bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTORC1 Restricts Hepatitis C Virus Replication Through ULK1-mediated Suppression of miR-122 and Facilitates Post-replication Events
Authors: Johri Manish Kumar , Lashkari Hiren Vasantrai , Vedagiri Dhiviya , Gupta Divya , Harshan Krishnan Harinivas 
Published: October 2018

ABSTRACTMechanistic target of rapamycin (mTOR) is an important kinase that assimilates several upstream signals including viral infection and facilitates appropriate response by the cell through two unique complexes mTORC1 and mTORC2. Here, we demonstrate that mTORC1 is activated early during HCV infection as antiviral response. Pharmacological inhibition of mTORC1 promoted HCV replication as suggested by elevated levels of HCV (+) and (-) RNA strands. This was accompanied by significant drop in extracellular HCV RNA levels indicating defective post-replication stages. The increase in viral RNA levels failed to augment intracellular infectious virion levels, suggesting that mTORC1 inhibition is detrimental to post-replication steps. Lower infectivity of the supernatant confirmed this observation. Depletion of Raptor and ULK1 accurately reproduced these results suggesting that mTORC1 imparted these effects on HCV through mTORC1-ULK1 arm. Interestingly, ULK1 depletion resulted in increased levels of miR-122, a critical host factor for HCV replication, thus revealing a new mechanism of regulation by ULK1. The binary effect of mTORC1 on HCV replication and egress suggests that mTORC1-ULK1 could be critical in replication: egress balance. Interestingly we discover that ULK1 depletion did not interfere with autophagy in Huh7.5 cells and hence the effects on HCV replication and post-replication events are not resultant of involvement of autophagy. Our studies demonstrate an overall ULK1 mediated anti-HCV function of mTORC1 and identifies an ULK1-independent autophagy that allows HCV replication in spite of mTORC1 activation.
Reconstructing the origins of the space-number association: spatial and number-magnitude codes must be used jointly to elicit spatially organised mental number lines
Authors: Pinto Mario , Pellegrino Michele , Marson Fabio , Lasaponara Stefano , Doricchi Fabrizio 
Published: October 2018

AbstractIn a series of recent studies we have pointed out that the use of contrasting left/right spatial codes, whether indirectly related to number magnitudes through response selection or directly associated to the same magnitudes to guide their spatial positioning on a mental number line, is crucial in eliciting space-number associations (Aiello, 2012; Fattorini et al., 2015; 2016; Pinto et al., 2018). Nonetheless, this conclusion is based on experiments in which spatial and number-magnitudes codes are used jointly during task performance. Here, in a series of unimanual Go/No-Go tasks with intermixed central numerical and pictorial targets, i.e. arrows pointing to the left or to the right, we explore whether spatial codes used in isolation inherently evoke the left-to-right representation of number magnitudes and, vice-versa, whether number-magnitude codes used in isolation inherently evoke the conceptual activation of left/right spatial codes. In a first series of experiments participants were asked to provide unimanual Go/N-Go responses based on instructions that activated only magnitude codes, e.g. “push only if the number is lower than 5 and whenever an arrow appears”, or only spatial codes, e.g. “push only when an arrow points to the left and whenever a number appears”. In a second series of experiments, the same numerical instructions were combined with the request of responding only to arrows in a specific colour, e.g. “push when the number is lower than 5 and whenever a blue arrow appears”. At variance with a recent experiment by Shaki and Fischer (2018), in our experiments no constant association was present between a specific arrow colour and a specific arrow direction. The results of these experiments highlight no space-number congruency effects: e.g. no faster RTs to arrows pointing to the left rather than to the right when participants attend to numbers lower than 5 and, vice-versa, no faster RTs to numbers lower than 5 rather than higher, when participants attend to arrows pointing to the left. Based on these findings it must be concluded that neither space codes used in isolation can elicit a spatial representation of number magnitudes nor number-magnitude codes used in isolation can trigger the activation of spatial codes. Thus, spatial and numerical codes must be used jointly to evoke spatially organised mental number lines.
Electron microscopic analysis of the exo-skeleton of hadal zone amphipodHirondellea gigas
Authors: Kobayashi Hideki , Shimoshige Hirokazu , Nakajima Yoshikata , Arai Wataru , Takami Hideto 
Published: October 2018

