bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in zygotic CRISPR/Cas9 gene editing outcomes generates novel reporter and deletion alleles at the Gdf11 locus
Authors: Goldstein Jill M. , Valido Austin , Lewandowski Jordan P. , Walker Ryan G. , Mills Melanie J. , Messemer Kathleen A. , Besseling Paul , Lee Kyu Ha , Wattrus Samuel J. , Cho Miook , Lee Richard T. , Wagers Amy J. 
Published: December 2019

AbstractRecent advances in CRISPR/Cas gene editing technology have significantly expanded the possibilities and accelerated the pace of creating genetically engineered animal models. However, CRISPR/Cas-based strategies designed to precisely edit the genome can often yield unintended outcomes. Here, we report the use of zygotic CRISPR/Cas9 injections to generate a knock-in GFP reporter mouse at the Gdf11 locus. Phenotypic and genomic characterization of founder animals from these injections revealed a subset that contained the correct targeting event and exhibited GFP expression that, within the hematopoietic system, was restricted predominantly to lymphoid cells. Yet, in another subset of founder mice, we detected aberrant integration events at the target site that dramatically and inaccurately shifted hematopoietic GFP expression from the lymphoid to the myeloid lineage. Additionally, we recovered multiple Gdf11 deletion alleles that modified the C-terminus of the GDF11 protein. When bred to homozygosity, most of these alleles recapitulated skeletal phenotypes reported previously for Gdf11 knockout mice, suggesting that these represent null alleles. However, we also recovered one Gdf11 deletion allele that encodes a novel GDF11 variant protein (“GDF11-WE”) predicted to contain two additional amino acids (tryptophan (W) and glutamic acid (E)) at the C-terminus of the mature ligand. Unlike the other Gdf11 deletion alleles recovered in this study, homozygosity for the Gdf11WE allele did not phenocopy Gdf11 knockout skeletal phenotypes. Further investigation using in vivo and in vitro approaches demonstrated that GDF11-WE retains substantial physiological function, indicating that GDF11 can tolerate at least some modifications of its C-terminus and providing unexpected insights into its biochemical activities. Altogether, our study confirms that one-step zygotic injections of CRISPR/Cas gene editing complexes provide a quick and powerful tool to generate gene-modified mouse models. Moreover, our findings underscore the critical importance of thorough characterization and validation of any modified alleles generated by CRISPR, as unintended on-target effects that fail to be detected by simple PCR screening can produce substantially altered phenotypic readouts.
Prey capture analyses in the carnivorous aquatic waterwheel plant (Aldrovanda vesiculosa L., Droseraceae)
Authors: Poppinga Simon , Smaij Jassir , Westermeier Anna Sofia , Horstmann Martin , Kruppert Sebastian , Tollrian Ralph , Speck Thomas 
Published: December 2019

AbstractWe investigated the predator-prey interactions between an Australian ecotype of the carnivorous waterwheel plant (Aldrovanda vesiculosa, Droseraceae) and its potential natural prey, the water flea Daphnia longicephala (Daphniidae), which also occurs in Australia. A. vesiculosa develops snap-traps, which close within ~10–100 ms after mechanical triggering by zooplankton prey. Prey capture attempts (PCAs) were recorded via high-speed cinematography in the laboratory. From 14 recorded PCAs, nine were successful for the plant (the prey was caught), and five were unsuccessful (prey could escape), resulting in a capture rate of ~64%. The prey animals’ locomotion behaviour (antenna beat frequency and movement type) in trap vicinity or inside the open traps is very variable. Traps were mainly triggered with the second antennae. During trap closure, the animals moved only very little actively. A flight response in reaction to an initiated trap closure was not observed. However, several animals could escape, either by having a “lucky” starting position already outside the triggered trap, by freeing themselves after trap closure, or by being pressed out by the closing trap lobes. According to our observations in the successful PCAs, we hypothesize that the convex curvature of the two trap lobes (as seen from the outside) and the infolded trap rims are structural means supporting the capture and retention of prey. Our results are discussed in a broader biological context and promising aspects for future studies are proposed.
Modeling somatic computation with non-neural bioelectric networks
Authors: Manicka Santosh , Levin Michael 
Published: December 2019

