bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary gland RNA-seq from arbovirus-infected Aedes aegypti and Aedes albopictus provides insights into virus transmission
Authors: Modahl Cassandra , Chowdhury Avisha , Oliveira Fabiano , Kini R. Manjunatha , Pompon Julien
Published: December 2019

Yellow fever mosquitoes (Aedes aegypti) and Asian tiger mosquitoes (Aedes albopictus) are the primary vectors of dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV). These viruses are transmitted to humans through mosquito saliva, making the vector salivary gland (SG) a critical tissue to identify transmission-blocking targets. We examined gene expression in infected SGs for both vector species and for three different virus infections. Aedes aegypti SGs were infected separately with DENV, ZIKV and CHIKV, and Ae. albopictus with CHIKV. RNA-sequencing identified differentially expressed coding and long non-coding RNAs (lncRNAs). Differentially expressed genes determined from genome annotations were greater in number and functional diversity in comparison to differentially expressed transcripts from de novo transcriptome assemblies. Salivary protein transcripts were the most abundant, but were downregulated in all three virus infections. Commonly upregulated genes were associated with apoptosis, cytoskeletal proteins, replication/transcription/translation, redox/stress and immunity. An enrichment of upregulated genes related to apoptosis were observed in CHIKV infection in comparison to DENV and ZIKV infections. Upregulation of serine proteases and other genes associated with immunity and cellular stress responses (cytochrome P450 genes) varied between vectors. There were also immune response commonalities between vectors, for instance RNA-interference was observed to be a non-specific antiviral defense. The number of lncRNA transcripts differentially expressed were few and none were common to all infections, likely having minor roles, unlike the lncRNA antiviral effects proposed for mosquito midgut. Determining common infection patterns for different viruses and vectors has applications in refractory vector engineering.
Transcriptomic analysis of human neurons and astrocytes infected with TBEV strains of different virulence
Authors: Selinger Martin , Vechtova Pavlina , Tykalova Hana , Sterba Jan , Grubhoffer Libor
Published: December 2019

Tick-borne encephalitis virus (TBEV; Flaviviridae) can cause serious infections in humans which may result in encephalitis/meningoencephalitis. It has been previously reported that TBEV infects both, neurons and astrocytes, however, with a different outcome. So far, the principle of this cell type-specific response to TBEV is not fully understood.

In order to gain more insight into this phenomenon, we described new in vitro infection model utilizing human neural stem cells (hNSCs) and two strains of Western European TBEV subtype varying in the pathogenicity - mild Neudoerfl and severe Hypr. In detail, neurons and astrocytes were artificially differentiated from hNSCs and presence of CNS markers was checked. TBEV infection in both cell types was characterised afterwards. As expected, both cell types proved to be susceptible to TBEV infection. Viability was negatively affected only in infected neurons. In order to identify possible effectors responsible for different susceptibility of neurons and astrocytes, the analyses of changes in poly-(A) and small RNA transcriptome upon TBEV infection were performed. Preliminary results from poly-(A) RNA transcriptome revealed that in both cell types mainly interferon-stimulated genes (ISGs) were up-regulated. However, the expression kinetics of particular ISGs varied. In addition, the vast spectrum of long non-coding RNAs was described to be differentially expressed upon infection. Surprisingly, U1 snRNA was found to be the most down-regulated RNA species among almost all infected samples.

Further analyses are in progress in order to get a complete description of virus-induced changes on the transcriptomic level.
Transcriptional and translation shut-off in TBEV infected neural cells and involvement of viral C protein
Authors: Tykalová Hana , Selinger Martin , Štěrba Ján , Věchtová Pavlína , Kohl Alain , Schnettler Esther , Grubhoffer Libor
Published: December 2019

Tick-borne encephalitis virus (TBEV, Flaviviridae) infection causes severe neurological disease and incapacitates more than 10 000 patients annually in the Eurasian region. Despite extensive studies, some areas of interaction of TBEV with the host cells remain undescribed. Here we investigated the interaction of TBEV and human neural DAOY HTB-186 cells on the transcriptional and translational level.

By labelling of nascent RNA and protein molecules in TBEV-infected DAOY cells, we showed that the virus-induced host translational shut-off. Moreover, TBEV interfered also with the expression of host ribosomal RNAs, in particular with the rRNA species transcribed by RNA polymerase I (18S rRNA, 28S rRNA, and their precursor 45-47S pre-rRNA). Synthesis of host rRNAs is an essential host cell process that is localized in the nucleus, namely nucleoli. By searching for virus factor that could be linked with these effects, we described so far unknown nucleolar localization of TBEV capsid protein C. More importantly, preliminary data from transfection of recombinant C protein led to the reduction in nascent protein synthesis indicating the link between TBEV capsid protein and shut-off phenomena which were described. Furthermore, we identified a potential nuclear localization signal, which seems not to be essential for the shut-down effect.

