bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a major QTL and associated marker for high arabinoxylan fibre in white wheat flour
Authors: Lovegrove Alison , Wingen Luzie U. , Plummer Amy , Wood Abigail , Passmore Diana , Kosik Ondrej , Freeman Jackie , Mitchell Rowan A.C. , Ulker Mehmet , Tremmel-Bede Karolina , Rakszegi Marianna , Bedő Zoltán , Petterant Marie-Reine , Charmet Gilles , Leverington Waite Michelle , Orford Simon , Burridge Amanda , Pellny Till , Shewry Peter R , Griffiths Simon
Published: July 2019

Dietary fibre (DF) has multiple health benefits, and wheat products are major sources of DF for human health. However, DF is depleted in white flour, which is most widely consumed, compared to wholegrain. The major type of DF in white wheat flour is the cell wall polysaccharide arabinoxylan (AX). Previous studies have identified the Chinese wheat cultivar Yumai 34 as having unusually high contents of AX in both water-soluble and insoluble forms. We have therefore used populations generated from crosses between Yumai 34 and four other wheat cultivars, three with average contents of AX (Ukrainka, Altigo and Claire) and one also having unusually high AX (Valoris), in order to map QTLs for soluble AX (determined as relative viscosity) of aqueous extracts of wholemeal flours) and total AX (determined by enzyme fingerprinting of white flour). A number of QTL were mapped, but most were only detected in one or two crosses. However, all four crosses showed strong QTLs for high RV/total AX on chromosome 1B, with Yumai 34 being the increasing parent, and a KASP marker for the high AX Yumai 34 allele was validated by analysis of high AX lines derived from Yumai 34 but selected by biochemical analysis. A QTL for RV was mapped on chromosome 6B in Yumai 34 × Valoris, with Valoris being the increasing allele, which was consistent with the observation of transgressive segregation for this trait. The data indicate that breeding can be used to develop wheat with high AX fibre in white flour.
Highly efficient and super-bright neurocircuit tracing using vector mixing-based virus cocktail
Authors: Sun Pei , Jin Sen , Tao Sijue , Wang Junjun , Li Anan , Li Ning , Wu Yang , Kuang Jianxia , Liu Yurong , Wang Lizhao , Lin Huimin , Lv Xiaohua , Liu Xiuli , Peng Jundan , Zhang Siyu , Xu Min , Luo Zhen , He Xiaobin , Xu Tonghui , Li Xiangning , Zeng Shaoqun , Zhang Yu-Hui , Xu Fuqiang
Published: July 2019

Mapping the detailed cell-type-specific input networks and neuronal projectomes are essential to understand brain function in normal and pathological states. However, several properties of current tracing systems, including labeling sensitivity, trans-synaptic efficiencies, reproducibility among different individuals and different Cre-driver animals, still remained unsatisfactory. Here, we developed MAP-ENVIVIDERS, a recombinase system-dependent vector mixing-based strategy for highly efficient neurocircuit tracing. MAP-ENVIVIDERS enhanced tracing efficiency of input networks across the whole brain, with over 10-fold improvement in diverse previously poor-labeled input brain regions and particularly, up to 70-fold enhancement in brainstem compared with the current standard rabies-virus-mediated systems. MAP-ENVIVIDERS was over 10-fold more sensitive for cell-type-specific labeling than previous strategies, enabling us to capture individual cell-type-specific neurons with extremely complex axonal branches and presynaptic axonal boutons, both about one order of magnitude than previously reported and considered. MAP-ENVIVIDERS provides powerful tools for deconstructing novel input/output circuitry towards functional studies and disorders-related mechanisms.
Heparanase-2 protects from endothelial injury by inhibiting TLR4 signaling
Authors: Kiyan Yulia , Tkachuk Sergey , Kurselis Kestutis , Shushakova Nelli , Stahl Klaus , Dawodu Damilola , Kiyan Roman , Chichkov Boris , Haller Hermann
Published: July 2019

Objective

The endothelial glycocalyx and the regulation of its shedding are important to vascular health. Endo-β-D-glucuronidase heparanase-1 (HPSE1) is the only enzyme that can shed heparan sulfate. However, the mechanisms are not well understood.

Approach and results

To investigate HPSE1 and its endogenous inhibitor, heparanase-2 (HPSE2), we used cell culture, lentiviral protein overexpression, a microfluidic chip model of cell culture under shear stress conditions, and lipopolysaccharide (LPS) injections in mice. We show that HPSE1 activity aggravated Toll-like receptor 4 (TLR4)-mediated response of endothelial cells to LPS. On the contrary, HPSE2 overexpression was protective. The microfluidic chip flow model confirmed that HPSE2 prevented heparan sulfate shedding by HPSE1. Furthermore, heparan sulfate did not interfere with cluster of differentiation-14 (CD14)-dependent LPS binding, but instead reduced the presentation of the LPS-CD14 complex to TLR4. HPSE2 reduced LPS-mediated TLR4 activation by LPS, subsequent cell signaling, and cytokine expression. Moreover, HPSE2-overexpressing endothelial cells remained protected against LPS-mediated loss of cell-cell contacts. In vivo, expression of HPSE2 in plasma and kidney medullary capillaries was decreased in mouse sepsis model. We next applied purified HPSE2 in mice and observed decreases in TNFα and IL-6 plasma concentrations after intravenous LPS injections.

