bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of evidence accumulation by pupil-linked arousal processes
Authors: Keung Waitsang , Hagen Todd A. , Wilson Robert C.
Published: April 2018

Integrating evidence over time is crucial for effective decision making. For simple perceptual decisions, a large body of work suggests that humans and animals are capable of integrating evidence over time fairly well, but that their performance is far from optimal. This suboptimality is thought to arise from a number of different sources including: (1) noise in sensory and motor systems, (2) unequal weighting of evidence over time, (3) order effects from previous trials and (4) irrational side biases for one choice over another. In this work we investigated these di.erent sources of suboptimality and how they are related to pupil dilation, a putative correlate of norepinephrine tone. In particular, we measured pupil response in humans making a series of decisions based on rapidly-presented auditory information in an evidence accumulation task. We found that people exhibited all four types of suboptimality, and that some of these suboptimalities covaried with each other across participants. Pupillometry showed that only noise and the uneven weighting of evidence over time, the ‘integration kernel’, were related to the change in pupil response during the stimulus. Moreover, these two different suboptimalities were related to different aspects of the pupil signal, with the individual differences in pupil response associated with individual differences in integration kernel, while trial-by-trial fluctuations in pupil response were associated with trial-by-trial fluctuations in noise. These results suggest that di.erent sources of suboptimality in human perceptual decision making are related to distinct pupil-linked processes possibly related to tonic and phasic norepinephrine activity.
Lactococcin B is inactivated by intrinsic proteinase PrtP digestion inLactococcus lactissubsp.lactisBGMN1-501
Authors: Vukotic Goran , Polovic Natalija , Mirkovic Nemanja , Jovcic Branko , Stanisavljevic Nemanja , Fira Djordje , Kojic Milan
Published: April 2018

In our previous study, we showed that PrtP is able to impair bacteriocin LcnB activity despite being produced by the same organism, and even if they were encoded by the same plasmid. However, exact cleavage site within LcnB bacteriocin, as well as the activity of the resulting peptides remained unknown. Here we further explored the interplay between these two proteins and defined, using mass spectrometry, that the hydrolysis occurs between the sixth and seventh amino acid on the N terminus of LcnB. Although it was suspected that the cleaved form of LcnB could retain some level of activity, both chemically synthesized and recombinant variant of truncated LcnB exhibited no antimicrobial activity. Wild type form of LcnB was recombinantly overexpressed using the same expression system, its antimicrobial activity was tested before and after the treatment with PrtP proteinase, and the degradation products were analyzed with reverse-phase high-pressure liquid chromatography. The results confirmed the inactivity of the truncated LcnB and additionally corroborated the PrtP cleavage site in LcnB bacteriocin.

Importance

Lactococcal enzyme PrtP, considered as a growth promoting factor, is involved in casein breakdown and enabling bacteria efficient growth in amino acids-poor, but protein-rich media. However, its interaction with bacteriocins was not known until recently. Bacteriocin LcnB can also be considered as growth promoting factor, since its known physiological role mirrors in preventing competing bacteria of reaching high growth densities. In this manuscript, we define the exact peptide bond inside the bacteriocin LcnB which is recognized by PrtP. This N-terminal removal of six amino acids completely inactivates the bacteriocin. The biological function of such action remains elusive. It is unexpected that in the same strain one enzyme inactivates a protein important for survival, unless it is some type of regulation.
Tricellular junction proteins promote disentanglement of daughter and neighbour cells during epithelial cytokinesis
Authors: Wang Zhimin , Bosveld Floris , Bellaïche Yohanns
Published: April 2018

In epithelial tissue, new cell-cell junctions are formed upon cytokinesis. To understand junction formation during cytokinesis, we explored in Drosophila epithelium, de novo formation of tricellular septate junctions (TCJs). We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells and their neighbours during cytokinesis.
Anxiety induced by extra-hypothalamic BDNF deficiency instigates resistance to diet-induced obesity
Authors: Xie Xiangyang , Yang Haili , An Juan Ji , Liao Guey-Ying , Xu Zhi-Xiang , Tan Jiwei , Xu Baoji
Published: April 2018

Anxiety disorders are associated with body weight changes in humans. However, mechanisms underlying anxiety-related weight changes remain poorly understood. Using Emx1Cre/+ mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some parts of the amygdala. The resulting mutant mice displayed elevated anxiety levels and were markedly lean when fed either chow diet or high-fat diet (HFD). The mice showed higher levels of sympathetic activity, thermogenesis and lipolysis in both brown and white adipose tissues, and higher oxygen consumption and body temperature, compared with control mice. They were still lean at thermoneurality when fed HFD, indicating elevated basal metabolism in addition to activated thermogenesis. Anxiety induced by site-specific Bdnf deletion similarly increased energy expenditure and minimized HFD-induced weight gain. These results reveal that anxiety can stimulate adaptive thermogenesis and basal metabolism by activating sympathetic nervous system, which enhances lipolysis and limits weight gain.
The landscape of selection in 551 Esophageal Adenocarcinomas defines genomic biomarkers for the clinic
Authors: Frankell AM , Jammula S , Li X , Contino G , Killcoyne S , Abbas S , Perner J , Bower L , Devonshire G , Ococks E , Grehan N , Mok J , O’Donovan M , MacRae S , Eldridge M , Tavare S , Fitzgerald RC ,   the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Published: April 2018

