bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the feasibility of accessing acute pain–related facial expressions in the human fetus and its potential implications: a case report
Authors: Bernardes Lisandra Stein , Ottolia Juliana Fontan , Cecchini Marina , Filho Antônio Gomes de Amorim , Teixeira Manoel Jacobsen , Francisco Rossana Pulcineli Vieira , de Andrade Daniel Ciampi ,   Grupo de Estudo da Dor Fetal (Fetal Pain Study Group)
Published: July 2018

Abstract

Introduction:
Although pain facial assessment is routinely performed in term and preterm newborns by the use of facial expression–based tools such as the Neonatal Facial Coding System, the assessment of pain during the intrauterine life has not been extensively explored.

Objective:
Describe for the first time, an experimental model to assess and quantify responses due to acute pain in fetuses undergoing anaesthesia for intrauterine surgery recorded by high-resolution 4D ultrasound machines.

Methods/results-case report:
A 33-year-old pregnant woman had congenital left diaphragmatic hernia of poor prognosis diagnosed, and her fetus was treated by fetoscopic endotracheal occlusion. Later, during the removal of the fetal endotracheal balloon by ultrasound-guided puncture, we have recorded facial expressions of the foetus before and after the anaesthetic puncture by the use of 4D ultrasound recordings, which were presented to 3 blinded coders instructed to use the Neonatal Facial Coding System for acute pain facial coding. The procedure was safe and feasible.

Conclusion:
This is the first description of a recordable acute pain model in the human fetus by the use of a facial expression–based tool. The possibility to assess pain-related intrauterine behaviours would allow not only for the monitoring of the efficacy of anaesthetic procedures in the fetus but would also open the way to explore the evolution of pain-related facial responses during the fetal neurodevelopment. This method may pave the way for objective assessments of pain in fetuses, should it endure the steps of formal validation studies.
Identification of a primitive intestinal transcription factor network shared between oesophageal adenocarcinoma and its pre-cancerous precursor state
Authors: Rogerson Connor , Britton Edward , Withey Sarah , Hanley Neil , Ang Yeng S. , Sharrocks Andrew D. 
Published: July 2018

AbstractOesophageal adenocarcinoma (OAC) is one of the most frequent causes of cancer deaths and yet compared to other common cancers, we know relatively little about the molecular composition of this tumour type. To further our understanding of this cancer we have used open chromatin profiling to decipher the transcriptional regulatory networks that are operational in OAC. We have uncovered a transcription factor network that is usually found in primitive intestinal cells during embryonic development, centred on HNF4A and GATA6. These transcription factors work together to control the OAC transcriptome. Importantly, we show that this network is activated in Barrett’s oesophagus, the putative precursor state to OAC thereby providing novel molecular evidence in support of stepwise malignant transition. Furthermore, we show that HNF4A alone, is sufficient to drive chromatin opening and activation of a Barrett’s-like chromatin signature when expressed in normal human epithelial cells. Collectively, these data provide a new way to categorise OAC at a genome scale and implicate HNF4A activation as a potential pivotal event in regulating its malignant transition from healthy cells.
Commonly-used FRET fluorophores promote collapse of an otherwise disordered protein
Authors: Riback Joshua A , Bowman Micayla A , Zmyslowski Adam M , Plaxco Kevin W , Clark Patricia L , Sosnick Tobin R 
Published: July 2018

ABSTRACTThe dimensions that unfolded proteins, including intrinsically disordered proteins (IDPs), adopt at low or no denaturant remains controversial. We recently developed an innovative analysis procedure for small-angle X-ray scattering (SAXS) profiles and found that even relatively hydrophobic IDPs remain nearly as expanded as the chemically denatured ensemble, rendering them significantly more expanded than generally inferred using fluorescence resonance energy transfer (FRET) measurements. We show here that fluorophores typical of those employed in FRET can contribute to this discrepancy. Specifically, we find that addition of Alexa488 to a normally expanded IDP causes contraction of its ensemble. In parallel, we also tested the recent suggestion that FRET and SAXS results can be reconciled if, in contrast to homopolymers, the radius of gyration (Rg) of an unfolded protein chain can vary independently from its end-to-end distance (Ree). To do so, we developed an analysis procedure that can accurately extract both Rg and Ree from SAXS profiles even if they are decoupled. Using this procedure, we find that Rg and Ree remain tightly coupled even for heteropolymeric IDPs. We thus conclude that, when combined with improved analysis procedures for both SAXS and FRET, fluorophore-driven interactions are sufficient to explain the preponderance of existing data regarding the nature of polypeptide chains unfolded in the absence of denaturant.
Extracting human data from published figures: implications for data science and bioethics
Authors: Cox Brian J. 
Published: July 2018