Taken together we described a brand new type of interaction between TBEV and host neural cells on the transcriptional and translational level and identified viral factor potentially responsible for the observed phenomena. However, further analyses are needed, and the particular mechanism of action remains still elusive.
Toolkit for the study of yellow fever virus
Authors: Velazquez Ricardo Sanchez , Lorenzo Giuditta De , Tandavanitj Rapeepat , Setthapramote Chayanee , Varjak Margus , Kohl Alain , Patel Arvind
Published: December 2019

Yellow fever virus (YFV) is a dangerous re-emerging mosquito borne flavivirus with a high lethality, which causes untreatable haemorrhagic fever in humans. Important disadvantages regarding safety and limited vaccine supply have been identified in the existing live attenuated vaccine. Alternative safer therapeutic strategies are needed to reduce the lethality of infections and protect a wider group of people. To this point, we created an array of essential tools for the study of YFV. We designed a novel YFV reporter virus to develop a highly sensitive high throughput neutralisation assay (Z’=0.65), which can screen virus inhibitors in only 48 hours. Moreover, we designed a site-specific biotinylated soluble YF envelope (E) protein by a cloning strategy involving the use of a biotin acceptor peptide and E. coli Biotin-protein birA ligase. The biotinylated E protein was used to develop a highly sensitive ELISA to screen antibodies that bind to the YFV E protein. Furthermore, we immunised mice with a soluble YFV E protein and generated anti-YFV E IgG secreting hybridoma cell lines. Monoclonal antibodies secreted by hybridomas were purified by affinity chromatography and are being characterised. The developed antibodies against YF E protein are a crucial tool for the molecular study of YF. Additionally, neutralising antibodies against YFV could potentially be developed into the first therapeutic treatment against YF infection. The toolkit developed in this project includes a neutralisation assay, a binding ELISA, and anti YFV E antibodies. These are essential instruments to expand the knowledge of YFV.
Implications of vertical transmission of Alphaviruses in Aedes aegypti mosquitoes
Authors: Rodriguez Julio , Fazakerley John
Published: December 2019

Mosquitoes are vectors for epidemic transmission of viruses of public and veterinary health. The mosquito vector is generally infected for life although, unlike the vertebrate counterpart, does not suffer a high fitness cost. Having a vector infected for the length of its life enables routes of viral transmission other than the classic infected bite (horizontal), including sexual (horizontal) and to the progeny (vertical). Vertical transmission is considered a route of transmission that allows for the persistence of the virus during adverse environmental periods (e.g., droughts, cold periods). Because Aedes aegypti and Aedes albopictus eggs are resistant to dessication, it is hypothesised that this attribute could promote arbovirus survival between transmission cycles, playing an important role in maintaining the pathogen.

Vertical transmission of arboviruses has been extensively documented for flaviviruses and bunyaviruses. However, there is very little and contradictory reports of vertical transmission of alphaviruses. In this research we establish the mechanisms of vertical transmission of the alphaviruses Semiliki Forest virus (SFV) and Ross river virus (RRV) and its implications in pathogen transmission of future generations.

Aedes aegypti mosquitoes were infected with SFV virus in different gonotrophic cycles. Their offspring was then reared and challenged with SFV, RRV and dengue virus (DENV). Offspring from infected parents showed significant reduction in viral load if infected with SFV or RRV but not with DENV.

Findings of this research highlight the importance of vertical transmission of alphaviruses in the general arbovirus infectious cycle.
JNK pathway-a key mediator of antiviral immunity in mosquito salivary glands
Authors: Chowdhury Avisha , Modahl Cassandra M. , Tan SiokThing , Wong Benjamin , Kini R. Manjunatha , Pompon Julien
Published: December 2019

Background: Mosquito salivary glands play crucial role in transmission of arboviral diseases like Dengue (DENV), Zika (ZIKV) and Chikungunya (CHIKV). We aimed to characterize virus responsive gene expression in Aedes aegypti salivary glands against these pathogenic arboviruses.

Methods: We performed high throughput RNA-sequencing on uninfected and virus-infected (DENV, ZIKV, CHIKV) female Ae. aegypti salivary glands to elucidate differential expression of genes at the transcript level. We validated the transcriptomic analysis by qPCR and performed RNA-i based functional characterization of virus-induced immune genes.

Results: DENV, ZIKV or CHIKV infected salivary gland transcriptome revealed regulations of genes related to blood feeding, metabolism, apoptosis, and immunity; the latter including Toll, IMD, and JNK pathway components. Silencing of Toll and IMD pathway components did not increase replication of all three viruses. However, depletion of infection induced JNK pathway activator and repressor showed conserved antiviral response of this pathway against the viral infections. We further showed that JNK activation by arboviruses is mediated by antiviral complement and apoptosis activation.