AbstractThe field of basal cognition seeks to understand how adaptive, context-specific behavior occurs in non-neural biological systems. Embryogenesis and regeneration require plasticity in many tissue types to achieve structural and functional goals in diverse circumstances. Thus, advances in both evolutionary cell biology and regenerative medicine require an understanding of how non-neural tissues could process information. Neurons evolved from ancient cell types that used bioelectric signaling to perform computation. However, it has not been shown whether or how non-neural bioelectric cell networks can support computation. We generalize connectionist methods to non-neural tissue architectures, showing that a minimal non-neural Bio-Electric Network (BEN) model that utilizes the general principles of bioelectricity (electrodiffusion and gating) can compute. We characterize BEN behaviors ranging from elementary logic gates to pattern detectors, using both fixed and transient inputs to recapitulate various biological scenarios. We characterize the mechanisms of such networks using dynamical-systems and information-theory tools, demonstrating that logic can manifest in bidirectional, continuous, and relatively slow bioelectrical systems, complementing conventional neural-centric architectures. Our results reveal a variety of non-neural decision-making processes as manifestations of general cellular biophysical mechanisms and suggest novel bioengineering approaches to construct functional tissues for regenerative medicine and synthetic biology as well as new machine learning architectures.
Gut Microbiota in Children With Cystic Fibrosis: A Taxonomic and Functional Dysbiosis
Authors: Coffey Michael J. , Nielsen Shaun , Wemheuer Bernd , Kaakoush Nadeem O. , Garg Millie , Needham Bronwen , Pickford Russell , Jaffe Adam , Thomas Torsten , Ooi Chee Y. 
Published: December 2019

AbstractIntestinal dysbiosis has been observed in children with cystic fibrosis (CF), yet the functional consequences are poorly understood. We investigated the functional capacity of intestinal microbiota and inflammation in children with CF. Stool samples were collected from 27 children with CF and 27 age and gender matched healthy controls (HC) (aged 0.8–18 years). Microbial communities were investigated by iTag sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun. Inflammation was measured by faecal calprotectin and M2-pyruvate kinase. Paediatric CF gastrointestinal microbiota demonstrated lower richness and diversity compared to HC. CF samples exhibited a marked taxonomic and inferred functional dysbiosis when compared to HC. In children with CF, we predicted an enrichment of genes involved in short-chain fatty acid (SCFA), antioxidant and nutrient metabolism (relevant for growth and nutrition) in CF. The notion of pro-inflammatory GI microbiota in children with CF is supported by positive correlations between intestinal inflammatory markers and both genera and functional pathways. We also observed an association between intestinal genera and both growth z-scores and FEV1%. These taxonomic and functional changes provide insights into gastrointestinal disease in children with CF and future gastrointestinal therapeutics for CF should explore the aforementioned pathways and microbial changes.
DAXX mutations as potential genomic markers of malignant evolution in small nonfunctioning pancreatic neuroendocrine tumors
Authors: Cives Mauro , Partelli Stefano , Palmirotta Raffaele , Lovero Domenica , Mandriani Barbara , Quaresmini Davide , Pelle’ Eleonora , Andreasi Valentina , Castelli Paola , Strosberg Jonathan , Zamboni Giuseppe , Falconi Massimo , Silvestris Franco 
Published: December 2019