AbstractThe advent of text mining and natural text reading artificial intelligence has opened new research opportunities on the large collections of research publications available through journal and other resources. These systems have begun to identify novel connections or hypotheses due to an ability to read and extract information from more literature than a single individual could in their lifetime. Most research publications contain figures where data is represented in a graph. Modern publication guidelines are strongly encouraging publication of graphs where all data is displayed as apposed to summary figures such as bar charts. Figures are often encoded in a graphing language that is interpreted and displayed as a graphics. Conversion figures in publications to the underlying code should enable text-based mining to extract the underlying raw data of the graph. Here I show that data from publications greater than 15 years old that contain time series data on human patients is extractable from the original publication and can be reassessed using modern tools. This could benefit cases where data sets are not available due to file loss or corruption. This may also create and issue for the publication of human data as sharing of human data often requires research ethics approval.Author summaryFigures embedded in published research manuscripts are a minable resource similar to text mining. Figures are text based code that draws the image, as such the underlying text of the code can be used to reassemble the original data set.
Transdiagnostic characterization of neuropsychiatric disorders by hyperexcitation-induced immaturity
Authors: Murano Tomoyuki , Hagihara Hideo , Tajinda Katsunori , Matsumoto Mitsuyuki , Miyakawa Tsuyoshi 
Published: July 2018

AbstractBiomarkers are needed to improve the diagnosis of neuropsychiatric disorders. Promising candidates are imbalance of excitation and inhibition in the brain, and maturation abnormalities. Here, we characterized different disease conditions by mapping changes in the expression patterns of maturation-related genes whose expression was altered by experimental neural hyperexcitation in published studies. This revealed two gene expression patterns: decreases in maturity markers and increases in immaturity markers. These two groups of genes were characterized by the overrepresentation of genes related to synaptic function and chromosomal modification, respectively. We used these two groups in a transdiagnostic analysis of 80 disease datasets for eight neuropsychiatric disorders and 12 datasets from corresponding animal models, and found that transcriptomic pseudoimmaturity inducible by neural hyperexcitation is shared by multiple neuropsychiatric disorders, such as schizophrenia, Alzheimer disorders, and ALS. Our results indicate that this endophenotype serve as a basis for transdiagnostic characterization of these disorders.
A junction coverage compatibility score to quantify the reliability of transcript abundance estimates and annotation catalogs
Authors: Soneson Charlotte , Love Michael I , Patro Rob , Hussain Shobbir , Malhotra Dheeraj , Robinson Mark D. 
Published: July 2018

AbstractMost methods for statistical analysis of RNA-seq data take a matrix of abundance estimates for some type of genomic features as their input, and consequently the quality of any obtained results are directly dependent on the quality of these abundances. Here, we present the junction coverage compatibility (JCC) score, which provides a way to evaluate the reliability of transcript-level abundance estimates as well as the accuracy of transcript annotation catalogs. It works by comparing the observed number of reads spanning each annotated splice junction in a genomic region to the predicted number of junction-spanning reads, inferred from the estimated transcript abundances and the genomic coordinates of the corresponding annotated transcripts. We show that while most genes show good agreement between the observed and predicted junction coverages, there is a small set of genes that do not. Genes with poor agreement are found regardless of the method used to estimate transcript abundances, and the corresponding transcript abundances should be treated with care in any downstream analyses.
Breaking the ladder: Evolution of the ventral nerve cord in Annelida
Authors: Helm Conrad , Beckers Patrick , Bartolomaeus Thomas , Drukewitz Stephan H. , Kourtesis Ioannis , Weigert Anne , Purschke Günter , Worsaae Katrine , Struck Torsten H. , Bleidorn Christoph 
Published: July 2018

AbstractA median, segmented, annelid nerve cord has repeatedly been compared to the arthropod and vertebrate nerve cords and became the most used textbook representation of the annelid nervous system. Recent phylogenomic analyses, however, challenge the hypothesis that a subepidermal rope-ladder-like ventral nerve cord (VNC) composed of a paired serial chain of ganglia and somata-free connectives represents neither a plesiomorphic nor a typical condition in annelids.Using a comparative approach by combining phylogenomic analyses with morphological methods (immunohistochemistry and CLSM, histology and TEM), we compiled a comprehensive dataset to reconstruct the evolution of the annelid VNC. Our phylogenomic analyses generally support previous topologies. However, the so far hard-to-place Apistobranchidae and Psammodrilidae are now incorporated among the basally branching annelids with high support. Based on this topology we reconstruct an intraepidermal VNC as ancestral state in Annelida. Thus, a subepidermal ladder-like nerve cord clearly represents a derived condition.Based on the presented data, a ladder-like appearance of the ventral nerve cord evolved repeatedly, and independently of the transition from an intraepidermal to a subepidermal cord during annelid evolution. Our investigations thereby question a common origin of the bilaterian median ganglionated VNC and propose an alternative set of neuroanatomical characteristics of the last common ancestor of Annelida or perhaps even Spiralia.
Sleep/wake synchronization across latitude
Authors: Martín-Olalla José María 
Published: July 2018

