bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Length of Promoter Sequence Affects TheDe NovoInitiation By T7 RNA Polymerase in Vitro: New Insights Into The Evolution of Promoters For Single Subunit RNA Polymerases
Authors: Padmanabhan Ramesh , Miller Dennis 
Published: April 2019

1.1AbstractRNA polymerases (RNAPs) differ from other polymerases in that they can bind promoter sequences and initiatede novotranscription. Promoter recognition requires the presence of specific DNA binding domains in the polymerase. The structure and mechanistic aspects of transcription by the bacteriophage T7 RNA polymerase (T7 RNAP) are well characterized. This single subunit RNAP belongs to the family of RNAPs which also includes the T3, SP6 and mitochondrial RNAPs. High specificity for its promoter, the requirement of no additional transcription factors, and high fidelity of initiation from a specific site in the promoter makes it the polymerase of choice to study the mechanistic aspects of transcription. The structure and function of the catalytic domains of this family of polymerases are highly conserved suggesting a common mechanism underlying transcription. Although the two groups of single subunit RNAPs, mitochondrial and bacteriophage, have remarkable structural conservation, they recognize quite dissimilar promoters. Specifically, the bacteriophage promoters recognize a 23 nucleotide promoter extending from −17 to + 6 nucleotides relative to the site of transcription initiation, while the well characterized promoter recognized by the yeast mitochondrial RNAP is nine nucleotides in length extending from −8 to +1 relative to the site of transcription initiation. Promoters recognized by the bacteriophage RNAPs are also well characterized with distinct functional domains involved in promoter recognition and transcription initiation. Thorough mutational studies have been conducted by altering individual base-pairs within these domains. Here we describe experiments to determine whether the prototype bacteriophage RNAP is able to recognize and initiate at truncated promoters similar to mitochondrial promoters. Using anin vitrooligonucleotide transcriptional system, we have assayed transcription initiation activity by T7 RNAP. When a complete or almost complete (20 to 16 nucleotide) double stranded T7 RNAP promoter sequence is present, small RNA’s are produced through template-independent and promoter-dependent stuttering corresponding to abortive initiation, and this effect was lost with a scrambled promoter sequence. When partial double stranded promoter sequences (10 to 12 nucleotides) are supplied, template dependentde novoinitiation of RNA occurs at a site different from the canonical +1-initiation site. The site of transcription initiation is determined by a recessed 3’ end based paired to the template strand of DNA rather than relative to the partial promoter sequence. Understanding the mechanism underlying this observation helps us to understand the role of the elements in the T7 promoter, and provides insights into the promoter evolution of the single-subunit RNAPs.
Behaviors and Energy Source ofMycoplasma gallisepticumGliding
Authors: Mizutani Masaki , Miyata Makoto 
Published: April 2019