AbstractManagement of localized well-differentiated pancreatic neuroendocrine tumors (panNETs) is controversial and primarily dependent on tumor size. Upfront surgery is usually recommended for tumors larger than 2 cm in diameter since they frequently show metastatic potential, whereas smaller panNETs are generally characterized by an indolent clinical course, with a rate of relapse or metastasis below 15%. To explore whether increased tumor size is paralleled by genomic variations, we compared the rate and the mutational patterns of putative driver genes that are recurrently altered in these tumors by investigating differential cohorts of panNET surgical specimens smaller (n = 27) or larger than 2 cm (n = 29). We found that the cumulative number of mutations detected in panNETs >2 cm was significantly higher (p = 0.03) relative to smaller tumors, while mutations of DAXX were significantly more frequent in the cohort of larger tumors (p = 0.05). Moreover, mutations of DAXX were associated with features of malignancy including increased grade, nodal involvement and lymphovascular invasion, and independently predicted both relapse after surgery (p = 0.05) and reduced DFS in multivariable analysis (p = 0.02). Our data suggest that alterations of the DAXX/ATRX molecular machinery increase the malignant potential of panNETs, and that identification of mutations of DAXX/ATRX in small, nonfunctioning tumors can predict the malignant progression observed in a minority of them.
The inability of a dengue NS1 ELISA to detect Zika infections
Authors: Lima Monique da Rocha Queiroz , Chouin-Carneiro Thais , Azeredo Elzinandes , Barbosa Luciana Santos , Souza Thiara Manuele Alves , Silva Jéssica Badolato Corrêa da , Nunes Priscila Conrado Guerra , Dal Fabbro Márcia , Facco Izilyanne H. Romanholi , Venâncio-da-Cunha Rivaldo , dos Santos Flavia Barreto 
Published: December 2019

AbstractThe presence of dengue virus (DENV), Zika virus (ZIKV) and Chikungunya virus (CHIKV) in Brazil, may result in a difficult diagnosis due to the signs and symptoms shared by those. Moreover, as DENV and ZIKV belong to the same family, serological assays may show a high rate of cross-reactivity. Here, we evaluated a Dengue NS1 capture assay for early and differential diagnosis of dengue during the Zika epidemic occurred in Brazil in 2016. Samples (n = 227) from 218 patients included sera, plasma and urine from previously confirmed acute cases of Zika, dengue and Zika/dengue co-infections. Nine of those patients presented two specimens. The Dengue NS1 test was very specific for dengue diagnosis (99.32%), even in the co-circulation with ZIKV, and exhibited a high accuracy in not detecting acute Zika infections (92.43%). Our findings showed that the dengue NS1 capture test analyzed here was not able to recognize the ZIKV NS1 and its potential for cross-reaction.
Population-based volume kinetics of crystalloids and colloids in healthy volunteers
Authors: Yi Jung-Min , Bang Ji-Yeon , Choi Bohyun , Cho Changhun , Lee Yong-Hun , Lee Eun-Kyung , Choi Byung-Moon , Noh Gyu-Jeong 
Published: December 2019

AbstractWe characterized the volume kinetics of crystalloid solutions (Ringer’s lactate solution and 5% dextrose water) and colloid solutions (6% tetrastarch and 10% pentastarch) by nonlinear mixed-effects modeling in healthy volunteers. We also assessed whether the bioelectrical impedance analysis parameters are significant covariates for volume kinetic parameters. Twelve male volunteers were randomly allocated to four groups, and each group received the four fluid solutions in specified sequences, separated by 1-week intervals to avoid any carryover effects. Volunteers received 40 ml/kg Ringer’s lactate solution, 20 ml/kg 5% dextrose water, 1000 ml 6% tetrastarch, and 1000 ml 10% pentastarch over 1 h. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. Bioelectrical impedance spectroscopy (BIS, INBODY S10, InBody CO., LTD, Seoul, Korea) was also carried out at preset time points. In total, 671 hemoglobin-derived plasma dilution data points were used to determine the volume kinetic characteristics of each fluid. The changes in plasma dilution induced by administration of crystalloid and colloid solutions were well-described by the two-volume and one-volume models, respectively. Extracellular water was a significant covariate for the peripheral volume of distribution at baseline in the volume kinetic model of Ringer’s lactate solution. When the same amount was administered, the colloid solutions had ~4 times more plasma expansion effect than did the crystalloid solutions. Starches with larger molecular weights maintained the volume expansion effect longer than those with smaller molecular weights.
Onset of summer monsoon in Northeast India is preceded by enhanced transpiration
Authors: Pradhan Rohit , Singh Nimisha , Singh Raghavendra P. 
Published: December 2019