Conclusion: This study determined the previously unknown antiviral mechanism of JNK pathway in mosquito salivary glands against important pathogenic arboviruses. This pathway shows potential to be utilized for developing effective transmission blocking tools.
The emerged genotype I of Japanese encephalitis virus shows an infectivity similar to genotype III in Culex pipiens mosquitoes
Authors: Hameed Muddassar
Published: December 2019

Japanese Encephalitis virus (JEV) is a zoonotic flavivirus that represents the most significant etiology of childhood viral neurological infections throughout the Asia. During the last 20 years, JEV genotype dominance has shifted from genotype III (GIII) to genotype I (GI). To date, the exact mechanism of this displacement is still not known. Culex (Cx.) mosquitoes are the most common species in China and play an essential role in maintaining JEV enzootic transmission cycle. In this study, we used Cx. pipiens mosquitoes from China as an in vivo mosquito model to explore if mosquitoes played a potential role in JEV genotype shift. We exposed female Cx. pipiens mosquitoes orally to either GI or GIII JEV strains. Midgut, whole mosquitoes, secondary organs, and salivary glands of JEV-infected mosquitoes were collected at 7 and 14 days of post infection (dpi) and subjected to measure the infection rate, replication kinetics, dissemination rate and transmission potential of the infected JEV strains in Cx. pipiens mosquitoes by 50% tissue culture infective dose assay. We found that Cx. pipiens mosquito was competent vector for both GI and GIII JEV infection, with similar infection rates and growth kinetics. After the establishment of infection, Cx. pipiens mosquitoes disseminated both JEV genotypes to secondary organs at similar rates of dissemination. A few GI-infected mosquito salivary glands (16.2%) were positive for GI virus, whereas GIII virus was undetectable in GIII-infected mosquito salivary glands at 7 dpi. However, 29.4% (5/17) and 36.3% (8/22) were positive for GI- and GIII-infected mosquito salivary glands at 14 dpi, respectively, showing an increase in JEV positive rate. No statistical difference in the transmission rate between GI- and GIII-infected mosquitoes was detected. Our experiment data demonstrated that GI and GIII viruses have similar infectivity in Cx. pipiens mosquitoes, suggesting that Cx. pipiens mosquitoes from China may not play a critical role in JEV genotype shift. Although the current data were obtained solely from Cx. pipiens mosquitoes, it is likely that the conclusion drawn could be extrapolated to the role of mosquitoes in JEV genotype shift.
St Abbs Head phlebovirus – a separate virus species or a strain of Uukuniemi phlebovirus?
Authors: Szemiel Agnieszka , Willett Brian , Ma Wing See
Published: December 2019

St Abbs Head virus (SAHV), member of Phlebovirus genus (family Phenuiviridae, order Bunyavirales), belongs to the largest group of negative strand RNA viruses. All phleboviruses share a genome structure that comprises three segments of negative-sense or ambi-sense RNA. The viral genome is composed of the small (S), medium (M) and large (L) RNA segments. The S segment encodes the nucleocapsid (N) protein, the M segment encodes the precursor for the viral glycoproteins (Gn and Gc) and the L segment encodes the viral RNA-dependent RNA polymerase (RdRp). Some viruses within the genus also encode non-structural proteins within their S or M segments.

SAHV was isolated from a pool of Ixodes uriae ticks collected at a seabird colony in Berwickshire, Scotland in 1979. There were quite a few related bunyaviruses found in tick and bird samples on the East Coast of Scotland and England in the 70s and 80s. Recently we have sequenced a sample of SAHV using next generation sequencing technology. The results suggested that this virus is very closely related to the Uukuniemi phlebovirus (UUKV). To determine how similar are SAHV and UUKV, we compared virus growth in various mammalian, bird and tick cell lines.
Alphavirus E1 fusion protein: alternative conformations of the post-fusion trimer depending on the alphavirus
Authors: GRAU Nina , MONCOQ Karine , ROUVINSKI Alexander , DUQUERROY Stéphane , HAOUZ Ahmed , VANEY Marie-Christine , REY Félix
Published: December 2019

Background. Some of the best characterized alphaviruses are chikungunya virus (CHIKV), Semliki Forest virus (SFV) and Sindbis virus (SINV). E1 is a class II fusion protein, containing 3 domains (DI, DII, DIII) folded essentially as β-sheet, plus a stem region connecting DIII to the transmembrane (TM) segment. The fusion loop (FL) is at the tip of the elongated DII. The X-ray structure of the SFV E1 post-fusion trimer, truncated of the stem region, displayed a tripod-shape with the DII legs open and the FLs away from each other, contrary to the class II viral fusion proteins from other viral genera, in which the FLs interact at the tip of the post-fusion trimer. Here, we set to identify if the stem plays a structural role in zippering together the E1 trimer to bring the fusion loops into contact.

Methods. We produced the recombinant ectodomains of E1 of CHIKV, SINV and SFV containing or not the stem, crystallized them and determined the X-ray structure.

Results. We observed that CHIKV and SINV display E1 in closed conformation, in contrast to SFV, which displays a tripod even with the full stem. We identified a sequence motif in the stem responsible for the conformational difference.

Conclusion. Our results point to potential mechanistic differences between alphavirus E1 in driving fusion. Further functional studies are ongoing to pin-point the significance of these new findings, and the reasons for the alternative post-fusion conformations.
SCHEEPDOG: programming electric cues to dynamically herd large-scale cell migration
Authors: Zajdel Tom J. , Shim Gawoon , Wang Linus , Rossello-Martinez Alejandro , Cohen Daniel J.
Published: December 2019