AbstractThe amphipodHirondellea gigasinhabits the deepest regions of the oceans in extra high-pressure. However, the mechanisms by which they adapt to their high-pressure environments remain unknown. In this study, we investigated elements of the exoskeleton ofH. gigascaptured from the deepest points of the Mariana Trench. TheH. gigasexoskeleton contained aluminum, as well as a major amount of calcium carbonate. Unlike other accumulated metals, aluminum was distributed on the surface of exoskeletons. To investigate howH. gigasobtains aluminum, we conducted a metabolome analysis and found that gluconic acid/gluconolactone was capable of extracting metals from the sediment under the habitat conditions ofH. gigas. The extracted aluminum ions are transformed into the gel state of aluminum hydroxide in alkaline seawater, and this gel covers the body to protect the amphipod. The aluminum gel would be one of good materials to adapt to such high-pressure environment.
Mechanistic basis for decreased antimicrobial susceptibility in a clinical isolate ofNeisseria gonorrhoeaepossessing a mosaic-likemtrefflux pump locus
Authors: Rouquette-Loughlin Corinne E. , Reimche Jennifer L. , Balthazar Jacqueline T. , Dhulipala Vijaya , Gernert Kim M. , Kersh Ellen N. , Pham Cau D. , Pettus Kevin , Abrams A. Jeanine , Trees David L. , Cyr Sancta St , Shafer William M. 
Published: October 2018

AbstractRecent reports suggest that mosaic-like sequences within themtr(multipletransferableresistance) efflux pump locus ofNeisseria gonorrhoeaelikely originating from commensalNeisseria sp.by transformation can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within themtrRgene encoding the transcriptional repressor (MtrR) of themtrCDEefflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (Wadsworthet al.2018. MBio. doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates including Azi. We report that a strongcis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of themtrCDEpromoter as well gain-of-function amino acid changes at theC-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-likemtrlocus.IMPORTANCEHistorically, after introduction of an antibiotic for treatment of gonorrhea, strains ofN. gonorrhoeaeemerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of theNeisseriagenus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented herein provide a framework for understanding how mosaic-like DNA sequences from commensalNeisseriathat recombine within the gonococcalmtrefflux pump locus function to decrease bacterial susceptibility to antimicrobials including antibiotics used in therapy of gonorrhea.
Assessing mitochondrial function in angiosperms with highly divergent mitochondrial genomes
Authors: Havird Justin C. , Noe Gregory R. , Link Luke , Torres Amber , Logan David C. , Sloan Daniel B. , Chicco Adam J. 
Published: October 2018

AbstractAngiosperm mitochondrial (mt) genes are generally slow-evolving, but multiple lineages have undergone dramatic accelerations in rates of nucleotide substitution and extreme changes in mt genome structure. While molecular evolution in these lineages has been investigated, very little is known about their mt function. Here, we develop a new protocol to characterize respiration in isolated plant mitochondria and apply it to species ofSilenewith mt genomes that are rapidly evolving, highly fragmented, and exceptionally large (∼11 Mbp). This protocol, complemented with traditional measures of plant fitness, cytochrome c oxidase activity assays, and fluorescence microscopy, was used to characterize inter-and intraspecific variation in mt function. Contributions of the individual “classic” OXPHOS complexes, the alternative oxidase, and external NADH dehydrogenases to overall mt respiratory flux were found to be similar to previously studied angiosperms with more typical mt genomes. Some differences in mt function could be explained by inter-and intraspecific variation, possibly due to local adaptation or environmental effects. Although this study suggests that theseSilenespecies with peculiar mt genomes still show relatively normal mt function, future experiments utilizing the protocol developed here can explore such questions in a more detailed and comparative framework.
Rapid high throughput SYBR green assay for identifying the malaria vectors Anopheles arabiensis, Anopheles coluzzii and Anopheles gambiae s.s. Giles
Authors: Chabi Joseph , Van’t Hof Arjen , N’dri Louis K. , Datsomor Alex , Okyere Dora , Njoroge Harun , Pipini Dimitra , Hadi Melinda P. , de Souza Dziedzom K. , Suzuki Takashi , Dadzie Samuel K. , Jamet Helen P. 
Published: October 2018