AbstractVariations in isotopic composition of water vapor in the atmosphere is an important indicator of the processes within the hydrological cycle. Isotopic signature of water vapor and precipitation can be helpful in partitioning evaporation and transpiration fluxes. It is well known that transpiration from forested regions supplies a significant amount of vapor to the atmosphere in monsoon and post-monsoon seasons. Here, we utilize observations from Tropospheric Emission Spectrometer (TES), Atmospheric Infra-Red Sounder (AIRS) and simulation models to ascertain that transpiration is dominant in the forests of Northeast India (NE) during pre-monsoon season. Our results show an increase in δD of 78.0 ± 7.1‰ and in specific humidity of 3.1 ± 0.2 g kg−1 during the pre-monsoon months of April-May compared to January-February. In the monsoon months of July-August, δD reduces by 53.0 ± 6.5‰ albeit the specific humidity increases by 3.4 ± 0.2 g kg−1. Using joint observations of specific humidity and isotope ratio in lower troposphere, we discern the moisture sources over NE India in pre-monsoon and monsoon seasons and posit the role of transpiration in continental recycling during pre-monsoon season.
Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos
Authors: Koca Yildiz , Housden Benjamin E. , Gault William J. , Bray Sarah J. , Mlodzik Marek 
Published: December 2019

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.
Optimal Contexts for Verb Learning
Authors: Horvath Sabrina , Arunachalam Sudha 
Published: December 2019

PurposeVerb learning is a critical but challenging part of language acquisition. Children with or at increased risk for developmental language disorder may particularly struggle with verb learning, and poor verb representations in turn may negatively impact children's language outcomes. Our goal is to examine literature on children's acquisition of verbs, identifying manipulable factors that may determine the ease or difficulty of acquiring a new verb meaning.MethodIn this narrative, nonsystematic review, we discuss findings about how verbs are learned and represented.ResultsSeveral aspects of the learning environment affect children's efforts to acquire verbs, including the linguistic context in which the verb is introduced, the timing of the linguistic label relative to the event it describes, the visual and linguistic variability, and the dose frequency.ConclusionsWe conclude that some learning situations are likely to be more helpful for children in the process of verb learning than others. We highlight some of the factors that contribute to good learning situations, and we discuss how these may differ depending on properties of the child and of the verb itself. Finally, we propose hypotheses for future translational and clinical research.
Identifying hot spots in GSU power transformers using multiple methods
Authors: Souza Melo André de , Venceslau Calil Wilerson , Marques Costa Eduardo Coelho , Bartocci Liboni Luisa H. , Giuseppe Di Santo Silvio 
Published: December 2019

A routine using multiple methods is proposed for detecting and locating hot spots in power transformers based on thermographic measurements and advanced computational and analytical techniques. The proposed method identifies oxide and hydrocarbon gases dissolved in the insulation oil of power transformers and use the well‐established key gas method to provide information about the cause of the hot spots, such as partial discharge, electric arc, and overload heating. The method then uses infrared mappings and temperature measurements to find the approximate location of the hot spots and, finally, the finite element method and an analytical formulation are employed to refine the location of the hotspots and the estimation of their temperature. The proposed method was developed during the design and manufacturing of a commercial 120 MVA generator step‐up transformer, produced by a well‐renowned manufacturer. The authors conclude that a method is a resourceful tool for identifying hot spots and could be used by manufacturers to identify and predict design and manufacturing failures.
A realistic two-dimensional model of Altair
Authors: Bouchaud K. , Domiciano de Souza A. , Rieutord M. , Reese D. R. , Kervella P. 
Published: December 2019

