bluuebunny/crossref_metadata_2025 huggingface dataset:
Are women leaders significantly better at controlling the contagion?
Authors: Purkayastha Soumik , Salvatore Maxwell , Mukherjee Bhramar
Published: June 2020

Recent media articles have suggested that women-led countries are doing better in terms of their responses to the COVID-19 pandemic. We examine an ensemble of public health metrics to assess the control of COVID-19 epidemic in women- versus men-led countries worldwide based on data available up to June 3. The median of the distribution of median time-varying effective reproduction number for women- and men-led countries were 0.89 and 1.14 respectively with the 95% two-sample bootstrap-based confidence interval for the difference (women - men) being [- 0.34, 0.02]. In terms of scale of testing, the median percentage of population tested were 3.28% (women), 1.59% (men) [95% CI: (−1.29%, 3.60%)] with test positive rates of 2.69% (women) and 4.94% (men) respectively. It appears that though statistically not significant, countries led by women have an edge over countries led by men in terms of public health metrics for controlling the spread of the COVID-19 pandemic worldwide.

One Sentence Summary

We quantitatively compare countries led by women with countries led by men in terms of public health metrics for controlling the spread of the novel coronavirus.
Explaining face representation in the primate brain using different computational models
Authors: Chang Le , Egger Bernhard , Vetter Thomas , Tsao Doris Y.
Published: June 2020

Understanding how the brain represents the identity of complex objects is a central challenge of visual neuroscience. The principles governing object processing have been extensively studied in the macaque face patch system, a sub-network of inferotemporal (IT) cortex specialized for face processing. A previous study reported that single face patch neurons encode axes of a generative model called the “active appearance” model, which transforms 50-d feature vectors separately representing facial shape and facial texture into facial images. However, a systematic investigation comparing this model to other computational models, especially convolutional neural network models that have shown success in explaining neural responses in the ventral visual stream, has been lacking. Here, we recorded responses of cells in the most anterior face patch AM to a large set of real face images and compared a large number of models for explaining neural responses. We found that the active appearance model better explained responses than any other model except CORnet-Z, a feedforward deep neural network trained on general object classification to classify non-face images, whose performance it tied on some face image sets and exceeded on others. Surprisingly, deep neural networks trained specifically on facial identification did not explain neural responses well. A major reason is that units in the network, unlike neurons, are less modulated by face-related factors unrelated to facial identification such as illumination.
SCHNAPPs - Single Cell sHiNy APPlication(s)
Authors: Jagla Bernd , Rouilly Vincent , Puceat Michel , Hasan Milena
Published: June 2020

Motivation

Single-cell RNA-sequencing (scRNAseq) experiments are becoming a standard tool for bench-scientists to explore the cellular diversity present in all tissues. On one hand, the data produced by scRNASeq is technically complex, with analytical workflows that are still very much an active field of bioinformatics research, and on the other hand, a wealth of biological background knowledge is often needed to guide the investigation. Therefore, there is an increasing need to develop applications geared towards bench-scientists to help them abstract the technical challenges of the analysis, so that they can focus on the Science at play. It is also expected that such applications should support closer collaboration between bioinformaticians and bench-scientists by providing reproducible science tools.

Results

We present SCHNAPPs, a computer program designed to enable bench-scientists to autonomously explore and interpret single cell RNA-seq expression data and associated annotations. The Shiny-based application allows selecting genes and cells of interest, performing quality control, normalization, clustering, and differential expression analyses, applying standard workflows from Seurat (Stuart et al., 2019) or Scran (Lun et al., 2016) packages, and most of the common visualizations. An R-markdown report can be generated that tracks the modifications, and selected visualizations facilitating communication and reproducibility between bench-scientist and bioinformatician. The modular design of the tool allows to easily integrate new visualizations and analyses by bioinformaticians. We still recommend that a data analysis specialist oversees the analysis and interpretation.

