bluuebunny/crossref_metadata_2025_split huggingface dataset:
Taxonomic synthesis of the eastern North American millipede genus Pseudopolydesmus (Diplopoda: Polydesmida: Polydesmidae), utilizing high-detail ultraviolet fluorescence imaging
Authors: Sierwald Petra , Hennen Derek A , Zahnle Xavier J , Ware Stephanie , Marek Paul E 
Published: February 2019

Abstract
The species of the eastern North American millipede genus Pseudopolydesmus are reviewed. Synonyms and comprehensive literature citations are provided for each of the eight recognized species. Diagnostic morphology of the genus, including clarification of male gonopod terminology, is reviewed and defined using scanning electron microscopy and high-quality macrophotographic images, including those in which ultraviolet fluorescence was induced to produce detailed images of morphological structures. Based on the examination of available type material, the following eight species are recognized: (1) Pseudopolydesmus erasus; (2) Pseudopolydesmus canadensis; (3) Pseudopolydesmus collinus; (4) Pseudopolydesmus pinetorum; (5) Pseudopolydesmus minor; (6) Pseudopolydesmus caddo; (7) Pseudopolydesmus paludicolus; and (8) Pseudopolydesmus serratus. The species names Polydesmus neoterus and Polydesmus euthetus are here placed as junior subjective synonyms of Ps. minor (both syn. nov.), and Polydesmus natchitoches is placed as a junior subjective synonym of Ps. pinetorum (syn. nov.).
How fast are cells dividing: Probabilistic model of continuous labeling assays
Authors: Rode Julian , Goerke Torsten , Brusch Lutz , Rost Fabian 
Published: February 2019

AbstractCorrect estimates of cell proliferation rates are crucial for quantitative models of the development, maintenance and regeneration of tissues. Continuous labeling assays are used to infer proliferation rates in vivo. So far, the experimental and theoretical study of continuous labeling assays focused on the dynamics of the mean labeling-fraction but neglected stochastic effects. To study the dynamics of the labeling-fraction in detail and fully exploit the information hidden in fluctuations, we developed a probabilistic model of continuous labeling assays which incorporates biological variability at different levels, between cells within a tissue sample but also between multiple tissue samples. Using stochastic simulations, we find systematic shifts of the mean-labeling fraction due to variability in cell cycle lengths. Using simulated data as ground truth, we show that current inference methods can give biased proliferation rate estimates with an error of up to 40 %. We derive the analytical solution for the Likelihood of our probabilistic model. We use this solution to infer unbiased proliferation rate estimates in a parameter recovery study. Furthermore, we show that the biological variability on different levels can be disentangled from the fluctuations in the labeling data. We implemented our model and the unbiased parameter estimation method as an open source Python tool and provide an easy to use web service for cell cycle length estimation from continuous labeling assays (https://imc.zih.tu-dresden.de/cellcycle).
Insect herbivory and avian insectivory in novel native oak forests: divergent effects of stand size and connectivity
Authors: Valdés-Correcher Elena , Halder Inge van , Barbaro Luc , Castagneyrol Bastien , Hampe Arndt 
Published: February 2019