Conclusions

Our data demonstrate the important role of heparan sulfate and the glycocalyx in endothelial cell activation and suggest a protective role of HPSE2 in microvascular inflammation. HPSE2 offers new options for protection against HPSE1-mediated endothelial damage and preventing microvascular disease.

Graphical abstract

Non standard abbreviations
Phazolicin – a Novel Thiazole/Oxazole-Modified Peptide Inhibiting the Bacterial Ribosome in a Species-Specific Way
Authors: Travin Dmitrii Y. , Watson Zoe L. , Metelev Mikhail , Ward Fred R. , Osterman Ilya A. , Khven Irina M. , Khabibullina Nelli F. , Serebryakova Marina , Mergaert Peter , Polikanov Yury S. , Cate Jamie H. D. , Severinov Konstantin
Published: July 2019

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly expanding and largely untapped class of natural products with various biological activities. Linear azol(in)e-containing peptides (LAPs) comprise a subclass of RiPPs that display an outstanding diversity of mechanisms of action while sharing common structural features. Here, we report the discovery of a new LAP biosynthetic gene cluster in the genome of Rhizobium sp. Pop5, which encodes the precursor peptide and modification machinery of phazolicin (PHZ) – an extensively modified peptide exhibiting narrow-spectrum antibacterial activity against some symbiotic bacteria of leguminous plants belonging to the Rhizobiales. PHZ inhibits prokaryotic translation through the obstruction of the passage of the nascent peptide through the ribosome exit channel. The cryo-EM structure of the Escherichia coli ribosome with bound PHZ revealed that the drug interacts with the 23S rRNA and ribosomal proteins uL4 and uL22 and obstructs the exit tunnel in a way that is distinct from other compounds blocking the exit channel. We show that the sequence of uL4 ribosomal protein loop involved in PHZ binding determines the species-specificity of antibiotic interaction with its target. PHZ and its predicted homologs from other bacterial species expand the known diversity of LAPs and may be used in the future as biocontrol agents for the needs of agriculture.
An integrative ENCODE resource for cancer genomics
Authors: Zhang Jing , Lee Donghoon , Dhiman Vineet , Jiang Peng , Xu Jie , McGillivray Patrick , Yang Hongbo , Liu Jason , Meyerson William , Clarke Declan , Gu Mengting , Li Shantao , Lou Shaoke , Xu Jinrui , Lochovsky Lucas , Ung Matthew , Ma Lijia , Yu Shan , Cao Qin , Harmanci Arif , Yan Koon-Kiu , Sethi Anurag , Gursoy Gamze , Schoenberg Michael Rutenberg , Rozowsky Joel , Warrell Jonathan , Emani Prashant , Yang Yucheng T. , Galeev Timur , Kong Xiangmeng , Liu Shuang , Li Xiaotong , Krishnan Jayanth , Feng Yanlin , Rivera-Mulia Juan Carlos , Adrian Jessica , Broach James R , Bolt Michael , Moran Jennifer , Fitzgerald Dominic , Dileep Vishnu , Liu Tingting , Mei Shenglin , Sasaki Takayo , Trevilla-Garcia Claudia , Wang Su , Wang Yanli , Zang Chongzhi , Wang Daifeng , Klein Robert , Snyder Michael , Gilbert David M. , Yip Kevin , Cheng Chao , Yue Feng , Liu X. Shirley , White Kevin , Gerstein Mark
Published: July 2019

ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types. A key aspect of this annotation is comprehensive and experimentally derived networks of both transcription factors and RNA-binding proteins (TFs and RBPs). Cancer, a disease of system-wide dysregulation, is an ideal application for such a network-based annotation. Specifically, for cancer-associated cell types, we put regulators into hierarchies and measure their network change (rewiring) during oncogenesis. We also extensively survey TF-RBP crosstalk, highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of MYC, a well-known oncogenic TF. Furthermore, we show how our annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend. Finally, we organize the resource into a coherent workflow to prioritize key elements and variants, in addition to regulators. We showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS. Targeted validations of the prioritized regulators, elements and variants using siRNA knockdowns, CRISPR-based editing, and luciferase assays demonstrate the value of the ENCODE resource.
Deformity Index: A semi-reference quality metric of phylogenetic trees based on their clades
Authors: Mahapatra Aritra , Mukherjee Jayanta
Published: July 2019

abstract

Measuring the correctness of a phylogenetic tree is one of the most fundamental tasks in phylogenetic study. A large number of methods have been proposed to measure the correctness of a tree. Such methods completely depend on the reference tree and they compute the distance between reference the tree and the target tree. But it is very difficult to obtain a precise and an accurate reference tree for a selected dataset. As a result, the existing methods for comparing the phylogenetic trees can behave unexpectedly in various scenarios. In this paper, we introduce a scoring function, called the Deformity Index, to measure the correctness of a tree based on the biological knowledge of the clades. The strength of our proposed method is that it does not consider any reference tree. We have also investigated the range and the distributions of the different modules of Deformity Index. Furthermore, we perform different goodness of fit tests to understand its cumulative distribution. We have also examined in detail the robustness as well as the scalability of our measure by different statistical tests under the Yule and the uniform models. Moreover, we show that our proposed scoring function can overcome the limitations of the conventional methods of tree comparing by experimenting on different biological datasets.
Calculating sample size for identifying cell subpopulation in single-cell RNA-seq experiments
Authors: Kim Kyung In , Youn Ahrim , Bolisetty Mohan , Palucka A. Karolina , George Joshy
Published: July 2019

