bluuebunny/crossref_metadata_2025 huggingface dataset:
Autism sensory dysfunction in an evolutionarily conserved system
Authors: Vilidaite Greta , Norcia Anthony M. , West Ryan J. H. , Elliott Christopher J. H. , Pei Francesca , Wade Alex R. , Baker Daniel H.
Published: December 2018

There is increasing evidence for a strong genetic basis for autism, with many genetic models being developed in an attempt to replicate autistic symptoms in animals. However, current animal behaviour paradigms rarely match the social and cognitive behaviours exhibited by autistic individuals. Here, we instead assay another functional domain—sensory processing—known to be affected in autism to test a novel genetic autism model in
Drosophila melanogaster
. We show similar visual response alterations and a similar development trajectory in
Nhe3
mutant flies (total
n
= 72) and in autistic human participants (total
n
= 154). We report a dissociation between first- and second-order electrophysiological visual responses to steady-state stimulation in adult mutant fruit flies that is strikingly similar to the response pattern in human adults with ASD as well as that of a large sample of neurotypical individuals with high numbers of autistic traits. We explain this as a genetically driven, selective signalling alteration in transient visual dynamics. In contrast to adults, autistic children show a decrease in the first-order response that is matched by the fruit fly model, suggesting that a compensatory change in processing occurs during development. Our results provide the first animal model of autism comprising a differential developmental phenotype in visual processing.
Ocean pH fluctuations affect mussel larvae at key developmental transitions
Authors: Kapsenberg L. , Miglioli A. , Bitter M. C. , Tambutté E. , Dumollard R. , Gattuso J.-P.
Published: December 2018

Coastal marine ecosystems experience dynamic fluctuations in seawater carbonate chemistry. The importance of this variation in the context of ocean acidification requires knowing what aspect of variability biological processes respond to. We conducted four experiments (ranging from 3 to 22 days) with different variability regimes (pHT7.4–8.1) assessing the impact of diel fluctuations in carbonate chemistry on the early development of the musselMytilus galloprovincialis. Larval shell growth was consistently correlated to mean exposures, regardless of variability regimes, indicating that calcification responds instantaneously to seawater chemistry. Larval development was impacted by timing of exposure, revealing sensitivity of two developmental processes: development of the shell field, and transition from the first to the second larval shell. Fluorescent staining revealed developmental delay of the shell field at low pH, and abnormal development thereof was correlated with hinge defects in D-veligers. This study shows, for the first time, that ocean acidification affects larval soft-tissue development, independent from calcification. Multiple developmental processes additively underpin the teratogenic effect of ocean acidification on bivalve larvae. These results explain why trochophores are the most sensitive life-history stage in marine bivalves and suggest that short-term variability in carbonate chemistry can impact early larval development.
The best smellers make the best choosers: mate choice is affected by female chemosensory receptor gene diversity in a mammal
Authors: Santos Pablo S. C. , Mezger Maja , Kolar Miriam , Michler Frank-Uwe , Sommer Simone
Published: December 2018

The products of the genes of the major histocompatibility complex (MHC) are known to be drivers of pathogen resistance and sexual selection enhancing offspring genetic diversity. The MHC further influences individual odour types and social communication. However, little is known about the receptors and their volatile ligands that are involved in this type of chemical communication. Here, we have investigated chemosensory receptor genes that ultimately enable females to assess male genes through odour cues. As a model, we used an invasive population of North American raccoons (
Procyon lotor
) in Germany. We investigated the effect of two groups of chemosensory receptor genes—trace amine-associated receptors (TAARs) and olfactory receptors (ORs)—on MHC-dependent mate choice. Females with more alleles of the TAAR or OR loci were more likely to choose a male with a diverse MHC. We additionally found that MHC class I genes have a stronger effect on mate choice than the recently reported effect for MHC class II genes, probably because of their immunological relevance for viral resistance. Our study is among the first to show a genetic link between behaviour and chemosensory receptor genes. These results contribute to understanding the link between genetics, olfaction and associated life-history decisions.
Principles of niche expansion
Authors: Sjödin Henrik , Ripa Jörgen , Lundberg Per
Published: December 2018

Niche expansion is attained by adaptations in two generalized phenotypical traits—niche position and niche width. This gives room for a wide range of conceptual ways of niche filling. The niche variation hypothesis reduces the range by predicting that expansion occurs by increasing variation in niche position, which has been debated on empirical and theoretical grounds as also other options seem possible. Here, we propose a general theory of niche expansion. We review empirical data and show with an eco-evolutionary model how resource diversity and a trade-off in resource acquisition steer niche evolution consistent with observations. We show that the range can be reduced to a discrete set of two orthogonal ways of niche filling, through (1) strict phenotypical differentiation in niche position or (2) strict individual generalization. When individual generalization is costly, niche expansion undergoes a shift from (2) to (1) at a point where the resource diversity becomes sufficiently large. Otherwise, niche expansion always follows (2), consistent with earlier results. We show that this either–or response can operate at both evolutionary and short-term time scales. This reduces the principles of niche expansion under environmental change to a notion of orthogonality, dictated by resource diversity and a resource-acquisition trade-off.
Formation of desiccation crack patterns in electric fields: a review
Authors: Tarafdar Sujata , Dutta Tapati
Published: December 2018

