bluuebunny/crossref_metadata_2025_split huggingface dataset:
Think zinc: Role of zinc poisoning in the intraphagosomal killing of bacteria by the amoeba Dictyostelium
Authors: Barisch Caroline , Kalinina Vera , Lefrançois Louise H. , Appiah Joddy , Soldati Thierry 
Published: June 2018

AbstractProfessional phagocytes have developed an extensive repertoire of autonomous immunity strategies to ensure killing of bacteria. Besides phagosome acidification and the generation of reactive oxygen species, deprivation of nutrients and the lumenal accumulation of toxic metals are essential to kill ingested bacteria or inhibit growth of intracellular pathogens. We use the soil amoeba Dictyostelium discoideum, a professional phagocyte that digests bacteria for nutritional purposes, to decipher the role of zinc poisoning during phagocytosis of non-pathogenic bacteria and visualize the temporal and spatial dynamics of compartmentalized, free zinc using fluorescent probes. Immediately after particle uptake, zinc is delivered to phagosomes by fusion with “zincosomes” of endosomal origin, but also by the action of one or more zinc transporters. We localize the four Dictyostelium ZnT transporters to endosomes, the contractile vacuole and the Golgi apparatus, and study the impact of znt knockouts on zinc homeostasis. Finally, we show that zinc is delivered into the lumen of Mycobacterium smegmatis-containing vacuoles, and that Escherichia coli deficient in the zinc efflux P1B-type ATPase ZntA is killed faster than wild type bacteria.Summary statementMetal poisoning is one of the bactericidal strategies of macrophages. Here, we describe the dynamics of free Zn and the role of Zn transporters during phagocytosis in Dictyostelium.
Difference in accumulation pattern of the allergens within the same PR10 family in transgenic rice
Authors: Takaiwa Fumio , Ogo Yuko , Wakasa Yuhya 
Published: June 2018

AbstractApple food allergen Mal d 1 and birch pollen allergen Bet v 1 belong to the same pathogen related protein 10 (PR10) family. When each of these allergens was expressed as a secretory protein by fusion with the GFP reporter in transgenic rice by ligating an N terminal signal peptide and a C terminal KDEL ER retention signal under the control of the maize ubiquitin constitutive promoter, the GFP:Mald1 highly accumulated in various tissues, whereas the accumulation level of GFP:Betv1 was remarkably reduced in vegetative tissues except for seed. Analysis by RT-PCR exhibited that there was little difference in transcript levels between them, indicating the involvement of post-transcriptional regulation. To investigate the cause of such difference in accumulation levels, deletion analysis of the Mal d 1 and domain swapping between them were carried out in transgenic rice. These results showed that the region between positions 41-90 in the Mal d 1 is predominantly implicated in higher level accumulation in vegetative tissues as well as seed compared with the Bet v 1. It is notable that GFP:Mald1 directed by the ubiquitin promoter is deposited in huge PBs in aleurone layer rather than starchy endosperm.HighlightSpecific region of PR10 proteins is mainly implicated in their stability in vegetative tissues when expressed in transgenic rice.
Integral Gene Drives: an “operating system” for population replacement
Authors: Nash Alexander , Urdaneta Giulia Mignini , K. Beaghton Andrea , Hoermann Astrid , Aris Papathanos Philippos , Christophides George K. , Windbichler Nikolai 
Published: June 2018

AbstractFirst generation CRISPR-based gene drives have now been tested in the laboratory in a number of organisms including malaria vector mosquitoes. A number of challenges for their use in the area-wide genetic control of vector-borne disease have been identified. These include the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and the practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. To address these challenges, we have evaluated the concept of Integral Gene Drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including both the drive and the anti-pathogen effector elements directly embedded within endogenous genes – an arrangement which we refer to as gene “hijacking”. This design would allow autonomous and non-autonomous IGD traits and strains to be generated, tested, optimized, regulated and imported independently. We performed quantitative modelling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population while hedging drive over multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target-site variation. IGD thus has the potential to yield more durable and flexible population replacement traits.
Dynamic m6A methylation facilitates mRNA triaging to stress granules
Authors: Anders Maximilian , Chelysheva Irina , Goebel Ingrid , Trenkner Timo , Zhou Jun , Mao Yuanhui , Verzini Silvia , Qian Shu-Bing , Ignatova Zoya 
Published: June 2018