Summary

Single-cell RNA sequencing (scRNA-seq) is a rapidly developing technology for studying gene expression at the individual cell level and is often used to identify subpopulations of cells. Although the use of scRNA-seq is steadily increasing in basic and translational research, there is currently no statistical model for calculating the optimal number of cells for use in experiments that seek to identify cell subpopulations. Here, we have developed a statistical method ncells for calculating the number of cells required to detect a rare subpopulation in a homogeneous cell population for the given type I and II error. ncells defines power as the probability of separation of subpopulations which is calculated from three user-defined parameters: the proportion of rare subpopulation, proportion of up-regulated marker genes of the subpopulation, and levels of differential expression of the marker genes. We applied ncells to the scRNA-seq data on dendritic cells and monocytes isolated from healthy blood donor to show its efficacy in calculating the optimal number of cells in identifying a novel subpopulation.
Accuracy of de novo assembly of DNA sequences from double-digest libraries varies substantially among software
Authors: LaCava Melanie E. F. , Aikens Ellen O. , Megna Libby C. , Randolph Gregg , Hubbard Charley , Buerkle C. Alex
Published: July 2019

Advances in DNA sequencing have made it feasible to gather genomic data for non-model organisms and large sets of individuals, often using methods for sequencing subsets of the genome. Several of these methods sequence DNA associated with endonuclease restriction sites (various RAD and GBS methods). For use in taxa without a reference genome, these methods rely on de novo assembly of fragments in the sequencing library. Many of the software options available for this application were originally developed for other assembly types and we do not know their accuracy for reduced representation libraries. To address this important knowledge gap, we simulated data from the Arabidopsis thaliana and Homo sapiens genomes and compared de novo assemblies by six software programs that are commonly used or promising for this purpose (ABySS, CD-HIT, Stacks, Stacks2, Velvet and VSEARCH). We simulated different mutation rates and types of mutations, and then applied the six assemblers to the simulated datasets, varying assembly parameters. We found substantial variation in software performance across simulations and parameter settings. ABySS failed to recover any true genome fragments, and Velvet and VSEARCH performed poorly for most simulations. Stacks and Stacks2 produced accurate assemblies of simulations containing SNPs, but the addition of insertion and deletion mutations decreased their performance. CD-HIT was the only assembler that consistently recovered a high proportion of true genome fragments. Here, we demonstrate the substantial difference in the accuracy of assemblies from different software programs and the importance of comparing assemblies that result from different parameter settings.
Genetic Bases Of Aposematic Traits: Insights from the Skin Transcriptional Profiles of Oophaga Poison Frogs
Authors: Posso-Terranova Andrés , Andres José
Published: July 2019

Abstract

Aposematic organisms advertise their defensive toxins to predators using a variety of warning signals, including bright coloration. While most Neotropical poison frogs (Dendrobatidae) rely on crypsis to avoid predators, Oophaga poison frogs from South America advertise their chemical defenses, a complex mix of diet-derived alkaloids, by using conspicuous hues. The present study aimed to characterize the skin transcriptomic profiles of the South American clade of Oophaga poison frogs (O. anchicayensis, O. solanensis, O. lehmanni and O. sylvatica). Our analyses showed very similar transcriptomic profiles for these closely related species in terms of functional annotation and relative abundance of gene ontology terms expressed. Analyses of expression profiles of Oophaga and available skin transcriptomes of cryptic anurans allowed us to propose possible mechanisms for the active sequestration of alkaloid-based chemical defenses and to highlight some genes that may be potentially involved in resistance mechanisms to avoid self-intoxication and skin coloration. In doing so, we provide an important molecular resource for the study of warning signals that will facilitate the assembly and annotation of future poison frog genomes.
Advanced Glycation End-Products Suppress Mitochondrial Function and Proliferative Capacity of Achilles Tendon-Derived Fibroblasts
Authors: Patel Shivam H. , Yue Feng , Saw Shannon K. , Foguth Rachel , Cannon Jason R. , Shannahan Jonathan H. , Kuang Shihuan , Sabbaghi Arman , Carroll Chad C.
Published: July 2019

Debilitating cases of tendon pain and degeneration affect the majority of diabetic individuals. The high rate of tendon degeneration persists even when glucose levels are well controlled, suggesting that other mechanisms may drive tendon degeneration in diabetic patients. The purpose of this study was to investigate the impact of advanced glycation end-products on tendon fibroblasts to further our mechanistic understanding of the development and progression of diabetic tendinopathy. We proposed that advanced glycation end-products would induce limitations to mitochondrial function and proliferative capacity in tendon-derived fibroblasts, restricting their ability to maintain biosynthesis of tendon extracellular matrix. Using an in-vitro cell culture system, rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived advanced glycation end-products (0, 50, 100, and 200μg/ml) for 48 hours in normal glucose (5.5mM) and high glucose (25mM) conditions. We demonstrate that tendon fibroblasts treated with advanced glycation end-products display reduced ATP production, electron transport efficiency, and proliferative capacity. These impairments were coupled with alterations in mitochondrial DNA content and expression of genes associated with extracellular matrix remodeling, mitochondrial energy metabolism, and apoptosis. Our findings suggest that advanced glycation end-products disrupt tendon fibroblast homeostasis and may be involved in the development and progression of diabetic tendinopathy.
Remodeling of theC. elegansNon-coding RNA Transcriptome by Heat Shock
Authors: Schreiner William P. , Pagliuso Delaney C. , Garrigues Jacob M. , Chen Jerry S. , Aalto Antti P. , Pasquinelli Amy E.
Published: July 2019