AbstractThe Anopheles gambiae sensu lato species complex consists of a number of cryptic species with different habitats and behaviours. These morphologically indistinct species are identified by chromosome banding and molecular diagnostic techniques which are still under improvement even though the current SINE method for identification between An. coluzzii and An. gambiae works reliably. This study describes a refinement of the SINE method to increase sensitivity and high throughput method for the identification of both species and An. arabiensis using amplicon dissociation characteristics.Field collected samples, laboratory reared colonies and crossed specimens of the two species were used for the design of the protocol. An. gambiae, An. coluzzii, and hybrids of the two species were provided by the insectary of Vestergaard-NMIMR Vector Labs at the Noguchi Memorial Institute for Medical Research (Ghana) and An. arabiensis from Kenya. Samples were first characterised using conventional SINE PCR method, and further assayed using SYBR green, an intercalating fluorescent dye.The three species and hybrids were clearly differentiated using the melting temperature of the dissociation curves, with derivative peaks at 72 Celsius for An. arabiensis, 75°C for An. gambiae and 86°C for An. coluzzii. The hybrids (An. gambiae / An. coluzzii) showed both peaks. This work is the first to describe a SYBR green real time PCR method for the characterization of An. arabiensis, An. gambiae and An. coluzzii and was purposely designed for basic melt-curve analysis (rather than high-resolution melt-curve) to allow it to be used on a wide range of real-time PCR machines.
Mutualism outcome across plant populations, microbes, and environments in the duckweedLemna minor
Authors: O’Brien Anna M. , Laurich Jason , Lash Emma , Frederickson Megan E 
Published: October 2018

AbstractThe picture emerging from the rapidly growing literature on host-associated micro-biota is that host traits and fitness often depend on complex and interactive effects of host genotype, microbial interactions, and abiotic environment. However, testing these main and interactive effects typically requires large, multi-factorial experiments and thus remains challenging in many systems. Furthermore, most studies of plant microbiomes focus on terrestrial hosts and microbes. Aquatic habitats may confer unique properties to plant micriobiomes. We grew different populations of duck-weed (Lemna minor), a floating aquatic plant of increasing popularity in freshwater phytoremediation, in three microbial treatments (adding no, “home”, or “away” microbes) at two levels of zinc, a common water contaminant in urban areas. Thus, we simultaneously manipulated plant source population, microbial community, and the abiotic environment, and measured both plant and microbial performance as well as plant traits. Although we found little evidence of interactive effects, we found strong main effects of plant source, microbial treatment, and zinc on both duckweed and microbial growth, with significant variation among both duckweed and microbial communities. Despite strong growth alignment between duckweed and microbes, zinc consistently decreased plant growth, but increased microbial growth. Furthermore, as in recent studies of terrestrial plants, microbial interactions altered a duckweed phenotype (frond aggregation). Our results suggest that the duckweed source population, its associated microbiome, and the contaminant environment may all need to be considered in real-world phytoremediation efforts. Lastly, we propose that duckweed microbes offer a robust experimental system for study of host-microbiota interactions under a range of environmental stresses.
Deciphering epigenomic code for cell differentiation using deep learning
Authors: Ni Pengyu , Su Zhengchang 
Published: October 2018

