bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correction and Prevention of the Pixie Ear Deformity: A Combined Technique
Authors: Kaye Kai O , Casabona Gabriela R , Kästner Sonja , Paprottka Felix J 
Published: April 2018

AbstractBackgroundEar and earlobe deformities after surgical rhytidectomy are common and can significantly diminish the aesthetic outcome. The main causes of ear/earlobe distortion are skin overresection, an imbalance between vertical/horizontal skin-lift vectors, and tractional distortions through superficial muscularaponeurotic system (SMAS) tension.ObjectivesTo demonstrate a new method for earlobe suturing and ear fixation that would prevent aesthetics-related complications after facelift surgery.MethodsA total of 105 primary SMAS facelift surgeries were performed between 2015 and 2016 by the first author. A combination technique consisting of a posterior earlobe rotation flap (PERF) and a concha-mastoid suspension suture (CMSS) was executed bilaterally within each facelift procedure (n = 210). A retrospective data analysis was conducted (preoperatively and one year postoperatively) using our hospital information system and a photometric data analysis to assess auricular displacement, earlobe distortion, and hypertrophic scarring.ResultsPseudoptosis of the earlobe was noted in two cases, and auricular displacement was observed in four cases. Bilateral mild hypertrophic scarring was seen in one patient. The postoperative photometric analysis showed a natural ptosis grade I/II in all the patients, with a statistically significantly reduced postoperative earlobe size (P &lt; 0.05). The total rate of aesthetics-related complications was 4% in our cohort (earlobe distortion with pseudoptosis: 1%; auricular displacement: 2%; hypertrophic scarring: 1%).ConclusionsOur modification of the facial flap anchoring at the ear base in combination with a CMSS stabilizes the natural position of the ear and prevents distortion while allowing better control over the earlobe’s aesthetic shaping. This novel method reduces the incidence of ear/earlobe deformities and hypertrophic scarring at the ear base after rhytidectomy and, therefore, promises to be a valuable advancement.Level of Evidence: 4
Deep learning of genomic variation and regulatory network data
Authors: Telenti Amalio , Lippert Christoph , Chang Pi-Chuan , DePristo Mark 
Published: April 2018

Abstract
The human genome is now investigated through high-throughput functional assays, and through the generation of population genomic data. These advances support the identification of functional genetic variants and the prediction of traits (e.g. deleterious variants and disease). This review summarizes lessons learned from the large-scale analyses of genome and exome data sets, modeling of population data and machine-learning strategies to solve complex genomic sequence regions. The review also portrays the rapid adoption of artificial intelligence/deep neural networks in genomics; in particular, deep learning approaches are well suited to model the complex dependencies in the regulatory landscape of the genome, and to provide predictors for genetic variant calling and interpretation.
How was the dageš in Biblical Hebrew Pronounced and Why is it There?
Authors: Khan Geoffrey 
Published: April 2018

Abstract
There is no consensus in the scholarly literature as to the pronunciation of the dageš in the Biblical Hebrew plural form ‘houses’. This article examines the evidence for the way the dageš was pronounced in this word in medieval sources that give us direct access to the Tiberian Masoretic reading tradition. It is shown that there was some degree of diversity of pronunciation across different biblical verses and different sub-traditions of the Tiberian Hebrew pronunciation. An explanation for the existence of the dageš in the word is offered on the basis of comparative evidence within Biblical Hebrew reading traditions and other Semitic languages.
MDM4 is an essential disease driver targeted by 1q gain in Burkitt lymphoma
Authors: Hüllein Jennifer , Słabicki Mikołaj , Rosolowski Maciej , Jethwa Alexander , Habringer Stefan , Tomska Katarzyna , Kurilov Roma , Lu Junyan , Scheinost Sebastian , Wagener Rabea , Huang Zhiqin , Lukas Marina , Yavorska Olena , Helferich Hanne , Scholtysik René , Bonneau Kyle , Tedesco Donato , Küppers Ralf , Klapper Wolfram , Pott Christiane , Stilgenbauer Stephan , Burkhardt Birgit , Löffler Markus , Trümper Lorenz , Hummel Michael , Brors Benedikt , Zapatka Marc , Siebert Reiner ,   consortium MMML, Keller Ulrich , Huber Wolfgang , Kreuz Markus , Zenz Thorsten 
Published: April 2018