Summary blurbm6A-modification in the 5’ vicinity of the coding sequence of transcripts provides a selective mechanism for triaging mRNAs to stress granules and is mediated by YTHDF3 ‘reader’ protein.AbstractReversible post-transcriptional modifications on messenger RNA emerge as prevalent phenomena in RNA metabolism. The most abundant among them is N6-methyladenosine (m6A) which is pivotal for RNA metabolism and function, its role in stress response remains elusive. We have discovered that in response to oxidative stress, transcripts are additionally m6A-modified in their 5’ vicinity. Distinct from that of the translationally-active mRNAs, this methylation pattern provides a selective mechanism for triaging mRNAs from the translatable pool to stress-induced stress granules. These stress-induced newly methylated sites are selectively recognized by the YTH domain family 3 (YTHDF3) ‘reader’ protein, thereby revealing a new role for YTHDF3 in shaping the selectivity of stress response. Our findings describe a previously unappreciated function for RNA m6A modification in the oxidative-stress response and expand the breadth of physiological roles of m6A.
Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome
Authors: Briggs Emma , Hamilton Graham , Crouch Kathryn , Lapsley Craig , McCulloch Richard 
Published: June 2018

AbstractR-loops are stable RNA-DNA hybrids that have been implicated in transcription initiation and termination, as well as in telomere homeostasis, chromatin formation, and genome replication and instability. RNA Polymerase (Pol) II transcription in the protozoan parasite Trypanosoma brucei is highly unusual: virtually all genes are co-transcribed from multigene transcription units, with mRNAs generated by linked trans-splicing and polyadenylation, and transcription initiation sites display no conserved promoter motifs. Here, we describe the genome-wide distribution of R-loops in wild type mammal-infective T. brucei and in mutants lacking RNase H1, revealing both conserved and diverged functions. Conserved localisation was found at centromeres, rRNA genes and retrotransposon-associated genes. RNA Pol II transcription initiation sites also displayed R-loops, suggesting a broadly conserved role despite the lack of promoter conservation or transcription initiation regulation. However, the most abundant sites of R-loop enrichment were within the intergenic regions of the multigene transcription units, where the hybrids coincide with sites of polyadenylation and nucleosome-depletion. Thus, instead of functioning in transcription termination, most T. brucei R-loops act in a novel role, promoting RNA Pol II movement or mRNA processing. Finally, we show there is little evidence for correlation between R-loop localisation and mapped sites of DNA replication initiation.
Benzo(a)pyrene (B[a]P) and its adverse effects on male testis
Authors: Liu Wei , Gu Aihua 
Published: June 2018

ABSTRACTIt has been proved that Benzo(a)pyrene (B[a]P) is mutagenic in somatic cells, whereas the adverse effect of BaP on male reproduction remains unclear. To investigate whether it can pass through the blood-testis barrier (BTB) and its potential reproductive toxicology and molecular mechanisms, mice were exposed to B[a]P (there are two doses, that is 13mg/kg body weight and 26 mg/kg body weight; three times per week) during 6 weeks and sacrificed 6 weeks after the final exposure to obtain B[a]P-exposed testis, blood and others. Electron microscopy analysis was performed to confirm whether the integrity of BTB and the ultra-structure changes in testes of B[a]P treated mice, which showed that the integrity of the BTB was disrupted, accompanied with the structure of sertoli cells seriously damaged, including the integrity of the nuclear membrane of the sertoli cells impaired and the basement membrane of the seminiferous tubules disrupted. X-ray imaging in vitro told us that BaP can overgo the BTB and gathered in the testis of mice. We found the significantly decreased expression of ZO-1, occludin, N-cadherin, vimentin and claudin-1 in the testes of B[a]P treated group by immunofluorescence detection. B[a]P induced BTB component protein decreased were also found in TM4 cells exposed to 5μmol/L B[a]P for 24h. We found a significantly decrease of testosterone level and a significantly increase of estrogen level in the serum of treated groups comparing with the control one by radioimmunoassay. TM4 cells, MLTC-1 cells and GC-2 cells was cultured with medium contains B[a]P. MTT Cell Proliferation and Cytotoxicity Assay, cell apoptosis analysis, FACScan analyzer, We observed apparent increase of TM4 and GC-2 cells apoptosis after expose to B[a]P for 24h. B[a]P induced TM4 cell, GC-2 cell and MLTC-1 cell G2/M phase cell arrest. In conclusion, these results suggested that BaP has an adverse impact on male reproduction, it can cross the blood-testis barrier and damage it, the component proteins of the BTB significantly decreased, it can also produce adverse impact on male germ cells.
G-quadruplex stabilization in the ions and maltose transporters inhibitSalmonella entericagrowth and virulence
Authors: Jain Neha , Mishra Subodh Kumar , Shankar Uma , Tawani Arpita , Jaiswal Ankit , Sharma Tarun Kumar , Kodgire Prashant , Kumar Amit 
Published: June 2018

