bluuebunny/crossref_metadata_2025 huggingface dataset:
More rule than exception: Parallel evidence of ancient migrations in grammars and genomes of Finno-Ugric speakers
Authors: Santos Patrícia , Gonzalez-Fortes Gloria , Trucchi Emiliano , Ceolin Andrea , Cordoni Guido , Guardiano Cristina , Longobardi Giuseppe , Barbujani Guido
Published: November 2020

To reconstruct aspects of human demographic history, linguistics and genetics complement each other, reciprocally suggesting testable hypotheses on population relationships and interactions. Relying on a linguistic comparative method exclusively based on syntactic data, here we focus on the complex relation of genes and languages among Finno-Ugric (FU) speakers, in comparison to their Indo-European (IE) and Altaic (AL) neighbors. Syntactic analysis supports three distinct clusters corresponding to these three Eurasian families; yet, the outliers of the FU group show linguistic convergence with their geographical neighbors. By analyzing genome-wide data in both ancient and contemporary populations, we uncovered remarkably matching patterns, with north-western FU speakers linguistically and genetically closer in parallel degrees to their IE-speaking neighbors, and eastern FU speakers to AL-speakers. Therefore, our study indicates plausible secondary convergence in the syntax of languages of different families, providing evidence that such interference effects were accompanied, and possibly caused, by recognizable processes at the population level. In particular, based on the comparison of modern and ancient genomes, our analysis identified the Pontic-Caspian steppes as the possible origin of the demographic processes that led to the expansion of the FU into Europe.
Ancient evolution of hepadnaviral paleoviruses and their impact on host genomes
Authors: Lytras Spyros , Arriagada Gloria , Gifford Robert J.
Published: November 2020

Hepadnaviruses (family Hepadnaviviridae) are reverse-transcribing animal viruses that infect vertebrates. Vertebrate genomes contain DNA sequences derived from ancient hepadnaviruses, and these ‘endogenous hepatitis B viruses’ (eHBVs) reveal aspects of the long-term coevolutionary relationship between hepadnaviruses and their vertebrate hosts. Here, we use a novel, data-oriented approach to recover and analyse the complete repertoire of eHBV elements in published animal genomes. We show that germline incorporation of hepadnaviruses is exclusive to a single vertebrate group (Sauria) and that the eHBVs contained in saurian genomes represent a far greater diversity of hepadnaviruses than previously recognised. Through in-depth characterisation of eHBV elements we establish the existence of four distinct subgroups within the genus Avihepadnavirus and trace their evolution through the Cenozoic Era. Furthermore, we provide a completely new perspective on hepadnavirus evolution by showing that the metahepadnaviruses (genus Metahepadnavirus) originated >300 million years ago in the Paleozoic Era, and has historically infected a broad range of vertebrates. We also show that eHBVs have been intra-genomically amplified in some saurian lineages, and that eHBVs located at approximately equivalent genomic loci have been acquired in entirely distinct germline integration events. These findings indicate that selective forces have favoured the accumulation of hepadnaviral sequences at specific loci in the saurian germline. Our investigation provides a range of new insights into the long-term evolutionary history of reverse-transcribing DNA viruses and demonstrates that germline incorporation of hepadnaviruses has played an important role in shaping the evolution of saurian genomes.
Growth and transgenerational acclimatization of juvenilePocillopora damicornis
Authors: Gerstle Lev
Published: November 2020

Global carbon emissions and associated increase in ocean temperatures are understood to be the main driving force in the degradation of coral reefs. Elevated temperatures impact various life stages of scleractinian corals, from the free-floating planulae of brooding corals to older, sexually viable individuals. With global warming, questions have arisen over whether organismal adaptation will be enough to keep up with the pace of environmental change. Researchers have pursued investigations of whether or not rapid acclimatization, through transgenerational plasticity, can help protect populations until genetic adaptation occurs. Acclimatization in corals has been widely studied in all life stages of corals, with the important exception of recently settled juveniles. In this study, I built upon past research by exposing adultPocillopora damicorniscolonies to elevated (28.5°C) or ambient (25.5°C) temperatures and examining the settlement ability and growth of their planulaeex situ. Juveniles from preconditioned parents fared better in higher temperatures compared to their naïve counterparts. Lunar timing of planula release between treatments peaked at different times in the lunar cycle. Peak planula release occurred on lunar day 23 for prestressed corals and on lunar day 7 for corals from ambient temperature seawaters. While future projects should follow up on these preliminary trials within situexperiments to assess this phenomenon in the field, this study represents an important step in understanding how corals may be able to acclimatize and eventually adapt to climate change.
Do Support Vector Machines play a role in stratifying patient population based on cancer biomarkers?
Authors: Lanza Ben , Parashar Deepak
Published: November 2020