AbstractOncogenic MYC activation promotes cellular proliferation in Burkitt lymphoma (BL), but also induces cell cycle arrest and apoptosis mediated by TP53, a tumor suppressor gene that is mutated in 40% of BL cases. To identify therapeutic targets in BL, we investigated molecular dependencies in BL cell lines using RNAi-based, loss-of-function screening. By integrating genotypic and RNAi data, we identified a number of genotype-specific dependencies including the dependence of TCF3/ID3 mutant cell lines on TCF3 and of MYD88 mutant cell lines on TLR signaling. TP53 wild-type (TP53wt) BL were dependent on MDM4, a negative regulator of TP53. In BL cell lines, MDM4 knockdown induced cell cycle arrest and decreased tumor growth in a xenograft model in a p53-dependent manner, while small molecule inhibition of the MDM4-p53 interaction restored p53 activity resulting in cell cycle arrest. Consistent with the pathogenic effect of MDM4 upregulation in BL, we found that TP53wt BL samples were enriched for gain of chromosome 1q which includes the MDM4 locus. 1q gain was also enriched across non-BL cancer cell lines (n=789) without TP53 mutation (23% in TP53wt and 12% in TP53mut, p<0.001). In a set of 216 cell lines representing 19 cancer entities from the Achilles project, MDM4 was the strongest genetic dependency in TP53wt cell lines (p<0.001).Our findings show that in TP53wt BL, MDM4-mediated inhibition of p53 is a mechanism to evade cell cycle arrest. The data highlight the critical role of p53 as a tumor suppressor in BL, and identifies MDM4 as a key functional target of 1q gain in a wide range of cancers, which is therapeutically targetable.
Recent demographic histories and genetic diversity across pinnipeds are shaped by anthropogenic interactions and mediated by ecology and life-history
Authors: Stoffel M.A. , Humble E. , Acevedo-Whitehouse K. , Chilvers B.L. , Dickerson B. , Galimberti F. , Gemmell N. , Goldsworthy S.D , Nichols H.J. , Krüger O , Negro S. , Osborne A. , Paijmans A.J. , Pastor T. , Robertson B.C. , Sanvito S. , Schultz J. , Shafer A.B.A , Wolf J.B.W. , Hoffman J.I. 
Published: April 2018

AbstractA central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and negatively impact population viability and adaptive potential. In an era of unprecedented biodiversity loss and climate change, understanding both the determinants and consequences of bottlenecks in wild populations is therefore an increasingly important challenge. However, as most studies have focused on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we used a comparative approach by integrating genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to elucidate the consequences of large-scale commercial exploitation by 18thand 19thcentury sealers. We show that around one third of these species exhibit strong genetic signatures of recent population declines, with estimated bottleneck effective population sizes reflecting just a few tens of surviving individuals in the most extreme cases. Bottleneck strength was strongly associated with both breeding habitat and mating system variation, and together with global abundance explained a large proportion of the variation in genetic diversity across species. Overall, there was no relationship between bottleneck intensity and IUCN status, although three of the four most heavily bottlenecked species are currently endangered. Our study reveals an unforeseen interplay between anthropogenic exploitation, ecology, life history and demographic declines, sheds new light on the determinants of genetic diversity, and is consistent with the notion that both genetic and demographic factors influence population viability.
Prospective Motion correction improves the sensitivity of fMRI pattern decoding
Authors: Huang Pei , Carlin Johan D. , Alink Arjen , Kriegeskorte Nikolaus , Henson Richard N. , Correia Marta M. 
Published: April 2018