Desiccation crack formation is an important and interesting part of the broad area of fracture mechanics. Generation of cracks due to drying depends on ambient conditions, which may include externally applied fields. In this review, we discuss the effect of both direct and alternating electrical fields on desiccation crack formation. After a brief introduction to materials which crack on drying, e.g. colloids, clay and ceramics we discuss how they respond to an electric field. Following that, we present an account of experiments and modelling studies performed on granular pastes or clays drying while exposed to an electric field. Specific patterns formed under different geometries, strengths and frequencies of the electric field are described and explained. The review includes work on cracks formed in clay droplets, where a memory effect has been observed and analysed using a generalized calculus formalism.

This article is part of the theme issue ‘Statistical physics of fracture and earthquakes’.
Constitutive and stimulated macropinocytosis in macrophages: roles in immunity and in the pathogenesis of atherosclerosis
Authors: Doodnauth Sasha A. , Grinstein Sergio , Maxson Michelle E.
Published: December 2018

Macrophages respond to several stimuli by forming florid membrane ruffles that lead to fluid uptake by macropinocytosis. This type of induced macropinocytosis, executed by a variety of non-malignant and malignant cells, is initiated by transmembrane receptors and is involved in nutrient acquisition and mTOR signalling. However, macrophages also perform a unique type of constitutive ruffling and macropinocytosis that is dependent on the presence of extracellular calcium. Calcium-sensing receptors are responsible for this activity. This distinct form of macropinocytosis enables macrophages to continuously sample their microenvironment for antigenic molecules and for pathogen- and danger-associated molecular patterns, as part of their immune surveillance functions. Interestingly, even within the monocyte lineage, there are differences in macropinocytic ability that reflect the polarized functional roles of distinct macrophage subsets. This review discusses the shared and distinct features of both induced and constitutive macropinocytosis displayed by the macrophage lineage and their roles in physiology, immunity and pathophysiology. In particular, we analyse the role of macropinocytosis in the uptake of modified low-density lipoprotein (LDL) and its contribution to foam cell and atherosclerotic plaque formation. We propose a combined role of scavenger receptors and constitutive macropinocytosis in oxidized LDL uptake, a process we have termed ‘receptor-assisted macropinocytosis'.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Function of small GTPases inDictyosteliummacropinocytosis
Authors: Williams Thomas D. , Paschke Peggy I. , Kay Robert R.
Published: December 2018

Macropinocytosis—the large-scale, non-specific uptake of fluid by cells—is used byDictyostelium discoideumamoebae to obtain nutrients. These cells form circular ruffles around regions of membrane defined by a patch of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the activated forms of the small G-proteins Ras and Rac. When this ruffle closes, a vesicle of the medium is delivered to the cell interior for further processing. It is accepted that PIP3 is required for efficient macropinocytosis. Here, we assess the roles of Ras and Rac inDictyosteliummacropinocytosis. Gain-of-function experiments show that macropinocytosis is stimulated by persistent Ras activation and genetic analysis suggests that RasG and RasS are the key Ras proteins involved. Among the activating guanine exchange factors (GEFs), GefF is implicated in macropinocytosis by an insertional mutant. The individual roles of Rho family proteins are little understood but activation of at least some may be independent of PIP3.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Rab8a localisation and activation by Toll-like receptors on macrophage macropinosomes
Authors: Wall Adam A. , Condon Nicholas D. , Luo Lin , Stow Jennifer L.
Published: December 2018

Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions. Cell surface ruffles give rise to phagosomes and to macropinosomes as multi-functional compartments that contribute to environmental sampling, pathogen entry, plasma membrane turnover and receptor signalling. Rapid, high resolution, lattice light sheet imaging demonstrates the dynamic nature of macrophage ruffling. Pathogen-mediated activation of surface and endosomal Toll-like receptors (TLRs) in macrophages upregulates macropinocytosis. Here, using multiple forms of imaging and microscopy, we track membrane-associated, fluorescently-tagged Rab8a expressed in live macrophages, using a variety of cell markers to demonstrate Rab8a localization and its enrichment on early macropinosomes. Production of a novel biosensor and its use for quantitative FRET analysis in live cells, pinpoints macropinosomes as the site for TLR-induced activation of Rab8a. We have previously shown that TLR signalling, cytokine outputs and macrophage programming are regulated by the GTPase Rab8a with PI3 Kγ as its effector. Finally, we highlight another effector, the phosphatase OCRL, which is located on macropinosomes and interacts with Rab8a, suggesting that Rab8a may operate on multiple levels to modulate phosphoinositides in macropinosomes. These findings extend our understanding of macropinosomes as regulatory compartments for innate immune function in macrophages.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
The pervasiveness of macropinocytosis in oncological malignancies
Authors: Commisso Cosimo
Published: December 2018