Esophageal Adenocarcinoma (EAC) is a poor prognosis cancer type with rapidly rising incidence. Our understanding of genetic events which drive EAC development is limited and there are few molecular biomarkers for prognostication or therapeutics. We have accumulated a cohort of 551 genomically characterised EACs (73% WGS and 27% WES) with clinical annotation and matched RNA-seq. Using a variety of driver gene detection methods, we discover 77 EAC driver genes (73% novel) and 21 non-coding driver elements (95% novel), and describe mutation and CNV types with specific functional impact. We identify a mean of 4.4 driver events per case derived from both copy number events and mutations. We compare driver mutation rates to the exome-wide mutational excess calculated using Non-synonymous vs Synonymous mutation rates (dNdS). We observe mutual exclusivity or co-occurrence of events within and between a number of EAC pathways (GATA factors, Core Cell cycle genes, TP53 regulators and the SWI/SNF complex) suggestive of important functional relationships. These driver variants correlate with tumour differentiation, sex and prognosis. Poor prognostic indicators (SMAD4, GATA4) are verified in independent cohorts with significant predictive value. Over 50% of EACs contain sensitising events for CDK4/6 inhibitors which are highly correlated with clinically relevant sensitivity in a panel EAC cell lines and organoids.
Ephemeral states in protein folding under force captured with a novel magnetic tweezers design
Authors: Tapia-Rojo Rafael , Eckels Edward C. , Fernandez Julio M.
Published: April 2018

Magnetic tape heads are ubiquitously used to read and record on magnetic tapes in technologies as diverse as old VHS tapes, modern hard drive disks, or magnetic bands on credit cards. Their design highlights the ability to convert electric signals into fluctuations of the magnetic field at very high frequencies, which is essential for the high density storage demanded nowadays. Here, we twist this conventional use of tape heads to implement one in a new magnetic tweezers design, which offers the unique capability of changing the force with a bandwidth of ~ 10 kHz. We calibrate our instrument by developing an analytical expression that predicts the magnetic force acting on a superparamagnetic bead based on the Karlqvist approximation of the magnetic field created by a tape head. This theory is validated by measuring the force dependence of protein L unfolding/folding step sizes, and the folding properties of the R3 talin domain. We demonstrate the potential of our instrument by carrying out millisecond-long quenches to capture the formation of the ephemeral molten globule state in protein L, which has never been observed before. Our instrument provides for the first time the capability of interrogating individual molecules under fast-changing forces with a control and resolution below a fraction of a pN, opening a range of novel force spectroscopy protocols to study protein dynamics under force.
Investigating the effect of Target of Rapamycin kinase inhibition on theChlamydomonas reinhardtiiphosphoproteome: from known homologs to new targets
Authors: Werth Emily G. , McConnell Evan W. , Couso Inmaculada , Perrine Zoee , Crespo Jose L. , Umen James G. , Hicks Leslie M.
Published: April 2018

Target of Rapamycin (TOR) kinase is a conserved regulator of cell growth whose activity is modulated in response to nutrients, energy and stress. Key proteins involved in the pathway are conserved in the model photosynthetic microalgaChlamydomonas reinhardtii, but the substrates of TOR kinase and downstream signaling network have not been elucidated. Our study provides a new resource for investigating the phosphorylation networks governed by the TOR kinase pathway in Chlamydomonas.

We used quantitative phosphoproteomics to investigate the effects of inhibiting Chlamydomonas TOR kinase on dynamic protein phosphorylation. Wild-type and AZD-insensitive Chlamydomonas strains were treated with TOR-specific chemical inhibitors (rapamycin, AZD8055 and Torin1), after which differentially affected phosphosites were identified.

Our quantitative phosphoproteomic dataset comprised 2,547 unique phosphosites from 1,432 different proteins. Inhibition of TOR kinase caused significant quantitative changes in phosphorylation at 258 phosphosites, from 219 unique phosphopeptides.

