bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of mothers’ past experience and early-life stress on aggression and cognition in adult male mice
Authors: Reshetnikov V. , Ryabushkina Yu. , Bondar N. 
Published: October 2018

AbstractEarly life is an important period for brain development and behavioral programming. Both reduced maternal care and stress in early life are risk factors for various psychiatric disorders. Here, we hypothesized that females’ stressful experience in their early life can lead to a disruption of mother-offspring interactions toward their own progeny. The objective of this study is to assess the effects of mothers’ past stressful experience, early-life stress alone or both on behavior in adult male mice. In this study, female mice were allowed to raise their pups either without exposure to stress (normal rearing condition, NC) or with exposure to maternal separation (3h/day, maternal separation, MS) on postnatal days 2–14. Adult F1 female mice who had experienced MS (stressed mothers, SM) or had been reared normally (undisturbed mothers, UM) were used for generating F2 offspring to be or not to be further exposed to early-life stress. We assessed anxiety-like behavior, exploratory activity, locomotor activity, aggression and cognition in four groups of adult F2 males (UM+NC, UM+MS, SM+NC, SM+MS). We found that SM+MS males become more aggressive if agonistic contact is long enough, suggesting a change in their social coping strategy. Moreover, these aggressive males tended to improve longterm spatial memory. Aggressive SM+NC males, in contrast, showed learning impairments. We did not find any significant differences in anxiety-like behavior or exploratory and locomotor activity. Overall, our findings suggest that mothers’ early-life experience may have important implications for the adult behavior of their offspring.
Development of a microfluidic cell culture and monitoring system for intracellular signaling studies
Authors: Ohkubo Tomoki , Kinoshita Haruyuki , Maekawa Toshiro , Kunida Katsuyuki , Kimura Hiroshi , Kuroda Shinya , Fujii Teruo 
Published: October 2018

AbstractWe describe a microfluidic cell culture and monitoring system that temporally controls molecule concentrations around cells cultured in a small space. The simple system consists of three syringe pumps and a microfluidic device with two inlet ports and two outlet ports. Each syringe pump discharges or draws culture medium, solutions containing signal molecules, or cell suspensions through a port in a programmed flow rate sequence. Signal molecule solutions of differing concentration are merged in a microchannel, mixed immediately, and transported into the cell culture chamber. Regulating the flow rate ratio of syringe pumps over time enables dynamic control of the concentration of signal molecules in the cell culture chamber. The system provides various time-dependent waveforms of concentration over cultured cells, including pulse, rectangular, and triangular. The practical performance of the system for concentration control was evaluated using fluorescent dye imaging. The system was also used with CHO-K1 cells to measure intracellular Ca2+ concentrations, which vary with extracellular ATP levels. When a rectangular pulse of ATP was applied to the cells, Ca2+ levels increased quickly. By contrast, several Ca2+ peaks were observed in response to stepwise increases in ATP concentration. Single-cell Ca2+ responses to ATP pulse stimulation were analyzed by quantitative fluorescence imaging. Hierarchical clustering and quantitative analysis of single-cell data revealed the diversity of Ca2+ responses to ATP pulse stimulation. These results demonstrate that the microfluidic cell culture system is useful for studying a variety of cellular responses, including cell signaling.
CBFβ-MYH11 interferes with megakaryocyte differentiation via modulating a gene program that includes GATA2 and KLF1
Authors: Yi Guoqiang , Mandoli Amit , Jussen Laura , Tijchon Esther , Cordonnier Gaëlle , Hansen Marten , Kim Bowon , Nguyen Luan N. , Jansen Pascal , Vermeulen Michiel , van den Akker Emile , Bond Jonathan , Martens Joost H.A. 
Published: October 2018