AbstractThe value of novel native broadleaf woodlands for biodiversity conservation is important to consider for adequate forest management in rural landscapes. Passive reforestation has been proposed as a cost-efficient tool for creating networks of novel native forest stands that would help restoring biodiversity and associated ecosystem services. Yet to date the ecological functioning of such stands remains strongly understudied compared to forest remnants resulting from longer-term fragmentation. We assessed how the size and connectivity of newly established Pedunculate oak (Quercus robur L.) stands in rural landscapes of SW France affect rates of herbivory by different insect guilds as well as rates of avian insectivory and the abundance and richness of insectivorous birds. Comparing 18 novel forest stands along a gradient of size (0.04-1.15 ha) and cover of broadleaf forests in the surroundings (0-30% within a 500 radius), we found that even the smallest stands are colonised by leaf miners and chewers/skeletonizers, and that rates of herbivory are globally comparable to those reported from older and larger oak forests. The size of stands had a relatively minor effect on herbivory, whereas it increased the abundance of insectivorous bird. It also determined rates of avian insectivory as estimated by an experiment with plasticine caterpillars. These rates were however rather low and unrelated with the extent of herbivory in the stand. Overall, our study indicates that insect herbivores tend to react more rapidly to the establishment of novel native forests than their avian predators as the latter may depend on the development of larger patches of suitable habitat in the surrounding landscape. To favour a rapid build-up of diverse, and hence stable, trophic networks involving insect herbivores and their predators, woodland creation schemes should therefore primarily focus on habitat size and quality.
Pancreatic Stellate Cells Secrete Deoxycytidine Conferring Resistance to Gemcitabine in PDAC
Authors: Dalin Simona , Sullivan Mark R. , Kreidl Emanuel , Lau Allison N. , Grauman-Boss Beatrice , Fenoglio Silvia , Luengo Alba , Vander Heiden Matthew G. , Lauffenburger Douglas A. , Hemann Michael T. 
Published: February 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analog gemcitabine is among the most effective therapies to treat PDAC; however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDAC is a striking accumulation of stromal tissue surrounding the tumor, and this accumulation of stroma can contribute to therapy resistance. To better understand how stroma limits response to therapy, we investigated cell-extrinsic mechanisms of resistance to gemcitabine. We show that conditioned media from pancreatic stellate cells (PSC), as well as from other fibroblasts, protects PDAC cells from gemcitabine toxicity. We find that the PSC conditioned media protective effect is mediated by secretion of deoxycytidine, but not other deoxynucleosides, through equilibrative nucleoside transporters. Deoxycytidine inhibits the processing of gemcitabine in PDAC cells, thus reducing the effect of gemcitabine and other nucleoside analogs on cancer cells. Our results suggest that reducing deoxycytidine production in PSCs may increase the efficacy of nucleoside analog therapies.Additional InformationFunding: This project was funded in part by the NIH (NCI U54-217377), the MIT Center for Precision Cancer Medicine, and by the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute. S.D. was supported by the David H. Koch Fellowship in Cancer Research. A.N.L was a Robert Black Fellow of the Damon Runyon Cancer Research Foundation, DRG-2241-15 and was supported by a NIH Pathway to Independence Award (K99/R00), 1K99CA234221. M.T.H and M.G.V.H. acknowledges funding from the MIT Center for Precision Cancer Medicine and the Ludwig Center at MIT. M.G.V.H also acknowledges funding from the Lustgarten Foundation, SU2C, the MIT Center for Precision Cancer Medicine, the NCI, and an HHMI Faculty Scholar award.Competing interests: M.G.V.H. is a consultant and advisory board member for Agios Pharmaceuticals, Aeglea Biotherapeutics, and Auron Therapeutics.
Experience-dependent tuning of early olfactory processing in the adult brain
Authors: Jernigan Christopher M. , Halby Rachael , Gerkin Richard C. , Sinakevitch Irina , Locatelli Fernando , Smith Brian H. 
Published: February 2019