ABSTRACTMycoplasma gallisepticum, an avian-pathogenic bacterium, glides on host tissue surfaces by using a common motility system withMycoplasma pneumoniae. In the present study, we observed and analyzed the gliding behaviors ofM. gallisepticumin detail by using optical microscopes.M. gallisepticumglided at a speed of 0.27 ± 0.09 µm/s with directional changes relative to the cell axis of 0.6 ± 44.6 degrees/5 s without the rolling of the cell body. To examine the effects of viscosity on gliding, we analyzed the gliding behaviors under viscous environments. The gliding speed was constant in various concentrations of methylcellulose but was affected by Ficoll. To investigate the relationship between binding and gliding, we analyzed the inhibitory effects of sialyllactose on binding and gliding. The binding and gliding speed sigmoidally decreased with sialyllactose concentration, indicating the cooperative binding of the cell. To determine the direct energy source of gliding, we used a membrane-permeabilized ghost model. We permeabilizedM. gallisepticumcells with Triton X-100 or Triton X-100 containing ATP and analyzed the gliding of permeabilized cells. The cells permeabilized with Triton X-100 did not show gliding; in contrast, the cells permeabilized with Triton X-100 containing ATP showed gliding at a speed of 0.014 ± 0.007 μm/s. These results indicate that the direct energy source for the gliding motility ofM. gallisepticumis ATP.IMPORTANCEMycoplasmas, the smallest bacteria, are parasitic and occasionally commensal.Mycoplasma gallisepticumis related to human pathogenicMycoplasmas—Mycoplasma pneumoniaeandMycoplasma genitalium—which causes so-called ‘walking pneumonia’ and non-gonococcal urethritis, respectively. TheseMycoplasmastrap sialylated oligosaccharides, which are common targets among influenza viruses, on host trachea or urinary tract surfaces and glide to enlarge the infected areas. Interestingly, this gliding motility is not related to other bacterial motilities or eukaryotic motilities. Here, we quantitatively analyze cell behaviors in gliding and clarify the direct energy source. The results provide clues for elucidating this unique motility mechanism.
Point mutations in topoisomerase I alter the mutation spectrum in E. coli and impact the emergence of drug resistance genotypes
Authors: Bachar Amit , Itzhaki Elad , Gleizer Shmuel , Shamshoom Melina , Milo Ron , Antonovsky Niv 
Published: April 2019

AbstractIdentifying the molecular mechanisms that give rise to genetic variation is essential for the understanding of evolutionary processes. Previously, we have used adaptive laboratory evolution to enable biomass synthesis from CO2 in E. coli. Genetic analysis of adapted clones from two independently evolving populations revealed distinct enrichment for insertion and deletion mutational events. Here, we follow these observations to show that mutations in the gene encoding for DNA Topoisomerase 1 (topA) give rise to mutator phenotypes with characteristic mutational spectra. Using genetic assays and mutation accumulation lines, we show that point mutations in topA increase the rate of sequence deletion and duplication events. Interestingly, we observe that a single residue substitution (R168C) results in a high rate of head-to-tail (tandem) short sequence duplications, which are independent of existing sequence repeats. Finally, we show that the unique mutation spectrum of topA mutants enhances the emergence of antibiotic resistance in comparison to mismatch-repair (mutS) mutators, and lead to new resistance genotypes. Our findings highlight a potential link between the catalytic activity of topoisomerases and the fundamental question regarding the emergence of de novo tandem repeats, which are known modulators of bacterial evolution.
Distribution and density of oxpeckers on giraffes in Hwange National Park, Zimbabwe
Authors: Gagnon Roxanne , Mabika Cheryl T. , Bonenfant Christophe 
Published: April 2019

AbstractOxpeckers (Buphagus sp.) are two bird species closely associated to large mammals, including giraffes (Giraffa camelopardalis). We tested whether oxpeckers distributed themselves at random across individuals or aggregated on individual giraffes, and if birds select the host’s body parts with the expected greatest amount of ticks. By counting oxpeckers on giraffe’s body from photographs, we quantified the distribution of birds per hosts and over predefined zones on the giraffe body. Oxpeckers displayed a strong aggregation behaviour with few hosts carrying many birds while many carried a limited number or no birds, a pattern that was most exaggerated for males. Oxpeckers were disproportionately found on the mane and back, where the density of ticks is presumably the highest. This high aggregation level of birds is typical of parasitic species and could suggest that oxpecker distribution may mirror the distribution of ticks, their primary food resource, on giraffes. Abundance of ticks appears as a major driver of the oxpecker foraging behaviour, and the oxpecker–large herbivores system proves to be highly relevant for the study of host–parasite dynamics.
Population position along the fast-slow life-history continuum predicts intraspecific variation in actuarial senescence
Authors: Cayuela Hugo , Lemaître Jean-François , Bonnaire Eric , Pichenot Julian , Schmidt Benedikt R. 
Published: April 2019

