bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASSESSMENT OF INDOOR GAMMA RADIATION AND DETERMINATION OF EXCESS LIFETIME CANCER RISK IN TEHRAN IN WINTER AND SPRING 2017
Authors: Hashemi Marjan , Akhoondi Leila , Saghi Mohammad Hossien , Eslami Akbar 
Published: October 2018

Abstract
Natural radiation is a feature of the environment in which we live. One of the contributions of human exposure to ionizing radiation due to natural sources arises from gamma radiation. Therefore, present study was aimed to evaluate and map indoor gamma dose rate in Tehran. The corresponding annual effective dose (AED) and excess lifetime cancer risk (ELCR) were also calculated. All measurements were performed by a Geiger Muller detector in 43 dwellings in Tehran. The average indoor gamma dose rate in Tehran was appointed as 343.2 nGy/h. AED and ELCR were calculated as 2.4 mSv and 10.3 × 10−3, respectively. The evaluated indoor gamma dose rate and calculated AEDs and lifetime cancer risk were found higher than the world average value.
Supra-molecular organization of the pyoverdine bio-synthetic pathway in Pseudomonas aeruginosa
Authors: Gasser Véronique , Malrieu Morgane , Forster Anne , Mély Yves , Schalk Isabelle J , Godet Julien 
Published: October 2018

The bio-synthesis of the pyoverdine siderophore (PVD) in Pseudomonas aeruginosa involves multiple enzymatic steps including the action of Non-Ribosomal Peptide Synthetases (NRPS). One hallmark of NRPS is their ability to make usage of non-proteinogenic amino-acids synthesised by co-expressed accessory enzymes. It is generally accepted that different enzymes of a secondary metabolic pathway must organise into macro-molecular complexes. However, evidence for complexes like siderosomes in the cellular context are missing.Here, we used in vitro single-molecule tracking and FRET–FLIM (Förster resonance energy transfer measured by fluorescence lifetime microscopy) to explore the spatial partitioning of the ornithine hydroxylase PvdA and its interactions with NRPS. We found PvdA was mostly diffusing bound to large complexes in the cytoplasm with a small exchangeable trapped fraction. FRET-FLIM clearly showed PvdA is physically interacting with PvdJ, PvdI, PvdL and PvdD, the four NRPS of the pyoverdine pathway. The binding modes of PvdA are strikingly different according to the NRPS it is interacting with suggesting that PvdA binding sites have co-evolved with the enzymatic active sites of NRPS.Our data provide evidence for strongly organised multi-enzymatic complexes responsible for the bio-synthesis of PVD and suggest that finely controlled co-localisation of sequential enzymes seems to be required to promote metabolic efficiency.
DPPA2 and DPPA4 are necessary to establish a totipotent state in mouse embryonic stem cells
Authors: De Iaco Alberto , Coudray Alexandre , Duc Julien , Trono Didier 
Published: October 2018

AbstractAfter fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through so-called zygotic genome activation (ZGA), occurring in the mouse at the 2-cell stage. Amongst the first elements to be transcribed are the Dux gene, the product of which secondarily induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons, which regulate chromatin accessibility in the early embryo. The maternally-inherited factors that activate Dux and LINE-1 transcription have so far remained unknown. Here we identify the paralog proteins DPPA2 and DPPA4 as responsible for this process.
Proteomics reveals profound metabolic changes in the alcohol use disorder brain
Authors: Enculescu Charmaine , Kerr Edward D. , Benjamin Yeo K. Y. , Dodd Peter R. , Schenk Gerhard , Fortes Marina R. S. , Schulz Benjamin L. 
Published: October 2018