ABSTRACTEpigenomic markers, such as histone modifications, play important roles in cell fate determination and type maintenance during cell differentiation. Although genomic sequence plays a crucial role in establishing the unique epigenome in each cell type produced during cell differentiation, little is known about the sequence determinants that lead to the unique epigenomes of the cells. Here, using a dataset of six histone markers measured in four human CD4+ T cell types produced at different stages of T cell development, we showed that two types of highly accurate deep convolutional neural networks (CNNs) constructed for each cell type and for each histone marker are a powerful strategy to uncover the sequence determinants of the various histone modification patterns in difference cell types. We found that sequence motifs learned by the CNN models are highly similar to known binding motifs of transcription factors known to play important roles in CD4+ T cell differentiation. Our results suggest that both the unique histone modification patterns in each cell type and the different patterns of the same histone marker in different cell types are determined by a set of motifs with unique combinations. Interestingly, the level of shared few motifs learned in the different cell models reflect the lineage relationships of the cells, while the level of few shared motifs learned in different histone marker models reflect their functional relationships. Furthermore, using these models, we can predict the importance of the learned motifs and their interactions in determining specific histone marker patterns in the cell types.
Predicting the Future with Multi-scale Successor Representations
Authors: Momennejad Ida , Howard Marc W. 
Published: October 2018

AbstractThe successor representation (SR) is a candidate principle for generalization in reinforcement learning, computational accounts of memory, and the structure of neural representations in the hippocampus. Given a sequence of states, the SR learns a predictive representation for every given state that encodes how often, on average, each upcoming state is expected to be visited, even if it is multiple steps ahead. A discount or scale parameter determines how many steps into the future SR’s generalizations reach, enabling rapid value computation, subgoal discovery, and flexible decision-making in large trees. However, SR with a single scale could discard information for predicting both the sequential order of and the distance between states, which are common problems in navigation for animals and artificial agents. Here we propose a solution: an ensemble of SRs with multiple scales. We show that the derivative of multi-scale SR can reconstruct both the sequence of expected future states and estimate distance to goal. This derivative can be computed linearly: we show that a multi-scale SR ensemble is the Laplace transform of future states, and the inverse of this Laplace transform is a biologically plausible linear estimation of the derivative. Multi-scale SR and its derivative could lead to a common principle for how the medial temporal lobe supports both map-based and vector-based navigation.
Direct and transgenerational effects of an experimental heat wave on early life stages in a freshwater snail
Authors: Leicht Katja , Seppälä Otto 
Published: October 2018

AbstractGlobal climate change imposes a serious threat to natural populations of many species. Estimates of the effects of climate change-mediated environmental stresses are, however, often based only on their direct effects on organisms, and neglect the potential transgenerational effects. We investigated whether high temperature (i.e. an experimental heat wave) that is known to reduce performance of adultLymnaea stagnalissnails affects their offspring through maternal effects. Specifically, we tested whether eggs and hatched juveniles are affected by maternal thermal environment, and how strong these effects are compared with direct effects of temperature on offspring. We examined the effect of maternal thermal environment (15°C versus 25°C) on per offspring investment (egg size), and the role of both maternal and offspring thermal environments (15°C versus 25°C) on hatching success and developmental time of eggs, offspring survival after hatching, and hatchling size at the age of five weeks. Exposure of mothers to high temperature increased hatching success of eggs, and also made the onset of hatching earlier. However, high maternal temperature reduced the survival and the final size of hatched juveniles. Direct effects of high temperature on offspring survival were negative (both eggs and hatchlings), but increased the developmental rate and growth of those eggs and hatchlings that survived. Interestingly, the magnitude of transgenerational effects of high temperature on hatching success of eggs and hatchling survival were similar to its direct effects. This indicates that heat waves can affect natural populations through transgenerational effects, and that the magnitude of such effects can be equally strong to the direct effects of temperature, although this depends on the trait considered. Our results highlight the importance of considering transgenerational effects of climate warming when estimating its effects in the wild.
The impact of bilingualism on executive functions and working memory in young adults
Authors: Antón Eneko , Carreiras Manuel , Duñabeitia Jon Andoni 
Published: October 2018