In tumour cells, macropinocytosis functions as an amino acid supply route and supports cancer cell survival and proliferation. Initially demonstrated in oncogenicKRAS-driven models of pancreatic cancer, macropinocytosis triggers the internalization of extracellular proteins via discrete endocytic vesicles called macropinosomes. The incoming protein cargo is targeted for lysosome-dependent degradation, causing the intracellular release of amino acids. These protein-derived amino acids support metabolic fitness by contributing to the intracellular amino acid pools, as well as to the biosynthesis of central carbon metabolites. In this way, macropinocytosis represents a novel amino acid supply route that tumour cells use to survive the nutrient-poor conditions of the tumour microenvironment. Macropinocytosis has also emerged as an entry mechanism for a variety of nanomedicines, suggesting that macropinocytosis regulation in the tumour setting can be harnessed for the delivery of anti-cancer therapeutics. A slew of recent studies point to the possibility that macropinocytosis is a pervasive feature of many different tumour types. In this review, we focus on the role of this important uptake mechanism in a variety of cancers and highlight the main molecular drivers of macropinocytosis in these malignancies.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Using macropinocytosis for intracellular delivery of therapeutic nucleic acids to tumour cells
Authors: Desai Arpan S. , Hunter Morag R. , Kapustin Alexander N.
Published: December 2018

Nucleic acids are a rapidly emerging therapeutic modality with the potential to become the third major drug modality alongside antibodies and small molecules. Owing to the unfavourable physico-chemical characteristics of nucleic acids, such as large size and negative charge, intracellular delivery remains a fundamental challenge to realizing this potential. Delivery technologies such as lipids, polymers and peptides have been used to facilitate delivery, with many of the most successful technologies using macropinocytosis to gain cellular entry; mostly by default rather than design. Fundamental knowledge of macropinocytosis is rapidly growing, presenting opportunities to better tailor design strategies to target this pathway. Furthermore, certain types of tumour cells have been observed to have high levels of macropinocytic activity and traffic cargo to favourable destinations within the cell for endosomal release, providing unique opportunities to further use this entry route for drug delivery. In this article, we review the delivery systems reported to be taken up by macropinocytosis and what is known about the mechanisms for regulating macropinocytosis in tumour cells. From this analysis, we identify new opportunities for exploiting this pathway for the intracellular delivery of nucleic acids to tumour cells.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Metabolic functions of macropinocytosis
Authors: Palm Wilhelm
Published: December 2018

Macropinocytosis is an evolutionarily conserved form of endocytosis that mediates non-selective uptake of extracellular fluid and the solutes contained therein. In mammalian cells, macropinocytosis is initiated by growth factor-mediated activation of the Ras and PI3-kinase signalling pathways. In malignant cells, oncogenic activation of growth factor signalling sustains macropinocytosis cell autonomously. Recent studies of cancer metabolism, discussed here, have begun to define a role for macropinocytosis as a nutrient uptake route. Macropinocytic cancer cells ingest macromolecules in bulk and break them down in the lysosome to support metabolism and macromolecular synthesis. Thereby, macropinocytosis allows cells to tap into the copious nutrient stores of extracellular macromolecules when canonical nutrients are scarce. These findings demonstrate that macropinocytosis promotes metabolic flexibility and resilience, which enables cancer cells to survive and grow in nutrient-poor environments. Implications for physiological roles of growth factor-stimulated macropinocytosis in cell metabolism and its relationship with other nutrient uptake pathways are considered.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration
Authors: Kawa Alex B. , Valenta Alec C. , Kennedy Robert T. , Robinson Terry E.
Published: December 2018

Recent studies suggest that the temporal pattern of drug use (pharmacokinetics) has a profound effect on the ability of self-administered cocaine to produce addiction-like behavior in rodents, and to change the brain. To further address this issue, we compared the effects of Long Access (LgA) cocaine self-administration, which is widely used to model the transition to addiction, with Intermittent Access (IntA), which is thought to better reflect the pattern of drug use in humans, on the ability of self-administered cocaine to increase dopamine (DA) overflow in the core of the nucleus accumbens (using in vivo microdialysis), and to produce addiction-like behavior. IntA experience was more effective than LgA in producing addiction-like behavior- a drug experience-dependent increase in motivation for cocaine assessed using behavioral economic procedures, and cue-induced reinstatement, despite much less total drug consumption. There were no group differences in basal levels of DA in dialysate, but a single self-administered IV injection of cocaine increased DA in the core of the nucleus accumbens to a greater extent in rats with prior IntA experience than those with LgA or Short Access (ShA) experience, and the latter two groups did not differ. Furthermore, high motivation for cocaine was associated with a high DA response. Thus, IntA, but not LgA, produced both incentive and DA sensitization. This is consistent with the notion that a hyper-responsive dopaminergic system may contribute to the transition from casual patterns of drug use to the problematic patterns that define addiction.
Engineered orthogonal quorum sensing systems for synthetic gene regulation
Authors: Tekel Stefan J. , Smith Christina L. , Lopez Brianna , Mani Amber , Connot Christopher , Livingstone Xylaan , Haynes Karmella A.
Published: December 2018