Directed cell migration is critical across biological processes spanning healing to cancer invasion, yet no existing tools allow real-time interactive guidance over such migration. We present a new bioreactor that harnesses electrotaxis—directed cell migration along electric field gradients—by integrating four independent electrodes under computer control to dynamically program electric field patterns, and hence steer cell migration. Using this platform, we programmed and characterized multiple precise, two-dimensional collective migration maneuvers in renal epithelia and primary skin keratinocyte ensembles. First, we demonstrated on-demand, 90-degree collective turning. Next, we developed a universal electrical stimulation scheme capable of programming arbitrary 2D migration maneuvers such as precise angular turns and migration in a complete circle. Our stimulation scheme proves that cells effectively time-average electric field cues, helping to elucidate the transduction time scales in electrotaxis. Together, this work represents an enabling platform for controlling cell migration with broad utility across many cell types.
rMSIcleanup: An open-source tool for matrix-related peak annotation in mass spectrometry imaging and its application to silver-assisted laser desorption/ionization
Authors: Baquer Gerard , Sementé LLuc , García-Altares María , Lee Young Jin , Chaurand Pierre , Correig Xavier , Ràfols Pere
Published: December 2019

Mass spectrometry imaging (MSI) has become a mature, widespread analytical technique to perform non-targeted spatial metabolomics. However, the compounds used to promote desorption and ionization of the analyte during acquisition cause spectral interferences in the low mass range that hinder downstream data processing in metabolomics applications. Thus, it is advisable to annotate and remove matrix-related peaks to reduce the number of redundant and non-biologically-relevant variables in the dataset. We have developed rMSIcleanup, an open-source R package to annotate and remove matrix-related signals based on its chemical formula and the spatial distribution of its ions. To validate the annotation method, rMSIcleanup was challenged with several images acquired using silver-assisted laser desorption ionization MSI (AgLDI MSI). The algorithm was able to correctly classifym/zsignals related to silver clusters. Visual exploration of the data using Principal Component Analysis (PCA) demonstrated that annotation and removal of matrix-related signals improved spectral data post-processing. The results highlight the need for including matrix-related peak annotation tools such as rMSIcleanup in MSI workflows.

Resources availability

The R package presented in this publication is freely available under the terms of the GNU General Public License v3.0 athttps://github.com/gbaquer/rMSIcleanup. The datasets used in the experiments can be accessed upon request to the corresponding author.
Big data from small tissues: extraction of high-quality RNA for different plant tissue types during oilseedBrassicaspp. seed development for RNA-Sequencing
Authors: Siles Laura , Eastmond Peter , Kurup Smita
Published: December 2019

Obtaining high-quality RNA for gene expression analyses from different seed tissues is challenging due to the presence of various contaminants, such as polyphenols, polysaccharides and lipids which interfere with RNA extraction methods. At present, the available protocols for extracting RNA from seeds require high amounts of tissue and are mainly focused on extracting RNA from whole seeds. However, extracting RNA at the tissue level enables more detailed studies regarding tissue specific transcriptome during development. Seeds from heart stage embryo to mature developmental stages ofBrassica napusandB. oleraceawere sampled for isolation of the embryo, endosperm and seed coat tissues. Ovules and gynoecia wall tissue were also collected at the pre-fertilization stage. After testing several RNA extraction methods, E.Z.N.A. Plant RNA Kit and Picopure RNA Isolation kit extraction methods with some modifications, as well as the use of PVPP for seed coats and endosperms at green stages, resulted in high RNA concentrations with clear 28S and 18S bands and high RIN values. Here, we present efficient and reliable RNA extraction methods for different genotypes ofBrassicaspp for different tissue types during seed development. The high-quality RNA obtained by using these methodologies is suitable for RNA-Sequencing and gene expression analyses.
Sex Differences in Behavioral Responses during a Conditioned Flight Paradigm
Authors: Borkar Chandrashekhar D. , Dorofeikova Mariia , Le Quan-Son Eric , Vutukuri Rithvik , Vo Catherine , Hereford Daniel , Resendez Alexis , Basavanhalli Samhita , Sifnugel Natalia , Fadok Jonathan P.
Published: December 2019

Females exhibit greater susceptibility to trauma- and stress-related disorders compared to males; therefore, it is imperative to study sex differences in the mode and magnitude of defensive responses in the face of threat. To test for sex differences in defensive behavior, we used a modified Pavlovian fear conditioning paradigm that elicits clear transitions between freezing and flight behaviors within individual subjects. Female mice subjected to this paradigm exhibited higher percentages of freezing behavior compared to males, especially during the intertrial interval period. Female mice also exhibited more cued freezing in response to the conditioned stimuli in the last block of extinction training. Furthermore, there were sex differences in the expression of other adaptive behaviors during fear conditioning. Assaying rearing, grooming, and tail rattling behaviors during the conditioned flight paradigm yielded measurable differences across sessions and between males and females. Overall, these results provide insight into sex-dependent alterations in mouse behavior induced by fear conditioning.

Highlights

Male and female mice do not differ in conditioned flight behavior.

Female mice exhibit more freezing behavior.

Rearing, self-grooming, and tail rattling behavior changes across days.

Male mice exhibit more rearing and grooming behavior.