AbstractChanges in brain metabolism are a hallmark of Alcohol Use Disorder (AUD). Determining how AUD changes the brain proteome is critical for understanding the effects of alcohol consumption on biochemical processes in the brain. We used data-independent acquisition mass spectrometry proteomics to study differences in the abundance of proteins associated with AUD in pre-frontal lobe and motor cortex from autopsy brain. AUD had a substantial effect on the overall brain proteome exceeding the inherent differences between brain regions. Proteins associated with glycolysis, trafficking, the cytoskeleton, and excitotoxicity were altered in abundance in AUD. We observed extensive changes in the abundance of key metabolic enzymes, consistent with a switch from glucose to acetate utilization in the AUD brain. We propose that metabolic adaptations allowing efficient acetate utilization contribute to ethanol dependence in AUD.
A Model for Time Interval Learning in The Purkinje Cell
Authors: Majoral Daniel , Zemmar Ajmal , Vicente Raul 
Published: October 2018

AbstractRecent experimental findings indicate that Purkinje cells in the cerebellum represent time intervals by mechanisms other than conventional synaptic weights. This finding adds to the theoretical and experimental observations suggesting the presence of intra-cellular mechanisms for adaptation and processing. To account for these experimental results we developed a biophysical model for time interval learning in a Purkinje cell. The numerical model focuses on a classical delay conditioning task (e.g. eyeblink conditioning) and relies on a few computational steps. In particular, the model posits the activation by the parallel fiber input of a local intra-cellular calcium store which can be modulated by intra-cellular pathways. The reciprocal interaction of the calcium signal with several proteins forming negative and positive feedback loops ensures that the timing of inhibition in the Purkinje cell anticipates the interval between parallel and climbing fiber inputs during training. We show that the model is able to learn along the 150-1000 ms interval range. Finally, we discuss how this model would allow the cerebellum to detect and generate specific spatio-temporal patterns, a classical theory for cerebellar function.Author SummaryThe prevailing view in neurosciences considers synaptic weights between neurons the determinant factor for learning and processing information in the nervous system. Theoretical considerations [1, 2] and experiments [3, 4] examined some potential limitations of this classical paradigm, pointing out that adaptation and computation might also have to rely on other mechanisms besides the learning of synaptic weights. Recent experimental findings [5–7] indicate that Purkinje cells in the cerebellum represent time intervals by mechanisms other than conventional synaptic weights. We propose here a biologically plausible model which complements the modification of synaptic weights for learning one time interval in one synapse of one Purkinje cell. In the model a calcium signal in a small domain keeps track of time. Several molecules read and modify this calcium signal to learn a time interval. We discuss how this model would allow the cerebellum to detect and generate specific patterns in space and time, a classical theory for cerebellar function proposed by Braitenberg [8, 9].
Coping with strangers: how familiarity and active interactions shape group coordination inCorydoras aeneus
Authors: Riley RJ , Gillie ER , Johnstone RA , Boogert NJ , Manica A 
Published: October 2018

AbstractSocial groups whose members have had sustained prior experience with each other frequently exhibit improved coordination and outperform groups whose members are unfamiliar with one another. The mechanisms by which familiarity assists coordination are not well known. Prior social experience may simply allow individuals to learn the behavioral tendencies of familiar group-mates and coordinate accordingly. In the absence of prior social experience, it would be adaptive for individuals to develop strategies for coping with unfamiliar others to minimize the disadvantage of unfamiliarity. To explore the dynamics of familiarity in shaping group behaviors, we used a highly social catfish,Corydoras aeneus, that utilizes a distinctive, observable tactile interactions. Here we describe this tactile interaction behavior, physical “nudges” that are deployed to initiate group movements and maintain contact with group-mates during group movements. We then report the results of two experiments exploring the relationship between nudges and coordination. First, within triplets of two familiar and one unfamiliar individual, we found no individual differences in nudging rate based on familiarity. Despite all individuals interacting at similar rates, however, unfamiliar individuals failed to coordinate as well as their familiar group-mates, and were more frequently absent from group movements. Second, comparing pairs of familiar with pairs of unfamiliar fish, there was no difference in the level of coordination between pairs. Instead, we found that unfamiliar pairs exhibited significantly higher nudging rates, suggesting that unfamiliar pairs could compensate for their unfamiliarity by nudging more frequently. In contrast, familiar individuals coordinated with comparatively little nudging, presumably because they were experienced with each other. Overall, these results suggest that nudges can be used to improve coordination of group activities, but that their usage is reduced in the case of familiar individuals, implying that these potential signals may be costly.
Intracellular Burkholderia Symbionts Induce Extracellular Secondary Infections; Driving Diverse Host Outcomes that Vary by Genotype and Environment
Authors: Khojandi Niloufar , Haselkorn Tamara S. , Eschbach Madison N. , Naser Rana A. , DiSalvo Susanne 
Published: October 2018