Gene regulators that are controlled by membrane-permeable compounds called Homoserine lactones (HSLs) have become popular tools for building synthetic gene networks that coordinate behaviors across populations of engineered bacteria. Synthetic HSL-signaling systems are derived from natural DNA and protein elements from microbial quorum signaling pathways. Crosstalk, where a single HSL can activate multiple regulators, can lead to faults in networks composed of parallel signaling pathways. Here, we report an investigation of quorum sensing components to identify synthetic pathways that exhibit little to no crosstalk in liquid and solid cultures. In previous work, we characterized the response of a single regulator (LuxR) to ten distinct HSL-synthase enzymes. Our current study determined the responses of five different regulators (LuxR, LasR, TraR, BjaR, and AubR) to the same set of synthases. We identified two sets of orthogonal synthase-regulator pairs (BjaI/BjaR + EsaI/TraR and LasI/LasR + EsaI/TraR) that show little to no crosstalk when they are expressed in Escherichia coli BL21. These results expand the toolbox of characterized components for engineering microbial communities.
Sharing cells with Wolbachia: the transovarian vertical transmission of Culex pipiens densovirus
Authors: Altinli MIne , Soms Julien , Ravallec Marc , Justy Fabienne , Bonneau Manon , Weill Mylene , Gosselin-Grenet Anne-Sophie , Sicard Mathieu
Published: December 2018

Culex pipiens densovirus (CpDV), a single stranded DNA virus, has been isolated from Culex pipiens mosquitoes but differs from other mosquito densoviruses in terms of genome structure and sequence identity. Its transmission from host to host, the nature of its interactions with both its host and host′s endosymbiotic bacteria Wolbachia are not known. Here we report the presence of CpDV in the ovaries and eggs of Cx. pipiens mosquitoes in close encounters with Wolbachia. In the ovaries, CpDV quantity significantly differed between mosquito lines harboring different strains of Wolbachia and these differences were not linked to variations in Wolbachia densities. CpDV was vertically transmitted in all laboratory lines to 17%-20% of the offspring. For some females, however, the vertical transmission reached 90%. Antibiotic treatment that cured the host from Wolbachia also significantly affected both CpDV quantity and vertical transmission suggesting an impact of host microbiota, including Wolbachia, on CpDV transmission. Overall our results show that CpDV is transmitted vertically via transovarian path along with Wolbachia with which it shares the same cells. Our results are primordial to understand the dynamics of densovirus infection, their persistence and spread in populations considering their potential use in the regulation of mosquito vector populations.
A Deep Learning Genome-Mining Strategy Improves Biosynthetic Gene Cluster Prediction
Authors: Hannigan Geoffrey D. , Prihoda David , Palicka Andrej , Soukup Jindrich , Klempir Ondrej , Rampula Lena , Durcak Jindrich , Wurst Michael , Kotowski Jakub , Chang Dan , Wang Rurun , Piizzi Grazia , Hazuda Daria J. , Woelk Christopher H. , Bitton Danny A.
Published: December 2018

Natural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers more accurate BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing tools. We supplemented this with downstream random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a significant step forward forin-silicoBGC identification.
Generation of Transgenic Human Malaria Parasites With Strong Fluorescence in the Transmission Stages
Authors: McLean Kyle J , Straimer Judith , Hopp Christine S , Vega-Rodriguez Joel , Tripathi Abhai , Mlambo Godfree , Doumolin Peter C , Harris Chantal T , Tong Xinran , Shears Melanie J , Ankarklev Johan , Kafsack Bjorn , Fidock David A , Sinnis Photini
Published: December 2018

Malaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of the effort to shrink the malaria map. The human parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria. Our goal was to generate transgenic P. falciparum lines that could complete the lifecycle and produce fluorescent transmission stages for more in-depth and high-throughput studies. Using zinc-finger nuclease technology to engineer a marker-free integration site, we generated three transgenic P. falciparum lines in which tdtomato or gfp were stably integrated into the genome. Expression was driven by either stage-specific peg4 and csp promoters or the constitutive ef1a promoter. Phenotypic characterization of these lines demonstrates that they complete the life cycle with high infection rates and give rise to fluorescent mosquito stages. The transmission stages are sufficiently bright for intra-vital imaging, flow cytometry and scalable screening of chemical inhibitors and potentially inhibitory antibodies.
Whole-Cortex Mapping of Common Genetic Influences on Depression and Social Deficits
Authors: Hatoum Alexander S. , Reinberg Andrew E. , Smolker Harry R. , Hewitt John K. , Friedman Naomi P.
Published: December 2018

Background

Social processes are associated with depression, particularly understanding and responding to others, deficits in which can manifest as callousness/unemotionality (CU). Thus, CU may reflect some of the genetic risk to depression. Further, this vulnerability likely reflects the neurological substrates of depression, presenting biomarkers to capture genetic vulnerability of depression severity. However, heritability varies within brain regions, so a high-resolution genetic perspective is needed.

