bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted control of pneumolysin production by a mobile genetic element inStreptococcus pneumoniae
Authors: Stevens Emily J. , Morse Daniel J. , Bonini Dora , Duggan Seána , Brignoli Tarcisio , Recker Mario , Lees John A. , Croucher Nicholas J. , Bentley Stephen , Wilson Daniel J. , Earle Sarah G. , Dixon Robert , Nobbs Angela , Jenkinson Howard , van Opijnen Tim , Thibault Derek , Wilkinson Oliver J. , Dillingham Mark S. , Carlile Simon , McLoughlin Rachel M. , Massey Ruth C.
Published: June 2020

Streptococcus pneumoniaeis a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated half a million deaths worldwide in those under five attributable to invasive pneumococcal disease each year. The cytolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion, and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance conferring Integrative and Conjugative Element (ICE) ICESp23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for theplyoperon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonisation, we further demonstrate that a ZomB mutant strain colonises both the upper respiratory tract and lungs at higher levels when compared to the wild type strain. While the antibiotic resistance conferring aspects of ICESp23FST81 is often credited with contributing to the success of theS. pneumoniaelineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role.
Towards a new treatment against polymicrobial infections: high antibacterial activity of lemon IntegroPectin againstPseudomonas aeruginosaandEscherichia coli
Authors: Presentato Alessandro , Scurria Antonino , Albanese Lorenzo , Picone Pasquale , Pagliaro Mario , Zabini Federica , Meneguzzo Francesco , Alduina Rosa , Nuzzo Domenico , Ciriminna Rosaria
Published: June 2020

Lemon IntegroPectin obtained via hydrodynamic cavitation of waste lemon peel in water only shows high antibacterial activity against two Gram-negative bacteria,Pseudomonas aeruginosaandEscherichia coli. The antibacterial effect against the ubiquitous pathogenP. aeruginosawas evaluated in terms of the minimal bactericidal (MBC) and minimal inhibitory concentration (MIC). Preliminary insight on the antibacterial mechanism of IntegroPectin originates from investigating its inhibitory activity againstE. coli. Given the non-cytotoxic nature of citrus IntegroPectin and the ease of its reproducible production in large amounts, the route is open to the industrial development of a new antimicrobial treatment against polymicrobial infections unlikely to develop drug resistance.
Comparing library preparation methods for SARS-CoV-2 multiplex amplicon sequencing on the Illumina MiSeq platform
Authors: Batty Elizabeth M. , Kochakarn Theerarat , Wangwiwatsin Arporn , Joonlasak Khajohn , Huang Angkana T. , Panthan Bhakbhoom , Jiaranai Poramate , Kümpornsin Krittikorn , Kotanan Namfon , Manasatienkij Wudtichai , Watthanachockchai Treewat , Rakmanee Kingkan , Jones Anthony R. , Fernandez Stefan , Sensorn Insee , Sungkanuparph Somnuek , Pasomsub Ekawat , Klungthong Chonticha , Chookajorn Thanat , Chantratita Wasun
Published: June 2020

Genomic surveillance has a key role in tracking the ongoing COVID-19 pandemic, but information on how different sequencing library preparation approaches affect the data produced are lacking. We compared three library preparation methods using both tagmentation (Nextera XT and Nextera Flex) and ligation-based (KAPA HyperPrep) approaches on both positive and negative samples to provide insights into any methodological differences between the methods, and validate their use in SARS-CoV-2 amplicon sequencing. We show that all three library preparation methods allow us to recover near-complete SARS-CoV-2 genomes with identical SNP calls. The Nextera Flex and KAPA library preparation methods gave better coverage than libraries prepared with Nextera XT, which required more reads to call the same number of genomic positions. The KAPA ligation-based approach shows the lowest levels of human contamination, but contaminating reads had no effect on the downstream analysis. We found some examples of library preparation-specific differences in minority variant calling. Overall our data shows that the choice of Illumina library preparation method has minimal effects on consensus base calling and downstream phylogenetic analysis, and suggests that all methods would be suitable for use if specific reagents are difficult to obtain.
Stage-specific muscle wasting mechanisms in a novel cancer cachexia mouse model for ovarian granulosa cell tumor
Authors: Zhang Yaqi , Zhu Jie , Kim So-Youn , Romero Megan M , Even Kelly A , Kurita Takeshi , Woodruff Teresa K
Published: June 2020

Cachexia is a progressive muscle wasting syndrome that increases mortality risk in cancer patients, while there are still no effective treatment due to the complexity of syndrome and the lack of preclinical models. We identified a transgenic mice model with ovarian granulosa cell tumors mimic the progression of cachexia seen in humans, including drastic weight loss, skeletal muscle wasting and increased serum cachexia biomarker activin A and GDF15. Hypercatabolism was detected in skeletal muscle, having upregulation of E3 ligasesAtrogin-1andMurf-1. Our cachexia model exhibited stage-specific muscle wasting mechanisms. At precachexia stage, elevation of activin A activates p38 MAPK. Inhibition of activin A with Follistatin reversed weight loss at precachexia stage. At cachexia stage, energy stress in skeletal muscle activates AMPKα and leads to upregulation ofFoxO3. Our results indicate this novel preclinical cancer cachexia model is exploitable for studying pathophysiological mechanisms and testing therapeutic agents of cachexia.
Peripheral Natural Killer cells from chronic hepatitis B patients display molecular hallmarks of T cell exhaustion
Authors: Marotel M. , Villard M. , Tout I. , Besson L. , Allatif O. , Pujol M. , Rocca Y. , Ainouze M. , Roblot G. , Viel S. , Gomez M. , Loustaud V. , Alain S. , Durantel D. , Walzer T. , Hasan U. , Marçais A.
Published: June 2020