Availability

The SCHNAPPs application, docker file, and documentation are available on GitHub:https://c3bi-pasteur-fr.github.io/UTechSCB-SCHNAPPs; Example contribution are available at the following GitHub site:https://github.com/baj12/SCHNAPPsContributions.
Decomposing metabolite set activity levels with PALS
Authors: McLuskey Karen , Wandy Joe , Vincent Isabel , van der Hooft Justin J.J. , Rogers Simon , Burgess Karl , Daly Rónán
Published: June 2020

Motivation

Related metabolites can be grouped into metabolite sets in many ways. Examples of these include the grouping of metabolites through their participation in a series of chemical reactions (forming metabolic pathways); or based on fragmentation spectral similarities and shared chemical substructures. Understanding how such metabolite sets change across samples can be incredibly useful in the interpretation and understanding of complex metabolomics data. However many of the available tools suitable for the enrichment analysis of metabolite sets are based on simple methods that badly handle the missing features inherent in untargeted metabolomics measurements and can be difficult to integrate into existing applications.

Results

We present PALS (Pathway Activity Level Scoring), a Python library, command-line tool and Web application that performs the ranking of significantly-changing metabolite sets over different experimental conditions. As example applications, PALS is used to analyse metabolites grouped as pathways and by common MS-MS fragmentation structures. A comparison of PALS with two other commonly used methods (ORA and GSEA) is also given, and reveals that PALS is more robust to missing peaks and noisy data than the alternatives. We report results from using PALS to analyse pathways from a study of Human African Trypanosomiasis. Finally, we also report how PALS used tandem MS fragmentation structures to reveal enriched metabolite sets between clades in Rhamnaceae plant data, and on American Gut Project data.

Availability

PALS is freely available from our project Web site athttps://pals.glasgowcompbio.org/. It can be imported as a Python library, run as a stand-alone tool or used as a web application.
TBPL2/TFIIA complex establishes the maternal transcriptome by an oocyte-specific promoter usage
Authors: Yu Changwei , Cvetesic Nevena , Hisler Vincent , Gupta Kapil , Ye Tao , Gazdag Emese , Negroni Luc , Hajkova Petra , Berger Imre , Lenhard Boris , Müller Ferenc , Vincent Stéphane D. , Tora László
Published: June 2020

During oocyte growth, transcription is required to create RNA and protein reserves to achieve maternal competence. During this period, the general transcription factor TATA binding protein (TBP) is replaced by its paralogue, TBPL2 (TBP2 or TRF3), which is essential for RNA polymerase II transcription. We show that in oocytes TBPL2 does not assemble into a canonical TFIID complex. Our transcript analyses demonstrate that TBPL2 mediates transcription of oocyte-expressed genes, including mRNA survey genes, as well as specific endogenous retroviral elements. Transcription start site (TSS) mapping indicates that TBPL2 has a strong preference for TATA-like motif in core promoters driving sharp TSS selection, in contrast with canonical TBP/TFIID-driven TATA-less promoters that have broader TSS architecture. Thus, we show a role for the TBPL2/TFIIA complex in the establishment of the oocyte transcriptome by using a specific TSS recognition code.
Arginine methylation promotes siRNA-binding specificity for a spermatogenesis-specific isoform of the Argonaute protein CSR-1
Authors: Nguyen Dieu An H. , Phillips Carolyn M.
Published: June 2020

CSR-1 is an essential Argonaute protein that binds to a subclass of 22G-RNAs targeting most germline-expressed genes. Here we show that the two isoforms of CSR-1 have distinct expression patterns; CSR-1B is ubiquitously expressed throughout the germline and during all stages of development while CSR-1A expression is restricted to germ cells undergoing spermatogenesis. Furthermore, CSR-1A associates preferentially with 22G-RNAs mapping to spermatogenesis-specific genes whereas CSR-1B-bound small RNAs map predominantly to oogenesis-specific genes. Interestingly, the exon unique to CSR-1A contains multiple dimethylarginine modifications, which are necessary for the preferential binding of CSR-1A to spermatogenesis-specific 22G-RNAs. Thus, we have discovered a regulatory mechanism forC. elegansArgonaute proteins that allows for specificity of small RNA binding between similar Argonaute proteins with overlapping temporal and spatial localization.
Pan-resistantCandida auris: New York Sub-cluster Susceptible to Antifungal Combinations
Authors: O’Brien Brittany , Liang Jiali , Chaturvedi Sudha , Jacobs Jonathan L. , Chaturvedi Vishnu
Published: June 2020