Method

In a sample of 258 same-sex twin pairs from the Colorado Longitudinal Twin Study (LTS), we developed a toolbox that maps genetic and environmental associations between brain and behavior at high resolution. We used this toolbox to estimate brain areas that are genetically associated with both depressive symptoms and CU. We then overlapped the two maps to generate coordinates that allow for tests of downstream effects of genes influencing our clusters.

Results

Genetic variance influencing cortical thickness in the right dorsal lateral prefrontal cortex (DLFPC) sulci and gyri, ventral posterior cingulate cortex (PCC), pre-somatic motor cortex (PreSMA), medial precuneus, left occipital-temporal junction (OTJ), parietal-temporal junction (PTJ), ventral somatosensory cortex (vSMA), and medial and lateral precuneus were genetically associated with both depression and CU. Split-half replication found support for both DLPFC clusters. Meta-analytic term search identified “theory of mind”, “inhibit”, and “pain” as likely functions. Gene and transcript mapping/enrichment analyses implicated calcium channels.

Conclusions

CU reflects genetic vulnerability to depression that likely involves executive and social functioning in a distributed process across the cortex. This approach works to unify neuroimaging, neuroinformatics, and genetics to discover pathways to psychiatric vulnerability.
State-dependent geometry of population activity in rat auditory cortex
Authors: Kobak Dmitry , Pardo-Vazquez Jose L. , Valente Mafalda , Machens Christian , Renart Alfonso
Published: December 2018

The accuracy of the neural code depends on the relative embedding of signal and noise in the activity of neural populations. Despite a wealth of theoretical work on population codes, there are few empirical characterisations of the high-dimensional signal and noise subspaces. We studied the geometry of population codes in the rat auditory cortex across brain states along the activation-inactivation continuum, using sounds varying in difference and mean level across the ears. As the cortex becomes more activated, single-hemisphere populations go from preferring contralateral loud sounds to a symmetric preference across lateralisations and intensities, gain-modulation effectively disappears, and the signal and noise subspaces become approximately orthogonal to each other and to the direction corresponding to global activity modulations. Level-invariant decoding of sound lateralisation also becomes possible in the active state. Our results provide an empirical foundation for the geometry and state-dependence of cortical population codes.
Improved representation of sequence Bloom trees
Authors: Harris Robert S. , Medvedev Paul
Published: December 2018

Algorithmic solutions to index and search biological databases are a fundamental part of bioinformatics, providing underlying components to many end-user tools. Inexpensive next generation sequencing has filled publicly available databases such as the Sequence Read Archive beyond the capacity of traditional indexing methods. Recently, the Sequence Bloom Tree (SBT) and its derivatives were proposed as a way to efficiently index such data for queries about transcript presence. We build on the SBT framework to construct the HowDe-SBT data structure, which uses a novel partitioning of information to reduce the construction and query time as well as the size of the index. We evaluate HowDe-SBT by both proving theoretical bounds on its performance and using real RNA-seq data. Compared to previous SBT methods, HowDe-SBT can construct the index in less than 36% the time, and with 39% less space, and can answer small-batch queries at least five times faster. HowDe-SBT is available as a free open source program on https://github.com/medvedevgroup/HowDeSBT.
Continuous in vivo metabolism by NMR
Authors: Judge Michael T , Wu Yue , Tayyari Fariba , Hattori Ayuna , Glushka John , Ito Takahiro , Arnold Jonathan , Edison Arthur S
Published: December 2018

Dense time-series metabolomics data are essential for unraveling the underlying dynamic properties of metabolism. Here we extend high-resolution-magic angle spinning (HR-MAS) to enable continuous in vivo monitoring of metabolism by NMR (CIVM-NMR) and provide analysis tools for these data. First, we reproduced a result in human chronic lymphoid leukemia cells by using isotope-edited CIVM-NMR to rapidly and unambiguously demonstrate unidirectional flux in branched-chain amino acid metabolism. We then collected untargeted CIVM-NMR datasets for Neurospora crassa, a classic multicellular model organism, and uncovered dynamics between central carbon metabolism, amino acid metabolism, energy storage molecules, and lipid and cell wall precursors. Virtually no sample preparation was required to yield a dynamic metabolic fingerprint over hours to days at ~4-min temporal resolution with little noise. CIVM-NMR is simple and readily adapted to different types of cells and microorganisms, offering an experimental complement to kinetic models of metabolism for diverse biological systems.
Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination
Authors: Moquin David M. , Genois Marie-Michelle , Zhang Jia-Min , Ouyang Jian , Yadav Tribhuwan , Buisson Rémi , Yazinski Stephanie A. , Tan Jun , Boukhali Myriam , Gagné Jean-Philippe , Poirier Guy G. , Lan Li , Haas Wilhelm , Zou Lee
Published: December 2018