Biomarkers are known to be the key driver behind targeted cancer therapies by either stratifying the patients into risk categories or identifying patient subgroups most likely to benefit. However, the ability of a biomarker to stratify patients relies heavily on the type of clinical endpoint data being collected. Of particular interest is the scenario when the biomarker involved is a continuous one where the challenge is often to identify cut-offs or thresholds that would stratify the population according to the level of clinical outcome or treatment benefit. On the other hand, there are well-established Machine Learning (ML) methods such as the Support Vector Machines (SVM) that classify data, both linear as well as non-linear, into subgroups in an optimal way. SVMs have proven to be immensely useful in data-centric engineering and recently researchers have also sought its applications in healthcare. Despite their wide applicability, SVMs are not yet in the mainstream of toolkits to be utilised in observational clinical studies or in clinical trials. This research investigates the very role of SVMs in stratifying the patient population based on a continuous biomarker across a variety of datasets. Based on the mathematical framework underlying SVMs, we formulate and fit algorithms in the context of biomarker stratified cancer datasets to evaluate their merits. The analysis reveals their superior performance for certain data-types when compared to other ML methods suggesting that SVMs may have the potential to provide a robust yet simplistic solution to stratify real cancer patients based on continuous biomarkers, and hence accelerate the identification of subgroups for improved clinical outcomes or guide targeted cancer therapies.
Density responses of lesser-studied carnivores to habitat and management strategies in southern Tanzania’s Ruaha-Rungwa landscape
Authors: Hardouin Marie , Searle Charlotte E. , Strampelli Paolo , Smit Josephine , Dickman Amy , Lobora Alex L. , Rowcliffe J. Marcus
Published: November 2020

Compared to emblematic large carnivores, less charismatic or smaller carnivore species often receive little conservation attention, despite facing increasing anthropogenic pressure, and their status being poorly understood across much of their range. We employed systematic camera trapping and spatially explicit capture-recapture modelling to estimate variation in population density of serval, striped hyaena and aardwolf across the mixed-use Ruaha-Rungwa landscape in southern Tanzania. Three sites were selected as representative of different habitat types, management strategies, and levels of anthropogenic pressure: Ruaha National Park’s core tourist area, dominated byAcacia-Commiphorabushlands and thickets; the Park’s miombo woodland; and the neighbouring community-run MBOMIPA Wildlife Management Area, also covered inAcacia-Commiphora.

Our results show that the Park’s miombo woodlands supported a higher serval density than the core tourist area and Wildlife Management Area, with 5.56 [Standard Error = ±2.45], 3.45 [±1.04] and 2.08 [±0.74] individuals per 100 km2, respectively. This variation is likely driven by precipitation, the abundance of apex predators, and the level of anthropogenic pressure.

Striped hyaena were detected only in the Wildlife Management Area and at low density (1.36 [±0.5] individuals per 100 km2), potentially due to the location of the surveyed sites at the edge of the species’ global range, high densities of sympatric competitors and anthropogenic edge effects.

Finally, aardwolf were captured in both the Park’s core tourist area and the Wildlife Management Area, with a higher density in the Wildlife Management Area (13.25 [±2.48] versus 9.19 [±1.66] individuals per 100 km2), possibly as a result of lower intraguild predation and late fire outbreaks in the area surveyed.

By shedding light on three understudied African carnivore species, this study highlights the importance of miombo woodland conservation and community-managed conservation, as well as the value of camera trap data to improve ecological knowledge of lesser-studied carnivores.
Liquid chalk is an antiseptic against SARS-CoV-2 and influenza A respiratory viruses
Authors: McAuley Julie L. , Deerain Joshua M. , Hammersla William , Aktepe Turgut E. , Purcell Damian J.F. , Mackenzie Jason M.
Published: November 2020

The COVID-19 pandemic has impacted and enforced significant restrictions within our societies, including the attendance of the public and professional athletes in gyms. Liquid chalk is a commonly used accessories in gyms and is comprised of magnesium carbonate and alcohol that quickly evaporates on the hands to leave a layer of dry chalk. We investigated whether liquid chalk is an antiseptic against highly pathogenic human viruses including, SARS-CoV-2, influenza virus and noroviruses. Chalk was applied before or after virus inoculum and recovery of infectious virus was determined to mimic the use in the gym. We observed that addition of chalk before or after virus contact lead to a significant reduction on recovery of infectious SARS-CoV-2 and influenza but had little impact on norovirus. These observations suggest that the use and application of liquid chalk can be an effective and suitable antiseptic for major sporting events, such as the Olympic Games.
Intercellular transfer of mitochondria between senescent cells through cytoskeleton-supported intercellular bridges requires mTOR and Cdc42 signalling
Authors: Walters Hannah , Cox Lynne S
Published: November 2020