AbstractExperience-dependent plasticity in the central nervous system allows an animal to adaptively change their responses to stimuli over different time scales. In this study we explored the different time frames and mechanisms over which olfactory experience-dependent plasticity works. We measured the impact of experience on early olfactory processing by comparing naturally foraging animals with a diverse olfactory experience to animals from the same cohort that experienced a chronic reduction in adult olfactory experience. We placed age-matched sets of full-sister honey bees, Apis mellifera, into two different olfactory conditions, in which animals were allowed to forage ad libitum. In one condition (T), we reduced the olfactory experience of foraging bees by placing them in a tent in which both sucrose and pollen resources were associated with a single odor. In the second condition (F), bees were allowed to forage freely and therefore receive a diversity of naturally occurring resource-associated olfactory experiences. We found that bees with a reduced olfactory experience had less developed antennal lobes when compared to experienced foragers, suggesting early-adult sensory experience influences the development of olfactory processing. We next measured the antennal lobe glomerular responses to odors using calcium imaging, and found that diverse olfactory experience of bees also enhances the inter-individual variation in the glomerular response profiles to odors. Last, we measured the impact of this treatment in an olfactory learning assay. We found that bees with a reduced olfactory experience had more difficulty picking an odor out of a mixture, which led them to generalize more (or respond similarly) to different mixture components than bees with richer olfactory experiences. Our study highlights the impact of individual experience at multiple levels (i.e., behavioral, physiological, developmental) on early olfactory processing.
Discordant gene responses to radiation in humans and mice: hematopoietically humanized mice may save the day for radiation biomarker identification
Authors: Ghandhi Shanaz A. , Smilenov Lubomir , Pujol-Canadell Monica , Amundson Sally A 
Published: February 2019

AbstractThe mouse (Mus musculus) is an extensively used model of human disease and responses to stresses such as ionizing radiation. As part of our work developing gene expression biomarkers of radiation exposure, dose, and injury, we have found many genes are either up-regulated (e.g. CDKN1A, MDM2, BBC3, and CCNG1) or down-regulated (e.g. TCF4 and MYC) in both species after irradiation. However, we have also found genes that are consistently up-regulated in humans and down-regulated in mice (e.g. DDB2, PCNA, GADD45A, SESN1, RRM2B, KCNN4, IFI30, and PTPRO). Here we test a hematopoietically humanized mouse as a potential in vivo model for biodosimetry studies, measuring the response of these 14 genes one day after radiation exposure, and comparing it with that of human blood irradiated ex vivo, and blood from whole body irradiated mice. We found that human blood cells in the hematopoietically humanized mouse in vivo environment recapitulated the gene expression pattern expected from human cells, not the pattern seen from in vivo irradiated normal mice. The results of this study support the use of hematopoietically humanized mice as an in vivo model for radiation gene expression studies relevant to humans.
Substrate Affinity and Specificity of theScSth1p Bromodomain Are Fine-Tuned for Versatile Histone Recognition
Authors: Blus Bartlomiej J. , Hashimoto Hideharu , Seo Hyuk-Soo , Krolak Aleksandra , Debler Erik W. 
Published: February 2019

SummaryBromodomains recognize a wide range of acetylated lysine residues in histones and other nuclear proteins. Substrate specificity is critical for their biological function and arises from unique acetyl-lysine binding sites formed by variable loop regions. Here, we analyzed substrate affinity and specificity of the yeastScSth1p bromodomain, an essential component of the “Remodels theStructure ofChromatin” complex, and found that the wild-type bromodomain preferentially recognizes H3K14ac and H4K20ac peptides. Mutagenesis studies—guided by our crystal structure determined at 2.7 Å resolution—revealed loop residues Ser1276 and Trp1338 as key determinants for such interactions. Strikingly, point mutations of each of these residues substantially increased peptide binding affinity and selectivity, respectively. Our data demonstrate that theScSth1p bromodomain is not optimized for binding to an individual acetylation mark, but fine-tuned for interactions with several such modifications, consistent with the versatile and multivalent nature of histone recognition by reader modules such as bromodomains.HighlightsTheScSth1p bromodomain preferentially recognizes H3K14ac and H4K20ac peptidesSer1276 and Trp1338 are key determinants of substrate affinity and specificityMutations of these residues drastically increase substrate affinity and specificityTheScSth1p bromodomain is fine-tuned for promiscuous histone tail recognitionGraphical Abstract
Biochemical and structural characterization of a highly active branched-chain amino acid aminotransferase from Pseudomonas sp. for efficient biosynthesis of chiral amino acids
Authors: Zheng Xinxin , Cui Yinglu , Li Tao , Li Ruifeng , Guo Lu , Li Defeng , Wu Bian 
Published: February 2019