Numerous DNA repair and signaling proteins function at DNA damage sites to protect the genome. Here, we show that fusion of the promiscuous biotin ligase BirAR118G with RAD18 leads to localized protein biotinylation at DNA damage sites, allowing identification of ZPET (zinc finger protein proximal to RAD eighteen)/ZNF280C as a potential DNA damage response (DDR) protein. ZPET binds ssDNA and localizes to DNA double-strand breaks (DSBs) and stalled replication forks. In vitro, ZPET inhibits MRE11 binding to ssDNA. In cells, ZPET delays MRE11 binding to chromatin after DSB formation and slows DNA end resection through binding ssDNA. ZPET hinders resection independently of 53BP1 and HELB. Cells lacking ZPET displayed enhanced homologous recombination (HR), accelerated replication forks under stress, and increased resistance to DSBs and PARP inhibition. These results not only reveal ZPET as an HR repressor but also suggest that localized protein biotinylation at DNA damage sites is a useful strategy to identify DDR proteins.
Scattering functions of carved-ellipsoid-shaped particles
Authors: Li Mu , Yin Panchao
Published: December 2018

Motivated by the enriched topologies from the newly discovered nano-scaled molecular clusters, custom carved-ellipsoid models are built and their scattering functions are explored. The scattering functions of these models are derived in ellipsoidal coordinates. The theoretical scattering curves of these models can be further obtained through numerical calculation. These models have been successfully applied to the fitting of experimental scattering curves of some so-called wheel-shaped metal oxide molecular clusters.
Implementation of software for data processing of X-ray optical measurements for the analysis of structural parameters
Authors: Petrakov Dmitry S. , Smirnov Dmitry I. , Gerasimenko Nikolay N. , Medetov Nurlan A. , Jikeev Azamat A.
Published: December 2018

The development of semiconductor nanoelectronic technology requires the use of new approaches to metrological control of critically important stages of device structure formation. The development and use of complex measurement methods based on various physical principles allowing one to obtain exhaustive information about the features of real structures, including the existence of hidden and unaccounted layers in transition areas, are of special interest. This paper presents the idea of implementing a complex approach to X-ray optical studies for a two-wavelength measurement scheme, including the methods of relative X-ray reflectometry, refractometry and diffuse X-ray scattering, and its application to the analysis of dimensional parameters of thin-film structures. The study was carried out with the help of a software package for analysing TiN diffusion-barrier layers. A comparison of the results obtained with the results of one-wavelength methods shows the high efficiency of the implemented approach for performing various tasks of metrological control of nanoelectronic devices.
Synthesis and crystal structures of some bis(3-methyl-1H-indol-2-yl)(salicyl)methanes
Authors: Cole Wyatt , Hemmingson Stephanie L. , Eisenberg Audrey C. , Ulman Catherine A. , Tanski Joseph M. , Getzler Yutan D. Y. L.
Published: December 2018

Four 2,2′-bisindolylmethanes (BIMs), a useful class of polyindolyl species joined to a central carbon, were synthesized using salicylaldehyde derivatives and simple acid catalysis; these are 2-[bis(3-methyl-1H-indol-2-yl)methyl]-6-methylphenol, (IIa), 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4,6-dichlorophenol, (IIb), 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4-nitrophenol, (IIc), and 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4,6-di-tert-butylphenol, (IId). BIMs (IIa) and (IIb) were characterized crystallographically as the dimethyl sulfoxide (DMSO) disolvates, i.e. C26H24N2O·2C2H6OS and C25H20Cl2N2O·2C2H6OS, respectively. Both form strikingly similar one-dimensional hydrogen-bonding chain motifs with the DMSO solvent molecules. BIM (IIa) packs into double layers of chains whose orientations alternate every double layer, while (IIb) forms more simply packed chains along the a axis. BIM (IIa) has a remarkably long c axis.
Exploring the quality of corporate environmental reporting
Authors: Helfaya Akrum , Whittington Mark , Alawattage Chandana
Published: December 2018

Purpose

The purpose of this paper is to provide a multidimensional model for assessing the quality of corporate environmental reporting (CER) incorporating both preparer- and user-based views.