Cellular senescence is a state of irreversible cell proliferation arrest induced by various stressors including telomere attrition, DNA damage and oncogene induction. While beneficial as an acute response to stress, accumulation of senescent cells with increasing age is through to contribute adversely to development of cancer and a number of other age-related diseases, including neurodegenerative diseases for which there are currently no effective disease-modifying therapies. Non-cell autonomous effects of senescent cells have been suggested to arise through the SASP, a wide variety of pro-inflammatory cytokines, chemokines and exosomes secreted by senescent cells. Here, we report an additional means of cell communication utilised by senescent cells via large numbers of membrane-bound intercellular bridges - or tunnelling nanotubes (TNTs) - containing the cytoskeletal components actin and tubulin, and which form direct physical connections between cells. We observe the presence of mitochondria in these TNTs, and show organelle transfer through the TNTs to adjacent cells. While transport of individual mitochondria along single TNTs appears unidirectional, we show by differentially labelled co-culture experiments that organelle transfer through TNTs can occur both between different cells within senescent cell populations, and also between senescent and proliferating cells. Using small molecule inhibitors, we demonstrate that senescent cell TNTs are dependent on signalling through the mTOR pathway, which we further show is mediated at least in part through downstream actin-cytoskeleton regulatory factor Cdc42. These findings have significant implications for development of senomodifying therapies, as they highlight the need to account for local direct cell-cell contacts as well as the SASP in order to treat cancer and diseases of ageing in which senescence is a key factor.
Production of nonulosonic acids in the extracellular polymeric substances of “CandidatusAccumulibacter phosphatis”
Authors: Tomás-Martínez Sergio , Kleikamp Hugo B.C. , Neu Thomas R. , Pabst Martin , Weissbrodt David G. , van Loosdrecht Mark C.M. , Lin Yuemei
Published: November 2020

Nonulosonic acids (NulOs) are a family of acidic carbohydrates with a nine-carbon backbone, which include different related structures, such as sialic acids. They have mainly been studied for their relevance in animal cells and pathogenic bacteria. Recently, sialic acids have been discovered as important compound in the extracellular matrix of virtually all microbial life and in “CandidatusAccumulibacter phosphatis”, a well-studied polyphosphate-accumulating organism, in particular. Here, bioaggregates highly enriched with these bacteria (approx. 95% based on proteomic data) were used to study the production of NulOs in an enrichment of this microorganism. Fluorescence lectin-binding analysis, enzymatic quantification, and mass spectrometry were used to analyze the different NulOs present, showing a wide distribution and variety of these carbohydrates, such as sialic acids and bacterial NulOs, in the bioaggregates. Phylogenetic analysis confirmed the potential of “Ca. Accumulibacter” to produce different types of NulOs. Proteomic analysis showed the ability of “Ca. Accumulibacter” to reutilize and reincorporate these carbohydrates. This investigation points out the importance of diverse NulOs in non-pathogenic bacteria, which are normally overlooked. Sialic acids and other NulOs should be further investigated for their role in the ecology of “Ca. Accumulibacter” in particular, and biofilms in general.

Key Points

“Ca.Accumulibacter” has the potential to produce a range of nonulosonic acids.

Mass spectrometry and lectin binding can reveal the presence and location of nonulosonic acids.

Role of nonulosonic acid in non-pathogenic bacteria needs to be studied in detail.
The effect of heat on SARS-CoV-2 viability and RNA integrity as determined by plaque assay, virus culture and real-time RT-PCR
Authors: Burton Jane , Love Hannah , Richards Kevin , Burton Christopher , Summers Sian , Pitman James , Easterbrook Linda , Davies Katherine , Spencer Peter , Killip Marian , Cane Patricia , Bruce Christine , Roberts Allen D G
Published: November 2020

The effect of heat on SARS-CoV-2/England/2/2020 viability was assessed by plaque assay and virus culture. Heating to 56°C and 60°C for 15, 30 and 60 minutes led to a reduction in titre of between 2.1 and 4.9 log10pfu/ml but complete inactivation was not observed. At 80°C plaques were observed after 15 and 30 minutes of heating, however after 60 minutes viable virus was only detected following virus culture. Heating to 80°C for 90 minutes and 95°C for 1 and 5 minutes resulted in no viable virus being detected. At 56°C and 60°C significant variability between replicates was observed and the titre often increased with heat-treatment time. Nucleic acids were extracted and tested by RT-PCR. Sensitivity of the RT-PCR was not compromised by heating to 56°C and 60°C. Heating to 80°C for 30 minutes or more and 95°C for 1 or 5 minutes however, resulted in an increase of at least three Ct values. This increase remained constant when different dilutions of virus underwent heat treatment. This indicates that high temperature heat inactivation of clinical samples prior to nucleic acid extraction could significantly affect the ability to detect virus in clinical samples from patients with lower viral loads by RT-PCR.
Robo recruitment of the Wave Regulatory Complex plays an essential and conserved role in midline repulsion
Authors: Chaudhari Karina , Gorla Madhavi , Chang Chao , Kania Artur , Bashaw Greg J.
Published: November 2020