Four pan-resistantCandia aurisstrains from New York outbreak were 100% inhibitedin vitroby combinations of two antifungal drugs using fixed concentrations achievablein vivo. Pan-resistantC. aurisstrains have mutations in eleven gene targets associated with major antifungal drugs, and constituted a distinct sub-cluster among NY strains.
EEG in Motion: Using an Oddball Task to Explore Motor Interference in Active Skateboarding
Authors: Robles Daniel , Kuziek Jonathan W. P. , Wlasitz Nicole A. , Bartlett Nathan T. , Hurd Pete L. , Mathewson Kyle E.
Published: June 2020

Recent advancements in portable computer devices have opened new avenues in the study of human cognition outside research laboratories. This flexibility in methodology has led to the publication of several Electroencephalography (EEG) studies recording brain responses in real-world scenarios such as cycling and walking outside. In the present study, we tested the classic auditory oddball task while participants moved around an indoor running track using an electric skateboard. This novel approach allows for the study of attention in motion while virtually removing body movement. Using the skateboard auditory oddball paradigm, we found reliable and expected standard-target differences in the P3 and MMN/N2b event-related potentials (ERPs). We also recorded baseline EEG activity and found that, compared to this baseline, alpha power is attenuated in frontal and parietal regions during skateboarding. In order to explore the influence of motor interference in cognitive resources during skateboarding, we compared participants’ preferred riding stance (baseline level of riding difficulty) vs their non-preferred stance (increased level of riding difficulty). We found that an increase in riding difficulty did not modulate the P3 and tonic alpha amplitude during skateboard motion. These results suggest that increases in motor demands might not lead to reductions in cognitive resources as shown in previous literature.
Split-HaloTag®Imaging Assay for Sophisticated Microscopy of Protein-Protein Interactionsin planta
Authors: Minner-Meinen Rieke , Weber Jan-Niklas , Albrecht Andreas , Matis Rainer , Behnecke Maria , Tietge Cindy , Frank Stefan , Schulze Jutta , Buschmann Henrik , Walla Peter Jomo , Mendel Ralf-R. , Hänsch Robert , Kaufholdt David
Published: June 2020

An ever-increasing number of intracellular multi-protein networks have been identified in plant cells. Split-GFP based protein-protein interaction assays combine the advantages ofin vivointeraction studies in a native environment with additional visualisation of protein complex localisation. Due to its simple protocols, it has become one of the most frequently used methods. However, standard fluorescent proteins entail several drawbacks for sophisticated microscopy.

With the HaloTag®system, these drawbacks can be overcome as this reporter forms covalent irreversible bonds with synthetic photostable fluorescent ligands. Dyes can be used in adjustable concentrations and are suitable for advanced microscopy methods. Therefore, we established the Split-HaloTag®imaging assay in plants which is based on the reconstitution of a functional HaloTag®protein upon protein-protein interaction and subsequent covalent binding of an added fluorescent ligand. Its suitability and robustness were demonstrated using well-characterised interactions as an example for protein-protein interaction at cellular structures: the molybdenum cofactor biosynthesis complex anchoring to filamentous actin. Additionally, a specific interaction was visualised with subdiffractional polarisation microscopy in a more distinctive manner as example for sophisticated imaging.

Split-GFP and Split-HaloTag®can complement one another as Split-HaloTag®represents an alternative option and an addition to the large toolbox ofin vivomethods. Therefore, this promising new Split-HaloTag®imaging assay provides a unique and sensitive approach for more detailed characterization of protein-protein interaction with specific microscopic techniques such as 3D-imaging, single molecule tracking and super-resolution microscopy.
Quantitative fluorescence lifetime imaging uncovers a novel role for KCC2 chloride transport in dendritic microdomains
Authors: Weilinger Nicholas L. , LeDue Jeffrey M. , Kahle Kristopher T. , MacVicar Brian A.
Published: June 2020