Design/methodology/approach

As opposed to frequently used researcher-chosen proxies, the authors used an online questionnaire asking preparers and users how they assess the quality of a company’s environmental report.

Findings

The analysis of the responses of 177 users and 86 preparers shows that quantity was not perceived as the most significant element in determining quality. Besides quantity, the respondents also perceived information types, measures used, themes disclosed, adopting reporting guidelines, inclusion of assurance statement and the use of visual tools as significant dimensions/features of reporting quality.

Research limitations/implications

The online questionnaire has some limitations, especially in terms of researcher being absent to clarify meanings and, hence, possibilities that respondents may misinterpret the questionnaire elements.

Practical implications

Considering that robust, reliable measurement of reporting quality is difficult, preparers, standard setters and policy makers need multidimensional quality models that incorporate both users’ perceptions of quality and preparers’ pragmatic understanding of the quality delivery process. These will make the preparers informed of whether their disclosure may be falling short of users’ expectations.

Originality/value

Amid, increasing complexity of CER, the research contributes to the growing body of literature on assessing the quality of CER by developing a less subjective, multidimensional, preparer–user-based quality model. This innovative quality model goes beyond the traditional quality models, subjective author-based quality measures. Focussing on the three dimensions of reporting quality – content, credibility and communication – it also offers a high-level resolution of meaning of CER quality.
Kindness among colleagues; identifying and exploring the gaps in employment contexts
Authors: Gibb Stephen , Rahman Shama
Published: December 2018

Purpose

The purpose of this study is to model and explore kindness as a factor in employment contexts. “Kindness among colleagues” is a particular context for the scientific study of kindness which has been under-researched. There is scope within the burgeoning study of kindness for research concerned with employment contexts and colleagues, adopting an employment context appropriate construct of kindness, generating and considering evidence that might be evaluated rigorously in the employment context where kindness is both advocated and critiqued.

Design/methodology/approach

The literature review identifies and explores the gaps in kindness research in the employment context. A construct distinguishing a set of antecedents of kindness among colleagues was developed to address these gaps. The relevance and usefulness of the construct was tested in semi-structured interviews among some work colleagues in a specific organization setting.

Findings

The results show that the four antecedents of kindness can be used to capture and explore perceptions and experiences of kindness among colleagues. There is scope for analysis at the levels of individuals, teams and organizations using data about these antecedents which allows for individual and more general workplace dynamics to be described and explored.

Research limitations/implications

The antecedents of kindness construct are validated to an extent by this initial study. The potential of this for describing and analyzing kindness and workplace relevant themes makes it worth further development; to refine and validate an instrument for measuring kindness among colleagues.

Practical implications

Kindness among colleagues, if understood in the nuanced way presented here, can help individuals, teams and organizations review and evaluate themselves in diverse contexts. Contexts can be expected to vary with workforce demographics, leadership style and organization cultures.

Social implications

Kindness is a burgeoning theme and concern across diverse social and cultural contexts for various reasons. The scientific contribution to the advocacy or critique of kindness, in this case kindness among colleagues, provides value in rigor, operationalization and evidencing of the case for and against advocacy of the value of kindness in general.

Originality/value

This is a focused review and study of kindness among colleagues which contributes to the nomological and methodological development of a scientific approach to organizational analysis concerns with this important theme in contemporary times.
Institutional contradiction and BSC implementation: comparative organizational analysis
Authors: Alsharari Nizar Mohammad , Eid Riyad , Assiri Ali
Published: December 2018

Purpose

This paper aims to explain institutional contradictions in the balanced scorecard (BSC) implementation process between organizations, which successfully implemented BSC. The purpose of this paper is to identify a comprehensive set of potential determinants influencing the successful implementation of BSC.

Design/methodology/approach

This study is an exploratory investigation into the BSC implementation based on a dialectical perspective. It uses the triangulation of data collection including interviews, documents and surveys. This also includes a comprehensive scrutiny of the relevant literature; a comprehensive analysis of case studies of BSC implementations in four organizations; and interviews and documents evidences that have already implemented or are in the process of implementing BSC.

Findings

The BSC was successfully implemented in the organizations, when the accounting systems introduced in these organization had already been institutionalized, that is, accepted and used on day-to-day basis. The dialectical perspective postulates that for change to become institutionalized in the organization, it needs to overcome the problem of embedded agency. This process of change is possible due to the accumulation of institutional contradiction that enables human praxis to introduce change (Seo and Creed, 2002).

Research limitations/implications

There is a need to empirically test and refine the proposed factors and explore relationships among the various variables by collecting data from organizations that have already implemented BSC.

Practical implications

The findings of this study are important and relevant to all the different-sized organizations in the different sectors and industries. This study also makes a significant contribution to society in general.