The Roundabout (Robo) guidance receptor family induces axon repulsion in response to its ligand Slit by inducing local cytoskeletal changes; however, the link to the cytoskeleton and the nature of these cytoskeletal changes are unclear. Here we show that the heteropentameric Scar/Wave Regulatory Complex (WRC) which drives Arp2/3-induced branched actin polymerization, is a direct effector of Robo signaling. Biochemical evidence shows that Slit triggers WRC recruitment to the Robo receptor’s WIRS motif. InDrosophilaembryos, mutants of the WRC enhance Robol-dependent midline crossing defects. Additionally, mutating Robo1’s WIRS motif significantly reduces receptor activity in rescue assaysin vivo, and CRISPR-Cas9 mutagenesis shows that the WIRS motif is essential for endogenous Robo1 function. Finally, axon guidance assays in mouse dorsal spinal commissural axons demonstrate that the WIRS motif is also required for Robo1 repulsion in mammals. Together, our data support an essential conserved role for the WRC in commissural axon repulsion.
A fine-tuned interplay of threeA. thalianaUDP glucosyltransferases orchestrates salicylic acid homeostasis
Authors: Bauer Sibylle , Georgii Elisabeth , Lange Birgit , Maksym Rafał P. , Janowski Robert , Geist Birgit , Schäffner Anton R.
Published: November 2020

Salicylic acid (SA) is a central signaling molecule in development and defense, therefore its levels are tightly controlled. One control mechanism is conjugation with sugar moieties by UDP glucosyltransferases (UGTs). In Arabidopsis, UGT76B1, UGT74F1, and UGT74F2 are known to glucosylate SA. We show that these are the main SA UGTs in leaves, since only marginal levels of SA glucosides were found in a triple loss-of-function mutant. Analyzing transcriptomes, metabolite levels, and phenotypes of a full combinatorial set of loss-of-function mutants, we resolved the mutual relationships and the individual roles of these enzymes in SA homeostasis. The strongest gene expression changes were observed for theugt76b1 ugt74f1double mutant, which downregulated developmental genes and most pronouncedly upregulated cell death-related genes. Among the single mutants,ugt76b1specifically exhibited increased production of reactive oxygen species, increased resistance to infection, and early senescence. Likewise, higher-order mutations confirmed the dominant role of UGT76B1 in controlling SA levels and thereby the expression of biotic stress response genes. Both UGT74F1 and UGT74F2 affectedUGT76B1expression. However, while UGT76B1 and UGT74F1 produced SA-2-O-β-glucoside, UGT74F2 did not contribute there substantially. Instead, UGT74F2 acted independently of UGT74F1, decreasing steady-state SA levels by producing salicyloyl glucose ester. Remarkably, this did not restrict defense responses. In contrast, UGT74F1 interacted with UGT76B1 in suppressing defense responses. Nevertheless, a benzothiadiazole-triggered defense scenario induced only UGT76B1, whereas UGT74F1 was linked to controlling abiotic stress responses. All three enzymes form a network that, in concert with other UGTs, regulates expression of developmental and stress-related genes.

One sentence summary

The salicylic acid glucosylating enzymes of Arabidopsis leaves are crucial for salicylic acid homeostasis and combinatorially impact defense responses and developmental processes.
In vivo optical metabolic imaging of long-chain fatty acid uptake in orthotopic models of triple negative breast cancer
Authors: Madonna Megan C. , Duer Joy E. , Lee Joyce V. , Williams Jeremy , Avsaroglu Baris , Zhu Caigang , Deutsch Riley , Wang Roujia , Crouch Brian T. , Hirschey Matthew D , Goga Andrei , Ramanujam Nirmala
Published: November 2020

Targeting a tumor’s metabolic dependencies is a clinically actionable therapeutic approach, but identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical models to aid in the development of new drugs to restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo, a tool relevant to study tumor metabolic reprogramming or for studying the effectiveness of drugs targeting lipid metabolism spanning beyond breast cancer and optical imaging alone. Specifically, we developed a quantitative optical approach to spatially and longitudinally map the kinetics of long-chain fatty acid uptake in in vivo murine models of breast cancer using a fluorescently labeled palmitate molecule, Bodipy FL c16. We chose intra-vital microscopy of mammary tumor windows to validate our approach in two orthotopic breast cancer models: a MYC-overexpressing transgenic triple-negative breast cancer (TNBC) model and a murine model of the 4T1 family. Following injection, Bodipy FL c16 fluorescence increased and reached its maximum after approximately 30 minutes, with the signal remaining stable during the 30-80-minute post-injection period. We used the fluorescence at 60 minutes (Bodipy60), the mid-point in the plateau region, as a summary parameter to quantify Bodipy FL c16 fluorescence in subsequent experiments. Using our imaging platform, we observed a two- to four-fold decrease in fatty acid uptake in response to the downregulation of the MYC oncogene consistent with findings from in vitro metabolic assays. In contrast, our imaging studies report an increase in fatty acid uptake with tumor aggressiveness (6NR, 4T07, and 4T1), and uptake was significantly decreased after treatment with a fatty acid transport inhibitor, perphenazine, in both normal mammary pads and in the most aggressive 4T1 tumor model. Our approach fills an important gap between in vitro assays, which provide rich metabolic information but at static time points, and imaging approaches that can visualize metabolism in whole organs, but which suffer from poor resolution.
Apicobasal surfaceome architecture encodes for polarized epithelial functionality and depends on tumor suppressor PTEN
Authors: Koetemann Anika , Wollscheid Bernd
Published: November 2020