AbstractPatterns of actuarial senescence can be highly variable among species. Previous comparative analyses revealed that both age at the onset of senescence and rates of senescence are linked to the species’ position along the fast-slow life-history continuum. As there are few long-term datasets of wild populations with known-age individuals, intraspecific (i.e. between-population) variation in senescence is understudied and limited to comparisons of wild and captive populations of the same species, mostly birds and mammals. In this paper, we examined how population position along the fast-slow life history continuum affects senescence patterns in an amphibian,Bombina variegata. We used capture-recapture data collected in four populations with contrasted life history strategies. Senescence trajectories were drawn using Bayesian capture-recapture models. We show that in “slow” populations the onset of senescence was earlier and individuals aged at a faster rate than individuals in “fast” populations. Our study provides one of the few empirical examples of between-population variation in senescence patterns in the wild and confirms that the fast-slow life history gradient is associated with both macroevolutionary and microevolutionary patterns of senescence.
On the cortical mapping function – visual space, cortical space, and crowding
Authors: Strasburger Hans 
Published: April 2019

AbstractThe retino-cortical visual pathway is retinotopically organized: Neighbourhood relationships on the retina are preserved in the mapping to the cortex. Size relationships in that mapping are also highly regular: The size of a patch in the visual field that maps onto a cortical patch of fixed size follows, along any radius and in a wide range, simply a linear function with retinal eccentricity. As a consequence, and under simplifying assumptions, the mapping of retinal to cortical locations follows a logarithmic function along that radius. While this has already been shown by Fischer (1973), the link between the linear function – which describes the local behaviour by the cortical magnification factor M – and the logarithmic location function for the global behaviour, has never been made fully explicit. The present paper provides such a link as a set of ready-to-use equations using Levi and Klein’s E2 nomenclature, and examples for their validity and applicability in the retinotopic mapping literature are discussed. The equations allow estimating M in the retinotopic centre and values thus derived from the literature are provided. A new structural parameter, d2, is proposed to characterize the cortical map, as a cortical counterpart to E2, and typical values for it are given. One pitfall is discussed and spelt out as a set of equations, namely the common myth that a pure logarithmic function will give an adequate map: The popular omission of a constant term renders the equations ill defined in, and around, the retinotopic centre. The correct equations are finally extended to describe the cortical map of Bouma’s law on visual crowding. The result contradicts recent suggestions that critical crowding distance corresponds to a constant cortical distance.
Stxbp1/Munc18-1 haploinsufficiency in mice recapitulates key features of STXBP1 encephalopathy and impairs cortical inhibition
Authors: Chen Wu , Cai Zhao-Lin , Chao Eugene S. , Chen Hongmei , Hao Shuang , Chao Hsiao-Tuan , Kim Joo Hyun , Messier Jessica E. , Zoghbi Huda Y. , Tang Jianrong , Swann John W. , Xue Mingshan 
Published: April 2019

AbstractMutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease pathogenesis.
Snail induces epithelial cell extrusion through transcriptional control of RhoA contractile signaling and cell matrix adhesion
Authors: Wee Kenneth , Zadeh Suroor , Verma Suzie , Daly Roger J. , Yap Alpha S. , Davis Melissa J. , Budnar Srikanth 
Published: April 2019

AbstractCell extrusion is a morphogenetic process that is implicated in epithelial homeostasis and highly dependent on the cellular insult and context. Minorities of cells expressing HRasV12or undergoing apoptosis are typically extruded apically in vertebrate cells. However, basal extrusion (delamination) predominates when mammalian cells express oncogenic KRas and during development in Drosophila. To explore if the morphogenetic transcription factor, Snail, induces extrusion, we inducibly expressed a metabolically stabilized Snail6SAtransgene mosaically in confluent MCF-7 monolayers. We found that the morphogenetic impact of Snail6SAwas critically influenced by the proportion of cells in which it was expressed. When expressed in small clusters (<3 cells) within confluent monolayers, Snail6SAexpression induced apical cell extrusion. In contrast, confluent cultures of Snail6SAexpressing cells were retained in the monolayer to eventually undergo basal extrusion (delamination). Transcriptomic profiling revealed that Snail6SAdid not substantively alter the balance of epithelial:mesenchymal genes. However, we identified a gene transcriptional network that led to the upregulation of RhoA signalling, actomyosin contractility and reduced basal adhesion in Snail6SAexpressing cells. We show that this was necessary to drive both apical extrusion and basal delamination. Thus, contractile upregulation by RhoA along with weakened basal adhesion provides a pathway for Snail to influence epithelial morphogenesis independently of classic Epithelial to Mesenchymal Transition (EMT).
Single-Cell Signature Explorer for comprehensive visualization of single cell signatures across scRNA-seq data sets
Authors: Pont Frédéric , Tosolini Marie , Fournié Jean Jacques 
Published: April 2019