Our results include Chlamydomonas homologs of TOR signaling-related proteins, including a site on RPS6 with a decrease in phosphorylation. Additionally, phosphosites on proteins involved in translation and carotenoid biosynthesis were identified. Follow-up experiments guided by these phosphoproteomic findings in lycopene beta/epsilon cyclase showed that carotenoid levels are affected by TORC1 inhibition and carotenoid production is under TOR control in algae.
A European whitefish linkage map and its implications for understanding genome-wide synteny between salmonids following whole genome duplication
Authors: De-Kayne Rishi , Feulner Philine G.D.
Published: April 2018

Genomic datasets continue to increase in size and ease of production for a wider selection of species including non-model organisms. For many of these species highly contiguous and well-annotated genomes are unavailable due to their prohibitive complexity and cost. As a result, a common starting point for genomic work in non-model species is the production of a linkage map, which involves the grouping and relative ordering of genetic markers along the genome. Dense linkage maps facilitate the analysis of genomic data in a variety of ways, from broad scale observations regarding genome structure e.g. chromosome number and type or sex-related structural differences, to fine scale patterns e.g. recombination rate variation and co-localisation of differentiated regions. Here we present both a sex-averaged and sex-specific linkage maps forCoregonus sp. “Albock”containing 5395 single nucleotide polymorphism (SNP) loci across 40 linkage groups to facilitate future investigation into the genomic basis of whitefish adaptation and speciation. The map was produced using restriction-site associated digestion (RAD) sequencing data from two wild-caught parents and 156 F1 offspring in Lep-MAP3. We discuss the differences between our sex-avagerated and sex-specific maps and identify synteny betweenC. sp. “Albock”linkage groups and the Atlantic salmon (Salmo salar) genome. Our synteny analysis confirms that many patterns of homology observed between Atlantic salmon andOncorhynchusandSalvelinusspecies are also shared by members of the Coregoninae subfamily.
A consistent picture of TRPV1 activation emerges from molecular simulations and experiments
Authors: Kasimova Marina A. , Yazici Aysenur Torun , Yudin Yevgen , Granata Daniele , Klein Michael L. , Rohacs Tibor , Carnevale Vincenzo
Published: April 2018

Although the structure of TRPV1 has been experimentally determined in both the closed and open states, very little is known about its activation mechanism. In particular, the conformational changes occurring in the pore domain and resulting in ionic conduction have not been identified yet. Here, we suggest a hypothetical molecular mechanism for TRPV1 activation, which involves the rotation of a conserved asparagine in S6 from the S4-S5 linker toward the pore. This rotation is correlated with the dehydration of four peripheral cavities located between S6 and the S4-S5 linker and the hydration of the pore. In light of our hypothesis, we perform bioinformatics analyses of TRP and other evolutionary related ion channels, analyze newly available structures and re-examine previously reported water accessibility and mutagenesis experiments. Overall, we provide several independent lines of evidence that corroborate our hypothesis. Finally, we show that the proposed molecular mechanism is compatible with the currently existing idea that in TRPV1 the selectivity filter acts as a secondary gate.
Identification of midbrain neurons essential for vocal communication
Authors: Tschida Katherine , Michael Valerie , Han Bao-Xia , Zhao Shengli , Sakurai Katsuyasu , Mooney Richard , Wang Fan
Published: April 2018

Vocalizations are an essential medium for communication and courtship in numerous mammalian species ranging from mice to humans. In mammals, the midbrain PAG serves as an obligatory node in a vocalization-related network that spans the forebrain and brainstem1–3, as bilateral lesions of the PAG result in mutism2–5. Despite the PAG’s importance for vocal production, the identity, function, and connectivity of PAG neurons involved in vocalization has remained elusive, in part because the PAG is a functionally and anatomically heterogeneous structure that serves myriad roles including nociception, defensive behaviors, and autonomic regulation6–9. Here we used a viral genetic “tagging” method10,11 to identify a distinct subset of PAG neurons in the male mouse that are selectively activated during the production of ultrasonic vocalizations (USVs) elicited by female cues. Silencing these PAG-USV neurons rendered males mute without affecting their other courtship behaviors and also impaired their ability to attract female mice in a social choice assay. Activating these neurons using chemogenetic or optogenetic methods strongly elevated USV production, even in the absence of female cues. Notably, the timing of individual USVs was entrained to the expiratory phase of breathing but not to the pattern of optogenetic stimulation, suggesting that PAG-USV neural activity initiates and sets the duration of vocal bouts and recruits downstream premotor circuits that precisely pattern vocal output. Consistent with this idea, we found that PAG-USV neurons extend axons into pontine and medullary regions that are speculated to contain premotor central pattern generators important for vocalization3,12,13. These experiments establish the identity of the PAG neurons selectively required for USV production in mice, map their efferent connections, and demonstrate the communicative salience of male USVs in promoting female social affiliation.
Site-specific transgenesis of theD. melanogasterY-chromosome using CRISPR/Cas9
Authors: Buchman Anna , Akbari Omar S.
Published: April 2018

Despite the importance of Y-chromosomes in evolution and sex determination, their heterochromatic, repeat-rich nature makes them difficult to sequence and genetically manipulate, and therefore they generally remain poorly understood. For example, theD. melanogasterY-chromosome, one of the best understood, is widely heterochromatic and composed mainly of highly repetitive sequences, with only a handful of expressed genes scattered throughout its length. Efforts to insert transgenes on this chromosome have thus far relied on either random insertion of transposons (sometimes harboring ‘landing sites’ for subsequent integrations) with limited success or on chromosomal translocations, thereby limiting the types of Y-chromosome related questions that could be explored. Here we describe a versatile approach to site-specifically insert transgenes on the Y-chromosome inD. melanogastervia CRISPR/Cas9-mediated HDR. We demonstrate the ability to insert, and detect expression from, fluorescently marked transgenic transgenes at two specific locations on the Y-chromosome, and we utilize these marked Y-chromosomes to detect and quantify rare chromosomal nondisjunction effects. Finally, we discuss how this Y-docking technique could be adapted to other insects to aid in the development of genetic control technologies for the management of insect disease vectors and pests.
Clairvoyante: a multi-task convolutional deep neural network for variant calling in Single Molecule Sequencing
Authors: Luo Ruibang , Sedlazeck Fritz J. , Lam Tak-Wah , Schatz Michael C.
Published: April 2018