AbstractThe inv(16) acute myeloid leukemia associated CBFβ-MYH11 fusion is proposed to block normal myeloid differentiation, but whether this subtype of leukemia cells is poised for a unique cell lineage remains unclear. Here, we surveyed the functional consequences ofCBFβ - MYH11in primary inv(16) patient blasts, upon expression during hematopoietic differentiationin vitroand upon knockdown in cell lines by multi-omics profiling. Our results reveal that primary inv(16) AML cells share common transcriptomic signatures and epigenetic determiners with megakaryocytes and erythrocytes. Usingin vitrodifferentiation systems, we reveal that CBFβ-MYH11 knockdown interferes with normal megakaryocyte maturation. Two pivotal regulators, GATA2 and KLF1, are identified to complementally occupy RUNX1 binding sites upon fusion protein knockdown, and overexpression of GATA2 partly restores megakaryocyte directed differentiation suppressed by CBFβ-MYH11. Together, our findings suggest that in inv(16) leukemia, the CBFβ-MYH11 fusion inhibits primed megakaryopoiesis by attenuating expression of GATA2/KLF1 and interfering with a balanced transcriptional program involving these two factors.
Reticulate evolution in eukaryotes: origin and evolution of the nitrate assimilation pathway
Authors: Ocaña-Pallarès Eduard , Najle Sebastián R. , Scazzocchio Claudio , Ruiz-Trillo Iñaki 
Published: October 2018

AbstractGenes and genomes can evolve through interchanging genetic material, this leading to reticular evolutionary patterns. However, the importance of reticulate evolution in eukaryotes, and in particular of horizontal gene transfer (HGT), remains controversial. Given that metabolic pathways with taxonomically-patchy distributions can be indicative of HGT events, the eukaryotic nitrate assimilation pathway is an ideal object of investigation, as previous results revealed a patchy distribution and suggested one crucial HGT event. We studied the evolution of this pathway through both multi-scale bioinformatic and experimental approaches. Our taxon-rich genomic screening shows this pathway to be present in more lineages than previously proposed and that nitrate assimilation is restricted to autotrophs and to distinct osmotrophic groups. Our phylogenies show a pervasive role of HGT, with three bacterial transfers contributing to the pathway origin, and at least seven well-supported transfers between eukaryotes. Our results, based on a larger dataset, differ from the previously proposed transfer of a nitrate assimilation cluster from Oomycota (Stramenopiles) to Dikarya (Fungi, Opisthokonta). We propose a complex HGT path involving at least two cluster transfers between Stramenopiles and Opisthokonta. We also found that gene fusion played an essential role in this evolutionary history, underlying the origin of the canonical eukaryotic nitrate reductase, and of a novel nitrate reductase in Ichthyosporea (Opisthokonta). We show that the ichthyosporean pathway, including this novel nitrate reductase, is physiologically active and transcriptionally co-regulated, responding to different nitrogen sources; similarly to distant eukaryotes with independent HGT-acquisitions of the pathway. This indicates that this pattern of transcriptional control evolved convergently in eukaryotes, favoring the proper integration of the pathway in the metabolic landscape. Our results highlight the importance of reticulate evolution in eukaryotes, by showing the crucial contribution of HGT and gene fusion in the evolutionary history of the nitrate assimilation pathway.
Simultaneous isotope dilution quantification and metabolic tracing of deoxyribonucleotides by liquid chromatography high resolution mass spectrometry
Authors: Kuskovsky Rostislav , Buj Raquel , Xu Peining , Hofbauer Samuel , Doan Mary T , Jiang Helen , Bostwick Anna , Mesaros Clementina , Aird Katherine M. , Snyder Nathaniel W. 
Published: October 2018

AbstractQuantification of cellular deoxyribonucleoside mono-(dNMP), di-(dNDP), triphosphates (dNTPs) and related nucleoside metabolites are difficult due to their physiochemical properties and widely varying abundance. Involvement of dNTP metabolism in cellular processes including senescence and pathophysiological processes including cancer and viral infection make dNTP metabolism an important bioanalytical target. We modified a previously developed ion pairing reversed phase chromatography-mass spectrometry method for the simultaneous quantification and 13C isotope tracing of dNTP metabolites. dNMPs, dNDPs, and dNTPs were chromatographically resolved to avoid mis-annotation of in-source fragmentation. We used commercially available 13C15N-stable isotope labeled analogs as internal standards and show that this isotope dilution approach improves analytical figures of merit. At sufficiently high mass resolution achievable on an Orbitrap mass analyzer, stable isotope resolved metabolomics allows simultaneous isotope dilution quantification and 13C isotope tracing from major substrates including 13C-glucose. As a proof of principle, we quantified dNMP, dNDP and dNTP pools from multiple cell lines. We also identified isotopologue enrichment from glucose corresponding to ribose from the pentose-phosphate pathway in dNTP metabolites.
Physiological Synchrony Predicts Observational Threat Learning in Humans
Authors: Pärnamets Philip , Espinosa Lisa , Olsson Andreas 
Published: October 2018