Female mice exhibit more tail rattling behavior.
Retrograde transport of mannose-6-phosphate receptor depends on several sorting machineries as analyzed by sulfatable nanobodies
Authors: Buser Dominik P. , Spiess Martin
Published: December 2019

Retrograde protein transport from the cell surface and endosomes to the trans-Golgi network (TGN) is essential for membrane homeostasis in general and for the recycling of mannose-6-phosphate receptors (MPRs) for sorting of lysosomal hydrolases in particular. Several different sorting machineries have been implicated in retrieval from early or late endosomes to the TGN, mostly for the cation-independent MPR (CIMPR), mainly by analysis of steady-state localization and by interaction studies. We employed a nanobody-based sulfation tool to more directly determine transport kinetics from the plasma membrane to the TGN – the site of sulfation – for the cation-dependent MPR (CDMPR) with and without silencing of candidate machinery proteins. The clathrin adaptor AP-1 that operates bidirectionally at the TGN-to-endosome interface, which had been shown to cause reduced sulfation when rapidly depleted, produced hypersulfation of nanobodies internalized by CDMPR upon long-term silencing, reflecting accumulation in the TGN. In contrast, knockdown of retromer (Vps26), epsinR, or Rab9 reduced CDMPR arrival to the TGN. No effect was observed upon silencing of TIP47. Most surprisingly, depletion of the GGA (Golgi-localized, γ-adaptin ear-containing, Arf-binding) proteins inhibited retrograde transport rather than TGN exit. This study illustrates the usefulness of derivatized, sulfation-competent nanobodies to analyze retrograde protein transport to identify the contributions of different machineries.
The functional organization of high-level visual cortex determines the representation of complex visual stimuli
Authors: Kliger Libi , Yovel Galit
Published: December 2019

A hallmark of high-level visual cortex is its functional organization of neighboring clusters of neurons that are selective to single categories such as faces, bodies and objects. However, visual scenes are typically composed of multiple categories. How does category-selective cortex represent such complex stimuli? According to a normalization mechanism, the response of a single neuron to multiple stimuli is normalized by the response of its neighboring neurons (normalization pool). Here we show that category-selectivity, measured with fMRI, can provide an estimate for the heterogeneity of the normalization pool, which determines the response to multiple stimuli. These results provide a general framework for the varying representations of multiple stimuli that were reported in different regions of category-selective cortex in neuroimaging and single-unit recording studies. This type of organization may enable a dynamic and flexible representation of complex visual scenes that can be modulated by higher-level cognitive systems according to task demands.
Unraveling nanotopography of cell surface receptors
Authors: Franke Christian , Chum Tomáš , Kvíčalová Zuzana , Glatzová Daniela , Rodriguez Alvaro , Helmerich Dominic A. , Frank Otakar , Brdička Tomáš , van de Linde Sebastian , Cebecauer Marek
Published: December 2019

Cells communicate with their environment via surface receptors, but nanoscopic receptor organization with respect to complex cell surface morphology remains unclear. This is mainly due to a lack of accessible, robust and high-resolution methods. Here, we present an approach for mapping the topography of receptors at the cell surface with nanometer precision. The method involves coating glass coverslips with glycine, which preserves the fine membrane morphology while allowing immobilized cells to be positioned close to the optical surface. We developed an advanced and simplified algorithm for the analysis of single-molecule localization data acquired in a biplane detection scheme. These advancements enable direct and quantitative mapping of protein distribution on ruffled plasma membranes with near isotropic 3D nanometer resolution. As demonstrated successfully for CD4 and CD45 receptors, the described workflow is a straightforward quantitative technique to study molecules and their interactions at the complex surface nanomorphology of differentiated metazoan cells.
TIMP-3 facilitates binding of target metalloproteinases to the endocytic receptor LRP-1 and promotes scavenging of MMP-1
Authors: Carreca Anna P. , Pravatà Veronica , Murphy Gillian , Nagase Hideaki , Troeberg Linda , Scilabra Simone D.
Published: December 2019

Matrix metalloproteinases (MMPs) and the related families of disintegrin metalloproteinases (ADAMs) and ADAMs with thrombospondin repeats (ADAMTSs) play a crucial role in the turnover of extracellular matrix (ECM) components and shedding of cell-surface molecules. The proteolytic activity of metalloproteinases is post-translationally regulated by their endogenous inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs). Several MMPs, ADAMTSs and TIMPs have been reported to be endocytosed by the low-density lipoprotein receptor-related protein-1 (LRP-1). Different binding affinities of these proteins for the endocytic receptor correlate with different turnover rates which, together with differences in their mRNA expression, determines their nett extracellular levels.

In this study, we used surface plasmon resonance to evaluate the affinity between LRP-1 and a number of MMPs, ADAMs, ADAMTSs, TIMPs and metalloproteinase/TIMP complexes. This identified MMP-1 as a new LRP-1 ligand. Among the proteins analysed, TIMP-3 bound to LRP-1 with highest affinity (KD= 1.68 nM). Additionally, we found that TIMP-3 can facilitate the clearance of its target metalloproteinases by bridging their binding to LRP-1. For example, the free form of MMP-1 was found to have aKDof 34.6 nM for LRP-1, while the MMP-1/TIMP-3 complex had a 7-fold higher affinity (KD= 4.96 nM) for the receptor. TIMP-3 similarly bridged binding of MMP-13 and MMP-14 to LRP-1. TIMP-1 and TIMP-2 were also found to increase the affinity of target metalloproteinases for LRP-1, albeit to a lesser extent. These findings suggest that LRP-1 scavenging of TIMP/metalloproteinase complexes may be a general mechanism by which inhibited metalloproteinases are removed from the extracellular environment.
Functional dynamics of dopamine synthesis during monetary reward and punishment processing
Authors: Hahn Andreas , Reed Murray B. , Pichler Verena , Michenthaler Paul , Rischka Lucas , Godbersen Godber M. , Wadsak Wolfgang , Hacker Marcus , Lanzenberger Rupert
Published: December 2019