Elevated temperatures activate a Heat Shock Response (HSR) to protect cells from the pathological effects of protein mis-folding, cellular mis-organization, organelle dysfunction and altered membrane fluidity. This response includes activation of the conserved transcription factor Heat Shock Factor 1 (HSF-1), which binds Heat Shock Elements (HSEs) in the promoters of genes induced by heat shock (HS). The up-regulation of protein-coding genes (PCGs), such as Heat Shock Proteins (HSPs) and cytoskeletal regulators, is critical for cellular survival during elevated temperatures. While the transcriptional response of PCGs to heat shock has been comprehensively analyzed in a variety of organisms, the effect of this stress on the expression of non-coding RNAs (ncRNAs) has not been systematically examined. Here we show that inCaenorhabditis elegansHS induces up- and down-regulation of specific ncRNAs from multiple classes, including miRNA, piRNA, lincRNA, pseudogene, and repeat elements. Moreover, some ncRNA genes appear to be direct targets of the HSR, as they contain HSF-1 bound HSEs in their promoters and their expression is regulated by this factor during HS. These results demonstrate that multiple ncRNA genes respond to HS, some as direct HSF-1 targets, providing new candidates that may contribute to organismal survival during this stress.
Lignin-based resistance toCuscuta campestrisparasitism in Heinz resistant tomato cultivars
Authors: Jhu Min-Yao , Farhi Moran , Wang Li , Philbrook Richard N. , Belcher Michael S. , Nakayama Hokuto , Zumstein Kristina S. , Rowland Steven D. , Ron Mily , Shih Patrick M. , Sinha Neelima R.
Published: July 2019

Cuscutaspecies (dodders) are agriculturally destructive parasitic angiosperms. These parasitic plants use haustoria as physiological bridges to extract nutrients and water from hosts.Cuscuta campestrishas a broad host range and wide geographical distribution. While some wild tomato relatives are resistant, cultivated tomatoes are generally susceptible toC. campestrisinfestations. However, some specific Heinz tomato hybrid cultivars exhibit resistance to dodders in the field, but their defense mechanism was unknown. Here, we discovered that the stem cortex in these resistant lines responds with local lignification uponC. campestrisattachment, preventing parasite entry into the host.LIF1(Lignin Induction Factor 1, anAP2-like transcription factor),SlMYB55, andCuRLR1(Cuscuta R-gene for Lignin-based Resistance 1, aCC-NBS-LRR) are identified as crucial factors conferring host resistance by regulating lignification.SlWRKY16is upregulated uponC. campestrisinfestation and acts as a negative regulator ofLIF1function. Intriguingly,CuRLR1may play a role in signaling or function as a receptor for receivingCuscutasignals or effectors to regulate lignification-based resistance. In summary, these four regulators control the lignin-based resistance response, preventingC. campestrisfrom parasitizing these resistant tomatoes. This discovery provides a foundation for investigating multilayer resistance againstCuscutaspecies and has potential for application in other essential crops attacked by parasitic plants.

One-sentence summary

Four key regulators confer lignin accumulation in the tomato stem cortex to blockC. campestrishost penetration upon infection.
Assessment of a split homing based gene drive for efficient knockout of multiple genes
Authors: Kandul Nikolay P. , Liu Junru , Buchman Anna , Gantz Valentino M. , Bier Ethan , Akbari Omar S.
Published: July 2019

Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host-encoded genes have been identified that are important for pathogen transmission, targeting these genes using guide RNAs as cargo genes linked to drives may provide a robust method to prevent transmission. However, effectiveness of the inclusion of additional guide RNAs that target separate host encoded genes has not been thoroughly explored. To test this approach, here we generated a split-HGD in Drosophila melanogaster that encoded a drive linked effector consisting of a second gRNA engineered to target a separate host encoded gene, which we term a gRNA-mediated effector (GME). This design enabled us to assess homing and knockout efficiencies of two target genes simultaneously, and also explore the timing and tissue specificity of Cas9 expression on cleavage/homing rates. We demonstrate that inclusion of a GME can result in high efficiency of disruption of its target gene during super-Mendelian propagation of split-HGD. However, maternal deposition and embryonic expression of Cas9 resulted in the generation of drive resistant alleles which can accumulate and limit the spread of such a drive. Alternative design principles are discussed that could mitigate the accumulation of resistance alleles while incorporating a GME.
Motor Output Matters: Evidence of a Continuous Relationship Between Stop/No-go P300 Amplitude and Response Force on Failed Inhibitions at the Trial-Level
Authors: Nguyen An T. , Albrecht Matthew A. , Lipp Ottmar V. , Marinovic Welber
Published: July 2019

Motor actions can be suppressed with varying degrees of success, but this variability is not captured in many experiments where responses are represented in binary (response vs. no-response). Although the Stop/No-go P300 (an enhanced frontocentral positivity in the event-related potential (ERP) peaking around 300 ms after a Stop/No-go stimulus, compared to Go trials) has been implicated as a measure of inhibitory-control, it is unclear how the range of motor outputs relates to the P300. We examined the nature of this association in two experiments using an Anticipatory Timing and a Go/No-go Task. Force, response onset time, and the P300 were measured.