A significant proportion of individuals infected by HBV develops chronic infection. Antiviral effectors such as Natural Killer (NK) cells have impaired functions in these patients, but the molecular mechanism responsible for this dysfunction remains poorly characterized. Here, we show that peripheral NK cells from chronic hepatitis B (CHB) patients have a defective capacity to produce IFN-γ, MIP1-β and TNF-α but retain an intact killing capacity. This functional phenotype was associated with a decrease in the expression of NKp30 and CD16, combined with defects in IL-15 stimulation of the mTOR pathway. Transcriptome analysis of NK cells in CHB patients further revealed a strong enrichment for transcripts typically expressed in exhausted T cells suggesting that NK cell dysfunction and T cell exhaustion rely on common molecular mechanisms. In particular, the transcription factor thymocyte selection-associated HMG box protein (TOX) and several of its targets, including immune checkpoints, were over-expressed in NK cells of CHB patients. This T cell exhaustion signature was predicted to be dependent on the calcium (Ca2+)-associated transcription factor NFAT. In line with this, when stimulating the Ca2+-dependent pathway in isolation, we recapitulated the dysfunctional phenotype. Thus, deregulated Ca2+signalling could be a central event in both T cell exhaustion and NK cell dysfunction that occur during chronic infections.
Fast EEG-based decoding of the directional focus of auditory attention using common spatial patterns
Authors: Geirnaert Simon , Francart Tom , Bertrand Alexander
Published: June 2020

Objective

Noise reduction algorithms in current hearing devices lack information about the sound source a user attends to when multiple sources are present. To resolve this issue, they can be complemented with auditory attention decoding (AAD) algorithms, which decode the attention using electroencephalography (EEG) sensors. State-of-the-art AAD algorithms employ a stimulus reconstruction approach, in which the envelope of the attended source is reconstructed from the EEG and correlated with the envelopes of the individual sources. This approach, however, performs poorly on short signal segments, while longer segments yield impractically long detection delays when the user switches attention.

Methods

We propose decoding the directional focus of attention using filterbank common spatial pattern filters (FB-CSP) as an alternative AAD paradigm, which does not require access to the clean source envelopes.

Results

The proposed FB-CSP approach outperforms both the stimulus reconstruction approach on short signal segments, as well as a convolutional neural network approach on the same task. We achieve a high accuracy (80% for 1 s windows and 70% for quasi-instantaneous decisions), which is sufficient to reach minimal expected switch durations below 4 s. We also demonstrate that the decoder can adapt to unlabeled data from an unseen subject and works with only a subset of EEG channels located around the ear to emulate a wearable EEG setup.

Conclusion

The proposed FB-CSP method provides fast and accurate decoding of the directional focus of auditory attention.

Significance

The high accuracy on very short data segments is a major step forward towards practical neuro-steered hearing devices.
Estrogen withdrawal alters oxytocin signaling in the paraventricular hypothalamus and dorsal raphe nucleus to increase postpartum anxiety
Authors: Hedges Valerie L. , Heaton Elizabeth C. , Amaral Claudia , Benedetto Lauren E. , Bodie Clio L. , D’Antonio Breanna I. , Davila Portillo Dayana R. , Lee Rachel H. , Levine M. Taylor , O’Sullivan Emily C. , Pisch Natalie P. , Taveras Shantal , Wild Hannah R. , Ross Amy P. , Albers H. Elliott , Been Laura E.
Published: June 2020

Background

Estrogen increases dramatically during pregnancy, but quickly drops below pre-pregnancy levels at birth and remains suppressed during the postpartum period. Clinical and rodent work suggests that this postpartum drop in estrogen results in an “estrogen withdrawal” state that is related to changes in affect, mood, and behavior. Most studies examining the effect of estrogen withdrawal on the brain have focused solely on the hippocampus.

Methods

We used a hormone-simulated pseudopregnancy model in Syrian hamsters, a first for this species. Ovariectomized females were given daily injections to approximate hormone levels during gestation and then withdrawn from estrogen to simulate postpartum estrogen withdrawal. Subjects were tested for behavioral assays of anxiety and anhedonia during estrogen withdrawal. Following sacrifice, neuroplasticity in oxytocin-producing neurons in the paraventricular nucleus of the hypothalamus (PVH) and its efferent targets was measured.

Results

Estrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus and open field, but did not differ from controls in sucrose preference. Furthermore, estrogen-withdrawn females had more oxytocin-immunoreactive cells and oxytocin mRNA in the PVH, as well as an increase in oxytocin receptor density in the dorsal raphe nucleus (DRN). Finally, blocking oxytocin receptors in the DRN during estrogen withdrawal prevented the high-anxiety behavioral phenotype in estrogen-withdrawn females.