Purpose

In the human brain endogenous dopamine release is commonly assessed by the PET competition model. Although thoroughly validated, cognitive processing yields low signal changes and the assessment of several task conditions requires repeated scanning. Using the framework of functional PET imaging we introduce a novel approach which leverages the incorporation of the radioligand 6-[18F]FDOPA into the dynamic fast-acting regulation of the corresponding enzyme activities by neuronal firing and neurotransmitter release. We demonstrate the feasibility of the approach by the assessment of widely described sex differences in dopamine neurotransmission.

Methods

Reward and punishment processing was behaviorally investigated in 36 healthy participants, where 16 underwent fPET and fMRI while performing the monetary incentive delay task. 6-[18F]FDOPA was applied as bolus+infusion during a single 50 min PET acquisition. Task-specific changes in dopamine synthesis were identified with the general linear model and quantified with the Gjedde-Patlak plot.

Results

Monetary gain induced 78% increase in nucleus accumbens dopamine synthesis vs. 49% for loss in men. Interestingly, the opposite was discovered in women (gain: 51%, loss: 78%). Behavioral modeling revealed direct associations of task-specific dopamine synthesis with reward sensitivity in men (rho = −0.7) and with punishment sensitivity in women (rho = 0.89). As expected, fMRI showed robust task-specific neuronal activation but no sex difference.

Conclusions

Our findings provide a dopaminergic basis for well-known behavioral differences in reward and punishment processing between women and men. This has important implications in psychiatric conditions showing sex-specific prevalence rates, altered reward processing and dopamine signaling. The high temporal resolution and pronounced magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive or emotional processing in various brain disorders.
Revised radii of the univalent Cu, Ag, Au and Tl cations
Authors: Batsanov Stepan S.
Published: December 2019

Radii of Cu+, Ag+, Au+ and Tl+ cations are determined by the additive method from interatomic distances in molecular and/or crystalline halides, oxides, chalcogenides and cyanides with different coordinations of atoms, and then recalculated for the 6-coordination number. The averaged (from 74 structures) values of revised radii are equal to r(Cu+) = 0.74 Å, r(Ag+) = 0.99 Å, r(Au+) = 0.92 Å, r(Tl+) = 1.22 Å, which are consistent with radii calculated from direct cation–cation contacts in ultimately compressed metals.
Consumers’ perception of a traditional fermented beverage in Central Mexico
Authors: Rojas-Rivas Edgar , Viesca-González Felipe Carlos , Favila-Cisneros Héctor Javier , Cuffia Facundo
Published: December 2019

Purpose

Pulque is a fundamental piece in the Mexican gastronomy and identifying consumers’ perception could help promote it and generate new opportunities of commercialization. The purpose of this paper is twofold: first, to explore the underlying factors that influence consumers’ perception toward pulque, and second, to identify groups of consumers according to their perception.

Design/methodology/approach

A questionnaire was designed and applied to 220 consumers within points of sales. Exploratory factor analysis (EFA) was undertaken and hierarchical cluster analysis (HCA) was used to identify different groups of consumers.

Findings

By means of EFA three factors were obtained: traditionality, bad reputation of pulquerías and functional beverage. In order to identify different consumption patterns among consumers, HCA was performed and three groups were identified: traditional, neo-consumers and neo-consumers in transition. The groups identified showed significant differences in their perception.

Practical implications

Pulque has recently gained interest in various consumer sectors, mainly among young consumers, who are consuming and promoting the beverage these days. In this sense, the results of this work could be used for its promotion and consumption in order to attract more consumers and make a contribution to the development of local economies.

Originality/value

This is the first work in Mexico to explore the perception of consumers toward pulque: the most important traditional fermented beverage in Central México. Results of this research suggest the appearance of a revaluation process among young consumers, more informed and with greater sensitivity toward traditional Mexican food, particularly in the case of pulque. Likewise, these results could be useful for producers and sellers to carry out commercial strategies and promote the drink.
Framework to analyze Sri Lanka disaster management mechanism
Authors: Randil Chameera , Siriwardana Chandana , Hewawasam Kalana
Published: December 2019

Purpose

The purpose of this study is to develop a framework to assess the disaster management mechanism in Sri Lanka by means of the established indicators and newly derived indicators. This could be used to identify the parameters, which should be paid much attention to improving the resilience of the built environment.

Design/methodology/approach

This paper initially examines the effectiveness of the existing mechanism using data from a field study, by identifying the parameters needed to be considered based on the existing literature. Then the study continues on identifying new parameters of evaluation, covering a broad multidisciplinary scope inclusive of geographic, demographic, environmental, technological, social, economic and political perspectives. The identification process is based on regression relationships; hence, a framework will be developed to assess the resilience of the built environment.