AbstractThe G-quadruplex structure forming motifs have recently emerged as a novel therapeutic drug target in various human pathogens. Herein, we report three highly conserved G-quadruplex motifs (SE-PGQ-1, 2, and3) in genome of all the 412 strains ofSalmonella enterica. Bioinformatics analysis inferred the presence of SE-PGQ-1 in the regulatory region ofmgtA, presence of SE-PGQ-2 in the open reading frame ofentAand presence of SE-PGQ-3 in the promoter region ofmalEandmalKgenes. The products ofmgtAandentAare involved in transport and homeostasis of Mg2+and Fe3+ion and thereby required for bacterial survival in the presence of reactive nitrogen/oxygen species produced by the host macrophages, whereas,malKandmalEgenes are involved in transport of maltose sugar, that is one of the major carbon source in the gastrointestinal tract of human. The formation of stable intramolecular G-quadruplex structures by SE-PGQs was confirmed by employing CD, EMSA and NMR spectroscopy. Cellular studies revealed the inhibitory effect of 9-amino acridine onSalmonella entericagrowth. Next, CD melting analysis demonstrated the stabilizing effect of 9-amino acridine on SE-PGQs. Further, polymerase inhibition and RT-qPCR assays emphasize the biological relevance of predicted G-quadruplex in the expression of PGQ possessing genes and demonstrate the G-quadruplexes as a potential drug target for the devolping novel therapeutics for combatingSalmonella enterica infection.Author SummarySince last several decades’ scientific community has witnessed a rapid increase in number of such human pathogenic bacterial species that acquired resistant to multiple antibacterial agents. Currently, emergence of multidrug-resistant strains remain a major public health concern for clinical investigators that rings a global alarm to search for novel and highly conserved drug targets. Recently, G-quadruplex structure forming nucleic acid sequences were endorsed as highly conserved Drug target for preventing infection of several human pathogens including viral and protozoan species. Therefore, here we explored the presence G-quadruplex forming motif in genome ofSalmonella entericabacteria that causes food poisoning, and enteric fever in human. The formation of intra molecular G-quadruplex structure in four genes (mgtA,entA,malEandmalK) was confirmed by NMR, CD and EMSA. The 9-amino acridine, a known G-quadruplex binder has been shown to stabilize the predicted G-quadruplex motif and decreases the expressioin of G-quadruplex hourbouring genes using RT-PCR and cellular toxicity assay. This study concludes the presence of G-quadruplex motifs in essential genes ofSalmonella entericagenome as a novel and conserved drug target and 9-amino acridine as candidate small molecule for preventing the infection ofSalmonella entericausing a G4 mediated inhibition mechanism.
Sinking rates and export flux of Transparent Exopolymer Particles (TEPs) in an eutrophic coastal sea: a case study in the Changjiang (Yangtze River) Estuary
Authors: Guo Shujin , Sun Jun 
Published: June 2018