ABSTRACTWe evaluated the effectiveness of prospective motion correction (PMC) on a simple visual task when no deliberate subject motion was present. The PMC system utilizes an in-bore optical camera to track an external marker attached to the participant via a custom-moulded mouthpiece. The study was conducted at two resolutions (1.5mm vs 3mm) and under three conditions (PMC On and Mouthpiece On vs PMC Off and Mouthpiece On vs PMC Off and Mouthpiece Off). Multiple data analysis methods were conducted, including univariate and multivariate approaches, and we demonstrated that the benefit of PMC is most apparent for multi-voxel pattern decoding at higher resolutions. Additional testing on two participants showed that our inexpensive, commercially available mouthpiece solution produced comparable results to a dentist-moulded mouthpiece. Our results showed that PMC is increasingly important at higher resolutions for analyses that require accurate voxel registration across time.
Creation and multi-omics characterization of a genomically hybrid strain in the nitrogen-fixing symbiotic bacteriumSinorhizobium meliloti
Authors: Checcucci Alice , diCenzo George C. , Ghini Veronica , Bazzicalupo Marco , Becker Anke , Decorosi Francesca , Döhlemann Johannes , Fagorzi Camilla , Finan Turlough M. , Fondi Marco , Luchinat Claudio , Turano Paola , Vignolini Tiziano , Viti Carlo , Mengoni Alessio 
Published: April 2018

AbstractMany bacteria, often associated with eukaryotic hosts and of relevance for biotechnological applications, harbour a multipartite genome composed by more than one replicon. Biotechnologically relevant phenotypes are often encoded by genes residing on the secondary replicons. A synthetic biology approach to developing enhanced strains for biotechnological purposes could therefore involve merging pieces or entire replicons from multiple strains into a single genome. Here we report the creation of a genomic hybrid strain in a model multipartite genome species, the plant-symbiotic bacteriumSinorhizobium meliloti. In particular, we moved the secondary replicon pSymA (accounting for nearly 20% of total genome content) from a donorS. melilotistrain to an acceptor strain. Thecis-hybrid strain was screened for a panel of complex phenotypes (carbon/nitrogen utilization phenotypes, intra- and extra-cellular metabolomes, symbiosis, and various microbiological tests). Additionally, metabolic network reconstruction and constraint-based modelling were employed forin silicoprediction of metabolic flux reorganization. Phenotypes of thecis-hybrid strain were in good agreement with those of both parental strains. Interestingly, the symbiotic phenotype showed a marked cultivar-specific improvement with thecis-hybrid strains compared to both parental strains. These results provide a proof-of-principle for the feasibility of genome-wide replicon-based remodelling of bacterial strains for improved biotechnological applications in precision agriculture.
Combining Deep Learning and Active Contours Opens The Way to Robust, Automated Analysis of Brain Cytoarchitectonics
Authors: Thierbach Konstantin , Bazin Pierre-Louis , Back Walter De , Gavriilidis Filippos , Kirilina Evgeniya , Jäger Carsten , Morawski Markus , Geyer Stefan , Weiskopf Nikolaus , Scherf Nico 
Published: April 2018

AbstractDeep learning has thoroughly changed the field of image analysis yielding impressive results whenever enough annotated data can be gathered. While partial annotation can be very fast, manual segmentation of 3D biological structures is tedious and error-prone. Additionally, high-level shape concepts such as topology or boundary smoothness are hard if not impossible to encode in Feedforward Neural Networks. Here we present a modular strategy for the accurate segmentation of neural cell bodies from light-sheet microscopy combining mixed-scale convolutional neural networks and topology-preserving geometric deformable models. We show that the network can be trained efficiently from simple cell centroid annotations, and that the final segmentation provides accurate cell detection and smooth segmentations that do not introduce further cell splitting or merging.
Applying generalised allometric regressions to predict live body mass of tropical and temperate arthropods
Authors: Sohlström Esra H. , Marian Lucas , Barnes Andrew D. , Haneda Noor F. , Scheu Stefan , Rall Björn C. , Brose Ulrich , Jochum Malte 
Published: April 2018