AbstractA bilingual advantage in a form of a better performance of bilinguals in tasks tapping into executive function abilities has been reported repeatedly in the literature. However, recent research defends that this advantage does not stem from bilingualism, but from uncontrolled factors or imperfectly matched samples. In this study we explored the potential impact of bilingualism on executive functioning abilities by testing large groups of young adult bilinguals and monolinguals in the tasks that were most extensively used when the advantages were reported. Importantly, the recently identified factors that could be disrupting the between groups comparisons were controlled for, and both groups were matched. We found no differences between groups in their performance. Additional bootstrapping analyses indicated that, when the bilingual advantage appeared, it very often co-occurred with unmatched socio-demographic factors. The evidence presented here indicates that the bilingual advantage might indeed be caused by spurious uncontrolled factors rather than bilingualism per se. Secondly, bilingualism has been argued to potentially affect working memory also. Therefore, we tested the same participants in both a forward and a backward version of a visual and an auditory working memory task. We found no differences between groups in either of the forward versions of the tasks, but bilinguals systematically outperformed monolinguals in the backward conditions. The results are analyzed and interpreted taking into consideration different perspectives in the domain-specificity of the executive functions and working memory.
Full Title: Growth substrate may influence biofilm susceptibility to antibiotics
Authors: Williams Dustin L. , Smith Scott R. , Peterson Brittany R. , Allyn Gina , Epperson Richard Tyler , Looper Ryan E. 
Published: October 2018

AbstractThe CDC biofilm reactor is a robust culture system with high reproducibility in which biofilms can be grown for a wide variety of analyses. Multiple material types are available as growth substrates, yet data from biofilms grown on biologically relevant materials is scarce, particularly for antibiotic efficacy against differentially supported biofilms. In this study, CDC reactor holders were modified to allow growth of biofilms on collagen, a biologically relevant substrate. Susceptibility to multiple antibiotics was compared between biofilms of varying species grown on collagen versus standard polycarbonate coupons. Data indicated that in 13/18 instances, biofilms on polycarbonate were more susceptible to antibiotics than those on collagen, suggesting that when grown on a complex substrate, biofilms may be more tolerant to antibiotics. These outcomes may influence the translatability of antibiotic susceptibility profiles that have been collected for biofilms on hard plastic materials. Data may also help to advance information on antibiotic susceptibility testing of biofilms grown on biologically relevant materials for futurein vitroandin vivoapplications.
Are working memory training effects paradigm-specific?
Authors: Holmes Joni , Woolgar Francesca , Hampshire Adam , Gathercole Susan E. 
Published: October 2018

AbstractA randomized controlled trial compared complex span and n-back training regimes to investigate the generality of training benefits across materials and paradigms. The memory items and training intensities were equated across programs, providing the first like-with-like comparison of transfer in these two widely-used training paradigms. The stimuli in transfer tests of verbal and visuo-spatial n-back and complex span differed from the trained tasks, but were matched across the untrained paradigms. Pre-to-post changes were observed for untrained n-back tasks following n-back training. Following complex span training there was equivocal evidence for improvements on a verbal complex span task, but no evidence for changes on an untrained visuo-spatial complex span activity. Relative to a no intervention group, the evidence supported no change on an untrained verbal complex span task following either n-back or complex span training. Equivocal evidence was found for improvements on visuo-spatial complex span and verbal and visuo-spatial n-back tasks following both training regimes. Evidence for selective transfer (comparing the two active training groups) was only found for an untrained visuo-spatial n-back task following n-back training. There was no evidence for cross-paradigm transfer. Thus transfer is constrained by working memory paradigm and the nature of individual processes executed within complex span tasks. However, within-paradigm transfer can occur when the change is limited to stimulus category, at least for n-back.