AbstractUnderstanding how information about threats in the environment is shared and transmitted between individuals is crucial for explaining adaptive, survival-related behavior in humans and other animals, and for developing treatments for phobias and other anxiety disorders. Research across species has shown that observing a conspecific’s, a “demonstrator’s”, threat responses causes strong and persistent threat memories in the “observer”. Here, we examined if physiological synchrony between demonstrator and observer can serve to predict the strength of observationally acquired conditioned responses. We measured synchrony between demonstrators’ and observers’ phasic electrodermal signals during learning, which directly reflects autonomic nervous system activity. Prior interpersonal synchrony predicted the strength of the observer’s later skin conductance responses to threat predicting stimuli, in the absence of the demonstrator. Dynamic coupling between an observer’s and a demonstrator’s autonomic nervous system activity may reflect experience sharing processes facilitating the formation of observational threat associations.
Improving the interpretability of species distribution models by using local approximations
Authors: Angelov Boyan 
Published: October 2018

ABSTRACTSpecies Distribution Models (SDMs) are used to generate maps of realised and potential ecological niches for a given species. As any other machine learning technique they can be seen as “black boxes”, due to a lack of interpretability. Advances in other areas of applied machine learning can be applied to remedy this problem. In this study we test a new tool relying on Local Interpretable Model-agnostic Explanations (LIME) by comparing its results of other known methods and ecological interpretations from domain experts. The findings confirm that LIME provides consistent and ecologically sound explanations of climate feature importance during the training of SDMs, and that the sdmexplain R package can be used with confidence.
Photoacoustic pigment relocalization sensor
Authors: Lauri Antonella , Soliman Dominik , Omar Murad , Stelzl Anja , Ntziachristos Vasilis , Westmeyer Gil G. 
Published: October 2018

ABSTRACTPhotoacoustic (optoacoustic) imaging can extract molecular information with deeper tissue penetration than possible by fluorescence microscopy techniques. However, there is currently still a lack of robust genetically controlled contrast agents and molecular sensors that can dynamically detect biological analytes of interest with photoacoustics. In this biomimetic approach, we took inspiration from cuttlefish who can change their color by relocalizing pigment-filled organelles in so-called chromatophore cells under neurohumoral control. Analogously, we tested the use of melanophore cells from Xenopus laevis, containing compartments (melanosomes) filled with strongly absorbing melanin, as whole-cell sensors for optoacoustic imaging. Our results show that pigment relocalization in these cells, which is dependent on binding of a ligand of interest to a specific G protein-coupled receptor (GPCR), can be monitored in vitro and in vivo using photoacoustic mesoscopy. In addition to changes in the photoacoustic signal amplitudes, we could furthermore detect the melanosome aggregation process by a change in the frequency content of the photoacoustic signals. Using bioinspired engineering, we thus introduce a photoacoustic pigment relocalization sensor (PaPiReS) for molecular photoacoustic imaging of GPCR-mediated signaling molecules.
The development of social interactions inCorydoras aeneuslarvae
Authors: Riley RJ , Roe T , Gillie ER , Boogert NJ , Manica A 
Published: October 2018

AbstractVery young animals develop life skills as they mature, and for social animals this includes the acquisition of social abilities such as communication. Many animals exhibit changeable patterns of social behavior based on development, and social experience during the juvenile period can be vital for the development of necessary social behaviors in adulthood. We investigated the development of a distinctive tactile interaction behavior inCorydoras aeneus, the Bronze Cory catfish. Adults use this behavior to coordinate group activities during foraging and flight responses from predators, and the development of this behavior in larvae is of interest in investigating how communication and social behaviors develop as an individual matures, and which factors affect their development. We found that larvae respond to applied tactile stimulation with a flight response far less often as larvae matured, implying that larvae become less sensitive to tactile stimulation with age. Given that adults frequently interact with one another tactilely, this development is consistent with developing appropriate social behavior in adulthood. We also found that social exposure affects the development of the larval response to tactile interactions with conspecifics, and that isolation in the earliest larval stage leads to a greater likelihood of responding to a tactile interaction with a conspecific with a flight response. This suggests that social exposure is important for developing an appropriate response to tactile stimulation in social settings and underscores the particular importance of early life experiences in the development of sociality.
Novel insights into the genetic relationship between growth and disease resistance in Pacific salmon
Authors: Barría Agustin , Doeschl-Wilson Andrea. B. , Lhorente Jean P. , Houston Ross. D. , Yáñez José. M. 
Published: October 2018