ABSTRACTThe momentum of scRNA-seq data sets prompts for simple and powerful tools exploring their meaningful signatures. Here we present Single-Cell_Signature_Explorer (https://sites.google.com/site/fredsoftwares/products/single-cell-signature-explorer), the first method for high throughput scoring at single cell level of any gene set-based signature and visualization across t-SNE. By scanning data sets for single or combined signatures, it quantitatively and qualitatively maps any multi-gene feature, exemplified here with signatures of cell lineages, biological hallmarks and metabolic pathways in large scRNAseq datasets of human PBMC, lung cancer and adult testis.
Germline-encoded TCR-MHC contacts promote TCR V gene bias in umbilical cord blood T cell repertoire
Authors: Gao Kai , Chen Lingyan , Zhang Yuanwei , Zhao Yi , Wan Ziyun , Wu Jinghua , Lin Liya , Kuang Yashu , Lu Jinhua , Zhang Xiuqing , Tian Lei , Liu Xiao , Qiu Xiu 
Published: April 2019

AbstractT cells recognize antigens as peptides bound to major histocompatibility complex (MHC) proteins through T cell receptors (TCRs) on their surface. To recognize a wide range of pathogens, each individual possesses a substantial number of TCRs with an extremely high degree of variability. It remains controversial whether germline-encoded TCR repertoire is shaped by MHC polymorphism and, if so, what is the preference between MHC genetic variants and TCR V gene compatibility. To investigate the “net” genetic association between MHC variations and TRBV genes, we applied quantitative trait locus (QTL) mapping to test the associations between MHC polymorphism and TCR β chain V (TRBV) genes usage using umbilical cord blood (UCB) samples of 201 Chinese newborns. We found TRBV gene and MHC loci that are predisposed to interact with one another differ from previous conclusions. The majority of MHC amino acid residues associated with the TRBV gene usage show spatial proximities in known structures of TCR-pMHC complexes. These results show for the first time that MHC variants bias TRBV gene usage in UCB of Chinese ancestry and indicate that germline-encoded contacts influence TCR-MHC interactions in intact T cell repertoires.
Theory of cyborg: a new approach to fish locomotion control
Authors: Jamali Mohammad , Jamali Yousef , Golshani Mehdi 
Published: April 2019

AbstractCyborg in the brain-machine interface field has attracted more attention in recent years. To control a creature via a machine called cyborg method, three stages are considerable: stimulation of neurons, neural response, and the behavioral reaction of the subject. Our main concern was to know how electrical stimulation induces neural activity and leads to a behavioral response. Additionally, we were interested to explore which type of electrical stimulation is optimal from different aspects such as maximum response with minimum induction stimulus field, minimum damage of the tissue and the electrode, reduction of the noxiousness of stimuli or pain in the living creature. In this article, we proposed a new model for the induction of neural activity led to locomotion responses through an electrical stimulation. Furthermore, based on this model, we developed a new approach of electrical neural stimulation to provide a better locomotion control of living beings. This approach was verified through the empirical data of fish cyborg. We stimulated the fish brain by use of an ultra-high frequency signal which careered by a random low frequency. According to our model, we could control the locomotion of fish in a novel and innovative way. In this study, we categorized the different cyborg methods based on the nervous system areas and the stimulation signal properties to reach the better and optimal behavioral control of creature. According to this, we proposed a new stimulation method theoretically and confirmed it experimentally.
Super resolution imaging of a distinct chromatin loop in human lymphoblastoid cells
Authors: Zhu Jacqueline Jufen , Parteka Zofia , Lee Byoungkoo , Szalaj Przemyslaw , Wang Ping , Jodkowska Karolina , Aaron Jesse , Chew Teng-Leong , Plewczynski Dariusz , Ruan Yijun 
Published: April 2019

