bluuebunny/crossref_metadata_2025_split huggingface dataset:
Honey Bee Diversity is Swayed by Migratory Beekeeping and Trade Despite Conservation Practices: Genetic Evidences for the Impact of Anthropogenic Factors on Population Structure
Authors: Kükrer Mert , Kence Meral , Kence Aykut 
Published: June 2017

AbstractIntense admixture of honey bee (Apis melliferaL.) populations is mostly attributed to migratory beekeeping practices and replacement of queens and colonies with non-native races or hybrids of different subspecies. These two practices are also heavily carried out in Anatolia and Thrace where 5 subspecies reside naturally.Here, we carried out an analysis of population structure of honey bees sampled from six different regions (n = 250) in order to test the genetic impacts of migratory beekeeping, queen and colony trade and conservation efficacy of isolated regions. A total of 30 microsatellite markers were used in four multiplex reactions.Direct genetic impact of migratory beekeeping was demonstrated first time based on a comparison of assignment of individuals to their geographically native populations where migratory colonies showed less fidelity. We found genetic evidence for them acting as a hybrid zone mobile in space and time, becoming vectors of otherwise local gene combinations.The effects of honey bee trade were revealed by the presence of very high introgression levels from the highly commercial Caucasian bees naturally limited to a narrow range. We also measured the direction and magnitude of this gene flow connected with bee trade.Comparison between regions that are either open to migratory beekeeping or not let us evaluate the status of isolated regions as centers of limited gene flow and showed the importance of establishing such regions.Despite signs of gene flow, our findings confirm high levels of geographically structured genetic diversity of four subspecies of honey bees in Turkey and emphasize the need to develop policies to maintain this diversity.Our overall results might potentially bear a wider interest to the community since they constitute an important attempt to quantify the effects of anthropogenic impacts on established patterns of honey bee diversity. Our measurable and justified findings on migratory beekeeping, queen and colony replacements as well as conservation implications will hopefully be of use for the decision makers and other stakeholders.
Can a red wood-ant nest be a trap for fault-related CH4 micro-seepage? A case study from continuous short-term in-situ sampling
Authors: Berberich G.M. , Ellison A.M. , Berberich M.B. , Grumpe A. , Becker A. , Wohler C. 
Published: June 2017

AbstractMethane (CH4) is common on Earth, forms the major commercial natural gas reservoirs, and is a key component of the global carbon cycle, but its natural sources are not well-characterized. We present a geochemical dataset acquired from a red wood-ant (RWA; Formica polyctena) nest in the Neuwied Basin, a part of the East Eifel Volcanic Field (EEVF), focusing on methane (CH4), stable carbon isotope of methane (δ13C-CH4), RWA activity patterns, earthquakes, and earth tides. Nest gas and ambient air were continuously sampled in-situ and analyzed to detect microbial, thermogenic, and abiotic fault-related micro-seepage. Methane degassing was not synchronized with earth tides. Elevated CH4 concentrations in nest gas appear to result from a combination of microbial activity and fault-related emissions moving via through fault networks through the RWA nest. Two δ13C-CH4 signatures were identified in nest gas: −69‰ and −37‰. The −69‰ signature of δ13C-CH4 within the RWA nest is attributed to microbial decomposition of organic matter. This finding supports previous findings that RWA nests are hot-spots of microbial CH4. Additionally, the −37% δ13C-CH4 signature is the first evidence that RWA nests also serve as traps for fault-related emissions of CH4. The −37‰ δ13C-CH4 signature can be attributed either to thermogenic/fault-related or to abiotic/fault-related CH4 formation originating from e.g. low-temperature gas-water-rock reactions in a continental setting at shallow depths (microseepage). Sources of these micro-seeps could be Devonian schists (“Sphaerosiderith Schiefer”) with iron concretions (“Eisengallen”), sandstones, or the iron-bearing “Klerf Schichten”. We cannot exclude overlapping micro-seepage of magmatic CH4 from the Eifel plume. Given the abundance of RWA nests on the landscape, their role as sources of microbial CH4 and traps for abiotically-derived CH4 should be included in estimation of methane emissions that are contributing to climatic change.
A model-free method for measuring dimerization free energies of CLC-ec1 in lipid bilayers
Authors: Chadda Rahul , Cliff Lucy , Brimberry Marley , Robertson Janice L. 
Published: June 2017

