bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent Activity Subspaces for Working Memory and Motor Preparation in the Lateral Prefrontal Cortex
Authors: Tang Cheng , Herikstad Roger , Parthasarathy Aishwarya , Libedinsky Camilo , Yen Shih-Cheng 
Published: September 2019

AbstractThe lateral prefrontal cortex is involved in the integration of multiple types of information, including working memory and motor preparation. However, it is not known how downstream regions can extract one type of information without interference from the others present in the network. Here we show that the lateral prefrontal cortex contains two independent low-dimensional subspaces: one that encodes working memory information, and another that encodes motor preparation information. These subspaces capture all the information about the target in the delay periods, and the information in both subspaces is reduced in error trials. A single population of neurons with mixed selectivity forms both subspaces, but the information is kept largely independent from each other. A bump attractor model with divisive normalization replicates the properties of the neural data. These results have implications for the neural mechanisms of cognitive flexibility and capacity limitations.
Kin discrimination promotes horizontal gene transfer between unrelated strains inBacillus subtilis
Authors: Stefanic Polonca , Belcijan Katarina , Kraigher Barbara , Kostanjšek Rok , Nesme Joseph , Madsen Jonas , Kovac Jasna , Sørensen Søren , Vos Michiel , Mandic-Mulec Ines 
Published: September 2019

AbstractB. subtilisis a surface-dwelling bacterium that is competent for natural transformation. Genetically distinctB. subtilisswarms form a boundary upon encounter, mediated by a fast-evolving molecular kin discrimination (KD) system. We here demonstrate that KD-mediated swarm antagonisms inB. subtilispromote transformation-mediated horizontal gene transfer between strains of low relatedness. Gene transfer is largely uni-directional and the result of the induction of competence of the recipient strain by the donor strain is linked to a sigW-mediated stress response. More closely related strains, which in theory would experience more efficient recombination due to increased sequence homology, did not upregulate transformation upon encounter, demonstrating that social interactions can override mechanistic barriers to horizontal gene transfer. KD-mediated competence in response to the encounter of distinct neighbouring strains could maximize the probability of efficient incorporation of novel alleles and genes that have proved to function in a genomically and ecologically similar context.
Plasticity in medaka gonadotropes via cell proliferation and phenotypic conversion
Authors: Fontaine Romain , Ager-Wick Eirill , Hodne Kjetil , Weltzien Finn-Arne 
Published: September 2019

ABSTRACTFollicle stimulating hormone (Fsh) and luteinizing hormone (Lh) produced by the gonadotropes, play a major role in control of reproduction. Contrary to mammals and birds, Lh and Fsh are mostly produced by two separate cell types in teleost. Here, we investigated gonadotrope plasticity, using transgenic lines of medaka (Oryzias latipes) where DsRed2 and hrGfpII are under the control of fshb and lhb promotors respectively. We found that Fsh cells first appear in the pituitary at 8 dpf. Similar to in Lh cells, Fsh cells show hyperplasia from juvenile to adult stages. Hyperplasia is stimulated by estradiol exposure. Both Fsh and Lh cells show hypertrophy during puberty with similar morphology. They also share similar behavior, using their cellular extensions to make networks. We observed bi-hormonal gonadotropes in juvenile and adult fish but not during larval stage where only mono-hormonal cells are observed, suggesting the existence of phenotypic conversion between Fsh and Lh in later stages. This is demonstrated in cell culture, where some Fsh start to producelhb, a phenomenon enhanced by gonadotropin releasing hormone (Gnrh) stimulation. We have previously shown that medaka Fsh cells lack Gnrh receptors, but here we show that with time in culture, some Fsh cells start responding to Gnrh, whilefshbmRNA levels are significantly reduced, both suggestive of phenotypic change. All together, these results reveal high plasticity of gonadotropes due to both estradiol sensitive proliferation and Gnrh promoted phenotypic conversion, and also shows that gonadotropes lose part of their identity when kept in cell culture.
Immunoinformatic and dynamic simulation-based designing of a multi-epitope vaccine against emerging pathogen Elizabethkingia anophelis
Authors: Nain Zulkar , Abdullah Faruq , Rahman M. Mizanur , Karim Mohammad Minnatul , Rahman S. M. Raihan , Khan Shakil Ahmed , Sayed Sifat Bin , Sheam Md. Moinuddin , Haque Zahurul , Adhikari Utpal Kumar 
Published: September 2019