In both experiments, our results showed that trial-by-trial P300 amplitude on Failed Inhibitions were continuously related to Force, where higher response forces (reflecting a greater degree of error) were associated with smaller P300 amplitudes. Compared to Successful Inhibitions, P300 amplitude was reduced and ERP onset latencies were delayed on Failed Inhibitions. Although the binary categorisation of inhibition-success (Successful vs. Failed) accounted for more variance in the data compared to force, it misses a reliable linear relationship that can be captured by continuous measures of motor output. Overall, the results provide strong evidence that the engagement of inhibitory-control varies on a continuum from trial-to-trial and that this engagement is reflected by the P300. We present an activation-to-threshold model of inhibitory-control to explain our results, which offers a new conceptual framework for describing the implementation of inhibitory-control in highly prepared motor responses. Our results also highlight the importance of studying the spectrum of motor outputs and the need for future models of inhibitory-control to account for motor output.
Identification and evolution of avian endogenous foamy viruses
Authors: Chen Yicong , Wei Xiaoman , Zhang Guojie , Holmes Edward C. , Cui Jie
Published: July 2019

A history of long-term co-divergence means that foamy viruses (familyRetroviridae) provide an ideal framework to understanding virus-host evolution over extended time periods. Endogenous foamy viruses (EndFVs) are rare, and to date have only been described in a limited number of mammals, amphibians, reptiles and fish genomes. By screening 414 avian genomes we identified EndFVs in two bird species: the Maguari Stork (Ciconia maguari) and the Oriental Stork (C. boyciana). Analyses of phylogenetic relationships, genome structures and flanking sequences revealed a single origin of EndFVs inCiconiaspecies. In addition, the marked incongruence between the virus and host phylogenies suggested that this integration event occurred independently in birds. In sum, by providing evidence that birds can be infected with foamy viruses, we fill the last major gap in the taxonomic distribution of foamy viruses and their animal hosts.
CT-FOCS: a novel method for inferring cell type-specific enhancer-promoter maps
Authors: Hait Tom Aharon , Elkon Ran , Shamir Ron
Published: July 2019

Spatiotemporal gene expression patterns are governed to a large extent by the activity of enhancer elements, which engage in physical contacts with their target genes. Identification of enhancer-promoter (EP) links that are functional only in a specific subset of cell types is a key challenge in understanding gene regulation. We introduce CT-FOCS, a statistical inference method that uses linear mixed effect models to infer EP links that show marked activity only in a single or a small subset of cell types out of a large panel of probed cell types. Analyzing 808 samples from FANTOM5, covering 472 cell lines, primary cells, and tissues, CT-FOCS inferred such EP links more accurately than recent state-of-the-art methods. Furthermore, we show that strictly cell type-specific EP links are very uncommon in the human genome.
SILAC-based quantitative proteomic analysis ofDrosophilagastrula stage embryos mutant for fibroblast growth factor signaling
Authors: Beati Hamze , Langlands Alistair , ’ten Have Sara , Müller H.-Arno J.
Published: July 2019

The application of quantitative proteomics in model organisms has been successful in determining changes in the proteome under distinct physiological conditions. Quantitative mass spectrometry-based proteomic analyses in combination with genetics provide powerful tools in developmental cell signaling research.Drosophila melanogasteris one of the most widely used genetic models for studying development and disease. Here we combined quantitative proteomics with genetic selection to determine global changes in the proteome upon depletion of the Heartless (Htl) Fibroblast-Growth Factor (FGF) receptor signaling inDrosophilaembryos at early gastrulation stages. We present a robust, single generation SILAC (stable isotope labeling with amino acids in cell culture) protocol for labeling proteins in early embryos and for selection of homozygously mutant embryos at pre-gastrula stages using an independent genetic marker. Our analyses detected quantitative changes in the global proteome ofhtlmutant embryos during gastrulation. We identified distinct classes of down-regulated and up-regulated proteins and network analyses indicates functionally related groups of proteins in each class. These data suggest that FGF signaling in the early embryo affects global changes in the abundance of metabolic, nucleoplasmic, cytoskeletal and endomembrane transport proteins.
Platelet Thrombus Formation in eHUS is Prevented by Anti-MBL2
Authors: Kushak R. I. , Boyle D.C , Rosales I.A. , Ingelfinger J.R. , Stahl G.L , Ozaki M , Colvin R.B. , Grabowski E.F.
Published: July 2019