AbstractTransparent exopolymer particles (TEPs) are ubiquitous throughout the oceans, and their sedimentation is considered an efficient biological carbon sink pathway. However, the role TEPs play as a carbon sink in eutrophic coastal seas is not well studied. In order to investigate this issue, two cruises in the spring and summer of 2011 were carried out in the Changjiang (Yangtze River) estuary, a typical eutrophic coastal sea. The concentrations, sinking rates, and export flux of TEPs were studied. TEP concentrations ranged from 40.00 to 1040.00 μg Xeq L−1 (mean = 209.70 ± 240.93 μg Xeq L−1) in spring and from 56.67 to 1423.33 μg Xeq L−1 (mean = 433.33 ± 393.02 μg Xeq L−1) in summer. A significant positive correlation between TEP concentrations and chlorophyll (Chl) a concentrations was observed. TEP sinking rates ranged from 0.08 to 0.57 m d−1 (mean = 0.28 ± 0.14 m d−1) in spring and from 0.10 to 1.08 m d−1 (mean = 0.34 ± 0.31 m d−1) in summer. TEP sinking rates were always higher in the upper layers than in the deeper layers during both seasons. The export flux of TEPs was also calculated, and it ranged from 4.95 to 29.40 mg C m−2 d−1 in spring (mean = 14.66 ± 8.83 mg C m−2 d−1) and from 6.80 to 30.45 mg C m−2 d−1 (mean = 15.71 ± 8.73 mg C m−2 d−1) in summer. This study is the first study on TEP sinking in the Changjiang (Yangtze River) Estuary, and it confirmed that TEP plays a significant role as a carbon sink in the eutrophic coastal sea.
Monitoring of language selection errors in switching: Not all about conflict
Authors: Zheng Xiaochen , Roelofs Ardi , Farquhar Jason , Lemhöfer Kristin 
Published: June 2018

AbstractAlthough bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. To investigate how bilinguals monitor their speech errors and control their languages in use, we recorded event-related potentials (ERPs) in unbalanced Dutch-English bilingual speakers in a cued language-switching task. We tested the conflict-based monitoring model by investigating the error-related negativity (ERN) and comparing the effects of the two switching directions (i.e., to the first language, L1 vs. to the second language, L2). Results show that the speakers made more language selection errors when switching from their L2 to the L1 than vice versa. In the EEG, we observed a robust ERN effect following language selection errors compared to correct responses, reflecting monitoring of speech errors. Most interestingly, the ERN effect was enlarged when the speakers were switching to their L2 (less conflict) compared to switching to the L1 (more conflict). Our findings do not support the conflict-based monitoring model. We discuss an alternative account in terms of error prediction and reinforcement learning.
An assessment of Causal Inference in visual-inertial traveled distance estimation
Authors: de Winkel K.N. , Diers D. , Laächele M. , Buülthoff H.H. 
Published: June 2018

AbstractRecent work indicates that the central nervous system assesses the causality of visual and inertial information in the estimation of qualitative characteristics of self-motion and spatial orientation, and forms multisensory perceptions in accordance with the outcome of these assessments. Here, we extend the assessment of this Causal Inference (CI) strategy to the quantitative domain of traveled distance. We present a formal model of how stimuli result in sensory estimates, how percepts are constructed from sensory estimates, and how responses result from percepts. Starting with this formalization, we derived probabilistic formulations of CI and competing models for perception of traveled distance.In an experiment, participants (n=9) were seated in the Max Planck Cablerobot Simulator, and shown a photo-realistic virtual rendering of the simulator hall via a Head-Mounted Display. Using this setup, the participants were presented with various unisensory and (incongruent) multisensory visual-inertial horizontal linear surge motions, differing only in amplitude (i.e., traveled distance). Participants performed both a Magnitude Estimation and a Two-Interval Forced Choice task.Overall, model comparisons favor the CI model, but individual analysis shows a Cue Capture strategy is preferred in most individual cases. Parameter estimates indicate that visual and inertial sensory estimates follow a Stevens’ power law with positive exponent, and that noise increases with physical distance in accordance with a Weber’s law. Responses were found to be biased towards the mean stimulus distance, consistent with an interaction between percepts and prior knowledge in the formulation of responses. Magnitude estimate data further showed a regression to the mean eﬀect.The experimental data did not provide unambiguous support for the CI model. However, model derivations and fit results demonstrate it can reproduce empirical findings, arguing in favor of the CI model. Moreover, the methods outlined in the present study demonstrate how different sources of distortion in responses may be disentangled by combining psychophysical tasks.
Decrease in Microbial Diversity Along a Pollution Gradient in Citarum River Sediment
Authors: de Jong Anniek , van der Zaan Bas , Geerlings Gertjan , Zandt Michiel in’t , Lufiandi  , Roosmini Dwina , Ariesyady Herto Dwi , Lüke Claudia , Jetten Mike 
Published: June 2018