Analysis of time use surveys in seventeen European countries and two American countries suggest that the winter sunrise —the latest sunrise year round— is a synchronizer for the sleep/wake cycle in standard population below 54° latitude, in competition with the noon synchronizer.When comparing industrialized data to data from hunter/gatherer, pre-industrial, Tropical societies only the late event survives as a synchronizer below 54° latitude. People rise immediately before sunrise —winter sunrise in industrialized mid-latitude societies— and abhor morning darkness. Synchronization propagates through the sleep/wake cycle so that people go to bed with increasing distance to sunset in winter as latitude increases in a scenario dominated by artificial light. This suggests a leading role of the homeostatic sleep pressure in understanding sleep/wake cycle at social level.WARNINGThis pre-print has been largely upgraded and restyled in “Sleep timing in industrial and pre-industrial societies sync to the light/dark cycle” (https://doi.org/10.1101/392035). In this new pre-print data coming from the Harmonsized European Time Use Surveys (HETUS) and referred to the “sleep/wake and other personal care” cycle were not analyzed. Instead two new pre-industrial data are included.Therefore this old pre-print you are about to read remains as a source for these data (see Figure 3 and Table III, Table VII to IX) and a source of information in the range of latitude above 54°.
Consistent pre-stimulus influences on auditory perception across the lifespan
Authors: McNair Steven W. , Kayser Stephanie J. , Kayser Christoph 
Published: July 2018

AbstractAs we get older, perception in cluttered environments becomes increasingly difficult as a result of changes in peripheral and central neural processes. Given the aging society it is important to understand the neural mechanisms constraining perception in the elderly. In young participants, the state of rhythmic brain activity prior to a stimulus has been shown to modulate the neural encoding and perceptual impact of this stimulus – yet it remains unclear whether, and if so, how, the perceptual relevance of pre-stimulus activity changes with age. Using the auditory system as a model, we recorded EEG activity during a frequency discrimination task from younger and older human listeners. By combining single-trial EEG decoding with linear modelling we demonstrate consistent statistical relations between pre-stimulus power and the encoding of sensory evidence in short-latency EEG components, and more variable relations between prestimulus phase and subjects’ decisions in fronto-parietal EEG components. At the same time, we observed a significant slowing of auditory evoked responses and a flattening of the overall EEG frequency spectrum in the older listeners. Our results point to mechanistically consistent relations between rhythmic brain activity and sensory encoding that emerge in large despite changes in neural response latencies and the relative amplitude of rhythmic brain activity with age.
Quantitative evaluation of ontology design patterns for combining pathology and anatomy ontologies
Authors: Alghamdi Sarah M. , Sundberg Beth A. , Sundberg John P. , Schofield Paul N. , Hoehndorf Robert 
Published: July 2018

ABSTRACTData are increasingly annotated with multiple ontologies to capture rich information about the features of the subject under investigation. Analysis may be performed over each ontology separately, but, recently, there has been a move to combine multiple ontologies to provide more powerful analytical possibilities. However, it is often not clear how to combine ontologies or how to assess or evaluate the potential design patterns available. Here we use a large and well-characterized dataset of anatomic pathology descriptions from a major study of aging mice. We show how different design patterns based on the MPATH and MA ontologies provide orthogonal axes of analysis, and perform differently in over-representation and semantic similarity applications. We discuss how such a data-driven approach might be used generally to generate and evaluate ontology design patterns.
Rosetta FunFolDes – a general framework for the computational design of functional proteins
Authors: Bonet Jaume , Wehrle Sarah , Schriever Karen , Yang Che , Billet Anne , Sesterhenn Fabian , Scheck Andreas , Sverrisson Freyr , Vollers Sabrina , Lourman Roxanne , Villard Melanie , Rosset Stéphane , Correia Bruno E. 
Published: July 2018

AbstractThe robust computational design of functional proteins has the potential to deeply impact translational research and broaden our understanding of the determinants of protein function, nevertheless, it remains a challenge for state-of-the-art methodologies. Here, we present a computational design approach that couples conformational folding with sequence design to embed functional motifs into heterologous proteins. We performed extensive benchmarks, where the most unexpected finding was that the design of function into proteins may not necessarily reside in the global minimum of the energetic landscape, which could have important implications in the field. We have computationally designed and experimentally characterized a distant structural template and a de novo “functionless” fold, two prototypical design challenges, to present important viral epitopes. Overall, we present an accessible strategy to repurpose old protein folds for new functions, which may lead to important improvements on the computational design of functional proteins.
3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling
Authors: Ceylan Hakan , Yasa I. Ceren , Yasa Oncay , Tabak A. Fatih , Giltinan Joshua , Sitti Metin 
Published: July 2018