ABSTRACTWe previously reported the equilibrium dimerization reaction of the CLC-ec1 Cl-/H+transporter in 2:1 POPE/POPG membranes (Chadda et al. 2016). This was determined by measuring the probability distributions of subunit capture into extruded liposomes by single-molecule photobleaching analysis across a wide range of subunit/lipid mole fraction densities. In this approach, knowledge of the liposome size distribution is necessary in order to correct the data for random co-capture events and extract the underlying dimerization reaction. For this we used a previously reported cryo-electron microscopy (cryo-EM) measured size distribution of 400 nm extruded liposomes made ofE. colipolar lipids (Walden et al. 2007). While the model and data agreed at low densities, we observed systematic inaccuracies at higher densities limiting our ability to extractFDimerin this range. To address this issue, we measured the 400 nm extruded 2:1 POPE/POPG liposome size distribution by cryo-EM and found that there is a small, but significant amount of larger liposomes in the population. Re-analysis of the I201W/I422W ‘WW’ photobleaching data using this distribution shows that the protein is monomeric in the membrane and can serve as an experimental control. Dimer controls were constructed by glutaraldehyde cross-linking of C85A/H234C ‘WT’ or introducing R230C/L249C, which forms a spontaneous disulfide bond. Determination ofFDimerbased on the experimental controls yields improved fits and no change in the previously reportedΔG° values, providing an alternate model-free approach to measuring CLC-ec1 dimerization in membranes.
Homeodomain interacting protein kinase promotes tumorigenesis and metastatic cell behavior
Authors: Blaquiere Jessica A. , Wong Kenneth Kin Lam , Kinsey Stephen D. , Wu Jin , Verheyen Esther M. 
Published: June 2017

AbstractAberrations in signaling pathways that regulate tissue growth often lead to tumorigenesis. Homeodomain interacting protein kinase (Hipk) family members are reported to have distinct and contradictory effects on cell proliferation and tissue growth. From these studies it is clear that much remains to be learned about the roles of Hipk family protein kinases in proliferation and cell behaviour. Previous work has shown that Drosophila Hipk is a potent growth regulator, thus we predicted that it could have a role in tumorigenesis. In our study of Hipk-induced phenotypes, we observed the formation of tumor-like structures in multiple cell types in larvae and adults. Furthermore, elevated Hipk in epithelial cells induces cell spreading, invasion and epithelial-to-mesenchymal transition in the imaginal disc. Further evidence comes from cell culture studies in which we expressed Drosophila Hipk in human breast cancer cells and show that it enhances proliferation and migration. Past studies have shown that Hipk can promote the action of conserved pathways implicated in cancer and EMT, such as Wnt/Wingless, Hippo, Notch and JNK. We show that Hipk-phenotypes are not likely due to activation of a single target, but rather through a cumulative effect on numerous target pathways. Most Drosophila tumor models involve mutations in multiple genes, such as the well-known RasV12model, in which EMT and invasiveness occur after the additional loss of the tumor suppressor genescribble. Our study reveals that elevated levels of Hipk on their own can promote both hyperproliferation and invasive cell behaviour, suggesting that Hipks could be potent oncogenes and drivers of EMT.Summary statementThe protein kinase Hipk can promote proliferation and invasive behaviors, as well as synergize with known cancer pathways, in a novel Drosophila model for tumorigenesis.
Distribution Shapes Govern the Discovery of Predictive Models for Gene Regulation
Authors: Munsky Brian E. , Li Guoliang , Fox Zachary R. , Shepherd Douglas P. , Neuert Gregor 
Published: June 2017