Context. Fast rotation is responsible for important changes in the structure and evolution of stars and the way we see them. Optical long baseline interferometry now allows for the study of its effects on the stellar surface, mainly gravity darkening and flattening.
Aims. We aim to determine the fundamental parameters of the fast-rotating star Altair, in particular its evolutionary stage (represented here by the core hydrogen mass fraction Xc), mass, and differential rotation, using state-of-the-art stellar interior and atmosphere models together with interferometric (ESO-VLTI), spectroscopic, and asteroseismic observations.
Methods. We use ESTER two-dimensional stellar models to produce the relevant surface parameters needed to create intensity maps from atmosphere models. Interferometric and spectroscopic observables are computed from these intensity maps and several stellar parameters are then adjusted using the publicly available MCMC algorithm Emcee.
Results. We determined Altair’s equatorial radius to be Req = 2.008 ± 0.006 R⊙, the position angle PA = 301.1 ± 0.3°, the inclination i = 50.7 ± 1.2°, and the equatorial angular velocity Ω = 0.74 ± 0.01 times the Keplerian angular velocity at equator. This angular velocity leads to a flattening of ε = 0.220 ± 0.003. We also deduce from the spectroscopically derived v sin i ≃ 243 km s−1, a true equatorial velocity of ∼314 km s−1 corresponding to a rotation period of 7h46m (∼3 cycles/day). The data also impose a strong correlation between mass, metallicity, hydrogen abundance, and core evolution. Thanks to asteroseismic data, and provided our frequencies identification is correct, we constrain the mass of Altair to 1.86 ± 0.03 M⊙ and further deduce its metallicity Z = 0.019 and its core hydrogen mass fraction Xc = 0.71, assuming an initial solar hydrogen mass fraction X = 0.739. These values suggest that Altair is a young star ∼100 Myr old. Finally, the 2D ESTER model also gives the internal differential rotation of Altair, showing that its core rotates approximately 50% faster than the envelope, while the surface differential rotation does not exceed 6%.
Onlinemonitoring der Vitalparameter bei Personen im Einsatz in extremen Umwelten
Authors: Werner Andreas 
Published: December 2019

ZUSAMMENFASSUNGTelemedizin (eHealth) ist aus der heutigen Welt nicht mehr wegzudenken. In manchen Bereichen geht es ohne diese Übertragung gar nicht – im Weltraum. Die modernsten und neuesten Informations- und Kommunikationssysteme werden im Gesundheitssystem eingesetzt; in Kliniken schon lange zum Monitoring von Patienten verwendet. Beim US-amerikanischen „soldier of the future“ soll ein Onlinemonitoring die Performancedaten während eines Einsatzes übertragen. Zukünftig sollen nicht nur Vitalparameter erfasst werden, sondern der kognitive, metabolische und „Combat-ready-Status“ zur Verfügung gestellt werden. Diese könnten operationell als situative Erkenntnisse für den Kommandeur oder für den Mediziner im Fall eines Patientenmonitorings zugänglich gemacht werden. Insgesamt ist überall die Absicht zu erkennen, dass es zukünftig möglich sein soll, ein Individuum über eine digitale, gesundheitsförderliche Plattform zu monitoren, um seine Gesundheit und Leistungsfähigkeit zu erhalten oder zu erhöhen.
Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma
Authors: Lim Chun Jye , Chew Valerie 
Published: December 2019

AbstractHepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20%), with mixed reports on response rates in hepatitis viral-related HCC as compared with nonviral HCC. Given such complexity in response to immunotherapy, it is increasingly appreciated that deeper understanding of the tumor molecular features and tumor microenvironment of hepatitis viral-related HCC is crucial for the design of more effective immunotherapeutics. We discuss herein the current knowledge in tumor genomic mutational and immune landscapes as well as the ongoing immunotherapy trials in HCC with the unique focus on their viral etiologies. Based on this understanding, we also outline perspectives and rationale on the design of potential immunotherapeutic strategies in HCC patients according to their viral etiologies.