AbstractSymbiotic associations impact and are impacted by their surrounding ecosystem. The association between Burkholderia bacteria and the soil amoeba Dictyostelium discoideum is a tractable model to unravel the biology underlying symbiont-endowed phenotypes and their impacts. Several Burkholderia species stably associate with D. discoideum and typically reduce host fitness in food-rich environments while increasing fitness in food-scarce environments. Burkholderia symbionts are themselves inedible to their hosts but induce co-infections with secondary bacteria that can serve as a food source. Thus, Burkholderia hosts are “farmers” that carry food bacteria to new environments, providing a benefit when food is scarce. We examined the ability of specific Burkholderia genotypes to induce secondary co-infections and assessed host fitness under a range of co-infection conditions and environmental contexts. Although all Burkholderia symbionts intracellularly infected Dictyostelium, we found that co-infections are predominantly extracellular, suggesting that farming benefits are derived from extracellular infection of host structures. Furthermore, levels of secondary infection are linked to conditional host fitness; B. agricolaris infected hosts have the highest level of co-infection and have the highest fitness in food scarce environments. This study illuminates the phenomenon of co-infection induction across Dictyostelium associated Burkholderia species and exemplifies the contextual complexity of these associations.
Effect of fire and thinning on fine-scale genetic structure and gene flow in fire-suppressed populations of sugar pine (Pinus lambertianaDouglas)
Authors: Lind Brandon M. , North Malcolm P. , Maloney Patricia E. , Eckert Andrew J. 
Published: October 2018

AbstractHistorically, frequent, low-severity fires in dry western North American forests were a major driver of ecological patterns and processes, creating resilient ecosystems dominated by widely-spaced pine species. However, a century of fire-suppression has caused overcrowding, altering forest composition to shade-tolerant species, while increasing competition and leaving trees stressed and susceptible to pathogens, insects, and high-severity fire. Exacerbating the issue, fire incidence is expected to increase with changing climate, while fire season has been observed to begin earlier and last longer than historic trends. Forest thinning and prescribed fire have been identified as important management tools to mitigate these risks. Yet little is known of how thinning, fire, or their interaction affect contemporary evolutionary processes of constituent pine species that influence fitness and play an important role in the opportunity for selection and population persistence. We assessed the impact of widely used fuel reduction treatments and prescribed fire on fine-scale gene flow on an ecologically important and historically dominant shade-intolerant pine species of the Sierra Nevada,Pinus lambertianaDougl. Treatment prescription (no-thin-no-fire, thin-no-fire, and fire-and-thin) was found to differentially affect both fine-scale spatial and genetic structure as well as effective gene flow in this species. Specifically, the thin-no-fire prescription increases genetic structure (spatial autocorrelation of relatives) between adults and seedlings, while seed and pollen dispersal increase and decrease, respectively, as a function of increasing disturbance intensity. While these results may be specific to the stands at our study site, they indicate how assumptions relating to genetic effects based on spatial structure can be misleading. It is likely that these disequilibrated systems will continue to evolve on unknown evolutionary trajectories. The long-term impacts of management practices on reduced fitness from inbreeding depression should be continually monitored to ensure resilience to increasingly frequent and severe fire, drought, and pest stresses.
Loss of the Heparan Sulfate Proteoglycan Glypican5 facilitates long range Shh signaling
Authors: Guo Wei , Roelink Henk 
Published: October 2018