AbstractAminotransferases (ATs) are important biocatalysts for the synthesis of chiral amines because of their capability of introducing amino group into ketones or keto acids as well as their high enantioselectivity, high regioselectivity and no requirement of external addition of cofactor. Among all ATs, branched-chain amino acid aminotransferase (BCAT) can reversibly catalyse branched-chain amino acids (BCAAs), including L-valine, L-leucine, and L-isoleucine, with α-ketoglutaric acid to form the corresponding ketonic acids and L-glutamic acid. Alternatively, BCATs have been used for the biosynthesis of unnatural amino acids, such as L-tert-leucine. In the present study, the BCAT from Pseudomonas sp. (PsBCAT) was cloned and expressed in Escherichia coli for biochemical and structural analyses. The optimal reaction temperature and pH of PsBCAT were 40 °C and 8.5, respectively. PsBCAT exhibited a comparatively broader substrate spectrum, and showed remarkably high activity with L-leucine, L-valine, L-isoleucine and L-methionine with activities of 105 U/mg, 127 U/mg, 115 U/mg and 98 U/mg, respectively. Additionally, PsBCAT had activities with aromatic L-amino acids, L-histidine, L-lysine, and L-threonine. To analyse the catalytic mechanism of PsBCAT with the broad substrate spectrum, the crystal structure of PsBCAT was also determined. Finally, conjugated with the ornithine aminotransferase (OrnAT) from Bacillus subtilis, the coupled system was applied to the preparation of L-tert-leucine with 83% conversion, which provided an approximately 2.7-fold higher yield than the single BCAT reaction.IMPORTANCEDespite the enormous potential of BCATs, the vast majority of enzymes still lack suitably broad substrate scope and activity, thus new sources and novel enzymes are currently being investigated. Here, we described a previously uncharacterized PsBCAT, which showed a surprisingly wide substrate range and was more active towards BCAAs. This substrate promiscuity is unique for the BCAT family and could prove useful in industrial applications. Based on the determined crystal structure, we found some differences in the organization of the substrate binding cavity, which may influence the substrate specificity of the enzyme. Moreover, we demonstrated efficient biocatalytic asymmetric synthesis of L-tert-leucine using a coupling system, which can be used to remove the inhibitory by-product, and to shift the reaction equilibrium towards the product formation. In summary, the structural and functional characteristics of PsBCAT were analysed in detail, and this information will play an important role in the synthesis of chiral amino acids and will be conducive to industrial production of enantiopure chiral amines by aminotransferase.
Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leukocyte antigen locus
Authors: Parks Tom , Elliott Katherine , Lamagni Theresa , Auckland Kathryn , Mentzer Alexander J. , Guy Rebecca , Cartledge Doreen , Strakova Lenka , O’Connor Daniel , Pollard Andrew J. , Neville Matthew J. , Mahajan Anubha , Ashrafian Houman , Chapman Stephen J. , Hill Adrian V. S. , Sriskandan Shiranee , Knight Julian C. 
Published: February 2019

AbstractInvasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1,540 controls. Using HLA imputation and linear mixed-models, we find each copy of theHLA-DQA1*01:03 allele associates with a two-fold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4,P=0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.
EXOCYST70A3 controls root system depth in Arabidopsis via the dynamic modulation of auxin transport
Authors: Ogura Takehiko , Goeschl Christian , Filiault Daniele , Mirea Madalina , Slovak Radka , Wolhrab Bonnie , Satbhai Santosh B. , Busch Wolfgang 
Published: February 2019