Conclusions

Estrogen withdrawal alters oxytocin signaling in the PVH and DRN to increase anxiety-like behavior during the postpartum period. More broadly, these experiments suggest Syrian hamsters as a novel organism in which to model the effects of postpartum estrogen withdrawal on the brain and anxiety-like behavior.
Metagenome-assembled genomes of phytoplankton communities across the Arctic Circle
Authors: Duncan A. , Barry K. , Daum C. , Eloe-Fadrosh E. , Roux S. , Tringe S. G. , Schmidt K. , Valentin K. U. , Varghese N. , Grigoriev I. V. , Leggett R. , Moulton V. , Mock T.
Published: June 2020

Phytoplankton communities significantly contribute to global biogeochemical cycles of elements and underpin marine food webs. Although their uncultured genetic diversity has been estimated by planetary-scale metagenome sequencing and subsequent reconstruction of metagenome-assembled genomes (MAGs), this approach has yet to be applied for eukaryote-enriched polar and non-polar phytoplankton communities. Here, we have assembled draft prokaryotic and eukaryotic MAGs from environmental DNA extracted from chlorophyll a maximum layers in the surface ocean across the Arctic Circle in the Atlantic. From 679 Gbp and estimated 50 million genes in total, we recovered 140 MAGs of medium to high quality. Although there was a strict demarcation between polar and non-polar MAGs, adjacent sampling stations in each environment on either side of the Arctic Circle had MAGs in common. Furthermore, phylogenetic placement revealed eukaryotic MAGs to be more diverse in the Arctic whereas prokaryotic MAGs were more diverse in the Atlantic south of the Arctic Circle. Approximately 60% of protein families were shared between polar and non-polar MAGs for both prokaryotes and eukaryotes. However, eukaryotic MAGs had more protein families unique to the Arctic whereas prokaryotic MAGs had more families unique to south of the Arctic circle. Thus, our study enabled us to place differences in functional plankton diversity in a genomic context to reveal that the evolution of these MAGs likely was driven by significant differences in the seascape on either side of an ecosystem boundary that separates polar from non-polar surface ocean waters in the North Atlantic.
Comparative genomics ofVerticillium dahliaeisolates reveals thein planta-secreted effector protein recognized inV2tomato plants
Authors: Chavarro-Carrero Edgar A. , Vermeulen Jasper P. , Torres David E. , Usami Toshiyuki , Schouten Henk J. , Bai Yuling , Seidl Michael F. , Thomma Bart P.H.J.
Published: June 2020

Plant pathogens secrete effector molecules during host invasion to promote host colonization. However, some of these effectors become recognized by host receptors, encoded by resistance genes, to mount defense response and establish immunity. Recently, a novel resistance was identified in tomato, mediated by the single dominantV2locus, to control strains of the soil-borne vascular wilt fungusVerticillium dahliaethat belong to race 2. We performed comparative genomics between race 2 strains and resistance-breaking race 3 strains to identify the avirulence effector that activatesV2resistance, termed Av2. We identified 277 kb of race 2-specific sequence comprising only two genes that encode predicted secreted proteins, both of which are expressed byV. dahliaeduring tomato colonization. Subsequent functional analysis based on genetic complementation into race 3 isolates confirmed that one of the two candidates encodes the avirulence effector Av2 that is recognized inV2tomato plants. The identification of Av2 will not only be helpful to select tomato cultivars that are resistant to race 2 strains ofV. dahliae, as the correspondingV2resistance gene has not yet been mapped, but also to monitor adaptations in theV. dahliaepopulation to deployment ofV2-containing tomato cultivars in agriculture.
Differential effects of human TAU isoforms: Somatic retention of 2N-TAU and increased microtubule number induced by 4R-TAU
Authors: Bachmann S. , Bell M. , Klimek J. , Zempel H.
Published: June 2020

In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3 and 10 of theMAPTgene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick’s Disease and Progressive Supranuclear Palsy, are characterized by the accumulation of specific TAU isoforms. The influence of the individual TAU isoforms in a cellular context, however, is understudied. In this report, we investigated the subcellular localization of the human-specific TAU isoforms in primary neurons, and analyzed TAU isoform-specific effects on cell area and microtubule dynamics in SH-SY5Y neuroblastoma cells. Our results show that 2N-TAU isoforms are particularly retained from axonal sorting and that axonal enrichment is independent from the number of repeat domains, but that the additional repeat domain of 4R-TAU isoform results in a general reduction of cell size and an increase of microtubule counts in cells expressing 4R-TAU isoforms. Our study points out that individual TAU isoforms may influence microtubule dynamics differentially both by different sorting patterns as well as by direct effects on microtubule dynamics.
PyXlinkViewer: a flexible tool for visualisation of protein chemical crosslinking data within the PyMOL molecular graphics system
Authors: Schiffrin Bob , Radford Sheena. E. , Brockwell David. J. , Calabrese Antonio N.
Published: June 2020