Epidemic Hemolytic Uremic Syndrome (eHUS) caused by Shiga toxin-producing bacteria is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury that cause acute renal failure in up to 65% of affected patients. We hypothesized that the mannose-binding lectin (MBL) pathway of complement activation plays an important role in human eHUS, as we previously demonstrated that injection of Shiga Toxin-2 (Stx-2) led to fibrin deposition in mouse glomeruli that was blocked by co-injection of the anti-MBL-2 antibody 3F8. However, the markers of platelet thrombosis in affected mouse glomeruli were not delineated. To investigate the effect of 3F8 on markers of platelet thrombosis, we used kidney sections from our mouse model (MBL-2+/+ Mbl-A/C−/−;MBL2 KI mouse). Mice in the control group received PBS, while mice in a second group received Stx-2, and those in a third group received 3F8 and Stx-2. Using double immunofluorescence (IF) followed by digital image analysis, kidney sections were stained for fibrin(ogen) and CD41 (marker for platelets), von-Willebrand factor (marker for endothelial cells and platelets), and podocin (marker for podocytes). Electron microscopy (EM) was performed on ultrathin sections from mice and human with HUS. Injection of Stx-2 resulted in an increase of both fibrin and platelets in glomeruli, while administration of 3F8 with Stx-2 reduced both platelet and fibrin to control levels. EM studies confirmed that CD41-positive objects observed by IF were platelets. The increases in platelet number and fibrin levels by injection of Stx-2 are consistent with the generation of platelet-fibrin thrombi that were prevented by 3F8.
Short-term synaptic plasticity makes neurons sensitive to the distribution of presynaptic population firing rates
Authors: Tauffer Luiz , Kumar Arvind
Published: July 2019

Abstract

The ability to discriminate spikes that encode a particular stimulus from spikes produced by background activity is essential for reliable information processing in the brain. We describe how synaptic short-term plasticity (STP) modulates the output of presynaptic populations as a function of the distribution of the spiking activity and find a strong relationship between STP features and sparseness of the population code, which could solve the discrimination problem. Furthermore, we show that feedforward excitation followed by inhibition (FF-EI), combined with target-dependent STP, promote substantial increase in the signal gain even for considerable deviations from the optimal conditions, granting robustness to this mechanism. A simulated neuron driven by a spiking FF-EI network is reliably modulated as predicted by a rate analysis and inherits the ability to differentiate sparse signals from dense background activity changes of the same magnitude, even at very low signal-to-noise conditions. We propose that the STP-based distribution discrimination is likely a latent function in several regions such as the cerebellum and the hippocampus.
The biosynthetic gene cluster of the C-nucleoside antibiotic pyrazomycin with a rare pyrazole moiety
Authors: Zhao Guiyun , Yao Shunyu , Rothchild Kristina W , Liu Tengfei , Liu Yu , Lian Jiazhang , He Hai-Yan , Ryan Katherine S , Du Yi-Ling
Published: July 2019

Pyrazomycin is a rare C-nucleoside antibiotic with a naturally occurring pyrazole ring, whose biosynthetic origin has remained obscure for decades. In this study, we report the identification of the gene cluster responsible for pyrazomycin biosynthesis in Streptomyces candidus NRRL 3601, revealing that StrR-family regulator PyrR is the cluster-situated transcriptional activator governing pyrazomycin biosynthesis. Furthermore, our results from in vivo reconstitution and stable-isotope feeding experiments support that PyrN is a new nitrogen-nitrogen bond forming enzyme linking the ε-NH2 nitrogen of l-N6-OH-lysine and α-NH2 nitrogen of l-glutamate. This study lays the foundation for further genetic and biochemical characterization of pyrazomycin pathway enzymes constructing the characteristic pyrazole ring.
Thera-SAbDab: the Therapeutic Structural Antibody Database
Authors: Raybould Matthew I. J. , Marks Claire , Lewis Alan P. , Shi Jiye , Bujotzek Alexander , Taddese Bruck , Deane Charlotte M.
Published: July 2019

The Therapeutic Structural Antibody Database (Thera-SAbDab; http://opig.stats.ox.ac.uk/webapps/therasabdab) tracks all antibody- and nanobody-related therapeutics recognised by the World Health Organisation (WHO), and identifies any corresponding structures in the Structural Antibody Database (SAbDab) with near-exact or exact variable domain sequence matches. Thera-SAbDab is synchronised with SAbDab to update weekly, reflecting new Protein Data Bank entries and the availability of new sequence data published by the WHO. Each therapeutic summary page lists structural coverage (with links to the appropriate SAbDab entries), alignments showing where any near-matches deviate in sequence, and accompanying metadata, such as intended target and investigated conditions. Thera-SAbDab can be queried by therapeutic name, by a combination of metadata, or by variable domain sequence - returning all therapeutics that are within a specified sequence identity over a specified region of the query. The sequences of all therapeutics listed in Thera-SAbDab (461 unique molecules, as of 5th August 2019) are downloadable as a single file with accompanying metadata.
P granules protect RNA interference genes from silencing by piRNAs
Authors: Ouyang John Paul T. , Folkmann Andrew , Bernard Lauren , Lee Chih-Yung , Seroussi Uri , Charlesworth Amanda G. , Claycomb Julie M. , Seydoux Geraldine
Published: July 2019