SUMMARYRoot system architecture (RSA), the distribution of roots in soil, plays a major role in plant survival. RSA is shaped by multiple developmental processes that are largely governed by the phytohormone auxin, suggesting that auxin regulates responses of roots that are important for local adaptation. However, auxin has a central role in numerous processes and it is unclear which molecular mechanisms contribute to the variation in RSA for environmental adaptation. Using natural variation in Arabidopsis, we identify EXOCYST70A3 as a modulator of the auxin system that causes variation in RSA by acting on PIN4 protein distribution. Allelic variation and genetic perturbation of EXOCYST70A3 leads to alteration of root gravitropic responses, resulting in a different RSA depth profile and drought resistance. Overall our findings suggest that the local modulation of the pleiotropic auxin pathway can gives rise to distinct root system architectures that can be adaptive in specific environments.
Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation
Authors: Hadjivasiliou Zena , Moore Rachel , McIntosh Rebecca , Galea Gabriel , Clarke Jon , Alexandre Paula 
Published: February 2019

SummaryDuring early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown.In vivoimaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.
Human pathogen co-occurrence in Ixodes ricinus ticks: effects of landscape topography, climatic factors and microbiota interactions
Authors: Aivelo Tuomas , Norberg Anna , Tschirren Barbara 
Published: February 2019

AbstractThe factors shaping microbial communities within organisms are still poorly understood. Besides ecological factors and host characteristics, direct interactions among microbes may shape the occurrence of microbes and the structure of communities. In the past it has been difficult to disentangle if patterns of microbial co-occurrence are due to facilitation or competition effects, or shaped by shared ecological preferences (i.e., environmental filtering). Here we use a joint species distribution model to characterize the bacterial microbiota composition of an important human disease vector, the sheep tick Ixodes ricinus, along ecological gradients in the Swiss Alps, and to test for facilitation or competition effects among human pathogens and tick endosymbionts. We identify a number of ecological variables that significantly predicted the diversity of tick microbial community and the occurrence of specific tick endosymbionts and human pathogens. However, ecological associations were generally microbe-specific rather than universal. We also found evidence for significant microbe interactions, in particular widespread facilitation among pathogens, which promotes pathogen co-infection within ticks, as well as competition between the tick endosymbiont Spiroplasma and a number of human pathogens. These findings highlight that direct interactions among microbes can affect the vector competence of ticks and thereby tick-borne disease dynamics.
Hierarchies & Lower Bounds in Theoretical Connectomics
Authors: Ramaswamy Venkatakrishnan 
Published: February 2019

AbstractConnectomics is a sub-field of Neuroscience aimed at determining connectomes – exact structures of neurons and their synaptic connections in nervous systems. A number of ongoing initiatives at the present time are working towards the goal of ascertaining the connectomes or parts thereof of various organisms. Determining the detailed physiological response properties of all the neurons in these connectomes is out of reach of current experimental technology. It is therefore unclear, to what extent knowledge of the connectome alone will advance a mechanistic understanding of computation occurring in these neuronal circuits, especially when the high-level function(s) of the said circuit is unknown.We are pursuing a research program to build theory in order to investigate these issues. In previously published work [1], towards this end, we have developed a theory of connectomic constraints for feedforward networks of neurons. Specifically, for feedforward networks equipped with neurons that obey a deterministic spiking neuron model, we asked if just by knowing the structure of a network, we could rule out spike-timed computations that it could be doing, no matter what response properties each of its neurons may have. Our neurons were abstract mathematical objects that satisfied a small number of axioms that correspond to certain broadly-obeyed properties of neurons.Here, we develop additional theoretical tools and notions to address these questions. The idea is to study the space of all possible spike-train to spike-train transformations. We are interested in asking how the subset of transformations spanned by networks of specific architectures can be related to hierarchical subsets of the space that are characterized by particular mathematical properties of transformations. In particular, given such a hierarchy of subsets, what is the “smallest” subset that contains the set of transformations spanned by networks of a specific class of architectures? Even if one cannot establish such a subset exactly, proving bounds on it (according to the hierarchy) might offer insight. After setting up the mathematical framework to make these notions precise, we construct explicit classes of hierarchies and prove a number of such lower bounds.