Chemical crosslinking-mass spectrometry (XL-MS) is a valuable technique for gaining insights into protein structure and the organization of macromolecular complexes. XL-MS data yields inter-residue restraints that can be compared with high-resolution structural data. Distances greater than the crosslinker spacer-arm can reveal lowly-populated “excited” states of proteins/protein assemblies, or crosslinks can be used as restraints to generate structural models in the absence of structural data. Despite increasing uptake of XL-MS, there are few tools to enable rapid and facile mapping of XL-MS data onto high-resolution structures or structural models. PyXlinkViewer is a user-friendly plugin for PyMOL v2 that maps intra-protein, inter-protein and dead-end crosslinks onto protein structures/models and automates the calculation of inter-residue distances for the detected crosslinks. This enables rapid visualisation of XL-MS data, assessment of whether a set of detected crosslinks is congruent with structural data, and easy production of high-quality images for publication.
Mast cells participate in the development of diastolic dysfunction in diabetic obese mice
Authors: Guimbal Sarah , Cornuault Lauriane , Hollier Pierre-Louis , Chapouly Candice , Bats Marie-Lise , Gadeau Alain-Pierre , Couffinhal Thierry , Renault Marie-Ange
Published: June 2020

Rational

Heart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic issue. However, to date, its pathophysiology remains poorly understood.

Objective

Our goal was to investigate the role of microvessel disease in the pathophysiology of diastolic dysfunction.

Findings

To do so, we used Leptin receptor deficient (Leprdb/db) female mice as a model of diastolic dysfunction. In these mice, the increased end diastolic pressure (EDP) signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Leprdb/dband control female mice confirmed endothelial dysfunction and systemic inflammation but also revealed a strong increase in several mast cell markers (notably FceR1a, Tryptase and Chymase). We then histologically confirmed an accumulation of activated mast cells in the heart of Leprdb/dbmice. Importantly, mast cell degranulation inhibition reduced EDP, vascular leakage and leucocyte infiltration in Leprdb/dbmice.

Conclusion

Mast cells play a critical role in the development of cardiac microvessel disease and diastolic dysfunction.
Targeting Scavenger Receptor Type B1 In Cholesterol-Addicted Lymphomas Abolishes Glutathione Peroxidase 4 and Results in Ferroptosis
Authors: Rink Jonathan S. , Lin Adam Yuh , McMahon Kaylin M. , Calvert Andrea E. , Yang Shuo , Taxter Tim , Moreira Jonathan , Chadburn Amy , Behdad Amir , Karmali Reem , Thaxton C. Shad , Gordon Leo I.
Published: June 2020

Normal human cells can either synthesize or uptake cholesterol from lipoproteins to meet their metabolic requirements. Some malignant cells absolutely require cholesterol uptake from lipoproteins for survival becausede novocholesterol synthesis genes are transcriptionally silent or mutated. Recent data suggest that lymphoma cells dependent upon lipoprotein-mediated cholesterol uptake are also dependent on the expression of the lipid hydroperoxidase enzyme glutathione peroxidase 4 (GPX4) to prevent cell death by ferroptosis. Ferroptosis is an oxygen-and iron-dependent cell death mechanism that results from the accumulation of oxidized lipids in cell membranes. To study mechanisms linking cholesterol uptake with ferroptosis, we employed lymphoma cell lines known to be sensitive to cholesterol uptake depletion and treated them with high-density lipoprotein-like (HDL) nanoparticles (HDL NPs). HDL NPs are a cholesterol-poor ligand of the receptor for cholesterol-rich HDL, scavenger receptor type B-1 (SCARB1). Our data reveal that HDL NP treatment activates a compensatory metabolic response in treated cells favoringde novocholesterol synthesis, which is accompanied by reduced expression of GPX4. As a result, accumulation of oxidized membrane lipids leads to cell death through a mechanism consistent with ferroptosis. Furthermore, ferroptosis was validatedin vivoafter systemic administration of HDL NPs in mouse lymphoma xenografts and in primary samples obtained from patients with lymphoma. In summary, targeting SCARB1 with HDL NPs in cholesterol uptake addicted lymphoma cells abolishes GPX4 and cancer cell death ensues through a mechanism consistent with ferroptosis.
Thermal niches of specialized gut symbionts: the case of social bees
Authors: Hammer Tobin J. , Le Eli , Moran Nancy A.
Published: June 2020

Responses to climate change are particularly complicated in species that engage in symbioses, as the niche of one partner may be modified by that of the other. We explored thermal traits in gut symbionts of honeybees and bumblebees, which are vulnerable to rising temperatures.In vitroassays of symbiont strains isolated from 16 host species revealed variation in thermal niches. Strains from bumblebees tended to be less heat-tolerant than those from honeybees, possibly due to bumblebees maintaining cooler nests or inhabiting cooler climates. Overall however, bee symbionts grew at temperatures up to 44 °C and withstood temperatures up to 52 °C, at or above the upper thermal limits of their hosts. While heat-tolerant, most strains of the symbiontSnodgrassellagrew relatively slowly below 35 °C, perhaps because of adaptation to the elevated body temperatures that bees maintain through thermoregulation. In a gnotobiotic bumblebee experiment,Snodgrassellawas unable to consistently colonize bees reared below 35 °C under conditions that limit thermoregulation. Thus, host thermoregulatory behavior appears important in creating a warm microenvironment for symbiont establishment. Bee-microbiome-temperature interactions could affect host health and pollination services, and inform research on the thermal biology of other specialized gut symbionts, such as those of humans.
Postsynaptic serine racemase regulates NMDA receptor function
Authors: Wong Jonathan M. , Folorunso Oluwarotimi , Barragan Eden V. , Berciu Cristina , Harvey Theresa L. , DeChellis-Marks Michael R. , Glausier Jill R. , MacDonald Matthew L. , Coyle Joseph T. , Balu Darrick T. , Gray John A.
Published: June 2020