AbstractElizabethkingia anophelis is an emerging human pathogen causing neonatal meningitis, catheter-associated infections and nosocomial outbreaks with high mortality rates. Besides, they are resistant to most antibiotics used in empirical therapy. In this study, therefore, we used immunoinformatic approaches to design an epitope-based vaccine against E. anophelis as an alternative preventive measure. Initially, T-cell (CTL and HTL) and B-cell (LBL) epitopes were predicted from the highest antigenic protein. The CTL and HTL epitopes together had a population coverage of 99.97% around the world. Eventually, 6 CTL, 7 HTL, and 2 LBL epitopes were selected and used to construct a multiepitope vaccine. The vaccine protein was found to be highly immunogenic, non-allergenic, and non-toxic. Codon adaptation and in silico cloning were performed to ensure better expression within E. coli K12 host system. The stability of the vaccine structure was also improved by disulphide bridging. In addition, molecular docking and dynamic simulation revealed good and stable binding affinity between the vaccine and receptor. The immune simulation showed higher levels of T-cell and B-cell activities which was in coherence with actual immune response. Repeated exposure simulation resulted in higher clonal selection and faster antigen clearance. Nevertheless, experimental validation is required to ensure the immunogenic potency and safety of this vaccine to control E. anophelis infection in the future.
Genotyping complex structural variation at the malaria-associated human glycophorin locus using a PCR-based strategy
Authors: Algady Walid , Weyell Eleanor , Mateja Daria , Garcia André , Courtin David , Hollox Edward J 
Published: September 2019

AbstractStructural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically-significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants and accurate genotyping of this complex structural variation remains a challenge. Here, we use a PCR-based strategy to genotype structural variation at the human glycophorin gene cluster. We validate our approach, based on a triplex paralogue ratio test (PRT) combined with junction-fragment specific PCR, on publically-available samples from the 1000 Genomes project. We then genotype a longitudinal birth cohort using small amounts of DNA at low cost. Our approach readily identifies known deletions and duplications, and can potentially identify novel variants for further analysis. It will allow exploration of genetic variation at the glycophorin locus, and investigation of its relationship with malaria, in large sample sets at minimal cost, using standard molecular biology equipment.
Deep Learning-Based Analysis of Macaque Corneal Sub-Basal Nerve Fibers in Confocal Microscopy Images
Authors: Oakley Jonathan D. , Russakoff Daniel B. , McCarron Megan E. , Weinberg Rachel L. , Izzi Jessica M. , Mankowski Joseph L. 
Published: September 2019

AbstractPurposeTo describe and assess different deep learning-based methods for automated measurement of macaque corneal sub-basal nerves using in vivo confocal microscopy (IVCM).MethodsThe automated assessment of corneal nerve fiber length (CNFL) in IVCM images is of increasing clinical interest. These measurements are important biomarkers in a number of diseases including diabetes mellitus, human immunodeficiency virus, Parkinson’s disease and multiple sclerosis. Animal models of these and other diseases play an important role in understanding the disease processes as efforts toward developing new and effective therapeutics are made. And while automated methods exist for nerve fiber analysis in clinical data, differences in anatomy and image quality make the macaque data more challenging and has motivated the work reported here.Toward this goal, nerves in macaque corneal IVCM images were manually labelled using an ImageJ plugin (NeuronJ). Different deep convolutional neural network (CNN) architectures were evaluated for accuracy relative to the ground truth manual tracings. The best performing model was used on separately acquired macaque ICVM images to additionally compare inter-reader variability.ConclusionsDeep learning-based segmentation of sub-basal nerves in IVCM images shows excellent correlation to manual segmentations in macaque data. The technique is indistinguishable across readers and paves the way for more widespread adoption of objective automated analysis of sub-basal nerves in IVCM.Translational RelevanceQuantitative measurements of corneal sub-basal nerves are important biomarkers for disease screening and management. This work reports on different approaches that, in using deep learning-based techniques, leverage state of the art analysis methods to demonstrate performance akin to human graders. In application, the approach is robust, rapid and objective, offering utility to a variety of clinical studies using IVCM.
Homo-Oligomerisation in Signal Transduction: Dynamics, Homeostasis, Ultrasensitivity, Bistability
Authors: Koch Daniel 
Published: September 2019