The loss of apicobasal polarity during the epithelial-to-mesenchymal transition (EMT) is a hallmark of cancer and metastasis. The key feature of this polarity in epithelial cells is the subdivision of the plasma membrane into apical and basolateral domains, with each orchestrating specific intra- and extracellular functions. Epithelial transport and signaling capacities are thought to be determined largely by the quality, quantity and nanoscale organization of proteins residing in these membrane domains, the apicobasal surfaceomes. Despite its implications for cancer, drug uptake and infection, our current knowledge of how the polarized surfaceome is organized and maintained is limited. Here we used chemoproteomic surfaceome scanning to establish proteotype maps of apicobasal surfaceomes and reveal quantitative distributions of i.a. surface proteases, phosphatases and tetraspanins as potential key regulators of polarized cell functionality. We show further that tumor-suppressor PTEN regulates polarized surfaceome architecture and uncover a potential role in collective cell migration. Our differential surfaceome analysis provides a molecular framework to elucidate polarized protein networks regulating epithelial functions and PTEN-associated cancer progression.

One cell, two functionally different surfaceomes: Chemoproteomic surfaceome scanning reveals quantitative polarization of protein networks across the epithelial cell membrane and unrecognized roles of tumor suppressor PTEN in surfaceome organization associated with cancer progression.
Transient K+current explains cross-species differences in the effects of myofibroblasts on myocytes
Authors: Liu Fusheng , Wu Hou , Yang Xiaoyu , Dong Yuqin , Huang Guoyou , Genin Guy M. , Lu Tian Jian , Xu Feng
Published: November 2020

Electrical and paracrine couplings between cardiomyocytes (CMs) and myofibroblasts (MFBs) affect both physiology and pathophysiology of cardiac tissues in a range of animal models, but relating these observations to humans is a challenge because effects vary greatly across species. To address this challenge, we developed a mathematical model for mechanoelectrical interactions between CM and MFB, considering both electrical and paracrine couplings between CMs and MFBs, with the aim of identifying the sources of cross-species variation and extrapolating animal models to predicted effects in humans. Our results revealed substantial differences across species in how these couplings modulate excitation-contraction coupling and Ca2+transients of CMs. Both classes of couplings prolong action potential and increase APD in rat CMs, but shorten action potential and decrease APD in human CMs. Electrical coupling attenuates Ca2+transients and active tension generation in human CMs, but has no significant effect on rat CMs. Paracrine coupling reduces Ca2+transients and active tension in both human and rat CM. The results suggest that the variance of functional interactions between CM and MFB in cross-species may be explained by differences in the transient outward K+currents associated with the KCND2 gene, and thus suggest potential therapeutic pathways for fibrotic cardiomyopathy.
Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes
Authors: Zhu Xinyu , Boulet Aren , Buckley Katherine M. , Phillips Casey B. , Gammon Micah G. , Oldfather Laura E. , Moore Stanley A. , Leary Scot C. , Cobine Paul A.
Published: November 2020

Mitochondrial carrier family (MCF/SLC25) proteins are selective transporters that maintain the mitochondrial metabolome. Here we combine computational, biochemical and phenotypic approaches to understand substrate selectivity of SLC25A3. In mammals, SLC25A3 transports both copper and phosphate, yet inSaccharomyces cerevisiaethe transport of these substrates is partitioned across two paralogs: PIC2, which transports copper, and MIR1, which transports phosphate. To understand whether the ancestral state of this transporter was a single promiscuous transporter that duplicated and gained selectivity, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses reveal that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating that the gene duplication that created these paralogs occurred early in eukaryotic evolution. Frequent lineage-specific gene duplications and losses suggest that substrate specificity may be evolutionarily labile. To link this phylogenetic signal to protein function and resolve the residues involved in substrate selection, we used structural modelling and site-directed mutagenesis to identify PIC2 residues involved in copper and phosphate transport activities. Based on these analyses, we generated a Leu175Ala variant of mouse SLC25A3 that retains the ability to transport copper, but not phosphate, and rescues the cytochromecoxidase defect inSLC25A3knockout cells. Taken together, this work uses an evolutionary framework to uncover amino acids involved in substrate recognition by MCF proteins responsible for copper and phosphate transport.
The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson’s disease
Authors: Castro Sandra L. , Rocha Emily M. , Bodle Christopher R. , Johnson Katrina E. , Greenamyre J. Timothy , De Miranda Briana R.
Published: November 2020