D-serine is the primary NMDA receptor (NMDAR) co-agonist at mature forebrain synapses and is synthesized by the enzyme serine racemase (SR). However, our understanding of the mechanisms regulating the availability of synaptic D-serine remains limited. Though early studies suggested D-serine is synthesized and released from astrocytes, more recent studies have demonstrated a predominantly neuronal localization of SR. More specifically, recent work intriguingly suggests that SR may be found at the postsynaptic density, yet the functional implications of postsynaptic SR on synaptic transmission are not yet known. Here, we show an age-dependent dendritic and postsynaptic localization of SR and D-serine by immunohistochemistry and electron microscopy in mouse CA1 pyramidal neurons, as well as the presence of SR in human hippocampal synaptosomes. In addition, using a single-neuron genetic approach in SR conditional knockout mice, we demonstrate a cell-autonomous role for SR in regulating synaptic NMDAR function at Schaffer collateral (CA3)-CA1 synapses. Importantly, single-neuron genetic deletion of SR resulted in the elimination of LTP at one month of age. Interestingly, there was a restoration of LTP by two months of age that was associated with an upregulation of synaptic GluN2B. Our findings support a cell-autonomous role for postsynaptic neuronal SR in regulating synaptic NMDAR function and suggests a possible autocrine mode of D-serine action.
Differential covariance: A new method to estimate functional connectivity in fMRI
Authors: Lin Tiger W. , Chen Yusi , Bukhari Qasim , Krishnan Giri P. , Bazhenov Maxim , Sejnowski Terrence J.
Published: June 2020

Measuring functional connectivity from fMRI recordings is important in understanding processing in cortical networks. However, because the brain’s connection pattern is complex, currently used methods are prone to producing false functional connections. We introduce differential covariance analysis, a new method that uses derivatives of the signal for estimating functional connectivity. We generated neural activities from Dynamical Causal Modeling and a neural network of Hodgkin-Huxley neurons and then converted them to hemodynamic signals using the forward Balloon model. The simulated fMRI signals together with the ground truth connectivity pattern were used to benchmark our method with other commonly used methods. Differential covariance achieved better results in complex network simulations. This new method opens an alternative way to estimate functional connectivity.
Nucleus accumbens melanin-concentrating hormone signaling promotes feeding in a sex-specific manner
Authors: Terrill Sarah J. , Subramanian Keshav , Lan Rae , Liu Clarissa M. , Cortella Alyssa M. , Noble Emily E. , Kanoski Scott E.
Published: June 2020

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced in the lateral hypothalamus and zona incerta that increases food intake. The neuronal pathways and behavioral mechanisms mediating the orexigenic effects of MCH are poorly understood, as is the extent to which MCH-mediated feeding outcomes are sex-dependent. Here we investigate the hypothesis that MCH-producing neurons act in the nucleus accumbens shell (ACBsh) to promote feeding behavior and motivation for palatable food in a sex-dependent manner. We utilized ACBsh MCH receptor (MCH1R)-directed pharmacology as well as a dual virus chemogenetic approach to selectively activate MCH neurons that project to the ACBsh. Results reveal that both ACBsh MCH1R activation and activating ACBsh-projecting MCH neurons increase consumption of standard chow and palatable sucrose in male rats without affecting motivated operant responding for sucrose, general activity levels, or anxiety-like behavior. In contrast, food intake was not affected in female rats by either ACBsh MCH1R activation or ACBsh-projecting MCH neuron activation. To determine a mechanism for this sexual dimorphism, we investigated whether the orexigenic effect of ACBsh MCH1R activation is reduced by endogenous estradiol signaling. In ovariectomized female rats on a cyclic regimen of either estradiol (EB) or oil vehicle, ACBsh MCH1R activation increased feeding only in oil-treated rats, suggesting that EB attenuates the ability of ACBsh MCH signaling to promote food intake. Collective results show that that MCH ACBsh signaling promotes feeding in an estrogen- and sex-dependent manner, thus identifying novel neurobiological mechanisms through which MCH and female sex hormones interact to influence food intake.
Methotrexate carried in lipid core nanoparticles reduces microglial activation and is neuroprotective after ischemic cortical stroke
Authors: Pereira Edmundo L. R. , Dias Michelle N.C. , dos Santos Ijair R. , Ramos Ana Carolina , Hamoy Moisés , Feio Danielle Cristine A. , Tavoni Thauany M. , da Silva Priscila Carvalho M. , Maranhão Raul , Gomes-Leal Walace
Published: June 2020