The accurate identification of DNA sequence variants is an important, but challenging task in genomics. It is particularly difficult for single molecule sequencing, which has a per-nucleotide error rate of ~5%-15%. Meeting this demand, we developed Clairvoyante, a multi-task five-layer convolutional neural network model for predicting variant type (SNP or indel), zygosity, alternative allele and indel length from aligned reads. For the well-characterized NA12878 human sample, Clairvoyante achieved 99.73%, 97.68% and 95.36% precision on known variants, and 98.65%, 92.57%, 87.26% F1-score for whole-genome analysis, using Illumina, PacBio, and Oxford Nanopore data, respectively. Training on a second human sample shows Clairvoyante is sample agnostic and finds variants in less than two hours on a standard server. Furthermore, we identified 3,135 variants that are missed using Illumina but supported independently by both PacBio and Oxford Nanopore reads. Clairvoyante is available open-source (https://github.com/aquaskyline/Clairvoyante), with modules to train, utilize and visualize the model.
Illuminating microbial metabolic activities in the dark deep ocean with metaproteomics
Authors: Xie Zhang-Xian , Zhang Shu-Feng , Zhang Hao , Kong Ling-Fen , Lin Lin , Wang Da-Zhi
Published: April 2018

The deep ocean is the largest habitat on earth and holds diverse microbial life forms. Significant advances have been made in microbial diversity and their genomic potential in the deep ocean, however, little is known about microbial metabolic activity that is crucial to regulate the bathypelagic carbon sequestration. Here, we characterized proteomes covering large particulate (>0.7 μm), small particulate (0.2-0.7 μm) and dissolved (10 kDa-0.2 μm) fractions collected at a depth of 3000 m in the South China Sea. The Rhodospirillales, SAR324, SAR11, Nitrosinae/Tectomicrobia were the major contributors in the particulate fraction whereas Alteromonadales and viruses dominated the dissolved counterpart. Frequent detection of transcription or translation proteins in the particulate fractions indicated active metabolism of SAR324, Archaea, SAR11, and possible viable surface microbes, e.g. Prochlorococcus. Transporters for diverse substrates were the most abundant functional groups, and numerous spectra of formate dehydrogenases and glycine betaine transporters unveiled the importance of methylated compounds for the survival of deep-sea microbes. Notably, abundant non-viral proteins, especially transporters and cytoplasmic proteins, were detected in the dissolved fraction, indicating their potential roles in nutrient scavenging and the stress response. Our size-based proteomic study implied the holistic microbial activity mostly acting on the labile dissolved organic matter as well as the potential activities of surface microbes and dissolved non-viral proteins in the deep ocean.

Importance

The deep ocean produces one third of the biological CO2 in the ocean. However, little is known about metabolic activity of the bathypelagic microbial community which is crucial for understanding the biogeochemical cycling of organic matter, especially the formation of bulk refractory dissolved organic matter (DOM), one of the largest reservoirs of reduced carbon on Earth. This study provided the protein evidence firstly including both particulate and dissolved fractions to comprehensively decipher the active microbes and metabolic processes involved in the DOM recycling in the deep ocean. Our data supported the hypothesis of the carbon and energy supply from the labile DOM after the solution of sinking particles to the bathypelagic microbial community.
Introducing ribosomal tandem repeat barcoding for fungi
Authors: Wurzbacher Christian , Larsson Ellen , Bengtsson-Palme Johan , den Wyngaert Silke Van , Svantesson Sten , Kristiansson Erik , Kagami Maiko , Henrik Nilsson R.
Published: April 2018

Sequence analysis of the various ribosomal genetic markers is the dominant molecular method for identification and description of fungi. However, there is little agreement on what ribosomal markers should be used, and research groups utilize different markers depending on what fungal groups are targeted. New environmental fungal lineages known only from DNA data reveal significant gaps in the coverage of the fungal kingdom both in terms of taxonomy and marker coverage in the reference sequence databases. In order to integrate references covering all of the ribosomal markers, we present three sets of general primers that allow the amplification of the complete ribosomal operon from the ribosomal tandem repeats. The primers cover all ribosomal markers (ETS, SSU, ITS1, 5.8S, ITS2, LSU, and IGS) from the 5’ end of the ribosomal operon all the way to the 3’ end. We coupled these primers successfully with third generation sequencing (PacBio and Nanopore sequencing) to showcase our approach on authentic fungal herbarium specimens. In particular, we were able to generate high-quality reference data with Nanopore sequencing in a high-throughput manner, showing that the generation of reference data can be achieved on a regular desktop computer without the need for a large-scale sequencing facility. The quality of the Nanopore generated sequences was 99.85 %, which is comparable with the 99.78 % accuracy described for Sanger sequencing. With this work, we hope to stimulate the generation of a new comprehensive standard of ribosomal reference data with the ultimate aim to close the huge gaps in our reference datasets.
Buffering gene expression noise by microRNA based feedforward regulation
Authors: Bokes Pavol , Hojcka Michal , Singh Abhyudai
Published: April 2018