Intracellular chloride ion ([Cl−]i) homeostasis is critical for synaptic neurotransmission yet variations in subcellular domains are poorly understood owing to difficulties in obtaining quantitative, high-resolution measurements of dendritic [Cl−]i. We combined whole-cell patch clamp electrophysiology with simultaneous fluorescence lifetime imaging (FLIM) of the Cl−dye MQAE to quantitatively map dendritic Cl−levels in normal or pathological conditions. FLIM-based [Cl−]iestimates were corroborated by Rubi-GABA uncaging to measured EGABA. Low baseline [Cl-]iin dendrites required Cl−efflux via the K+-Cl−cotransporter KCC2 (SLC12A5). In contrast, pathological NMDA application generated spatially heterogeneous subdomains of high [Cl−]ithat created dendritic blebs, a signature of ischemic stroke. These discrete regions of high [Cl−]iwere caused by reversed KCC2 transport. Therefore monitoring [Cl−]imicrodomains with a new high resolution FLIM-based technique identified novel roles for KCC2-dependent chloride transport to generate dendritic microdomains with implications for disease.
Time-resolved profiling reveals ATF3 as a novel mediator of endocrine resistance in breast cancer
Authors: Borgoni Simone , Sofyalı Emre , Soleimani Maryam , Wilhelm Heike , Müller-Decker Karin , Will Rainer , Noronha Ashish , Verschure Pernette J. , Yarden Yosef , Magnani Luca , van Kampen Antoine H.C. , Moerland Perry D. , Wiemann Stefan
Published: June 2020

Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α (ERα) account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, 40% of these tumors eventually relapse due to resistance development and further treatment of these patients is highly ineffective. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmedin vivoin a mouse model and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities.
Differential causal involvement of human auditory and frontal cortices in vocal motor control
Authors: Cardenas Araceli R. , Behroozmand Roozbeh , Kocsis Zsuzsanna , Gander Phillip E. , Nourski Kirill V. , Kovach C Christopher K. , Ibayashi Kenji , Pipoly Marco , Kawasaki Hiroto , Howard Matthew A. , Greenlee Jeremy D.W.
Published: June 2020

Speech motor control requires integration of sensory and motor information. Bidirectional communication between frontal and auditory cortices is crucial for speech production, self-monitoring and motor control. We used cortical direct electrical stimulation (DES) to functionally dissect audio-motor interactions underlying speech production and motor control. Eleven neurosurgical patients performed a visually cued vocal task in which a short auditory feedback perturbation was introduced during vocalization. We evaluated the effect of DES on vocal initiation, voice fundamental frequency (F0) and feedback-dependent motor control. DES of frontal sites modulated vocal onset latencies. Stimulation of different inferior frontal gyrus sites elicited either shortening or prolongation of vocal latencies. DES distinctly modulated voice F0 at different vocalization stages. Frontal and temporal areas played an important role in setting voice F0 in the first 250 ms of an utterance, while Heschl’s gyrus was involved later when auditory input is available for self-monitoring. Vocal responses to pitch-shifted auditory feedback were mostly reduced by DES of non-core auditory cortices. Overall, we demonstrate that vocal planning and initiation are driven by frontal cortices, while feedback-dependent control relies predominantly on non-core auditory cortices. Our findings represent direct evidence of the role played by different auditory and frontal regions in vocal motor control.
Modelling fibrillogenesis of collagen-mimetic molecules
Authors: Hafner A. E. , Gyori N. G. , Bench C. A. , Davis L. K. , Šarić A.
Published: June 2020

One of the most robust examples of self-assembly in living organisms is the formation of collagen architectures. Collagen type I molecules are a crucial component of the extracellular-matrix where they self-assemble into fibrils of well defined striped patterns. This striped fibrilar pattern is preserved across the animal kingdom and is important for the determination of cell phenotype, cell adhesion, and tissue regulation and signalling. The understanding of the physical processes that determine such a robust morphology of self-assembled collagen fibrils is currently almost completely missing. Here we develop a minimal coarse-grained computational model to identify the physical principles of the assembly of collagen-mimetic molecules. We find that screened electrostatic interactions can drive the formation of collagen-like filaments of well-defined striped morphologies. The fibril pattern is determined solely by the distribution of charges on the molecule and is robust to the changes in protein concentration, monomer rigidity, and environmental conditions. We show that the fibril pattern cannot be easily predicted from the interactions between two monomers, but is an emergent result of multi-body interactions. Our results can help address collagen remodelling in diseases and ageing, and guide the design of collagen scaffolds for biotechnological applications.

