are always on-target. However, it has been shown that most siRNAs exhibit strong off-target effects, which further confound the data, resulting in unreliable reconstruction of networks by NEMs. Here, we present an extension of NEMs called probabilistic combinatorial nested effects models (pc-NEMs), which capitalize on the ancillary siRNA off-target effects for network reconstruction from combinatorial gene knockdown data. Our model employs an adaptive simulated annealing search algorithm for simultaneous inference of network structure and error rates inherent to the data. Evaluation of pc-NEMs on simulated data with varying number of phenotypic effects and noise levels demonstrates improved reconstruction compared to classical NEMs. Application to Bartonella henselae infection RNAi screening data yielded an eight node network largely in agreement with previous works, and revealed novel binary interactions of direct impact between established components.Availability: The software used for the analysis is freely available as an R package at https://github.com/cbg-ethz/pcNEM.gitContact: niko.beerenwinkel@bsse.ethz.ch
Identification of endogenous Adenomatous polyposis coli interaction partners and β-catenin-independent targets by proteomics
Authors: Popow Olesja , Tatham Michael H. , Paulo João A. , Rojas-Fernandez Alejandro , Loyer Nicolas , Newton Ian P. , Januschke Jens , Haigis Kevin M. , Näthke Inke 
Published: February 2018

SummaryAdenomatous polyposis coli(APC) is the most frequently mutated gene in colorectal cancer. APC negatively regulates the pro-proliferative Wnt signaling pathway by promoting the degradation of β-catenin, but the extent to which APC exerts Wnt/β-catenin-independent tumor suppressive activity is unclear. To identify interaction partners and β-catenin-independent targets of endogenous, full-length APC, we applied label-free and multiplexed TMT mass spectrometry. Affinity enrichment-mass spectrometry revealed over 150 previously unidentified APC interaction partners. Moreover, our global proteomic analysis revealed that roughly half of the protein expression changes that occur in response to APC loss are independent of β-catenin. By combining these two analyses, we identified Misshapen-like kinase 1 (MINK1) as a putative substrate of an alternative APC-containing destruction complex and provide evidence for the potential contribution of MINK1 toAPCmutant phenotypes. Collectively, our results highlight the extent and importance of Wnt-independent APC functions in epithelial biology and disease.
Germline DNA replication timing shapes mammalian genome composition
Authors: Yehuda Yishai , Blumenfeld Britny , Mayorek Nina , Makedonski Kirill , Vardi Oriya , Mansour Yousef , Masika Hagit , Farago Marganit , Baror-Sebban Shulamit , Buganim Yosef , Koren Amnon , Simon Itamar 
Published: February 2018

AbstractMammalian DNA is replicated in a highly organized and regulated manner. Large, Mb-sized regions are replicated at defined times along S phase. DNA Replication Timing (RT) has been suggested to play an important role in shaping the mammalian genome by affecting mutation rates. Previous analyses relied on somatic DNA RT profiles, while to fully understand the influences of RT on the mammalian genome, germ cell RT information is necessary, as only germline mutations are passed to offspring and thus affect genomic composition. Using an improved RT mapping technique that allows mapping the RT from limited amounts of cells, we measured RT from two stages in the mouse germline - primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). The germ cell RT profiles were distinct from those of both somatic and embryonic tissues. The correlations between RT and both mutation rate and recombination hotspots were not only confirmed in the germline tissues, but were shown to be stronger compared to correlations with RT of somatic tissues, emphasizing the importance of using RT profiles from the correct tissue of origin. Expanding the analysis to additional genetic features such as GC content, transposable elements (SINEs and LINEs) and gene density, also revealed a stronger correlation with the germ cell RT maps. GC content stratification along with multiple regression analysis revealed the independent contribution of RT to SINE, gene, mutation and recombination hotspot densities. Taken together, our results point to the centrality of RT in shaping multiple levels of mammalian genome composition.
Type-I interferons inhibit interleukin-10 signaling and favor type 1 diabetes development in NOD mice
Authors: Iglesias Marcos , Arun Anirudh , Chicco Maria , Lam Brandon , Talbot Conover , Ivanova Vera , Lee W. P. A , Brandacher Gerald , Raimondi Giorgio 
Published: February 2018

AbstractDestruction of insulin-producing β-cells by autoreactive T lymphocytes leads to the development of type 1 diabetes. Type I interferons (TI-IFN) and interleukin-10 (IL-10) have been connected with the pathophysiology of this disease; however, their interplay in the modulation of diabetogenic T cells remains unknown. We have discovered that TI-IFN cause a selective inhibition of IL-10 signaling in effector and regulatory T cells, altering their responses. This correlates with diabetes development in NOD mice, where the inhibition is also spatially localized to T cells of pancreatic and mesenteric lymph nodes. IL-10 signaling inhibition is reversible and can be restored via blockade of TI-IFN/IFN-R interaction, paralleling with the resulting delay in diabetes onset and reduced severity. Overall, we propose a novel molecular link between TI-IFN and IL-10 signaling that helps better understand the complex dynamics of autoimmune diabetes development and reveals new strategies of intervention.AbbreviationsALNaxillary lymph nodesIL-10interleukin-10MFImean fluorescence intensityMLNmesentheric lymph nodesNODnonobese diabetic micePLNpancreatic lymph nodesTI-IFNtype-1 InterferonsTmemmemory T cellsTregregulatory T cells