Gene-environment interaction is implicated in the majority of idiopathic Parkinson’s disease (PD) risk, and some of the most widespread environmental contaminants are selectively toxic to dopaminergic neurons. Pesticides have long been connected to PD incidence, however, it has become increasingly apparent that other industrial byproducts likely influence neurodegeneration. For example, organic solvents, which are used in chemical, machining, and dry-cleaning industries, are of growing concern, as decades of solvent use and their effluence into the environment has contaminated much of the world’s groundwater and soil. Like some pesticides, certain organic solvents, such as the chlorinated halocarbon trichloroethylene (TCE), are mitochondrial toxicants, which are collectively implicated in the pathogenesis of dopaminergic neurodegeneration. Recently, we hypothesized a possible gene-environment interaction may occur between environmental mitochondrial toxicants and the protein kinase LRRK2, mutations of which are the most common genetic cause of familial and sporadic PD. In addition, emerging data suggests that elevated wildtype LRRK2 kinase activity also contributes to the pathogenesis of idiopathic PD. To this end, we investigated whether chronic, systemic TCE exposure (200 mg/kg) in aged rats produced wildtype LRRK2 activation and influenced predegenerative dopaminergic dysfunction. Interestingly, we found that TCE not only induced LRRK2 kinase activity in the brain, but produced a significant dopaminergic lesion in the nigrostriatal tract, elevated oxidative stress, and caused endolysosomal dysfunction and protein accumulation (α-synuclein). Together, these data suggest that TCE-induced LRRK2 kinase activity contributed to the selective toxicity of dopaminergic neurons. We conclude that gene-environment interactions between certain industrial contaminants and LRRK2 likely influence PD risk.
The G protein-Coupled Metabotropic Glutamate Receptor 1 controls neuronal macroautophagy
Authors: Donoso Maribel , Speranza Luisa , Kalinowska Magdalena , Castillo Catherine , De Sanctis Claudia , Francesconi Anna
Published: November 2020

Autophagy is an evolutionarily conserved, highly regulated catabolic process critical to neuronal homeostasis, function and survival throughout organismal lifespan. However, the external factors and signals that control autophagy in neurons are still poorly understood. Here we report that the G protein-coupled metabotropic glutamate receptor 1 (mGlu1) contributes to control basal autophagy in the brain. Autophagy is upregulated in the brain of adult mGlu1 knockout mice and genetic deletion or pharmacological inhibition of native mGlu1 receptors enhances autophagy flux in neurons. The evolutionarily conserved adaptor protein FEZ1, identified by a genome-wide screen as mGlu1 receptor interacting partner, was found to participate in the regulation of neuronal autophagy and to be required for repression of autophagy flux by the mGlu1 receptor. Furthermore, FEZ1 appears to enable association of mGlu1 with Ulk1, a core component of the autophagy pathway. Thus, we propose that the mGlu1 receptor contributes to restrain constitutive autophagy in neurons.
Selection on old variants drives adaptive radiation ofMetrosiderosacross the Hawaiian Islands
Authors: Choi Jae Young , Dai Xiaoguang , Peng Julie Z. , Rughani Priyesh , Hickey Scott , Harrington Eoghan , Juul Sissel , Ayroles Julien , Purugganan Michael , Stacy Elizabeth A.
Published: November 2020

Some of the most spectacular adaptive radiations begin with founder populations on remote islands. How genetically limited founder populations give rise to the striking phenotypic and ecological diversity characteristic of adaptive radiations is a paradox of evolutionary biology. We conducted an evolutionary genomic analysis of genusMetrosideros, a landscape-dominant, incipient adaptive radiation of woody plants that spans a striking range of phenotypes and environments across the Hawaiian Islands. Using nanopore-sequencing, we created a chromosome-level genome assembly forM. polymorphavar.incanaand analyzed wholegenome sequences of 131 individuals from 11 taxa sampled across the islands. We found evidence of population structure that grouped taxa by island. Demographic modeling showed concordance between the divergence times of island-specific lineages and the geological formation of individual islands. Gene flow was also detected within and between island taxa, suggesting a complex reticulated evolutionary history. We investigated genomic regions with increased differentiation as these regions may harbor variants involved in local adaptation or reproductive isolation, thus forming the genomic basis of adaptive radiation. We discovered differentiation outliers have arisen from balancing selection on ancient divergent haplotypes that formed before the initial colonization of the archipelago. These regions experienced recurrent divergent selection as lineages colonized and diversified on new islands, and hybridization likely facilitated the transfer of these ancient variants between taxa. Balancing selection on multiple ancient haplotypes–or time-tested variants–may help to explain how lineages with limited gene pools can rapidly diversify to fill myriad ecological niches on remote islands.