Findings

The findings showed that the existing disaster management mechanism should be improved in terms of authoritative assistance while the humanitarian assistance is fulfilled to a satisfactory level as the resilience of the built environment is often community-based in Sri Lanka. Furthermore, resilience of a certain region could be effectively assumed with the indicators within the developed framework.

Originality/value

The existing evaluation criteria of the resilience framework in Sri Lanka is rather qualitative than quantitative. Therefore, this paper focuses on developing a framework where quantitative parameters are used to evaluate the existing mechanism from a number of responses from field surveys. In addition, recommendations for the key areas to be focused on developing the existing mechanism are stated.
Teachers’ job satisfaction at well-performing, historically disadvantaged schools
Authors: Matla Shabe Jonas , Xaba Mgadla Ike
Published: December 2019

Purpose

The purpose of this paper is to investigate the levels of the job satisfaction of teachers at historically disadvantaged secondary schools and to determine the correlation effects among job satisfaction dimensions as they relate to these teachers.

Design/methodology/approach

A quantitative survey design using Spector’s Job Satisfaction Survey was used, with 1,035 teachers from 30 secondary schools in the Sedibeng and Johannesburg South districts of the Gauteng Department of Education in the Gauteng Province of South Africa. Overall, 738 usable questionnaires were returned.

Findings

Teachers at well-performing, historically disadvantaged schools experience ambivalent job satisfaction levels. For this reason, they indicate satisfaction with supervision, co-workers and the nature of work; ambivalence with promotion, contingent rewards and communication; and no satisfaction with pay and operating conditions. Correlations between job satisfaction dimensions are significant. Their correlations indicate relationships that range between moderate and strong. While mostly indicating relationships of no practical effect, most of Herzberg’s hygiene factors are projected as strong moderating factors of job dissatisfaction as seen in relationships between dimensions reflecting hygiene factors and total job satisfaction.

Originality/value

This study pioneers the discourse on teacher job satisfaction at historically disadvantaged secondary schools, which still experience apartheid legacies: poor socio-economic conditions of their communities in South Africa. Strikingly, they consistently perform well in the National Senior Certificate – the basic education exit point. Lessons for educational management and policy practice can be learnt from these secondary schools, including lessons for underperforming schools’ leadership.
Warehouse configuration in omni-channel retailing: a multiple case study
Authors: Kembro Joakim Hans , Norrman Andreas
Published: December 2019

Purpose

The purpose of this study is to explore warehouse configuration in omni-channel retailing.

Design/methodology/approach

A multiple case study is conducted with six large omni-channel retailers from three different sectors.

Findings

The study shows an increase in the number, variation and frequency of flows passing through omni-channel warehouses. Along with an increased variety of stock keeping units (including singles vs multipacks), there is an increase in the complexity of planning and coordination of order fulfillment. Retailers test a mix of different solutions for storage and picking and partly shift focus to advanced sorting operations. The companies already have or plan to invest in substantial automation systems, which emphasize the importance of capturing and using accurate master data.

Research limitations/implications

The study highlights the need to understand the interrelations and co-development of configuration elements in omni-channel warehousing. The findings also suggest that a successful transformation requires increased collaboration with upstream and downstream partners. Conceptual models are developed to illustrate strategies and development paths in omni-channel warehousing, and suggestions for future research are summarized in a research agenda. A research limitation is the focus on Swedish retailers in three sectors (fashion, consumer electronics and DIY/construction material). Future studies can include additional sectors, extend the geographical scope and explore cross-regional differences.

Practical implications

As one of the few deeper case studies on omni-channel warehousing, practitioners will find new configurations described and analyzed here. Along with conceptual models, a synthesis of challenges and potential solutions are presented to support retailers’ practical analysis and decision making.

Originality/value

This is one of the first multiple case studies that go deeper into omni-channel warehouse configuration, which is of increasing importance to both scholars and practitioners in the field.
The impact of smoke from grilled fish on the hematological parameters of Indonesian grilled fish sellers
Authors: Purbayanti Dwi , Ardina Rinny , Ardhany Syahrida Dian , Gunawan Rudi , Pratama Mohammad Rizki Fadhil
Published: December 2019

Purpose

Fish processing by grilling can produce emissions that contain toxic compounds that can have short- and long-term effects on human health. Another study reported that exposure to air pollutants is hematotoxic. The purpose of this paper is to determine the effect of smoke exposure on fish grill results on hematological parameters.

Design/methodology/approach

The subjects of this study were 90 grilled fish sellers, with 32 processed food sellers who did not sell grill food as a control. The hematological analysis was performed using the Hematology Analyzers KX300 instrument.

Findings

The results showed that the mean value of hematological parameters in the test group was higher than the control group except for the number of lymphocytes and mixed cell parameters.

Originality/value

The content of harmful compounds contained in fish grill smoke can increase hematological value in the blood of exposed individuals, which has the potential for health problems and disease progression.
An investigation of biases in web search engine query suggestions
Authors: Bonart Malte , Samokhina Anastasiia , Heisenberg Gernot , Schaer Philipp
Published: December 2019

Purpose

Survey-based studies suggest that search engines are trusted more than social media or even traditional news, although cases of false information or defamation are known. The purpose of this paper is to analyze query suggestion features of three search engines to see if these features introduce some bias into the query and search process that might compromise this trust. The authors test the approach on person-related search suggestions by querying the names of politicians from the German Bundestag before the German federal election of 2017.