Cells use various regulatory motifs, including feedforward loops, to control the intrinsic noise that arises in gene expression at low copy numbers. Here we study one such system, which is broadly inspired by the interaction between an mRNA molecule and an antagonistic microRNA molecule encoded by the same gene. The two reaction species are synchronously produced, individually degraded, and the second species (microRNA) exerts an antagonistic pressure on the first species (mRNA). Using linear-noise approximation, we show that the noise in the first species, which we quantify by the Fano factor, is sub-Poissonian, and exhibits a nonmonotonic response both to the species lifetime ratio and to the strength of the antagonistic interaction. Additionally, we use the Chemical Reaction Network Theory to prove that the first species distribution is Poissonian if the first species is much more stable than the second. Finally, we identify a special parametric regime, supporting a broad range of behaviour, in which the distribution can be analytically described in terms of the confluent hypergeometric limit function. We verify our analysis against large-scale kinetic Monte Carlo simulations. Our results indicate that, subject to specific physiological constraints, optimal parameter values can be found within the mRNA-microRNA motif that can benefit the cell by lowering the gene-expression noise.
Sexual maturation and embryonic development in octopus: use of energy and antioxidant defence mechanisms usingOctopus mimusas a model
Authors: Olivares Alberto , Rodríguez-Fuentes Gabriela , Mascaró Maite , Sánchez Ariadna , Ortega Karen , Caamal-Monsreal Claudia , Tremblay Nelly , Rosas Carlos
Published: April 2018

Sexual maturation and reproduction influence the status of a number of physiological processes and consequently the ecology and behaviour of cephalopods. UsingOctopus mimusas model species, the present study examined the changes in biochemical composition that take place during gonadal maturation of octopus females and its consequences in embryo and hatchlings characteristics, including energetic metabolites, digestive enzymes and antioxidant defence mechanisms. A total of 32Octopus mimusadult females were sampled during ovarian maturation; biochemical composition (metabolites and digestive enzymes) of digestive gland (DG) and ovaries (only metabolites) were followed during physiological and functional maturation. Levels of protein (Prot), triacyl glycerol (TG), cholesterol (Chol), glucose (Glu) and glycogen (Gly) were evaluated. The activity of alkaline and acidic enzymes also was measured in DG. Simultaneously, groups of eggs coming from mature females were sampled along development, and metabolites (Prot, TG, Glu, Gly, TG, Chol), digestive enzymes activity (Lipases, alkaline and acidic), antioxidant defence mechanisms and radical oxygen species (ROS) were evaluated. This study shows that ovarium is a site for reserve of some nutrients for reproduction. Presumably, TG where stored at the beginning of the maturation processes followed by Chol, both at the same time were energetically supported by Glu, derived from Gly following gluconeogenic pathways. Nutrients and enzymes (metabolic, digestive and REDOX system) where maintained without significant changes and in a low activity during organogenesis. Our findings suggest that activity was not energetically costly; in contrast, during the embryo growth there was mobilization of nutrients and activation of the metabolic and digestive enzymes. Increments in consumption of yolk and glycogen, and reduction in molecules associated with oxidative stress allowed paralarvae to hatch with the antioxidant defence mechanisms ready to support ROS production.
SMURF-seq for fast, multiplexed copy number profiling with long-read sequencers
Authors: Prabakar Rishvanth K. , Xu Liya , Hicks James , Smith Andrew D.
Published: April 2018

We present SMURF-seq, a protocol to efficiently sequence short DNA molecules on a long-read sequencer by randomly ligating them to form long molecules. Applying SMURF-seq using Oxford Nanopore Technologies MinION yields up to 30 countable fragments per read at present, which generates multiple copy number profiles in a single run at a reduced time and cost. More broadly, SMURF-seq expands the utility of long-read sequencers for read-counting applications, which do not benefit from increased read length.
Classification of the gifted natural product producerStreptomyces roseofacienssp. nov. by polyphasic taxonomy
Authors: van der Aart Lizah T. , Nouinoui Imen , Kloosterman Alexander , Ingual José Mariano , Willemse Joost , Goodfellow Michael , van Wezel Gilles P.
Published: April 2018