AbstractDespite substantial experimental and computational efforts, mechanistic modeling remains more predictive in engineering than in systems biology. The reason for this discrepancy is not fully understood. Although randomness and complexity of biological systems play roles in this concern, we hypothesize that significant and overlooked challenges arise due to specific features of single-molecule events that control crucial biological responses. Here we show that modern statistical tools to disentangle complexity and stochasticity, which assume normally distributed fluctuations or enormous datasets, don't apply to the discrete, positive, and non-symmetric distributions that characterize spatiotemporal mRNA fluctuations in single-cells. We demonstrate an alternate approach that fully captures discrete, non-normal effects within finite datasets. As an example, we integrate single-molecule measurements and these advanced computational analyses to explore Mitogen Activated Protein Kinase induction of multiple stress response genes. We discover and validate quantitatively precise, reproducible, and predictive understanding of diverse transcription regulation mechanisms, including gene activation, polymerase initiation, elongation, mRNA accumulation, spatial transport, and degradation. Our model-data integration approach extends to any discrete dynamic process with rare events and realistically limited data.Significance StatementSystems biology seeks to combine experiments with computation to predict complex biological behaviors. However, despite tremendous data and knowledge, most biological models make terrible predictions. By analyzing single-cell-single-molecule measurements of mRNA in yeast during stress response, we explore how prediction accuracy is controlled by experimental distributions shapes. We find that asymmetric data distributions, which arise in measurements of positive quantities, can cause standard modeling approaches to yield excellent fits but make meaningless predictions. We demonstrate advanced computational tools that solve this dilemma and achieve predictive understanding of many spatiotemporal mechanisms of transcription control including RNA polymerase initiation and elongation and mRNA accumulation, transport and decay. Our approach extends to any discrete dynamic process with rare events and realistically limited data.
Histone demethylation and c-MYC activation enhance translational capacity in response to amino acid restriction
Authors: Cheng Chen , Su Trent , Morselli Marco , Kurdistani Siavash K. 
Published: June 2017

AbstractNutrient limitation may elicit adaptive epigenetic changes but the nature and mechanisms of the cellular response to specific nutrient deficiencies are incompletely understood. We report that depriving human cells of amino acids (AAs) induces specific loss of H4K20me1 from gene bodies and elevated binding of c-MYC at promoters genome-wide. These effects are most pronounced at ribosomal protein and translation initiation genes, which are upregulated, leading to enhanced protein synthetic capacity. Combination of H4K20 methyltransferase depletion and c-MYC over-expression in rich media is required and sufficient to recapitulate the effects of AA restriction. Our data reveal an unexpected and epigenetically implemented increase in translational capacity when AAs are limiting, likely to safeguard the proteome by making effective use of limited resources.One Sentence Summary:Combination of H4K20me1 demethylation and c-MYC activation enhance translational capacity in response to amino acid restriction.
winglessis a positive regulator of eyespot color patterns inBicyclus anynanabutterflies
Authors: Özsu Nesibe , Chan Qian Yi , Chen Bin , Gupta Mainak Das , Monteiro Antónia 
Published: June 2017

SummaryEyespot patterns of nymphalid butterflies are an example of a novel trait yet, the developmental origin of eyespots is still not well understood. Several genes have been associated with eyespot development but few have been tested for function. One of these genes is the signaling ligand,wingless, which is expressed in the eyespot centers during early pupation and may function in eyespot signaling and color ring differentiation. Here we tested the function ofwinglessin wing and eyespot development by down-regulating it in transgenicBicyclus anynanabutterflies via RNAi driven by an inducible heat-shock promoter. Heat-shocks applied during larval and early pupal development led to significant decreases inwinglessmRNA levels and to decreases in eyespot size and wing size in adult butterflies. We conclude thatwinglessis a positive regulator of eyespot and wing development inB. anynanabutterflies.
Aerobiosis is not associated with GC content and G to T mutations are not the signature of oxidative stress in prokaryotic evolution
Authors: Aslam Sidra , Lan Xin-Ran , Zhang Bo-Wen , Chen Zheng-Lin , Niu Deng-Ke 
Published: June 2017