P granules are perinuclear condensates in C. elegans germ cells proposed to serve as hubs for self/non-self RNA discrimination by Argonautes. We report that a mutant (meg-3 meg-4) that does not assemble P granules in primordial germ cells loses competence for RNA-interference over several generations and accumulates silencing small RNAs against hundreds of endogenous genes, including the RNA-interference genes rde-11 and sid-1. In wild-type, rde-11 and sid-1 transcripts are heavily targeted by piRNAs, accumulate in P granules, but maintain expression. In the primordial germ cells of meg-3 meg-4 mutants, rde-11 and sid-1 transcripts disperse in the cytoplasm with the small RNA biogenesis machinery, become hyper-targeted by secondary sRNAs, and are eventually silenced. Silencing requires the PIWI-class Argonaute PRG-1 and the nuclear Argonaute HRDE-1 that maintains trans-generational silencing of piRNA targets. These observations support a “safe harbor” model for P granules in protecting germline transcripts from piRNA-initiated silencing.
A novel mass assay to measure phosphatidylinositol-5-phosphate from cells and tissues
Authors: Ghosh Avishek , Sharma Sanjeev , Shinde Dhananjay , Ramya Visvanathan , Raghu Padinjat
Published: July 2019

Phosphatidylinositol-5-phosphate (PI5P) is a low abundance lipid proposed to have functions in cell migration, DNA damage responses, receptor trafficking and insulin signalling in metazoans. However, studies of PI5P function are limited by the lack of scalable techniques to quantify its level from cells and tissues in multicellular organisms. Currently, PI5P measurement requires the use of radionuclide labelling approaches that are not easily applicable in tissues or in vivo samples. In this study, we describe a simple and reliable, non-radioactive mass assay to measure total PI5P levels from cells and tissues of Drosophila, a genetically tractable multicellular model. We use 18O-ATP to label PI5P from tissue extracts while converting it into PI(4,5)P2 using an in vitro kinase reaction. The product of this reaction can be selectively detected and quantified with high sensitivity using a liquid chromatography-tandem mass spectrometry platform. Further, using this method, we capture and quantify the unique acyl chain composition of PI5P from Drosophila cells and tissues. Finally, we demonstrate the use of this technique to quantify elevations in PI5P levels, from both Drosophila larval tissues and cultured cells depleted of phosphatidylinositol 5 phosphate 4-kinase (PIP4K), that metabolizes PI5P into PI(4,5)P2 thus regulating its levels. Thus, we demonstrate the potential of our method to quantify PI5P levels with high sensitivity levels from cells and tissues of multicellular organisms thus accelerating understanding of PI5P functions in vivo.
Board diversity and corporate social responsibility: the moderating role of Shariah compliance
Authors: Azam Muhammad , Khalid Muhammed Usman , Zia Syeda Zinnaira
Published: July 2019

Purpose

The purpose of this study is to investigate the effect of board diversity on corporate social responsibility (CSR) practices and the interaction effect of Shariah compliance of firms with religious and ethical principles.

Design/methodology/approach

A total of 65 firms listed on the Pakistan Stock Exchange (PSX) were selected. The data were collected from the companies’ financial reports from 2012 to 2018 (n=455). The data were analyzed using fixed and random effects regression models to test the effect of board diversity on firms’ CSR activities, while hierarchical moderated regression analysis was used to determine the moderating effects of Shariah compliance.

Findings

The study found evidence for a moderating effect of Shariah compliance on the relationship between board diversity and CSR activities. The findings suggest that a high level of Shariah compliance together with diverse educational backgrounds and presence of both genders among corporate members significantly promoted CSR activities.

Research limitations/implications

The present study included the demographic variables, gender, ethnicity and education; but excluded language and culture. The results suggest that the Security and Exchange Commission of Pakistan should attach more importance to Shariah compliance by firms in developing their CSR policies to improve social development and human well-being. Policy-makers should encourage more women to become directors on company boards and to increase philanthropic and charitable activities. These findings possess important implications for many Islamic countries irrespective of whether they are developed or developing.

Originality/value

To the best of the authors’ knowledge, this study provides the first empirical analysis of the relationship between CSR and board diversity from the perspective of Islamic Shariah law. The findings will contribute both theoretically and empirically to the existing body of knowledge.
Long-wave evolution model of thermocapillary convection in an evaporating thin film of pseudoplastic fluids
Authors: Lim Elaine , Hung Yew Mun
Published: July 2019

Purpose

By solving a long-wave evolution model numerically for power-law fluids, the authors aim to investigate the hydrodynamic and thermal characteristics of thermocapillary flow in an evaporating thin liquid film of pseudoplastic fluid.

Design/methodology/approach

The flow reversal attributed to the thermocapillary action is manifestly discernible through the streamline plots.

Findings

The thermocapillary strength is closely related to the viscosity of the fluid, besides its surface tension. The thermocapillary flow prevails in both Newtonian and pseudoplastic fluids at a large Marangoni number and the thermocapillary effect is more significant in the former. The overestimate in the Newtonian fluid is larger than that in the pseudoplastic fluid, owing to the shear-thinning characteristics of the latter.

Originality/value

This study provides insights into the essential attributes of the underlying flow characteristics in affecting the thermal behavior of thermocapillary convection in an evaporating thin liquid film of the shear-thinning fluids.
The influence of CEOs’ equity-based compensation on restaurant firms’ CSR initiatives
Authors: Park Sungbeen , Song Sujin , Lee Seoki
Published: July 2019

Purpose

Based on the agency theory and risk management perspective, this study aims to examine the relationship between CEOs’ pay schemes and corporate social responsibility (CSR) activities in the restaurant industry. Specifically, the authors propose that CEOs with a higher proportion of equity-based compensation (EBC), which induces a greater propensity for risk-taking, are prone to indulge less in CSR. In addition, the authors investigate how institutional ownership moderates the proposed main relationship.