AbstractThe three-dimensional genome structure plays a fundamental role in gene regulation and cellular functions. Recent studies in genomics based on sequencing technologies inferred the very basic functional chromatin folding structures of the genome known as chromatin loops, the long-range chromatin interactions that are often mediated by protein factors. To visualize the looping structure of chromatin we applied super-resolution microscopy iPALM to image a specific chromatin loop in GM12878 cells. Totally, we have generated six images of the target chromatin region at the single molecule resolution. To infer the chromatin structures from the captured images, we modeled them as looping conformations using different computational algorithms and then evaluated the models by comparing with Hi-C data to examine the concordance. The results showed a good correlation between the imaging data and sequencing data, suggesting the visualization of higher-order chromatin structures for the very short genomic segments can be realized by microscopic imaging.
Synthetic lethality targeting LKB1 mutant and EGFR wild type human non-small cell lung cancer cells by glucose starvation and SGLT2 inhibition
Authors: Ren Yi , Chen Jiaqing , Mo Xiaofan , Yang Qiqi , Chen Peishi , Lu Guang , Tan Hayden Weng-Siong , Yi Juan , Yu Qiang , Kim You-Sun , Mallilankaraman Karthik , Shen Han-Ming 
Published: April 2019

SUMMARYIn this study, we aimed to discover novel therapeutic approaches targeting non-small cell lung cancer (NSCLC) patients without EGFR mutation. First, we found that mutations of EGFR and LKB1 are mutually exclusive in NSCLC. EGFR-WT/LKB1-mutant cells are resistant to EGFR inhibitor erlotinib but are highly susceptible to glucose starvation or SGLT2 inhibitor canagliflozin. Mechanistically, in these cells, glucose starvation causes suppression of AMPK and induction of oxidative stress, leading to cell death. Finally, canagliflozin effectively reduces tumor growth of EGFR-WT/LKB1-mutant NSCLC cells in the mice xenograft model. Our data thus demonstrate that synthetic lethality can be achieved by glucose starvation or SGLT2 inhibition in EGFR-WT/LKB1-mutant NSCLC.SIGNIFICANCEAt present, EGFR inhibitor-based targeted therapy can only benefit those non-small cell lung cancer (NSCLC) patients with EGFR mutation. Therefore, there is an urgent need to develop alternate targeted therapy for NSCLC with WT EGFR. In this study, we found that mutations of EGFR and LKB1 are mutually exclusive in NSCLC, and more importantly, synthetic lethality can be achieved in EGFR-WT/LKB1-mutant NSCLC cells with glucose starvation or SGLT2 inhibition. Since SGLT2 inhibitors such as canagliflozin are FDA-approved drugs for type II diabetes, our study thus points out a possibility of developing SGLT2 inhibitors as a targeted therapy for NSCLC patients with WT EGFR and mutant LKB1, which will benefit about 15-30% of NSCLC patients.HIGHLIGHTSEGFR and LKB1 mutations are mutually exclusive in NSCLCEGFR-WT/LKB1-mutant NSCLC cells are sensitive to cell death induced by glucose starvation and SGLT2 inhibitionGlucose starvation suppresses AMPK activity in LKB1-mutant NSCLC cellsSGLT2 inhibitor canagliflozin causes synthetic lethality in LKB1-mutant NSCLC cells