Originality/value

This paper contributes to the literature on organizational and accounting change that emphasis the crucial role that institutional contradiction plays in the process of BSC implementation. The findings of this study will help management in making crucial decisions and in resource allocations that are required to make the BSC implementation a success.
Playing catch-up: how less developed nations can jump-start technology innovation
Authors: Xu Lu , Kim Seong-Young , Xiong Jie , Yan Jie , Huang Han
Published: December 2018

Purpose

This study aims to investigate the historical technological catch-up processes with particular attention to the role of windows of opportunity (WoO). As Industry 4.0 becomes the benchmark of many latecomer countries, this paper may provide guidelines to both policymakers and business practitioners. For clarifying how to catch up with the incumbents and leaders, the authors summarize the lessons based on the historical observations to conclude the pathways for latecomers who aim to reduce the gaps to leaders and manage catch-up. This study enriches the literature of catch-up from a holistic view with fresh insights into how and where to catch up.

Design/methodology/approach

The authors analyze the technological catch-up processes emerged in advanced industrial powers, newly industrialized countries (NICs) and emerging economies (EEs). By categorizing the countries into three kinds, they summarize the processes of catch-up along with the industry evolutions. Moreover, they explore how WoO may facilitate the catch-up processes from one stage to the next in above-mentioned categories. Doing so helps to further examine how technological catch-up and WoO interplay and differ among countries. Then, the authors further investigate the latecomers and incumbents and conclude the target choosing, path setting and direction selecting when implementing a catch-up strategy.

Findings

This study shows that technological catch-up emerged first in advanced industrial powers (AIPs), then in NICs and recently in EEs. Technological catch-up processes in AIPs and NICs take longer time than those in EEs. WoO from policy, market and technology usually collaboratively facilitate the technological catch-up processes in AIPs and NICs. However, in EEs, single WoO can lead to a successful catch-up. The authors further summarize the directions and pathways of catch-up: AIPs and NICs are normally considered by some latecomers to catch up with, while EEs are not.

Originality/value

This study is among the first to systematically review the historical developments of industry evolutions by focusing the technological catch-up based on the different categories of countries: AIPs, NICs and EEs. Moreover, the authors are also among the first few integrating the WoO and technological catch-up processes in different kinds of countries. To the best of the authors’ knowledge, they are also one of the pioneers who highlight the directions and pathways of latecomers and target choosing to catch up with. They also explore the possibility of selecting EEs as catch-up targets.
How smaller firms can outperform their peers
Authors: Pett Timothy L. , Errami Youssef , Sié Laurent
Published: December 2018

Purpose

This paper aims to study the performance of small- and medium-sized enterprises (SMEs) within the French hospitality sector and to determine what firm characteristics (particularly entrepreneurship orientation and strategic initiatives) explain differences in performance. The study is based on data from hotels and differentiates between high- and low-performing businesses. The study examines performance differences relating to entrepreneurial orientation and strategic initiatives. The conclusions indicate that there are differences between high- and low-performing groups, and overall, it seems that there is a relationship between high performance and entrepreneurial, well-planned strategic initiatives.

Design/methodology/approach

This study uses a structured telephone interview procedure to solicit respondents from owner/operators of the hotels throughout the region. The process for gathering data resulted in 66 hotels providing complete responses during interview sessions.

Findings

The primary intent of this study was to examine the relationships between entrepreneurial orientation and strategic initiatives with SME performance. The findings suggest that differences exists. Interestingly, we found that better performing group used more people and tended to see business environment much more favorable compared to low-performing group.

Originality/value

Entrepreneurial orientation research suggest that SMEs firms operate distinct from other ones given different patterns used. These differences come from how SMEs leverage the proactiveness, risk-taking and innovativeness dimensions of entrepreneurial orientation in a firm. Waal and his colleagues suggested that activities associated with creating a high-performing organization using strategic initiatives will lead to subsequent high financial performance. The research found here would also support such an assertion. However, care should be taken in interpreting the generalizability of these results given the limited number of hotels participating in this study; more work is still needed.
Diversity and group performance in a real estate project
Authors: Schrand Liesa , Just Tobias
Published: December 2018

Purpose

Successful developers need to manage a large number of cooperation partners and find innovative solutions for specific tasks, as each real estate project is somehow unique. Thus, the question arises as to whether intelligent group formation for real estate development calls for more or rather less diverse project groups.

Design/methodology/approach

This paper aims to test the impact of group diversity on overall group performance with a unique data set. The authors collected the results of 150 project assignments from real estate executive education students at the IREBS Real Estate Academy from 2010 until 2016.

Findings

The authors find that group results were impacted positively for groups with disparity in work experience and ability. Differences in sex and age did not yield any measurable impact, neither positive nor negative.

Originality/value

To the best of the authors’ knowledge, this is the first time that the relationship between work group diversity and group performance was tested for real estate educational projects. The authors believe that the results are highly relevant for all university work, for which teams have to cooperate on complex rather than basic assignments and problems. Moreover, they are the first to develop a framework that combines diversity theories with a clear distinction between three diversity concepts.