Significance statement

Some of the most spectacular adaptive radiations of plants and animals occur on remote oceanic islands, yet such radiations are preceded by founding events that severely limit genetic variation. How genetically depauperate founder populations give rise to the spectacular phenotypic and ecological diversity characteristic of island adaptive radiations is not known. We generated novel genomic resources for HawaiianMetrosideros––a hyper-variable incipient adaptive radiation of woody taxa—for insights into the paradox of remote island radiations. We found thatMetrosideroscolonized each island shortly after formation and diversified within islands through recurrent selection on ancient variations that predate the radiation. Recurring use of ancient variants may explain how genetically depauperate lineages can diversify to fill countless niches on remote islands.
Ownership structure and R&D investment: the role of identity and contestability in Spanish listed firms
Authors: García-García Laura , Gonzalo Alonso-Buenaposada Macarena , Romero-Merino M. Elena , Santamaria-Mariscal Marcos
Published: November 2020

Purpose

The purpose of this paper is to analyze the relationship between the ownership structure and the investment in research and development (R&D) for a sample of listed Spanish companies.

Design/methodology/approach

Following the agency theory and the socioemotional wealth (SEW) perspective, the authors propose that R&D investment is affected by ownership structure, specifically by the identity of the controlling owner (family firms and firms with an institutional investor) and the level of contestability by other shareholders. In order to test these hypotheses, the authors build an original database identifying, at a 10% threshold, the ultimate shareholders of a sample of 96 Spanish firms listed during 2008–2018 (1,002 obs).

Findings

The results show that there is no significant relationship between the ownership concentration and the R&D investment. Only when the authors consider the nature of the main shareholder, the authors find that in family firms there is an invertedUrelationship between ownership and R&D, so that at low levels of ownership, the R&D increases, while at high levels of ownership (that we compute around 54%) the R&D decreases. Also, when the main shareholder is an institutional investor, the greater its ownership, the higher the R&D investment. Finally, the authors test that, contrary to what mainstream suggests, contestability in family firms is higher when ownership in the hands of other family shareholders increases.

Originality/value

The work uses an original database to test a nonlinear relationship between ownership and R&D investment in family firms. Also, the study addresses a topic hardly ever discussed in the literature about R&D as it is the role of the contestability by other controlling shareholders.
How to deal with policy uncertainty to attain sustainable growth: the role of corporate governance
Authors: Ahsan Tanveer , Mirza Sultan Sikandar , Al-Gamrh Bakr , Bin-Feng Chai , Rao Zia-Ur-Rehman
Published: November 2020

Purpose

The purpose of this study is to investigate the moderating impact of corporate governance (CG) on the relationship between economic policy uncertainty (EPU) and the sustainable growth (SG) of Chinese firms.

Design/methodology/approach

The study collects data of 975 Chinese non-financial listed firms for the period from 2010 to 2017. The study measures SG using a comprehensive index based on nine financial indicators and applies industry and year fixed effects regression to investigate the direct and moderating impact of CG on the relationship between EPU and SG of Chinese firms.

Findings

The results of the study explain that EPU negatively affects SG, while concentrated ownership, board independence and board gender diversity (BGD) positively contribute to the SG of the Chinese firms. The results also explain that concentrated ownership and BGD reduce the negative impact of EPU on the SG of the Chinese firms.

Research limitations/implications

The study considers only non-financial firms; therefore, the results of this study cannot be generalized for financial firms. Future research can be carried out while considering financial firms as a unit of analysis.

Practical implications

The investigation of the negative impact of policy uncertainty on SG is essential for the government and policymakers to devise policies to reduce uncertainty. The investigation of the moderating effect of CG enriches the literature on corporates’ response to policy uncertainty. It provides valuable insights for corporates regarding CG mechanisms to attain SG.

Originality/value

To the best of the authors’ knowledge, this is the first study that investigates the moderating impact of CG on the SG of Chinese firms using an index-based measurement of SG.
How do students perceive their own and their peers' progress in e-learning?
Authors: Somyürek Sibel , Brusilovsky Peter , Çebi Ayça , Akhüseyinoğlu Kamil , Güyer Tolga
Published: November 2020

Purpose

Interest is currently growing in open social learner modeling (OSLM), which means making peer models and a learner's own model visible to encourage users in e-learning. The purpose of this study is to examine students' views about the OSLM in an e-learning system.

Design/methodology/approach

This case study was conducted with 40 undergraduate students enrolled in advanced programming and database management system courses. A Likert-type questionnaire and open-ended questions were used to obtain the students' views. System usage data were also analyzed to ensure the richness and diversity of the overall data set.

Findings

The quantitative data of the students' views were analyzed with descriptive statistics; the results are presented as graphics. The qualitative data of the students' views were examined by content analysis to derive themes. These themes are organized into four subtopics: the students' positive views, their negative views, their improvement suggestions and their preferences about using similar OSLM visualizations in other e-learning systems. The students' subjective views are discussed in the context of their recorded interactions with the system.