Abstract1. The ecological implications of body size extend from the biology of individual organisms to ecosystem–level processes. Measuring body mass for high numbers of invertebrates can be logistically challenging, making length-mass regressions useful for predicting body mass with minimal effort. However, standardised sets of scaling relationships covering a large range in body length, taxonomic groups, and multiple geographical regions are scarce.2. We collected 6293 arthropods from 19 higher-level taxa in both temperate and tropical locations to compile a comprehensive set of linear models relating live body mass to a range of predictor variables. For each individual, we measured live weight (hereafter, body mass), body length and width, and conducted linear regressions to predict body mass using body length, body width, taxonomic group and geographic region. Additionally, we quantified prediction error when using parameters from arthropods of a different geographic region.3. Incorporating body width into taxon- and region-specific length-mass regressions yielded the highest prediction accuracy for body mass. Using regression parameters from a different geographic location increased prediction error, causing over- or underestimation of body mass depending on geographical origin and whether body width was included.4. We present a comprehensive range of parameters for predicting arthropod body mass and provide guidance for selecting optimal scaling relationships. Given the importance of body mass for functional invertebrate ecology and a paucity of adequate regressions to predict arthropod body mass from different geographical regions, our study provides a long-needed resource for quantifying live body mass in invertebrate ecology research.
Chromatin remodelers couple inchworm motion with twist-defect formation to slide nucleosomal DNA
Authors: Brandani Giovanni B. , Takada Shoji 
Published: April 2018

ABSTRACTATP-dependent chromatin remodelers are molecular machines that control genome organization by repositioning, ejecting, or editing nucleosomes, activities that confer them essential regulatory roles on gene expression and DNA replication. Here, we investigate the molecular mechanism of active nucleosome sliding by means of molecular dynamics simulations of the Snf2 remodeler in complex with a nucleosome. During its inchworm motion driven by ATP consumption, the remodeler overwrites the original nucleosome energy landscape via steric and electrostatic interactions to induce sliding of nucleosomal DNA unidirectionally. The sliding is initiated at the remodeler binding location via the generation of twist defects, which then spontaneously propagate to complete sliding throughout the entire nucleosome. We also reveal how remodeler mutations and DNA sequence control active nucleosome repositioning, explaining several past experimental observations. These results offer a detailed mechanistic picture of remodeling important for the complete understanding of these important biological processes.
Analyzing the symmetrical arrangement of structural repeats in proteins with CE-Symm
Authors: Bliven Spencer E , Lafita Aleixa , Rose Peter W , Capitani Guido , Prlić Andreas , Bourne Philip E 
Published: April 2018

AbstractMany proteins fold into highly regular and repetitive three dimensional structures. The analysis of structural patterns and repeated elements is fundamental to understand protein function and evolution. We present recent improvements to the CE-Symm tool for systematically detecting and analyzing the internal symmetry and structural repeats in proteins. In addition to the accurate detection of internal symmetry, the tool is now capable of i) reporting the type of symmetry, ii) identifying the smallest repeating unit, iii) describing the arrangement of repeats with transformation operations and symmetry axes, and iv) comparing the similarity of all the internal repeats at the residue level. CE-Symm 2.0 helps the user investigate proteins with a robust and intuitive sequence-to-structure analysis, with many applications in protein classification, functional annotation and evolutionary studies. We describe the algorithmic extensions of the method and demonstrate its applications to the study of interesting cases of protein evolution.Availabilit: CE-Symm is an open source tool integrated into the BioJava library(www.biojava.org)and freely available at https://github.com/rcsb/symmetry.
A circadian output circuit controls sleep-wake arousal threshold in Drosophila
Authors: Guo Fang , Holla Meghana , Díaz Madelen M. , Rosbash Michael 
Published: April 2018