AbstractBackgroundBreeding for disease resistance has become a highly desirable strategy for mitigating infectious disease problems in aquaculture. However, knowledge of the genetic relationship between resistance and other economically important traits, such as growth, is important to assess prior to including disease resistance into the breeding goal. Our study assessed the genetic correlations between growth and survival traits in a large bacterial infection challenge experiment. A population of 2,606 coho salmon individuals from 107 full-sibling families were challenged with the bacteria Piscirickettsia salmonis. Growth was measured as average daily gain prior (ADG0) and during (ADGi) the experimental infection and as harvest weight (HW). Resistance was measured as Survival time (ST) and binary survival (BS). Furthermore, individual measures of bacterial load (BL) were assessed as new resistance phenotypes and to provide an indication of genetic variation in tolerance in salmonid species.ResultsSignificant moderate heritabilities were estimated for ADG0 (0.30 ± 0.05), HW (0.38 ± 0.03), and for the survival traits ST (0.16 ± 0.03) and BS (0.18 ± 0.03). In contrast, heritabilities for ADGi and log-transformed BL were low (0.07 ± 0.02 (significant) and 0.04 ± 0.03, respectively), although these increased to moderate significant levels (0.20 ± 0.09 and 0.12 ± 0.05, respectively) when traits were assessed in survivors only. Significant and favorable genetic correlations were found between ADG0 and the growth traits ADGi (0.40 ± 0.16) and HW (0.64 ± 0.09), as well as with resistance as ST (0.43 ± 0.18), indicating that fish with higher genetic growth rate early on and prior to infection not only tend to maintain their genetic growth advantage until harvest, but also tend to grow faster and survive longer during infection. Furthermore, no robust unfavorable genetic correlations between ADG0 and any of the other traits considered in this study, in particular BL, was identified. Adding log BL as covariates into the models for growth under infection and survival provided an indication for genetic variation in tolerance.ConclusionsThese results suggest that selective breeding for early growth would be expected to simultaneously increase survival time and growth performance during an infection with Piscirickettsia salmonis after accounting for variation in bacterial load, and harvest weight in this coho salmon population, without negatively impacting on pathogen burden.
Bioinorganic Angiogenesis
Authors: Maillard Sophie , Charbonnier Baptiste , Sayed Omaer , Baradaran Aslan , Manga Harshdeep , Dallison Benjamin , Zhang Zishuai , Zhang Yu Ling , Hussain Sabah N.A. , Mayaki Dominique , Seitz Hermann , Harvey Edward J. , Gilardino Mirko , Gbureck Uwe , Makhoul Nicholas , Barralet Jake 
Published: October 2018

AbstractCausing a large diameter blood vessel to sprout branches and a capillary network on demand to create a new angiosome is key to harnessing to potential of regenerative medicine and advancing reconstructive surgery. Currently this can only be achieved by connecting a vein graft to an artery by microsurgery, the arteriovenous loop technique (AVL). The arterial blood pressure in the thin-walled vein is thought to drive remodelling to create branches, however the surgical complexity limits the application of the technique. In this study we demonstrate that unexpectedly, a vessel density of luminal branches in excess of that achieved by the surgical AVL approach can be induced simply by placing a vein in contact with a microporous calcium phosphate. Only osteoinductive biomaterials have been reported previously, this is thought to be the first report of an angio-inductive material. Pilot studies indicated that the material type greatly affected the degree of luminal vascularization. Material contact with the vein is not a requirement for luminal angiogenesis of the vein and together these findings point to a bioinorganic effect, wherein the degradation of the material both releases a stimulatory ionic milieu and creates space for the developing angiosome.
Characterising Genetic Diversity in Cassava Brown Streak Virus
Authors: Crotty Stephen M , Rohrlach Adam B , Ndunguru Joseph , Boykin Laura M 
Published: October 2018