A novel verticillate strain of streptomycetes,Streptomycesstrain MBT76T, was isolated from the QinLing mountains, which harbours more than 40 biosynthetic gene clusters for natural products. Here we present full taxonomic classification of strain MBT76T, and show that it has chemotaxonomic, genomic and morphological properties consistent with its classification in the genusStreptomyces. Strain MBT76Tis part of the cluster of Streptoverticillates, a group within the genusStreptomycesthat has characteristic whorl-forming spores produced in chains along the lateral wall of the hyphae. Multi-locus sequence analysis based on five housekeeping gene alleles showed that MBT76Tis closely related toStreptomyces hiroshimensis. Average Nucleotide Identification (ANI) and Genome to Genome Distance Calculation (GGDC) of the genomes of strain MBT76TandS. hiroshimensisseparated them into distinct species. Strain MBT76Trepresents a novel species of the genusStreptomycesfor which we propose the nameStreptomyces roseofacienssp. nov. The type strain is MBT76T(=NCCB 100637T=DSM 106196T). The whole genome of MBT76Thas 7974 predicted open reading frames and a total genome size of 8.64 Mb. Further genomic analysis showed that verticillate streptomycetes lack the sporulation genessgE, and our data suggest that this is a useful genetic marker for the spore-chain morphology of the verticillates.
Association of tumor necrosis factor alpha gene polymorphisms with Helicobacter pylori infection in dyspeptic patients in Sri Lanka
Authors: Arachchi Piyumali Sandareka , Weerasekera Manjula Manoji , Senevirathna Bimalka , Weerasekera Deepaka , Fernando Neluka , Gunasekara Chinthika Prabhashinie
Published: April 2018

Single nucleotide polymorphisms present on the promoter sequence of the TNF‐α gene may affect production of TNF‐α, a pro‐inflammatory cytokine, during immune responses. The presence of TNF‐α polymorphisms is also reportedly associated with more severe manifestations of Helicobacter pylori infection. However, the frequency of TNF‐α polymorphisms and the associated disease severity vary between different patient groups. In this study, gastric biopsies and blood specimens were collected from 138 patients with dyspepsia undergoing routine upper gastrointestinal endoscopy. Our institution's Ethics Review Committee approved the study and written informed consent was obtained from all participants. The presence of H. pylori was confirmed histologically in all patients. The frequency of TNF‐α polymorphisms in the study cohort was investigated using PCR–restriction fragment length polymorphism and expression of serum TNF‐α quantitated using a commercial ELISA assay. The proportions of selected TNF‐α polymorphisms (TNF‐α ‐238, ‐308 and ‐863) were similar in H. pylori‐positive and ‐negative patients. Homozygous mutations of TNF‐α polymorphisms were rarely detected in the study group. There was a significant difference in TNF‐α concentrations between patients with mild chronic gastritis and TNF‐α ‐308 GG genotype and patients with moderate to severe chronic gastritis (P = 0.008). It was not possible to identify an association between these genotypes and disease severity because of the low frequency of heterozygous and homozygous mutated genes in Sri Lankan patients with dyspepsia.
Non‐GAAP Earnings Disclosure in Loss Firms
Authors: LEUNG EDITH , VEENMAN DAVID
Published: April 2018

This study examines the incremental information in loss firms’ non‐GAAP earnings disclosures relative to GAAP earnings. Using a large sample obtained through textual analysis and hand‐collection, we posit and find that loss firms’ non‐GAAP earnings exclusions offset the low informativeness of GAAP losses for forecasting and valuation. Loss firms’ non‐GAAP earnings are highly predictive of future performance and are valued by investors, while the expenses excluded from GAAP earnings are not. Additional tests suggest that loss firms disclosing non‐GAAP profits have significantly better future performance than GAAP‐only loss firms and are not overvalued by investors. Comparing non‐GAAP earnings of profitable firms to those of loss firms, we find that loss firms’ non‐GAAP metrics are significantly more predictive and less strategic. We conclude that non‐GAAP earnings disclosures are particularly informative about loss firms and help investors disaggregate losses into components that have differential implications for forecasting and valuation.
Tracing resident antagonisms in urban development: agonistic pluralism and participatory planning
Authors: McAuliffe Cameron , Rogers Dallas
Published: April 2018

This article draws on research with resident action groups and other alliances in Sydney. It investigates the ways in which citizens work beyond the formal planning system to approach and achieve their urban development goals. The post‐political treatment of community voices in planning relies on the centrality of consensus politics in current participatory planning regimes. By providing a democratic outlet that is far removed from the actual development outcome, powerful urban actors can silence through inclusion. Planning theorists have posited that one pathway beyond this post‐political moment in urban planning is provided by Chantal Mouffe's critique of Habermasian communicative theory and consensus politics, which she bases on her theory of agonistic pluralism. Following Mouffe, to achieve a productive agonistic politics, any rigid antagonisms between “enemies” need to be moderated to more mutable “adversarial” positions. However, we have little knowledge of the conditions that might precipitate such a change in praxis. To address this gap between theory and praxis, we use focus group data to show how local resident action groups and urban alliances work through three modalities of antagonism to achieve their urban development goals. We add empirical weight to the idea that citizens can shift from rigid and fundamental antagonisms to the potentially more productive adversarial politics of agonistic pluralism but therein expose some limitations with how Mouffe's ideas are being applied to urban planning.
Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction
Authors: Diaz‐Ruiz Alberto , Lanasa Michael , Garcia Joseph , Mora Hector , Fan Frances , Martin‐Montalvo Alejandro , Di Francesco Andrea , Calvo‐Rubio Miguel , Salvador‐Pascual Andrea , Aon Miguel A. , Fishbein Kenneth W. , Pearson Kevin J. , Villalba Jose Manuel , Navas Placido , Bernier Michel , de Cabo Rafael
Published: April 2018

Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH‐dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD+/sirtuin pathway. The results highlight the importance of these NAD+ producers for the promotion of health and extended lifespan.
Renal safety of short‐term empiric gentamicin therapy in aged patients
Authors: Sia Christopher SB , Ananda‐Rajah Michelle R , Adler Nikki R , Yi‐Wei Baey , Liew Danny , Tong Erica Y , Aung Ar Kar
Published: April 2018

Objective

To determine the incidence of acute kidney injury (AKI) in aged patients receiving empiric gentamicin therapy.

Methods

Patients aged ≥65 years receiving gentamicin upon admission between 2013 and 2015 at two Australian hospitals were retrospectively studied. AKI was defined as a rise in creatinine by ≥50% and/or ≥26.5 μmol/L.

Results

Most patients (95%) received a single dose of gentamicin. The incidence of AKI was 15% (36/242 patients). A composite outcome of persistent kidney injury, requirement for renal replacement therapy or inpatient death in a patient with AKI occurred in 10 (4%) patients. Patients who developed AKI were older (median 80.5 vs 78 years, P = 0.03), had higher Charlson Co‐morbidity Index (median 7 vs 5, P = 0.0004) and had more advanced chronic kidney disease at baseline (Stages IV and V) (OR 4.38, 95% confidence interval 1.45–13.2, P = 0.01).

Conclusion

Empiric gentamicin use in patients with advancing age is associated with low rates of predominantly transient renal impairment.
Long‐term study showed that vaccination protected paediatric renal transplant recipients from life‐threatening varicella zoster virus
Authors: Lindahl Jenny K. , Friman Vanda , Ladfors Susanne Westphal , Hansson Sverker , Andersson Rune , Jertborn Marianne , Woxenius Susanne
Published: April 2018

Aim

Renal transplant patients are particularly susceptible to highly contagious diseases due to their reduced immunity. We studied transplant recipients to gauge their varicella zoster virus (VZV) serology status over time and the outcome of any VZV infections.

Method

This retrospective study comprised 85 children who underwent renal transplants in Gothenburg, Sweden, from 1986 to 2014, at a mean age of eight (1–18) years. The children's medical records were reviewed and 47 had the VZV infection pre‐transplant and 38 had been vaccinated pre‐transplant. Clinical outcomes were available for 85 children and serology results for 72.

Results

At transplantation, the VZV seropositivity rate was 50% in the vaccination group and 94% in the infection group and the antibody titres were significantly lower in the vaccination group (p = 0.031). During the median follow‐up period of five years post‐transplant, 28% of the vaccinated children and 97% of the infection group remained seropositive and the varicella infection affected eight children: one in the infection group and seven in the vaccination group. The herpes zoster was observed in two children in the infection group.

Conclusion

This study demonstrated that VZV vaccination protected from symptomatic infections to a lesser extent than natural infection, but provided effective protection from life‐threatening disease.
Children with a very low birthweight showed poorer reading skills at eight years of age but caught up in most areas by the age of 10
Authors: Leijon Ingemar , Ingemansson Fredrik , Nelson Nina , Samuelsson Stefan , Wadsby Marie
Published: April 2018

Aim

We evaluated the development of reading skills in very low birthweight (VLBW) children and controls at 8–10 years of age.

Methods

This study was part of a longitudinal study of VLBW infants born between January 1998 and December 1999 in Sweden. We recruited 49 VLBW children and 44 sex and age‐matched full‐term controls when they started school at the age of seven and tested them using identical methods for decoding, rapid naming ability, reading comprehension, and spelling and cognitive skills at about eight and 10 years of age. Univariate analysis of variance was performed to assess the effects of VLBW on reading performance at each age and to evaluate the differences between the groups and ages.

Results

Very low birthweight children scored significantly lower in all domains of reading at 7.8 ± 0.3 years, but the performance gap had narrowed by 9.8 ± 0.3 years. Significant catch‐up gains were found in phonological awareness, rapid naming ability and reading comprehension. The differences between the groups were minor at 10 years, when controlled for non‐verbal cognition.