AbstractBackground:Among the four bases, guanine is the most susceptible to damage from oxidative stress. Replication of DNA containing damaged guanines result in G to T mutations. Therefore, the mutations resulting from oxidative DNA damage are generally expected to predominantly consist of G to T (and C to A when the damaged guanine is not in the reference strand) and result in decreased GC content. However, the opposite pattern was reported 16 years ago in a study of prokaryotic genomes. Although that result has been widely cited and confirmed by nine later studies with similar methods, the omission of the effect of shared ancestry requires a re-examination of the reliability of the results.Results:We retrieved 70 aerobe-anaerobe pairs of prokaryotes, and members of each pair were adjacent on the phylogenetic tree. Pairwise comparisons of either whole-genome GC content or the GC content at 4-fold degenerate sites of orthologous genes among these 70 pairs did not show significant differences between aerobes and anaerobes. The signature of guanine oxidation on GC content evolution has not been detected even after extensive controlling of other influencing factors. Furthermore, the anaerobes were not different from the aerobes in the rate of either G to T, C to A, or other directions of substitutions. The presence of the enzymes responsible for guanine oxidation in anaerobic prokaryotes provided additional evidence that guanine oxidation might be prevalent in anaerobic prokaryotes. In either aerobes or anaerobes, the rates of G:C to T:A mutations were not significantly higher than the reverse mutations.Conclusions:The previous counterintuitive results on the relationship between oxygen requirement and GC content should be attributed to the methodological artefact resulting from phylogenetically non-independence among the analysed samples. Our results showed that aerobiosis does not increase or decrease GC content in evolution. Furthermore, our study challenged the widespread belief that abundant G:C to T:A transversions are the signature of oxidative stress in prokaryotic evolution.
Boosting Felsenstein’s Phylogenetic Bootstrap
Authors: Lemoine F. , Domelevo Entfellner J.-B. , Wilkinson E. , De Oliveira T. , Gascuel O. 
Published: June 2017

AbstractFelsenstein’s article describing the application of the bootstrap to evolutionary trees, is one of the most cited papers of all time. That statistical method, based on resampling and replications, is used extensively to assess the robustness of phylogenetic inferences. However, increasing numbers of sequences are now available for a wide variety of species, and phylogenies with hundreds or thousands of taxa are becoming routine. In that framework, Felsenstein’s bootstrap tends to yield very low supports, especially on deep branches. We propose a revised version, in which the presence of inferred branches in replications is measured using a gradual “transfer” distance, as opposed to the original version using a binary presence/absence index. The resulting supports are higher, while not inducing falsely supported branches. Our method is applied to large simulation, mammal and HIV datasets, for which it reveals the phylogenetic signal, while Felsenstein’s bootstrap fails to do so.
Coupling of replisome movement with nucleosome dynamics can contribute to the parent-daughter information transfer
Authors: Bameta Tripti , Das Dibyendu , Padinhateeri Ranjith 
Published: June 2017

AbstractPositioning of nucleosomes along the genomic DNA is crucial for many cellular processes that include gene regulation and higher order packaging of chromatin. The question of how nucleosome-positioning information from a parent chromatin gets transferred to the daughter chromatin is highly intriguing. Accounting for experimentally known coupling between replisome movement and nucleosome dynamics, we propose a model that can explain the inheritance of nucleosome positioning. Simulating nucleosome dynamics during replication we argue that short pausing of the replication fork, associated with nucleosome disassembly, can be the event crucial for communicating nucleosome positioning information from parent to daughter. We show that the interplay of timescales between nucleosome disassembly (τp) at the replication fork and nucleosome sliding behind the fork (τs) can give rise to a rich “phase diagram” having different inherited patterns of nucleosome organization. Our model predicts that only whenτp≥τsthe daughter chromatin can inherit the precise nucleosome positioning of the parent.
TRIM9-dependent ubiquitination of DCC constrains kinase signaling, exocytosis, and axon branching
Authors: Plooster Melissa , Menon Shalini , Winkle Cortney C. , Urbina Fabio L. , Monkiewicz Caroline , Phend Kristen D. , Weinberg Richard J. , Gupton Stephanie L. 
Published: June 2017