SummaryThe Drosophila core circadian circuit contains distinct groups of interacting neurons that give rise to diurnal sleep-wake patterns. Previous work showed that a subset of Dorsal Neurons 1 (DN1s) are sleep-promoting through their inhibition of activity-promoting circadian pacemakers. Here we show that these anterior-projecting DNs (APDNs) also “exit” the circadian circuitry and communicate with the homeostatic sleep center in higher brain regions to regulate sleep and sleep-wake arousal threshold. These APDNs connect to a small discrete subset of tubercular-bulbar neurons, which are connected in turn to specific sleep-centric Ellipsoid Body (EB)-Ring neurons of the central complex. Remarkably, activation of the APDNs produces sleep-like oscillations in the EB and also raises the arousal threshold, which requires neurotransmission throughout the circuit. The data indicate that this APDN-TuBusup-EB circuit temporally regulates sleep-wake arousal threshold in addition to the previously defined role of the TuBu-EB circuit in vision, navigation and attention.
Mapping the Peaks: Fitness Landscapes of the Fittest and the Flattest
Authors: Franklin Joshua , LaBar Thomas , Adami Christoph 
Published: April 2018

AbstractBackgroundPopulations exposed to a high mutation rate harbor abundant deleterious genetic variation, leading to depressed mean fitness. This reduction in mean fitness presents an opportunity for selection to restore adaptation through the evolution of mutational robustness. In extreme cases, selection for mutational robustness can lead to “flat” genotypes (with low fitness but high robustness) out-competing “fit” genotypes with high fitness but low robustness—a phenomenon known as “survival of the flattest”. While this effect was previously explored using the digital evolution system Avida, a complete analysis of the local fitness landscapes of “fit” and “flat” genotypes has been lacking, leading to uncertainty about the genetic basis of the survival of the flattest effect.ResultsHere, we repeated the survival of the flattest study and analyzed the mutational neighborhoods of fit and flat genotypes. We found that flat genotypes, compared to the fit genotypes, had a reduced likelihood of deleterious mutations as well as an increased likelihood of neutral and, surprisingly, of lethal mutations. This trend holds for mutants one to four substitutions away from the wild-type sequence. We also found that flat genotypes have, on average, no epistasis between mutations, while fit genotypes have, on average, positive epistasis.ConclusionsOur results demonstrate that the genetic causes of mutational robustness on complex fitness landscapes are multifaceted. While the traditional idea of the survival of the flattest effect emphasized the evolution of increased neutrality, others have argued for increased mutational sensitivity in response to strong mutational loads. Our results show that both increased neutrality and increased lethality can lead to the evolution of mutational robustness. Furthermore, strong negative epistasis is not required for mutational sensitivity to lead to mutational robustness. Overall, these results suggest that mutational robustness is achieved by minimizingheritabledeleterious variation.
A critical assessment of single-cell transcriptomes sampled following patch-clamp electrophysiology
Authors: Tripathy Shreejoy J. , Toker Lilah , Bomkamp Claire , Mancarci B. Ogan , Belmadani Manuel , Pavlidis Paul 
Published: April 2018

AbstractPatch-seq, combining patch-clamp electrophysiology with single-cell RNA-sequencing (scRNAseq), enables unprecedented single-cell access to a neuron’s transcriptomic, electrophysiological, and morphological features. Here, we present a systematic review and re-analysis of scRNAseq profiles from 4 recent patch-seq datasets, benchmarking these against analogous profiles from cellular-dissociation based scRNAseq. We found an increased likelihood for off-target cell-type mRNA contamination in patch-seq, likely due to the passage of the patch-pipette through the processes of adjacent cells. We also observed that patch-seq samples varied considerably in the amount of mRNA that could be extracted from each cell, strongly biasing the numbers of detectable genes. We present a straightforward marker gene-based approach for controlling for these artifacts and show that our method improves the correspondence between gene expression and electrophysiological features. Our analysis suggests that these technical confounds likely limit the interpretability of patch-seq based single-cell transcriptomes. However, we provide concrete recommendations for quality control steps that can be performed prior to costly RNA-sequencing to optimize the yield of high quality samples.