AbstractHomo-oligomerisation of proteins is a ubiquitous phenomenon whose exact role remains unclear in many cases. To identify novel functions, this paper provides an exploration of general dynamical mathematical models of homo-oligomerisation. Simulation and analysis of these models show that homo-oligomerisation on its own allows for a remarkable variety of complex dynamic and steady-state regulatory behaviour such as transient overshoots or homeostatic control of monomer concentration. If post-translational modifications are considered, however, conventional mass-action kinetics leads to thermodynamic inconsistencies due to asymmetric combinatorial expansion of reaction routes. Introducing a conservation principle to balance rate equations re-establishes thermodynamic consistency. Using such balanced models it is shown that oligomerisation can lead to bistability by enabling pseudo-multisite modification and kinetic pseudo-cooperativity via multi-enzyme regulation, thereby constituting a novel motif for bistable modification reactions. Due to these potential signal processing capabilities, homo-oligomerisation could play far more versatile roles in signal transduction than previously appreciated.
Anti-angiogenic activities of the leaves of Tapinanthus bangwensis (Engl. and K. Krause) Danser Loranthaceae growing on three host trees in south-western Nigeria
Authors: Diyaolu Oluwatofunmilayo Arike , Attah Alfred Francis , Adeagbo AS , Fukushi Y , Moody Jones Olanrewaju 
Published: September 2019

AbstractThe control of angiogenic process is of immense importance to the overall health of mankind to avert out-of-control complications such as tumours and cancers. Tapinanthus bangwensis (TBG) is a semi-parasitic plant with multipurpose uses in Nigerian ethno-medicine among which is its anti-infective properties as well as the anti-tumor and restoration of damaged tissues. Despite the wide and varied uses of TBG, the anti-angiogenic investigation of the plant on different host trees is lacking while the documentation and scientific validation of indigenous knowledge on plants’ use is urgent. The present work focuses on the anti-angiogenic activities of the crude extracts and partitioned fractions of the leaves of Tapinanthus bangwensis (TBG) using the Chick chorio allantoic membrane (CAM) model. The plant was collected from three different host trees namely Albizia lebbeck (AL), Stereospermum kunthianum (SK) and Tabebuia rosea (TR). The methanolic crude extracts and solvent-partitioned fractions of TBG-SK samples were assessed for their anti-angiogenic activities using the chick chorio allantoic membrane (CAM) in ovo and in vitro assay methods respectively. Purification and isolation of major compound(s) in the chloroform fraction of TBG extract obtained from Stereospermum kunthianum host tree (TBG-SK) was carried out using chromatographic and spectroscopic methods (NMR, MS).The crude methanolic extract of TBG-SK was most potent (100% activity) in the CAM in ovo assay while the chloroform fraction produced a significantly (p<0.05) highest average reduction in blood vessels with resultant formation of large avascular zones on CAM following an in vitro CAM assay. The anti-angiogenic chloroform fraction revealed the presence of a UV-active triterpenoid moiety. Findings from this work, has provided some justification for the folkloric use of TBG and thus forms a potential basis for drug discovery for wide-ranging disease states.
Systems biology analysis of publicly available transcriptomic data reveals a critical link between AKR1B10 gene expression, smoking and occurrence of lung cancer
Authors: Cubillos-Angulo Juan M. , Fukutani Eduardo R. , Cruz Luís A. B. , Arriaga María B. , Lima João Victor , Andrade Bruno B. , Queiroz Artur T. L. , Fukutani Kiyoshi F. 
Published: September 2019