ABSTRACTPollution of water resources is a major risk to human health and water quality throughout the world. Here, we studied the effect of river pollution on the microbial community composition in the Citarum River Basin, West Java, Indonesia. Sediment was collected at six sampling points along a gradient of pollution, from the pristine source of the river to the heavily polluted downstream site in the densely populated urban area of Bandung. After DNA extraction, microbial diversity and potential for nitrogen cycling were analyzed based on 16S rRNA gene amplicon sequencing and metagenomics. Comparing the pristine sediment to the polluted site showed a lower microbial diversity and higher dominance of anaerobic processes than at the polluted site. The most dominant phylum within the Bacteria were theProteobacteria, which shifted fromBeta- andDeltaproteobacteriain the pristine site toAlpha- andGammaproteobacteriain the polluted sediment. With pollutionActinobacteria, Bacteroidetes,andFirmicutesincreased in relative abundance. Relative high abundance ofSoil Crenarchaeotic groupwas found in all sample sites, whilst the methanogenic archaea became more abundant with increased pollution and anaerobicity. The study of the nitrogen cycling potential revealed that ammonium oxidation and denitrification appeared to be abundant processes in the pristine site, whereas ammonification seemed to be more important in the polluted site. Increased water treatment would restore water quality and microbial diversity in Citarum river sediments.
Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity
Authors: Iyer K. Venkatesan , Piscitello-Gómez Romina , Jülicher Frank , Eaton Suzanne 
Published: June 2018

AbstractStudying how epithelia respond to mechanical stresses is key to understanding tissue shape changes during morphogenesis. Here, we study the viscoelastic deformation of the Drosophila pupal wing epithelium in response to mechanical stress that evolves during morphogenesis. We show that wing epithelial tissue viscoelasticity depends on endocytic turnover of E-Cadherin. The fraction of ECadherin undergoing turnover depends on mechanical stress in the epithelium. We identified mechanosensitive binding of the endocytic regulator p120-Catenin (p120) as a mechanism to regulate E-Cadherin turnover. Under high stress, p120 is released into the cytoplasm, destabilizing E-Cadherin complexes and increasing its turnover. In p120 mutants, E-Cadherin turnover is insensitive to mechanical stress. Furthermore, we show that p120 is crucial for the viscoelastic deformation of the wing epithelium. Taken together, our findings reveal that mechanosensitive binding of p120-Catenin tunes epithelial tissue viscoelasticity during morphogenesis.
MODE for detecting and estimating genetic causal variants
Authors: Sundar V. S. , Fan Chun-Chieh , Holland Dominic , Dale Anders M. 
Published: June 2018

AbstractDetermining the genetic causal variants and estimating their effect sizes are considered to be correlated but independent problems. Fine-mapping studies often rely on the ability to integrate useful functional annotation information into genome wide association univariate/multivariate analysis. In the present study, by modeling the probability of a SNP being causal and its effect size as a set of correlated Gaussian/non-Gaussian random variables, we design an optimization routine for simultaneous fine-mapping and effect size estimation. The algorithm is released as an open source C package MODE.Availability and Implementation:http://sites.google.com/site/sundarvelkur/modeContact:amdale@ucsd.edu, svelkur@ucsd.edu
Dopaminergic genes are associated with both directed and random exploration
Authors: Gershman Samuel J. , Tzovaras Bastian Greshake 
Published: June 2018

AbstractIn order to maximize long-term rewards, agents must balance exploitation (choosing the option with the highest payoff) and exploration (gathering information about options that might have higher payoffs). Although the optimal solution to this trade-off is intractable, humans make use of two effective strategies: selectively exploring options with high uncertainty (directed exploration), and increasing the randomness of their choices when they are more uncertain (random exploration). Using a task that independently manipulates these two forms of exploration, we show that single nucleotide polymorphisms related to dopamine are associated with individual differences in exploration strategies. Variation in a gene linked to prefrontal dopamine (COMT) predicted the degree of directed exploration, as well as the overall randomness of responding. Variation in a gene linked to striatal dopamine (DARPP-32) predicted the degree of both directed and random exploration. These findings suggest that dopamine makes multiple contributions to exploration, depending on its afferent target.