AbstractExtracellular netrin-1 and its receptor DCC promote axon branching in developing cortical neurons. Netrin-dependent morphogenesis is preceded by multimerization of DCC, activation of FAK and Src family kinases, and increases in exocytic vesicle fusion, yet how these occurrences are linked is unknown. Here we demonstrate that TRIM9-dependent ubiquitination of DCC blocks the interaction with and phosphorylation of FAK. Upon netrin-1 stimulation TRIM9 promotes DCC multimerization, but TRIM9-dependent ubiquitination of DCC is reduced, which promotes an interaction with FAK and subsequent FAK activation. We found that inhibition of FAK activity blocks elevated frequencies of exocytosisin vitroand elevated axon branchingin vitroandin vivo.Although FAK inhibition decreased SNARE-mediated exocytosis, assembled SNARE complexes and vesicles adjacent to the plasma membrane were increased, suggesting a novel role for FAK in the progression from assembled SNARE complexes to vesicle fusion in developing murine neurons.Abbreviations used in this paperDCCDeleted in Colorectal CancerTRIMTripartite MotifSFKsrc family kinaseDCCKRnon ubiquitinatable DCC mutantVAMPvesicle associated membrane proteinTRIM9ΔRINGTRIM9 lacking the ubiquitin ligase RING domainTRIM9ΔSPRYTRIM9 variant lacking the DCC-binding SPRY domainTIRFTotal Internal Reflection FluorescencepYphosphotyrosineFAKipharmacological FAK inhibitor 14FRNKFAK related non-kinaseSTX-1Asyntaxin 1AIPimmunoprecipitate
Computational Investigation of O2Diffusion Through an Intra–molecular Tunnel in AlkB; Influence of Polarization on O2Transport
Authors: Torabifard Hedieh , Cisneros G. Andrés 
Published: June 2017

AbstractE. ColiAlkB catalyzes the direct dealkylation of various alkylated bases in damaged DNA. The diffusion of molecular Oxygen to the active site in AlkB is an essential step for the oxidative dealkylation activity. Despite detailed studies on the stepwise oxidation mechanism of AlkB, there is no conclusive picture of how O2molecules reach the active site of the protein. Yuet al. (Nature,439, 879) proposed the existence of an intra–molecular tunnel based on their initial crystal structures of AlkB. We have employed computational simulations to investigate possible migration pathways inside AlkB for O2molecules. Extensive molecular dynamics (MD) simulations, including explicit ligand sampling and potential of mean force (PMF) calculations, have been performed to provide a microscopic description of the O2delivery pathway in AlkB. Analysis of intra–molecular tunnels using the CAVER software indicates two possible pathways for O2to diffuse into the AlkB active site. Explicit ligand sampling simulations suggests that only one of these tunnels provides a viable route. The free energy path for an oxygen molecule to travel along each of these tunnels has been determined with AMBER and AMOEBA. Both PMFs indicate passive transport of O2from the surface of the protein. However, the inclusion of explicit polarization shows a very large barrier for diffusion of the co–substrate out of the active site, compared with the non–polarizable potential. In addition, our results suggest that the mutation of a conserved residue along the tunnel, Y178, has dramatic effects on the dynamics of AlkB and on the transport of O2along the tunnel.
Discriminative aversive learning and amygdala responsivity is enhanced in mice with reduced serotonin transporter activity
Authors: Lima João , Sharp Trevor , Taylor Amy M. , Bannerman David M. , McHugh Stephen B. 
Published: June 2017

AbstractThe serotonin (5-HT) transporter (5-HTT) regulates 5-HT availability at the synapse. Low or null 5-HTT expression results in increased 5-HT availability and has been reported to produce anxious and depressive phenotypes, although this remains highly controversial despite two decades of investigation. Paradoxically, SSRIs, which also increase 5-HT availability, reduce the symptoms of anxiety and depression. An emerging ‘network plasticity’ theory of 5-HT function argues that, rather than influencing mood directly, increasing 5-HT availability enhances learning about emotionally-significant events but evidence supporting this theory is inconclusive. Here, we tested one key prediction of this theory: that increased 5-HT availability enhances aversive learning. In experiment 1, we trained 5-HTT knock-out mice (5-HTTKO), which have increased 5-HT availability, and wild-type mice (WT) on an aversive discrimination learning task in which one auditory cue was paired with an aversive outcome whereas a second auditory cue was not. Simultaneously we recorded neuronal and hemodynamic responses from the amygdala, a brain region necessary for aversive learning. 5-HTTKO mice exhibited superior discrimination learning than WTs, and had stronger theta-frequency neuronal oscillations and larger amygdala hemodynamic responses to the aversive cues, which predicted the extent of learning. In experiment 2, we found that acute SSRI treatment (in naïve non-transgenic mice), given specifically before fear learning sessions, enhanced subsequent fear memory recall. Collectively, our data demonstrate that reducing 5-HTT activity (and thereby increasing 5-HT availability) enhances amygdala responsivity to aversive events and facilitates learning for emotionally-relevant cues. Our findings support the network plasticity theory of 5-HT function.