Methotrexate carried in lipid core nanoparticles (LDE-MTX) is a low toxicity compound effective in reducing inflammation and secondary damage in experimental models of arthritis, atherosclerosis, myocardial infarction, cardiac allograft vasculopathy and other pathological conditions. Nevertheless, whether it is neuroprotective after stroke is unknown. Here, we explored whether LDE-MTX could cross blood brain barrier (BBB) to exert anti-inflammatory and neuroprotecive effects after experimental cortical stroke in rats. Tissue uptake was assessed by injecting radioactively labeled-LDE through the caudal vein into both sham (n=18) and adult Wistar rats submitted to endothelin-1 (ET-1)-induced cortical stroke (n=11). To address possible neuroprotective effects of LDE-MTX after stroke, 10 adult male Wistar rats were randomly allocated in two groups: animals treated with LDE-MTX (1 mg/kg,i.v., n=5) or LDE-alone (i.v., n=5) at 4 hours after stroke induction. Animals were perfused with 0.9% saline and 4% paraformaldehyde at 7 days post-injury. Histopathology was assessed by cresyl violet staining. Mature neuronal bodies (anti-NeuN), astrocytes (anti-GFAP) and microglia (anti-Iba1) were immunolabeled by immunohistochemistry. Scintigraphy technique revealed accumulation of tritiated LDE in different brain regions and in non-neural organs without overt toxicity in both sham and ischemic rats. LDE-MTX treatment induced a 10-fold (1000%) reduction in microglial activation in the ischemic cortex and afforded a 319% increase in neuronal preservation in the ischemic periinfarct region compared to LDE-alone group. There was no effect of LDE-MTX treatment on primary infarct area and astrocytosis. The results suggest that LDE-MTX formulation must be considered a very promising neuroprotective agent for ischemic stroke. Future studies using different concentrations and longer survival times are needed before assessing the suitability of LDE-MTX as a neuroprotective agent for human stroke.
Four different mechanisms for switching cell polarity
Authors: Tostevin Filipe , Wigbers Manon , Søgaard-Andersen Lotte , Gerland Ulrich
Published: June 2020

The mechanisms and design principles of regulatory systems establishing stable polarized protein patterns within cells are well studied. However, cells can also dynamically control their cell polarity. Here, we ask how an upstream signaling system can switch the orientation of a polarized pattern. We use a mathematical model of a core polarity system based on three proteins as the basis to study different mechanisms of signal-induced polarity switching. The analysis of this model reveals four general classes of switching mechanisms with qualitatively distinct behaviors: the transient oscillator switch, the reset switch, the prime-release switch, and the push switch. Each of these regulatory mechanisms effectively implements the function of a spatial toggle switch, however with different characteristics in their nonlinear and stochastic dynamics. We identify these characteristics and also discuss experimental signatures of each type of switching mechanism.
Formula 1, city and tourism: a research theme analyzed on the basis of a systematic literature review
Authors: Roult Romain , Auger Denis , Lafond Marie-Pierre
Published: June 2020

Purpose

This paper aims to draw up the state of scientific knowledge in the field of Formula 1 with relation to tourism and urban studies.

Design/methodology/approach

This study is based on a systematic review of the scientific literature regarding this issue. Using targeted keywords and the analysis of various documentary databases, 8,075 references were identified and 40 documents were analyzed in an exhaustive manner.

Findings

This study presents a very nuanced portrait of the urban and tourism impacts of Formula 1 on the host territories. In many of the studies analyzed, a gap may be noted, sometimes flagrant, between the development goals of the promoters of these mega-events and local realities. This study also highlights the fact that Formula 1 has established itself as a sports events industry that can renew and enhance the brand image of certain cities.

Originality/value

Very few recent studies have exhaustively reviewed the scientific literature published in English and French with regard to the field of Formula 1 from a tourism and urban perspective. This study makes it possible to identify the main analytical findings and research perspectives resulting from this scientific work while discussing them using a theoretical framework related to the hypermodern character of different societies.
Impact of natural disasters on New Zealand regional family businesses: perspectives of baby boomer family business owners
Authors: Wu Julia Yonghua
Published: June 2020

Purpose

This paper aims to describe what baby boomer family business owners in New Zealand perceive the implications of earthquakes on their business and succession planning. The current study focuses on how some businesses have survived significant uncontrollable contingencies, for instance, natural disasters. This paper also documents the insight of what baby boomer family business owners value in their succession planning.

Design/methodology/approach

Qualitative method was undertaken, comprising face-to-face in-depth interviews with 18 participants, who are baby boomers family business owners in New Zealand.

Findings

Driven by the unique social and political conditions in New Zealand, baby boomer family business owner’s revealed unique mind-sets and motivations that are oriented in their family value and/or the sense of self-fulfillment. As a result, they are able to adapt to uncertainties and reflect on their adaptability. Although approaching their retirement age and survived earthquakes, most interviewees neither have any urgency to establish or execute succession plans nor are they prepared for contingencies. A profitable trade sale has been identified as a preferred exit strategy.