ABSTRACTMiniaturization of interventional medical devices can leverage minimally invasive technologies by enabling operational resolution at cellular length scales with high precision and repeatability. Untethered micron-scale mobile robots can realize this by navigating and performing in hard-to-reach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 μm length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibody-tagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.
Does Adaptive Protein Evolution Proceed by Large or Small Steps at the Amino Acid Level?
Authors: Bergman Juraj , Eyre-Walker Adam 
Published: July 2018

AbstractA longstanding question in evolutionary biology is the relative contribution of large and small effect mutations to the adaptive process. We have investigated this question in proteins by estimating the rate of adaptive evolution between all pairs of amino acids separated by one mutational step using a McDonald-Kreitman type approach and genome-wide data from severalDrosophilaspecies. We find that the rate of adaptive evolution is higher amongst amino acids that are more similar. This is partly due to the fact that the proportion of mutations that are adaptive is higher amongst more similar amino acids. We also find that the rate of neutral evolution between amino acids is higher amongst similar amino acids. Overall our results suggest that both the adaptive and non-adaptive evolution of proteins is dominated by substitutions between amino acids that are more similar.
Occurrence and predictive utility of isochronal, equiproportional, and other types of development among arthropods
Authors: Quinn Brady K. 
Published: July 2018

ABSTRACTIn isochronal (ICD) and equiproportional development (EPD), the proportion of total immature (egg, larval, and/or juvenile) development spent in each stage (developmental proportion) does not vary among stages or temperatures, respectively. ICD and EPD have mainly been reported in copepods, and whether they occur in other arthropods is not known. If they did, then rearing studies could be simplified because the durations of later developmental stages could be predicted based on those of earlier ones. The goal of this study was to test whether different taxa have ICD, EPD, or an alternative development type in which stage-specific proportions depend on temperature, termed ‘variable proportional’ development (VPD), and also how well each development type allowed later-stage durations to be predicted from earlier ones. Data for 71 arthropods (arachnids, copepod and decapod crustaceans, and insects) were tested, and most (85.9 %) species were concluded to have VPD, meaning that ICD and EPD do not occur generally. However, EPD predicted later-stage durations comparably well to VPD (within 19-23 %), and thus may still be useful. Interestingly, some species showed a ‘mixed’ form of development, where some stages’ developmental proportions varied with temperature while those of others did not, which should be further investigated.HighlightsWhether arthropod development is generally isochronal or equiproportional was testedDevelopmental proportions of most species’ stages varied with temperatureMany species had ‘mixed’ development between variable and equiproportional typesThe general occurrence of isochronal and equiproportional development was rejectedEquiproportional development did make reasonable predictions of stage durations
Computationally Reconstructing Cotranscriptional RNA Folding Pathways from Experimental Data Reveals Rearrangement of Non-Native Folding Intermediates
Authors: Yu Angela M , Gasper Paul M. , Strobel Eric J. , Watters Kyle E. , Chen Alan A. , Lucks Julius B. 
Published: July 2018

SummaryThe series of RNA folding events that occur during transcription, or a cotranscriptional folding pathway, can critically influence the functional roles of RNA in the cell. Here we present a method, Reconstructing RNA Dynamics from Data (R2D2), to uncover details of cotranscriptional folding pathways by predicting RNA secondary and tertiary structures from cotranscriptional SHAPE-Seq data. We applied R2D2 to the folding of the Escherichia coli Signal Recognition Particle (SRP) RNA sequence and show that this sequence undergoes folding through non-native intermediate structures that require significant structural rearrangement before reaching the functional native structure. Secondary structure folding pathway predictions and all-atom molecular dynamics simulations of folding intermediates suggest that this rearrangement can proceed through a toehold mediated strand displacement mechanism, which can be disrupted and rescued with point mutations. These results demonstrate that even RNAs with simple functional folds can undergo complex folding processes during synthesis, and that small variations in their sequence can drastically affect their cotranscriptional folding pathways.Highlights- Computational methods predict RNA structures from cotranscriptional SHAPE-Seq data- The E. coli SRP RNA folds into non-native structural intermediates cotranscriptionally- These structures rearrange dynamically to form an extended functional fold- Point mutations can disrupt and rescue cotranscriptional RNA folding pathways