Design/methodology/approach

This study performs two-way fixed-effects models and clustered standard errors to test the proposed hypotheses.

Findings

The results of the panel analysis show a significant negative effect of CEOs’ EBC on CSR. Also, the authors found a significant positive moderating effect of institutional ownership between CEOs’ EBC and CSR.

Originality/value

Given the lack of empirical studies that incorporate both agency theory and the risk management perspective, and given the importance of understanding the determinants of restaurant firms’ CSR activities, this study expands upon the existing literature by showing the relationship between CEOs’ compensation schemes and restaurant firms’ CSR activities.
Role of network capability, structural flexibility and management commitment in defining strategic performance in hospitality industry
Authors: Majid Abdul , Yasir Muhammad , Yousaf Zahid , Qudratullah Hassan
Published: July 2019

Purpose

This study aims to present an empirical model related to strategic performance (SP) of the hospitality industry. It focuses on the role of network capability (NC) in defining SP through the mediating role of structural flexibility (SF). Furthermore, the interaction effect of NC and top management commitment to strategic performance (MCSP) on SP is also tested.

Design/methodology/approach

A sample of 279 managerial-level employees of four-star and five-star hotels has been used to confirm the proposed hypotheses by using the technique of structural equation modeling.

Findings

The results reveal that NC positively affects SP. Moreover, the mediating role of SF in defining the nexus of NC and SP has also been confirmed. Results of moderation analysis reveal that MCSP strengthens the relationship between NC and SP.

Research limitations/implications

This study used a cross-sectional design for data collection, which prevents strong causal inferences. The authors recommend scholars to explicitly test for causal effect. This study used a cross-sectional design for data collection, which prevents strong causal inferences. The authors recommend scholars to explicitly test for causal effect among all these variables by using a longitudinal study in the future.

Practical implications

In developing countries, it has been observed that the hospitality industry pays less attention to its strategic targets. Operating in a network or adapting flexible structures is also not on their priority list. This study presents a pragmatic approach based on strong theoretical grounds to attain the goals of SP in the hospitality industry through NC and SF. Therefore, this study suggests that organization operating in the tourism and hospitality industry should pay greater attention toward synergies and business networks to achieve SP.

Originality/value

This research enriches the prevailing knowledge by testing a mediating role of SF between NC-SP link and, therefore, makes an important addition to the existing knowledge on tourism and hospitality industry by concentrating on the relationship between NC, SF, MCSP and SP.
Measuring Malaysian housing affordability: the lifetime income approach
Authors: Rangel Gary John , Ng Jason Wei Jian , Murugasu Thangarajah Thiyagarajan , Poon Wai Ching
Published: July 2019

Purpose

The purpose of this paper is to measure the long-run housing affordability of Malaysia over time for households at various income levels and to demonstrate how short- and long-run affordability measures can reach contradicting conclusions.

Design/methodology/approach

In this study, a long-run housing affordability index (HAI) for Malaysia was constructed for the sample period 1995 to 2014, using data from house prices and household incomes. The HAI was also modified to compute a mortgage affordability index (MAI) to account for intergenerational transfers.

Findings

The results show that households at the 25th income percentile cannot afford any of the four dwelling types in Malaysia. For households at the 40th income percentile and the median income levels, high-rise and terrace housing are affordable. However, significant downward trends in HAI and MAI are documented beginning 2009, which indicates increasing housing stress for households at or below the median income. The short-run affordability measure represented by the median multiple (MM) indicator showed bleaker conclusion for housing affordability, with all dwelling types considered unaffordable over the entire sample period

Practical implications

On the basis of the empirical results, this paper provided several long-term proposals to ameliorate the housing affordability problem in Malaysia.

Originality/value

With the MM ratio being the official affordability measure reported for Malaysia, this study introduces the nation’s first long-run housing affordability measure. It is hoped that this long-run measure will achieve widespread adoption in Malaysia. Given the deteriorating long-term affordability, this study offers several possible long-term solutions.
Firm performance: is organizational learning capability the magic wand?
Authors: Hooi Lai Wan
Published: July 2019

Purpose

The purpose of this paper is to focus on human resource practices contribution to retail SMEs performance through its role in developing organizational learning capability (OLC).

Design/methodology/approach

A cross-sectional design was adopted, where data were collected from a sample of 214 managers of retail SMEs, utilizing a survey questionnaire. Structural equation modeling was used to test the hypothesized relationships.

Findings

The results indicate that incentive reward has the strongest significance on firm performance with a stronger influence on economic performance. Performance appraisal has the greatest effect on system perspective, followed by the impact of employee selection on managerial commitment (MC). MC strongly affects firm performance while openness and experimentation influences satisfaction performance. Additionally, OLC fully mediates the relationship between high-performance human resource management (HRM) practices and firm performance.

Research limitations/implications

It did not include large organizations nor consider other SME contextual variables which may otherwise exert significant impact on OLC.

Practical implications

A profound understanding of distinctive high-performance HRM practices effect on firm performance and the needed employee capabilities that would assist organizations to implement strategies to attain sustainable competitive advantage.

Originality/value

The study advances knowledge on HRM practices among SMEs by proposing that distinctive high-performance HRM practices can leverage OLC to enhance firm performance.