Research limitations/implications

The current study is aimed to fill in the gap of exploring how some baby boomers’ family businesses in New Zealand survived deadly earthquakes and how they approach their own succession planning.

Practical implications

It is hoped that this research will contribute to the well-being of family businesses and be of value to practitioners who provide professional advises for family firms and those who aspire to a career in family businesses. This paper also aims to shed light on the implication of aging population and government policies on family businesses. The findings are, therefore, useful for academics, professional consultants, advisors and regulators.

Originality/value

However, natural disasters, social unrest and many uncontrollable events disrupt business operations and can be viewed as uncontrollable contingencies. Ageing population and generation-based similarities are also common to many countries and communities. Nonetheless, the interdisciplinary research on ageing population is scant in the context of financial planning, management accounting or taxation at the firm level. This paper also calls for more in-depth exploration on the implications of demographical factors on the organisations and their success or demise.
BIM-based integrated solution for analysis and management of mismatches during construction
Authors: Gharouni Jafari Kobra , Ghazi Sharyatpanahi Nozhat Sadat , Noorzai Esmatullah
Published: June 2020

Purpose

Prompt and effective responses to incompatibilities between as-designed and as-built drawings prevent cost and time overruns and material waste. This paper aims to provide an efficient framework to handle mismatches between these two models with the least negative impact on the whole project.

Design/methodology/approach

First, 11 most frequent mismatches were identified through questionnaires. Also, the respondents were asked to determine the mismatches’ roots and solutions and the impact of applying solutions on the whole project. Afterward, the process to present the optimum solution to one of these mismatches was modeled. After running the application programming interface developed in Navisworks software, decision-makers access a form, showing mismatches, their causes and solutions, as well as the solutions’ effect. To finalize the optimal solution, a platform was provided on whether to accept the system solution or to propose an alternative.

Findings

To empirically validate the reliability of the proposed framework, two projects were investigated. Two different approaches to dealing with the same mismatch occurred in these projects were compared in terms of time, cost and material required. The results showed that addressing the mismatches through the proposed framework can efficiently enhance time, cost and material consumption, in comparison with the traditional approach.

Originality/value

There is currently no building information modeling-based holistic framework for managing mismatches between as-designed and as-built drawings. The results of this research can help contractors to make the best decision, saving project resources, when setting about a mismatch during construction.
Exploring knowledge flow within a technology domain by conducting a dynamic analysis of a patent co-citation network
Authors: Smojver Vladimir , Štorga Mario , Zovak Goran
Published: June 2020

Purpose

This paper aims to present a methodology by which future knowledge flow can be predicted by predicting co-citations of patents within a technology domain using a link prediction algorithm applied to a co-citation network.

Design/methodology/approach

Several methods and approaches are used: a dynamic analysis of a patent citation network to identify technology life cycle phases, patent co-citation network mapping from the patent citation network and the application of link prediction algorithms to the patent co-citation network.

Findings

The results of the presented study indicate that future knowledge flow within a technology domain can be predicted by predicting patent co-citations using the preferential attachment link prediction algorithm. Furthermore, they indicate that the patent – co-citations occurring between the end of the growth life cycle phase and the start of the maturation life cycle phase contribute the most to the precision of the knowledge flow prediction. Finally, it is demonstrated that most of the predicted knowledge flow occurs in a time period closely following the application of the link – prediction algorithm.

Practical implications

By having insight into future potential co-citations of patents, a firm can leverage its existing patent portfolio or asses the acquisition value of patents or the companies owning them.

Originality/value

It is demonstrated that the flow of knowledge in patent co-citation networks follows a rich get richer intuition. Moreover, it is show that the knowledge contained in younger patents has a greater chance of being cited again. Finally, it is demonstrated that these co-citations can be predicted in the short term when the preferential attachment algorithm is applied to a patent co-citation network.
Understanding relational virtual community members’ satisfaction from a social learning perspective
Authors: Chou Shih-Wei
Published: June 2020

Purpose

This study develops a belief-value-satisfaction model based on social cognitive theory. This paper aims to explain how relational virtual community (RVC) members’ beliefs on individual features and environments can be transformed into satisfaction through social learning strategies.

Design/methodology/approach

The authors followed a longitudinal, quasi-experimental field approach to collect data from two phases, which entailed the key informant approach to get the responses from those who participated in knowledge exchange in VC. The authors used partial least squares to examine the proposed hypotheses.

Findings

Satisfaction is measured as two dimensions – outcome and process. Value creation is conceptualized as social self-regulated learning (SRL), and its antecedents include lead userness, learning goal orientation and social influence. The results show that both dimensions of satisfaction are affected by social SRL, which in turn is influenced by learning goal orientation and social influence.

Originality/value

A systematic research for understanding satisfaction from a social learning perspective in relational virtual community settings remains absent. This study explains why and how relational virtual community members’ social SRL serves the role in leveraging resources and reducing uncertainty, from which they gain satisfaction.
Ownership-motivated income shifting: evidence from European Multinational Groups
Authors: Medioli Alice , Azzali Stefano , Mazza Tatiana
Published: June 2020

Purpose

Although tax-motivated income shifting has been widely explored, no studies have as yet analyzed the association between ownership structure and management decisions about income shifting. The ownership structure of multinational groups is characterized by different levels of minority interests, and our aim is to establish whether income shifting is explained by the aim of expropriation of minorities, as well as taxation avoidance.