AbstractBackgroundCigarette smoking is associated with increased risk of developing respiratory diseases and various types of cancer. Early identification of such unfavorable outcomes in patients who smoke is critical for optimizing personalized medical care.MethodsHere, we perform a comprehensive analysis using Systems Biology tools of publicly available data from a total of six transcriptomic studies, which examined different specimens of lung tissue and/or cells of smokers and nonsmokers to identify potential markers associated with lung cancer.ResultsExpression level of twenty-two genes was capable of classifying smokers from non-smokers. A machine learning algorithm revealed that AKR1B10 was the most informative gene among the 22 DEGs accounting for the classification of the clinical groups. AKR1B10 expression was higher in smokers compared to non-smokers in datasets examining small and large airway epithelia, but not in the data from a study of sorted alveolar macrophages. We next tested whether AKR1B10 expression could be useful in identification of cancer tissue in patients who were not exposed to smoking. AKR1B10 expression was substantially higher in lung cancer specimens compared to matched healthy tissue obtained from nonsmoking individuals (accuracy: 80%, p<0.0001). Finally, we searched the expression of 11 single nucleotide polymorphisms (SNPs) of AKR1B10 worldwide. We found that the SNP rs782881 was the most frequent mutant allele in the majority of continents. Africa was the continent which exhibited higher frequency of SNPs associated with lower AKR1B10 expression and displayed lower lung cancer incidence and deaths attributable to tobacco.ConclusionThe systematic analysis of transcriptomic studies performed here revealed a potential critical link between AKR1B10 expression, smoking and occurrence of lung cancer.
Effects of Transcranial Direct Current Stimulation on GABA and Glutamate in Children: A Pilot Study
Authors: Nwaroh C , Giuffre A , Cole L , Bell T , Carlson H. L. , MacMaster F. P. , Kirton A , Harris AD 
Published: September 2019

AbstractTranscranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS) it has been shown that tDCS can affect local levels of γ-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right handed children ages 12–18 years participated in five consecutive days of tDCS intervention (sham, a-tDCS or HD-tDCS) targeting the right M1 while training in a fine motor task (Purdue Pegboard Task) with their left hand. Glutamate and GABA were measured before and after the protocol (at day 5 and 6 weeks) using conventional MRS and GABA-edited MRS in the sensorimotor cortices. Glutamate measured in the left sensorimotor cortex was higher in the HD-tDCS group compared to a-tDCS and sham at 6 weeks (p = 0.001). No changes in GABA were observed in either sensorimotor cortex at any time. These results suggest that neither a-tDCS or HD-tDCS locally affect GABA and glutamate in the developing brain and therefore it may demonstrate different responses in adults.
Efficacy and safety of a monodisperse solid-in-oil-in-water emulsion in transcatheter arterial chemoembolization in a rabbit VX2 tumor model
Authors: Yasui Daisuke , Yamane Aya , Itoh Hiroshi , Kobayashi Masayuki , Kumita Shin-ichiro 
Published: September 2019

AbstractTranscatheter arterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma; however, it does not always result in tumor control. Nevertheless, treatment outcome can be improved with monodisperse emulsions of anticancer agents. In this study, the efficacy and safety of a monodisperse miriplatin-Lipiodol emulsion were evaluated in Japanese white rabbits. VX2 tumor was implanted into the left liver lobe of each rabbit. The animals were divided into control and experimental groups (of five animals each) and respectively administered a conventional miriplatin suspension or the emulsion via the left hepatic artery. Computed tomography (CT) was performed before, immediately after, and two days following TACE. All rabbits were sacrificed two days after the procedure. Each tumor was removed and cut in half for assessment of iodine concentration in one half by mass spectroscopy and evaluation of Lipiodol accumulation and adverse events in the other half. Mean Hounsfield unit (HU) values were measured using plain CT images taken before and after TACE. Iodine concentration was higher in the experimental group [1100 (750–1500) ppm] than in the control group [840 (660–1800) ppm]. Additionally, the HU value for the experimental group was higher than that for the control group immediately after [199.6 (134.0– 301.7) vs. 165.3 (131.4–280.5)] and two days after [114.2 (56.1–229.8) vs. 58.3 (42.9–132.5)] TACE. Cholecystitis was observed in one rabbit in the control group. Ischemic bile duct injury was not observed in any group. The results show that Lipiodol accumulation and retention in VX2 tumor may be improved by using a monodisperse emulsion. Moreover, no significant adverse events are associated with the use of the emulsion.
Senolytic treatment targets aberrant p21-expression to restore liver regeneration in adult mice
Authors: Ritschka Birgit , Knauer-Meyer Tania , Mas Alba , Plassat Jean-Luc , Gonçalves Daniel Sampaio , Jacobs Hugues , Pedone Elisa , Di Vicino Umberto , Cosma Maria Pia , Keyes William M. 
Published: September 2019