Research limitations/implications

Competition due to seeing peer models was considered by participants both as positive and negative features of the learning system. So, this study revealed that, the ways to combine peer learner models to e-learning systems that promote positive competition without resulting social pressure, still need to be explored.

Practical implications

By combining open learner models with open peer models, OSLM enhances the learning process in three different ways: it supports self-regulation, encourages competition and empowers self-evaluation. To take advantage of these positive contributions, practitioners should consider enhancing e-learning systems with both own learner and peer model features.

Originality/value

Despite increasing interest in OSLM studies, several limitations and problems must be addressed such as sparsity of data and lack of study of different contexts and cultures. To date, no published study in this area exists in Turkey. The purpose of this study is to fill this gap by examining OSLM features in an e-learning system from the perspectives of Turkish students by using both their system interaction data and their subjective views.
Do firm-specific risks affect bank performance?
Authors: Hunjra Ahmed Imran , Mehmood Asad , Nguyen Hung Phu , Tayachi Tahar
Published: November 2020

Purpose

The authors examine the impact of credit, liquidity and operational risks on the financial performance of commercial banks of South Asia.

Design/methodology/approach

Data are extracted from DataStream of 76 commercial banks of four countries, i.e. Pakistan, India, Bangladesh and Sri Lanka for the period 2009–2018. The generalized method of moments (GMM) is used to analyze the results.

Findings

All three risks are significantly associated with financial performance. The authors find thatZ-score positively affects the bank performance, whereas the nonperforming loans (NPLs) ratio has a negative impact on financial performance of bank. Liquidity risk analyses show the current and loan-to-deposit (LTD) ratios positively and negatively, respectively, affect financial performance. While operational risk positively affects financial performance. The authors further present the significant effects of joint occurrence of credit and liquidity risks on financial performance.

Practical implications

For managing credit risk, banking management should ensure the policies for granting loans and timely reimbursement of the loan installments from customers. Bank managers should regularly monitor the liquidity position by maintaining the necessary levels of loans and deposits. Management should retain a healthy capital charge to meet operational risks.

Originality/value

Credit, liquidity and operational risks are considered the most important categories of risk which are faced by financial institutions. To the best of the authors’ knowledge, this is the first study which investigates the impact of these risks on banks’ financial performance in selected South Asian countries. The results of this study have relevance and probable generalizability about the impact of risks on the performance of banks in emerging markets.
The effect of employment on the subjective well-being of 60–80 years old people
Authors: Axelrad Hila , Sherman Arie , Luski Israel
Published: November 2020

Purpose

The current study investigates the association of employment at older age (60–80 years ) with the cognitive component of subjective well-being (SWB): life satisfaction.

Design/methodology/approach

Out of the Survey of Health, Ageing and Retirement in Europe (SHARE), the present study’s sample included 58,197 observations of participants aged 60–80 years from 18 countries. The authors estimate the direct effects of employment and number of working hours on life satisfaction while considering the characteristics of the job and their impact.

Findings

Results reveal that individuals who do not work enjoy a higher level of life satisfaction and so do those who work in developing jobs. Work under pressure reduces the level of SWB and working in physically demanding jobs has no significant impact on SWB. The results confirm previous findings regarding the positive contribution of self-employment to individuals’ SWB.

Originality/value

The results allow policy makers to implement policy measures that can improve older workers' SWB.
Brand community motives and their impact on brand community engagement: variations between diverse audiences
Authors: Haverila Matti , McLaughlin Caitlin , Haverila Kai Christian , Viskovics Julio
Published: November 2020

Purpose

The purpose of this research is to compare two different sample populations (student and general) to determine the impact of brand community motives on brand community engagement.

Design/methodology/approach

Two samples were drawn for the purpose of the current research. The first sample was drawn among the members of various brand communities from a general North American population sample (N = 503). The second sample was drawn purely from students, belonging to a variety of brand communities, from a middle-sized Canadian university (N = 195). Partial least squares structural equation modelling was used to analyse the strength, significance and effect sizes of the relationships between brand community motive and engagement constructs.

Findings

The findings indicate that the impact of brand community motives varied by sample population. The information and entertainment motives were significantly related to brand community engagement in both sample populations with roughly equal effect sizes. The social integration motive was again significantly related to the brand community engagement construct in the student sample population – but not for the general North American general population sample. Further, the self-discovery motive and status enhancement motives were significantly related to brand community engagement in the North American sample, but not for the student sample. This indicates significant differences between the two sample populations.

Originality/value

The results of the current research demonstrate that student populations are significantly different from the general population regarding their motives towards brand communities. This indicates that brand community managers need to be aware of the motives of different brand community members and also that they need to exercise caution about utilizing purely student data to make decisions about brand community management.