Design/methodology/approach

This study introduces a framework to systematically examine and automatically analyze the varieties in different query suggestions for person names offered by major search engines. To test the framework, the authors collected data from the Google, Bing and DuckDuckGo query suggestion APIs over a period of four months for 629 different names of German politicians. The suggestions were clustered and statistically analyzed with regards to different biases, like gender, party or age and with regards to the stability of the suggestions over time.

Findings

By using the framework, the authors located three semantic clusters within the data set: suggestions related to politics and economics, location information and personal and other miscellaneous topics. Among other effects, the results of the analysis show a small bias in the form that male politicians receive slightly fewer suggestions on “personal and misc” topics. The stability analysis of the suggested terms over time shows that some suggestions are prevalent most of the time, while other suggestions fluctuate more often.

Originality/value

This study proposes a novel framework to automatically identify biases in web search engine query suggestions for person-related searches. Applying this framework on a set of person-related query suggestions shows first insights into the influence search engines can have on the query process of users that seek out information on politicians.
Legitimacy and relevance of a performance measurement system in a Finnish public-sector case
Authors: Mättö Toni , Anttonen Jenna , Järvenpää Marko , Rautiainen Antti
Published: December 2019

Purpose

This study investigates the difficulties involved in translating stakeholder expectations into action and maintaining legitimacy through the use of a performance measurement system (PMS) created in a Finnish regional development company (RDC). This longitudinal case study illustrates the fluctuating and socially constructed nature of legitimacy in the public sector.

Design/methodology/approach

This qualitative case study longitudinally analyzes the various developments occurring during and after the development of a PMS system for the case organization. Empirical data include interviews, workshops, observation and other materials relating to the case organization.

Findings

The initial interest in operational improvement changed to legitimation-seeking behavior by the case organization when the measures created were modified to accord with the changed preferences of the key stakeholders. However, the pursuit of legitimacy for the RDC was made difficult by the outcome-oriented, changing and contradictory nature of stakeholders’ demands. This study’s findings reveal a continuous mismatch between organizational activities and the board’s expectations, leading to the eventual closure of the organization.

Practical implications

The findings help to analyze the legitimacy and relevance of PMSs in public-sector projects. The study highlights the practical importance of analyzing the different legitimacy priorities of various stakeholder groups, such as politicians and entrepreneurs.

Originality/value

The study analyzes the fluctuating nature of legitimacy longitudinally in the public-sector context from the stakeholder perspective. This study analyzes a situation where the stakeholders’ evaluations of the legitimacy of the organization, and the PMS developed, change over time, complicating the accounting for stakeholders.
Impact of Custodiol‐N cardioplegia on acute kidney injury after cardiopulmonary bypass
Authors: Feirer Nina , Dieterlen Maja‐Theresa , Klaeske Kristin , Kiefer Philipp , Oßmann Susann , Salameh Aida , Borger Michael A. , Hoyer Alexandro
Published: December 2019

Myocardial protection during cardiopulmonary bypass (CPB) can be achieved using cardioplegic solutions. Although, acute kidney injury (AKI) is a common complication following CPB, the effects of cardioplegic solutions on AKI have rarely been investigated. Within this study, the effects of the cardioplegic solutions histidine‐tryptophan‐ketoglutarate (HTK; Custodiol) and HTK‐N (Custodiol‐N) on AKI in a large animal model were compared. Therefore, Landrace pigs underwent median sternotomy, CPB at 34°C, 90 minutes of cardiac arrest and 120 minutes of reperfusion. Animals were randomized for single‐shot cardioplegia with either HTK (n = 10) or HTK‐N (n = 10). Renal biopsies and sera were analyzed to determine AKI biomarkers and apoptosis. Compared to HTK, HTK‐N induced a decreased extent of proximal tubule swelling (48.3 ± 1.6 µm vs 52.3 ± 1.1 µm, P = .05) and decreased cytochrome c release (0.26 ± 0.04 vs 0.46 ± 0.08, P = .04) without reaching statistical significance due to Bonferroni correction. Comparing baseline and postreperfusion levels, the hemoglobin (Hb) and blood calcium levels were lower in HTK‐N (Hbbaseline: 6.0 ± 0.6 mmol/L, Hbreperfusion: 6.2 ± 0.7 mmol/L, P = .12; Ca2+baseline: 1.36 ± 0.05 mmol/L, Ca2+reperfusion: 1.28 ± 0.05 mmol/L, P = .16) compared to the HTK group (Hbbaseline: 5.9 ± 0.4 mmol/L, Hbreperfusion: 4.7 ± 0.8 mmol/L, P < .01; Ca2+baseline: 1.34 ± 0.07 mmol/L, Ca2+reperfusion: 1.24 ± 0.06 mmol/L, P < .01). The present study showed that HTK‐N could positively affect the kidney during CPB. Hb and calcium levels were stabilized. A statistical trend was found showing that AKI‐related proximal tubule swelling and cytochrome c release were diminished.