Statement of Significance

Collagen type I protein is the most abundant protein in mammals. It is a crucial component of the extracellular-matrix where it robustly self-assembles into fibrils of specific striped architectures that are crucial for the correct collagen function. The molecular features that determine such robust fibril architectures are currently not well understood. Here we develop a minimal coarse-grained model to connect the design of collagen-like molecules to the architecture of the resulting self-assembled fibrils. We find that the pattern of charged residues on the surface of molecules can drive the formation of collagen-like fibrils and fully control their architectures. Our findings can help understand changes in collagen architectures observed in diseases and guide the design of synthetic collagen scaffolds.
A transplantation experiment yields no evidence for phenotypic plasticity in shell band width inCepaea nemoralis
Authors: Schilthuizen Menno , Scheid Ruth K. , den Daas Lia J. J.
Published: June 2020

The common European grove snail,Cepaea nemoralis(Helicidae), has been a model species in genetics and evolutionary biology for over a century thanks largely to its genetic shell colour polymorphism. Although most aspects of its shell colour variation are known to be purely genetic, with little or no phenotypic plasticity involved, the width of the spiral bands has been suspected to display a certain amount of plasticity. To test this, we conducted a transplantation experiment, in which 548 growing banded snails were marked and transplanted, either within the same habitat (open or closed vegetation, displaying 19% and 61% band fusion, respectively) or between habitat types. The numbers recaptured were low: 8%, 5% after removal of individuals that had not grown. Based on these samples, we did not find any substantial influence of transplantation on band width.
Heterotrimeric PCNA Increases the Activity and Fidelity of Dbh, a Y-family Translesion DNA Polymerase Prone to Creating Single-Base Deletion Mutations
Authors: Wu Yifeng , Jaremko William , Wilson Ryan C. , Pata Janice D.
Published: June 2020

Dbh is a Y-family translesion DNA polymerase fromSulfolobus acidocaldarius, an archaeal species that grows in harsh environmental conditions. Biochemically, Dbh displays a distinctive mutational profile, creating single-base deletion mutations at extraordinarily high frequencies (up to 50%) in specific repeat sequences. In cells, however, Dbh does not appear to contribute significantly to spontaneous frameshifts in these same sequence contexts. This suggests that either the error-prone DNA synthesis activity of Dbh is reduced in vivo and/or Dbh is restricted from replicating these sequences. Here, we test the hypothesis that the propensity for Dbh to make single base deletion mutations is reduced through interaction with theS. acidocaldariusheterotrimeric sliding clamp processivity factor, PCNA-123. We first confirm that Dbh physically interacts with PCNA-123, with the interaction requiring both the PCNA-1 subunit and the C-terminal 10 amino acids of Dbh, which contain a predicted PCNA-interaction peptide (PIP) motif. This interaction stimulates the polymerase activity of Dbh, even on short, linear primer-template DNA by increasing the rate of nucleotide incorporation. This stimulation requires an intact PCNA-123 heterotrimer and a DNA duplex length of at least 18 basepairs, the minimal length predicted from structural data to bind to both the polymerase and the clamp. Finally, we find that PCNA-123 increases the fidelity of Dbh on a single-base deletion hotspot sequence 3-fold by promoting an increase in the rate of correct, but not incorrect, nucleotide addition and propose that PCNA-123 induces Dbh to adopt a more active conformation that is less prone to creating deletions during DNA synthesis.

Highlights

PCNA increases the fidelity of Dbh polymerase on a deletion-hotspot sequence.

The interaction stimulates incorporation of the correct, but not incorrect, nucleotide.

A minimal duplex length of 18 bp is required for PCNA to stimulate polymerase activity.

Structural modeling suggests that PCNA induces a conformational change in Dbh.
Baseline epidemiology and associated dog ecology study towards stepwise elimination of rabies in Kwara state, Nigeria
Authors: Al-Mustapha Ahmad Ibrahim , Tijani Abubakar Ahmed , Muftau Oyewo , Bamidele Folashade Onatola , Ibrahim Ahmed , Osu Muhammad Shuaib , Olugasa Babasola , Balogun Muhammad Shakir , Kia Grace , Mazeri Stella , Heikinheimo Annamari
Published: June 2020

Understanding domestic dog population dynamics and ecology is necessary for any effective rabies control program. This study was conducted as part of the baseline epidemiological studies necessary for the establishment of the Kwara Rabies Rapid Alert System “KRRAS”. The aim of this study was to determine the dog population structure of Kwara State by assessing the dog ownership, vaccination status, and prevalence of dog bites.

A total of 1,460 questionnaires were administered to respondents in the three senatorial zones of the state using Open Data Kit (ODK) between June 2019 to January 2020.