Design/methodology/approach

We collect data on a sample of European parent companies located in five countries and their foreign subsidiaries, and run a multivariate regression based on the Huizinga and Laeven (2008) model.

Findings

Our results support the idea of minority expropriation, finding evidence of ownership-motivated income shifting. We also find that the level of minority protection affects ownership-motivated income shifting, and that, when both are present, expropriation is statistically significant.

Research limitations/implications

Although the study looks at a wide range of subsidiaries, a limitation may be that it examines only firms having parent companies in five European countries. Further research would overcome this limitation and extend the literature and take into account other income-shifting contextual variables. Our results may lead regulators to pay more attention to the protection of minority interests.

Practical implications

This research offers insights to companies and investors, and should help them to make better-informed decisions and evaluate the best contexts for investments.

Originality/value

This study enriches the literature on income shifting by revealing that it can be caused by factors other than the desire to avoid taxation. It suggests that ownership structure is crucial.
Flexible bar buckling under short-time and long-term compressions
Authors: Egorov Anton , Egorov Vitaly
Published: June 2020

Purpose

The purpose of this paper is to expand possibilities of stability computing method when performing a dynamic analysis of bar- or rod-shaped elements for actual structures.

Design/methodology/approach

The methodology is based on the changes of stress–strain state of the bar-shaped elements at the moment of buckling. The proposed method is based on three assumptions. Firstly, the spatial stress–strain state is determined in the bar. Secondly, technological deviations inherent in real structures are introduced into the bar. Thirdly, mechanical behaviour of the bar is investigated in the mode of real time, which makes it possible to take into account wave deformation processes in the bar. To implement the suggested method of analysis, LS-DYNA package was selected in a dynamic formulation using solid finite elements.

Findings

Validity of the proposed method is shown by an example of dynamic stability analysis of a steel flat thin bar with two types of loads: short-time and long-term axial compressions. Comparison of the results showed different nature of the mechanical behaviour of the bar: wave processes are observed under short-time loading, and continuous monotone ones are stated under long-term loads.

Practical implications

Research results are applicable in the rocket and space industry.

Originality/value

A new computer-based methodology for dynamic analysis of heterogeneous elastic-plastic bar-, rod-shaped structures under shock axial compressive loads is proposed.
Development of new modified electrode based on β-cyclodextrin for methylene blue detection
Authors: Ghodbane Ilhem , Zougar Saida , Lamari Rim , Kherrrat Rochdi
Published: June 2020

Purpose

This paper aims to focus on the development and characterization of a new electrochemical sensor, designed for the detection of methylene blue present in aqueous medium.

Design/methodology/approach

This sensor is obtained through the coupling of a polymeric membrane and an ion-sensitive electrode (platinum electrode). The preparation of the polymeric membrane involves the incorporation of a receptor: β-cyclodextrin (β-CD), a polymer (polyvinylchloride) and a plasticizer (dioctylphtalate). Cyclic voltammetry method (CV) was used to investigate the electrical properties of this electrochemical sensor. The effect of the experimental parameters such as dye initial concentration, scan rate, interfering elements presence and additional Nafion membrane presence was investigated in this paper.

Findings

The results are interesting because the developed sensor gives a linear response in concentrations range of 10−13 M–10−3 M with a good correlation coefficient of 0.979 and a detection limit of 10−13 M, which reflects the sensitivity of this sensor to the target element. The sensibility value is equal to 2. 40 µA mol−1 L.

Originality/value

The present study has shown that the modified electrode is a very good candidate in terms of price, sensibility and reproducibility for the construction of the sensitive sensor for the control of wastewater containing methylene blue.
Investigation of input variables on temperature rise while end milling Al/SiC metal matrix composite
Authors: Sridhar Srinath , Sellamani Rajeswari
Published: June 2020

Purpose

The purpose of this paper is to find out the optimal level as well as the influence of end mill cutter geometrical and machining parameters while machining metal matrix composite. End milling is carried out on Al 356/SiC metal matrix composites (MMC) using high-speed steel (HSS) end mill cutter. The optimum level of input parameters such as helix angle, nose radius, rake angle, cutting speed, feed rate and depth of cut are calculated for minimum temperature rise.

Design/methodology/approach

L27 Taguchi orthogonal design, signal-to-noise (S/N) ratio, are applied for conducting experiments, and to find the optimal level of input parameters for minimum temperature rise, respectively. Analysis of variance (ANOVA) is used to analyze the significance of input parameters on temperature rise.

Findings

It is found that the optimal combination of helix angle 400, nose radius 0.8 mm, rake angle 80, cutting speed 30 m/min, feed rate 0.04 mm/rev and depth of cut 0.5 mm have generated minimum temperature rise. From ANOVA analysis, it is found that rake angle influence is more on output performance followed by cutting speed and nose radius compared with other machining and geometrical parameters.

Originality/value

The influence of geometrical parameters such as helix angle, nose radius and rake angle of end mill cutter on temperature rise while machining MMC has not been explored previously.