AbstractPlant viruses represent a significant threat to food security for many global populations. Cassava Brown Streak Virus (CBSV) causes immense damage to cassava crops in Eastern, Central and Southern Africa. The eradication of CBSV is a difficult challenge, as it has been shown to be fast-evolving and it is transmitted by flying insects that are ubiquitous in cassava growing regions. In this paper we demonstrate the ability of two new developments in bioinformatics that can be used to increase our understanding of CBSV and ultimately inform strategies for its combat. We reconstruct the phylogeny of 29 whole-genome virus isolates using the GHOST model. This phylogeny identifies three distinct clades among the viruses and highlights a section of the genomes that is highly influential in their divergence. We also perform Multiple Correspondence Analysis on the alignment which is consistent in recovering the three clades, and offers insight on the significance of the influence of a variety of external variables on the evolution of the viruses. Knowledge and information from this analysis will be used as a base on which to formulate sustainable Cassava Brown Streak Disease (CBSD) management strategies in Africa.
Multi-SNP Mediation Intersection-Union Test
Authors: Zhong Wujuan , Spracklen Cassandra N. , Mohlke Karen L. , Zheng Xiaojing , Fine Jason , Li Yun 
Published: October 2018

ABSTRACTTens of thousands of reproducibly identified GWAS (Genome-Wide Association Studies) variants, with the vast majority falling in non-coding regions resulting in no eventual protein products, call urgently for mechanistic interpretations. Although numerous methods exist, there are few, if any methods, for simultaneously testing the mediation effects of multiple correlated SNPs via some mediator (for example, the expression of a gene in the neighborhood) on phenotypic outcome. We propose SMUT, multi-SNPMediation intersection-UnionTest to fill in this methodological gap. Our extensive simulations demonstrate the validity of SMUT as well as substantial, up to 92%, power gains over alternative methods. In addition, SMUT confirmed known mediators in a real dataset of Finns for plasma adiponectin level, which were missed by many alternative methods. We believe SMUT will become a useful tool to generate mechanistic hypotheses underlying GWAS variants, facilitating functional follow-up. The R package SMUT is publicly available from CRAN athttps://CRAN.R-project.org/package=SMUT.
Use of a corneal impression membrane for the detection of Herpes Simplex Virus type-1
Authors: Brunner Matthias , Somerville Tobi , Corless Caroline E , Myneni Jayavani , Rajhbeharrysingh Tara , Tiew Stephenie , Neal Timothy , Kaye Stephen B. 
Published: October 2018

AbstractPurposeTo investigate the use of a corneal impression membrane (CIM) for the detection of Herpes Simplex Virus type 1 (HSV-1) in suspected Herpes Simplex Keratitis (HSK).Materials and MethodsIn the laboratory study, swabs and CIMs made from polytetrafluoroethylene were spiked with different concentrations of HSV-1. DNA was extracted and real time PCR undertaken using 2 sets of primers. In the clinical study consecutive patients presenting with suspected HSK were included. For each patient, samples were collected from corneal lesions with a swab and a CIM in random order. Clinical details were collected using a standardised clinical form and patients were categorized into probable, presumed and possible HSK.ResultsThere was no difference in the performance of both primer sets for all HSV-1 dilutions (p=0.83) or between a CIM and a swab (p=0.18). 110 patients were included. Seventy-three patients (66.4%) had probable, 20 patients (18.2%) presumed, and 17 patients (15.5%) possible HSV-1 keratitis. The HSV-1 detection rate was significantly higher using a CIM (40/110, 36.4%) than a swab (28/110, 25.5%) (p=0.004). In the probable HSV keratitis group, the detection rate using a CIM was 43.8% compared to 27.4% for a swab (p=0.004). The Cp values obtained for the conjunctival swabs were higher than those obtained for the CIMs (p<0.001).ConclusionsIn suspected HSK, a CIM is a useful alternative to a swab and more likely to detect the presence of HSV-1.