Of the 1460 households surveyed, 293 (20.1%) owned at least one dog with an average of 2.25 dogs per household. The male to female ratio was 2.2:1 and 85% (n=250/293) of the owned dogs were local breeds. A total of 785 dogs was enumerated (659 dogs from 293 households and 126 free-roaming dogs) and 7811 persons which resulted in a dog-human ratio of 1:9.95. The estimated dog population is 376,789 (95% CI: 343,700 – 379,878). The dog anti-rabies vaccination coverage was 31% (n=92/293). The prevalence of dog-bite was 13% (n=193/1460) of which only 27% of the victims (n=61/225) received post-exposure prophylaxis (PEP). The ethnicity of respondents had a significant impact on dog ownership. Yoruba’s more often (OR: 2.2-5; 95% CI: 1.2 − 12.4; p < 0.001) owned dogs than other tribes. The vaccination status of owned dogs was greatly impacted by the level of education of the respondents (OR: 5.03; 95% CI: 1.5073 − 16.8324; p<0.001); the breed of the dog with exotic dogs being more vaccinated (OR: 2.8; 95% CI: 0.7150 − 10.857; p<0.001) and the confinement of the dog (OR: 2.07; 95% CI: 1.1592 – 3.7037; p < 0.001). Always confined dogs were twice more vaccinated than non-confined dogs. The results of the study showed that the vaccination coverage needs to be increased, the number of dog bites needs to be reduced, the number of non-confined dogs needs to be reduced and stray dog control strategies need to be implemented. The findings of this study showed very low vaccination coverage for dogs which is below the 70-80% target recommended for herd immunity by the world health organization.
DotMotif: An open-source tool for connectome subgraph isomorphism search and graph queries
Authors: Matelsky Jordan K. , Reilly Elizabeth P. , Johnson Erik C. , Stiso Jennifer , Bassett Danielle S. , Wester Brock A. , Gray-Roncal William
Published: June 2020

Recent advances in neuroscience have enabled the exploration of brain structure at the level of individual synaptic connections. These connectomics datasets continue to grow in size and complexity; methods to search for and identify interesting graph patterns offer a promising approach to quickly reduce data dimensionality and enable discovery. These graphs are often too large to be analyzed manually, presenting significant barriers to searching for structure and testing hypotheses. We combine graph database and analysis libraries with an easy-to-use neuroscience grammar suitable for rapidly constructing queries and searching for subgraphs and patterns of interest. Our approach abstracts many of the computer science and graph theory challenges associated with nanoscale brain network analysis and allows scientists to quickly conduct research at scale. We demonstrate the utility of these tools by searching for motifs on simulated data and real public connectomics datasets, and we share simple and complex structures relevant to the neuroscience community. We contextualize our findings and provide case studies and software to motivate future neuroscience exploration.
Structural basis of client specificity in mitochondrial membrane-protein chaperones
Authors: Sučec Iva , Wang Yong , Dakhlaoui Ons , Weinhäupl Katharina , Jores Tobias , Costa Doriane , Hessel Audrey , Brennich Martha , Rapaport Doron , Lindorff-Larsen Kresten , Bersch Beate , Schanda Paul
Published: June 2020

Chaperones are essential for assisting protein folding, and for transferring poorly soluble proteins to their functional locations within cells. Hydrophobic interactions drive promiscuous chaperone–client binding, but our understanding how additional interactions enable client specificity is sparse. Here we decipher what determines binding of two chaperones (TIM8·13, TIM9·10) to different integral membrane proteins, the alltransmembrane mitochondrial carrier Ggc1, and Tim23 which has an additional disordered hydrophilic domain. Combining NMR, SAXS and molecular dynamics simulations, we determine the structures of Tim23/TIM8·13 and Tim23/TIM9·10 complexes. TIM8·13 uses transient salt bridges to interact with the hydrophilic part of its client, but its interactions to the trans-membrane part are weaker than in TIM9·10. Consequently, TIM9·10 is outcompeting TIM8·13 in binding hydrophobic clients, while TIM8·13 is tuned to few clients with both hydrophilic and hydrophobic parts. Our study exemplifies how chaperones fine-tune the balance of promiscuityvs. specificity.
Design of optical imaging probes by screening of diverse substrate libraries directly in disease tissue extracts
Authors: Tholen Martina , Yim Joshua J. , Groborz Katarzyna , Yoo Euna , Martin Brock A. , van den Berg Nynke S. , Drag Marcin , Bogyo Matthew
Published: June 2020