AbstractAs a morphogen, Sonic Hedgehog (Shh) mediates signaling at a distance from its sites of synthesis. After secretion, Shh must traverse a distance through the extracellular matrix (ECM) to reach the target cells and activate the Hh response. Extracellular matrix proteins, in particular the Heparan Sulfate Proteoglycans (HSPGs) of the Glypican family have both negative and positive effects on non-cell autonomous Shh signaling, all attributed to their ability to bind Shh. Using mouse embryonic stem cell-derived mosaic tissues with compartments that lack the glycosyltransferases Exostosin1 (Ext1) and Exostosin2 (Ext2), or the HSPG core proteinGlypican5we show that cells surrounded by a mutated extracellular matrix are highly proficient distributing Shh. In contrast, cells that lackExt1function poorly secrete Shh. Our results confirm earlier observations that HSPGs can have both positive (Shh export) and negative influences (Shh distribution), and are supporting a model in which Shh presented on the cell surface in the context of HSPGs preferentially distributes into ECM that lacks HSPGs, possibly due to the absence of Shh sequestering molecules.
CRISPR/Cas9 screens Reveal Dasatinib Targets of Inhibiting T cell Activation and Proliferation
Authors: Wang Mei , Chen Qilong , Liu Hailing , Chen Hao , Wang Binbin , Zhang Wubing , Mading Ailu , Li Wenjing , Li Shuangqi , Liu Hang , Gu ZhongKai , Liu Shuxian , Guo Rui , Li Wei , Xiao Tengfei , Wu Feizhen 
Published: October 2018

AbstractImmune response by T cells is essential for a healthy body against cancer, infection, and pathophysiological alteration. The activation and expansion of T cells can be inhibited by dasatinib, a tyrosine inhibitor, thus improving the outcome of diseases, such as autoimmune disease, graft-versus-host disease, and transplant rejection. The underlying mechanism of inhibition by dasatinib is elusive. Here, we designed and synthesized a CRISPR/Cas9 screening library that includes 6,149 genes. Using the library, we performed dasatinib CRISPR/cas9 screening in Jurkat cell, a T lymphocyte cell. We firstly identified survival essential genes for Jurkat cells. Comparing with other CRISPR/Cas9 screenings, we obtained Jurkat cell specific essential genes. By comparing dasatinib treatment to control, we identified a set of dasatinib targets, which includes known targets: CSK, LCK, ZAP70, and previously unknown targets: ZFP36L2, LRPPRC, CFLAR, PD-1, CD45 et al. Visualizing these target genes on T cell receptor signaling pathway, we found several genes could be inhibited by dasatinib. Furthermore, we introduced a framework, 9-square, to classify genes and found a group of genes that are associated with dasatinib resistance, possibly linking the side effects of dasatinib. These data reveal a set of dasatinib targets and demonstrate the molecular potential functions of dasatinib. Identification of dasatinib targets will broaden our understanding to its molecular mechanism, and thus benefits to clinical outcome.
A piggyBac-based toolkit for inducible genome editing in mammalian cells
Authors: Schertzer Megan D. , Thulson Eliza , Braceros Keean C.A. , Lee David M. , Hinkle Emma R. , Murphy Ryan M. , Kim Susan O. , Vitucci Eva C.M. , Calabrese J. Mauro 
Published: October 2018

AbstractWe describe the development and application of a novel series of vectors that facilitate CRISPR-Cas9-mediated genome editing in mammalian cells, which we call CRISPR-Bac. CRISPR-Bac leverages the piggyBac transposon to randomly insert CRISPR-Cas9 components into mammalian genomes. In CRISPR-Bac, a single piggyBac cargo vector containing a doxycycline-inducible Cas9 or catalytically-dead Cas9 (dCas9) variant and a gene conferring resistance to Hygromycin B is co-transfected with a plasmid expressing the piggyBac transposase. A second cargo vector, expressing a single-guide RNA (sgRNA) of interest, the reverse-tetracycline TransActivator (rtTA), and a gene conferring resistance to G418, is also cotransfected. Subsequent selection on Hygromycin B and G418 generates polyclonal cell populations that stably express Cas9, rtTA, and the sgRNA(s) of interest. Using Mus musculus-derived embryonic and trophoblast stem cells, we show that CRISPR-Bac can be used to knockdown proteins of interest, to create targeted genetic deletions with high efficiency, and to activate or repress transcription of protein-coding genes and an imprinted long noncoding RNA. The ratio of sgRNA-to-Cas9-to-transposase can be adjusted in transfections to alter the average number of cargo insertions into the genome. sgRNAs targeting multiple genes can be inserted in a single transfection. CRISPR-Bac is a versatile platform for genome editing that simplifies the generation of mammalian cells that stably express the CRISPR-Cas9 machinery.
Cell type-specific role of lamin-B1 and its inflammation-driven reduction in organ building and aging
Authors: Yue Sibiao , Zheng Xiaobin , Zheng Yixian 
Published: October 2018

SummaryCellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell-type specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin-B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. An upregulation of proinflammatory cytokines in the intra-thymic myeloid immune cells during aging accompanies a gradual reduction of adult TEC lamins-B1. These cytokines cause adult TEC senescence and lamin-B1 reduction. We identify 17 adult TEC subsets and show that TEC lamin-B1 maintains the composition of these TECs. Lamin-B1 supports the expression of TEC genes needed for maintaining adult thymic architecture and function. Thus, structural proteins involved in organ building and maintenance can undergo inflammation-driven decay which can in turn contribute to age-associated organ degeneration.
Risk of stillbirth in low‐risk singleton term pregnancies following fertility treatment: a national cohort study
Authors: Bay B , Boie S , Kesmodel US 
Published: October 2018

ObjectiveTo assess the risk of stillbirth in low‐risk in vitro fertilisation (IVF) pregnancies.DesignRegister‐based national cohort study.SettingDenmark 2003–2013.PopulationCohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived.MethodsInformation on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6. We estimated the overall and gestational age‐specific risk of stillbirth in low‐risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen‐thawed embryo transfer.Main outcome measuresRisk of stillbirth.ResultsThe number of stillbirths in spontaneously conceived and IVF/ICSI low‐risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4–3.1). The risk of stillbirth was correspondingly increased in time‐to‐event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6–3.6). In sub‐analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2–3.1), but not IVF (odds ratio 1.7, 95% CI 0.9–3.1).ConclusionWe found a systematically increased risk of stillbirth in low‐risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term.Tweetable abstractIncreased risk of stillbirth in low‐risk term pregnancies following fresh cycle IVF/ICSI.
Heterologous coexpression of the benzoate‐para‐hydroxylase CYP53B1 with different cytochrome P450 reductases in various yeasts
Authors: Theron Chrispian W. , Labuschagné Michel , Albertyn Jacobus , Smit Martha S. 
Published: October 2018

SummaryCytochrome P450 monooxygenases (P450) are enzymes with high potential as biocatalysts for industrial applications. Their large‐scale applications are, however, limited by instability and requirement for coproteins and/or expensive cofactors. These problems are largely overcome when whole cells are used as biocatalysts. We previously screened various yeast species heterologously expressing self‐sufficient P450s for their potential as whole‐cell biocatalysts. Most P450s are, however, not self‐sufficient and consist of two or three protein component systems. Therefore, in the present study, we screened different yeast species for coexpression of P450 and P450‐reductase (CPR) partners, using CYP53B1 from Rhodotorula minuta as an exemplary P450. The abilities of three different coexpressed CPR partners to support P450 activity were investigated, two from basidiomycetous origin and one from an ascomycete. The various P450‐CPR combinations were cloned into strains of Saccharomyces cerevisiae, Kluyveromyces marxianus, Hansenula polymorpha, Yarrowia lipolytica and Arxula adeninivorans, using a broad‐range yeast expression vector. The results obtained supported the previous finding that recombinant A. adeninivorans strains perform excellently as whole‐cell biocatalysts. This study also demonstrated for the first time the P450 reductase activity of the CPRs from R. minuta and U. maydis. A very interesting observation was the variation in the supportive activity provided by the different reductase partners tested and demonstrated better P450 activity enhancement by a heterologous CPR compared to its natural partner CPR. This study highlights reductase selection as a critical variable for consideration in the pursuit of optimal P450‐based catalytic systems. The usefulness of A. adeninivorans as both a host for recombinant P450s and whole‐cell biocatalyst was emphasized, supporting earlier findings.