Conclusion

Very low birthweight children demonstrated worse reading performance at eight years of age than term‐born controls. The gap in reading skills between the groups had largely narrowed two years later.
Design, synthesis chalcone derivatives as AdipoR agonist for type 2 diabetes
Authors: Zhu Panhu , Huang Weijun , Li Jiaming , Ma Xiaodong , Hu Mengqi , Wang Yujun , Xu Qinlong , Wang Xianna
Published: April 2018

Two structurally novel series of chalcone derivatives were designed and synthesized as potential agents against type 2 diabetes. As a result of the antidiabetic biological evaluation in streptozotocin (STZ)‐induced type 2 diabetes animal model, 13e, 13g, and 19f showed more significant reduction in serum Glu, TG, TC levels by contrast to the positive control AdipoRon. In addition to upregulating the expression of AdipoR1 and AdipoR2, 13e and 19f treatment also increased expression of AMPK and PPAR‐α. Taken together, these results suggested that 13e and 19f might be a promising compound for type 2 diabetes treatment.
Association between glutathione S‐transferase gene M1 and T1 polymorphisms and chronic obstructive pulmonary disease risk: A meta‐analysis
Authors: Ding Z. , Wang K. , Li J. , Tan Q. , Tan W. , Guo G.
Published: April 2018

Chronic obstructive pulmonary disease (COPD) is a severe lung disease characterized by long‐term breathing problems. A series of studies have indicated that the glutathione S‐transferase genes M1 and T1 are associated with COPD susceptibility; however, the result still remains inconclusive. This meta‐analysis was performed to estimate the effect of GSTM1 and GSTT1 polymorphisms in COPD risk. Eligible case‐control studies published between January 2000 and December 2017 was searched and retrieved. A total of 37 articles were screened out, including 4674 COPD patients and 5006 controls. Overall, our results found that GSTM1 and GSTT1 null genotypes significantly increased the risk of COPD (GSTM1: odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.31‐1.77, P <.00001; GSTT1: OR = 1.28, 95% CI = 1.09‐1.50, P = .003). Subgroup analysis by ethnicity suggested that there was a close association between GSTM1 null polymorphism and COPD susceptibility in each studied ethnicity, while GSTT1 null polymorphism only showed association with Asian COPD patients. Moreover, we also found that joint GSTM1/GSTT1 null genotypes showed a high association with increased COPD susceptibility (OR = 1.42, 95% CI = 1.21‐1.66, P < .0001). In conclusion, our results indicated that GSTM1 null, GSTT1 null, and the combined GSTM1/GSTT1 null genotypes might be risk factors in the development of COPD. However, future case‐control studies with large‐scale participants are still required to further estimate these associations.
Immigration, internal migration and crime in South Africa: A multi‐level model analysis
Authors: Kollamparambil Umakrishnan
Published: April 2018

A review of South African literature on crime confirms the lack of a study that considers the impact of migration on the crime rate in the country. The high levels of crime in South Africa aside, additional motivation behind the study has been the increasing rhetoric in media and by politicians insinuating the prominent role of foreign immigrants in the high crime levels of the country. While this is the first attempt to study this relationship in the South African context, it also stands apart from existing studies undertaken in the developed countries by accounting for both internal migrants as well as foreign immigrants. Further, the study claims the use of multi‐level regression estimations as an improvement from the existing studies on the issue by accounting for variance clustering across different spatial levels. In all the estimated models, internal migrant ratio came out as being positively and significantly related to crime rates across five different crime categories, with the sole exception of sexual crime rate. There was no evidence of foreign immigrant ratio impacting on crime rate in any of the crimes analysed except crime relating to property. Further, income inequality and sex ratio figure as determining factors across most types of crime in South Africa.
Molecular basis of the skin barrier structures revealed by electron microscopy
Authors: Ishida‐Yamamoto Akemi , Igawa Satomi , Kishibe Mari
Published: April 2018

The barrier function of skin is indispensable for terrestrial animals. This function is mainly carried out by the epidermis, more specifically by its granular and cornified layers. The major structural components associated with this function are the intercellular lipid layer, desmosomes, corneodesmosomes, tight junctions, cornified cell envelope and keratin filaments. In this review, we discuss the current knowledge of their ultrastructure, their molecular basis and their relevance to skin disease.
Inhibition of interleukin‐12 and/or interleukin‐23 for the treatment of psoriasis: What is the evidence for an effect on malignancy?
Authors: Ergen Elizabeth N. , Yusuf Nabiha
Published: April 2018

Immune cells and cytokines play an important role in the pathogenesis of psoriasis. Interleukin‐12 (IL‐12) and IL‐23 promote cellular responses mediated by T cells, which contribute to an inflammatory loop responsible for the induction and maintenance of psoriatic plaques. Antibodies that inhibit IL‐12/23 or IL‐23 are key treatment options for patients with psoriasis. IL‐12 and IL‐23 also play a key role in immune responses to infections and tumors. A growing body of information from clinical trials, cohort studies, postmarketing reports, genetic studies and animal models provides insights into the potential biological relationships between IL‐12/23 inhibition and malignancies. We summarize this information in tables and provide some context for the interpretation of these data with the goal of informing dermatologists who are using IL‐12/23 or IL‐23 inhibitors to treat patients with psoriasis.