SUMMARYYoung mammals possess a limited regenerative capacity in tissues such as the liver, heart and limbs, but which is quickly lost upon maturation or transition to adulthood. Chronic cellular senescence is a known mediator of decreased tissue function in aging and disease. Here we investigated whether senescence plays a role in the progressive loss of liver regenerative capacity that develops in young adult mice. We find that following partial hepatectomy, the senescence markers p21, p16Ink4a and p19Arf become dynamically expressed at an age when regenerative capacity decreases. In addition, we demonstrate that treatment with a senescence-inhibiting drug improves regenerative capacity, through targeting of aberrant p21 expression. Surprisingly, we also find that the senescence marker p16Ink4a is expressed in a different cell-population to p21, and is unaffected by senescence targeting. This work suggests that senescence may initially develop as a heterogeneous cellular response, and that treatment with senolytic drugs may aid in promoting organ regeneration.
Generation of Recombinant Mammalian Selenoproteins through Genetic Code Expansion with Photocaged Selenocysteine
Authors: Peeler Jennifer C. , Kelemen Rachel E. , Abo Masahiro , Edinger Laura C. , Chen Jingjia , Chatterjee Abhishek , Weerapana Eranthie 
Published: September 2019

ABSTRACTSelenoproteins contain the amino acid selenocysteine and are found in all domains of life. The functions of many selenoproteins are poorly understood, partly due to difficulties in producing recombinant selenoproteins for cell-biological evaluation. Endogenous mammalian selenoproteins are produced through a non-canonical translation mechanism requiring suppression of the UGA stop codon, and a selenocysteine insertion sequence (SECIS) element in the 3’ untranslated region of the mRNA. Here, recombinant selenoproteins are generated in mammalian cells through genetic code expansion, circumventing the requirement for the SECIS element, and selenium availability. An engineered orthogonal E. coli leucyl-tRNA synthetase/tRNA pair is used to incorporate a photocaged selenocysteine (DMNB-Sec) at the UAG amber stop codon. Recombinantly expressed selenoproteins can be photoactivated in living cells with spatial and temporal control. Using this approach, the native selenoprotein methionine-R-sulfoxide reductase 1 is generated and activated in mammalian cells. The ability to site-specifically introduce selenocysteine directly in mammalian cells, and temporally modulate selenoprotein activity, will aid in the characterization of mammalian selenoprotein function.
High-throughput isolation and sorting of gut microbes reduce biases of traditional cultivation strategies
Authors: Watterson William J. , Tanyeri Melikhan , Watson Andrea R. , Cham Candace M. , Shan Yue , Chang Eugene B. , Eren A. Murat , Tay Savaş 
Published: September 2019

AbstractTraditional cultivation approaches in microbiology are labor-intensive, low-throughput, and often yield biased sampling of taxa due to ecological and evolutionary factors. New strategies are needed to enable ample representation of rare taxa and slow-growers that are outcompeted by fast-growing organisms. We developed a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts droplets based on colony density. We applied our strategy to mouse and human gut microbiomes and used 16S ribosomal RNA gene amplicons to characterize taxonomic composition of cells grown using different media. We found up to 4-fold increase in richness and larger representation of rare taxa among cells grown in droplets compared to conventional culture plates. Automated sorting of droplets for slow-growing colonies further enhanced the relative abundance of rare populations. Our method improves the cultivation and analysis of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.