Fluorescently-quenched probes that are specifically activated in the cancer microenvironment have great potential application for diagnosis, early detection and surgical guidance. These probes are often designed to target specific enzymes associated with disease by direct optimization using single purified targets. However, this can result in painstaking chemistry efforts to produce a probe with suboptimal performance when appliedin vivo. We describe here an alternate, unbiased activity-profiling approach in which whole tissue extracts are used to directly identify optimal peptide sequences for probe design. Screening of mouse mammary tumor extracts with a hybrid combinatorial substrate library (HyCoSuL) identified a combination of natural and non-natural amino acid residues that could be used to generate highly efficient tumor-specific fluorescently quenched substrate probes. The most effective probe is significantly brighter than any of our previously reported tumor imaging probes designed for specific proteases and robustly discriminates tumor tissue from adjacent healthy tissue in a mouse model of cancer. Importantly, although the probes were developed by screening mouse mammary tumor tissues, they are able to effectively distinguish human ductal carcinomas from normal breast tissue with similar reactivity profiles to those observed in mouse tissues. This new strategy simplifies and enhances the process of probe optimization by direct screening in a tissue of interest without any a priori knowledge of enzyme targets. It has the potential to be applied to advance the development of probes for diverse disease states for which clinical or animal model tissues are available.
Time-series plasma cell-free DNA analysis reveals disease severity of COVID-19 patients
Authors: Chen Xinping , Lin Yu , Wu Tao , Xu Jinjin , Ma Zhichao , Sun Kun , Li Hui , Luo Yuxue , Zhang Chen , Chen Fang , Wang Jiao , Kuo Tingyu , Li Xiaojuan , Geng Chunyu , Lin Feng , Huang Chaojie , Hu Junjie , Yin Jianhua , Liu Ming , Tao Ye , Zhang Jiye , Ou Rijing , Xiao Furong , Yang Huanming , Wang Jian , Xu Xun , Fu Shengmiao , Jin Xin , Jiang Hongyan , Chen Ruoyan
Published: June 2020

Clinical symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. Detection of individuals at high risk for critical condition is crucial for control of the disease. Herein, for the first time, we profiled and analyzed plasma cell-free DNA (cfDNA) of mild and severe COVID-19 patients. We found that in comparison between mild and severe COVID-19 patients, Interleukin-37 signaling was one of the most relevant pathways; top significantly altered genes included POTEH, FAM27C, SPATA48, which were mostly expressed in prostate and testis; adrenal glands, small intestines and liver were tissues presenting most differentially expressed genes. Our data thus revealed potential tissue involvement, provided insights into mechanism on COVID-19 progression, and highlighted utility of cfDNA as a noninvasive biomarker for disease severity inspections.

One Sentence Summary

CfDNA analysis in COVID-19 patients reveals severity-related tissue damage.
Seroprevalence of IgG antibodies against SARS coronavirus 2 in Belgium – a serial prospective cross-sectional nationwide study of residual samples (March – October 2020)
Authors: Herzog Sereina , De Bie Jessie , Abrams Steven , Wouters Ine , Ekinci Esra , Patteet Lisbeth , Coppens Astrid , De Spiegeleer Sandy , Beutels Philippe , Van Damme Pierre , Hens Niel , Theeten Heidi
Published: June 2020

To assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the national lock-down in Belgium, a nationwide seroprevalence study, stratified by age, sex and region using 3000-4000 residual samples was performed during 7 periods between 30 March and 17 October 2020. Residual sera from ambulatory patients were analyzed for IgG antibodies against S1 proteins of SARS-CoV-2 with a semi-quantitative commercial ELISA. Weighted seroprevalence (overall, by age category and sex) and seroincidence during 7 consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity.

The weighted overall seroprevalence initially increased from 1.8% (95% CrI 1.0-2.6) to 5.3% (95% CrI 4.2-6.4), implying a seroincidence of 3.4% (95% CrI 2.4-4.6) between the 1st and 2nd collection period over a period of 3 weeks during the lockdown period (start lockdown mid March 2020). Thereafter, seroprevalence stabilized, however, significant decreases are observed when comparing the 3rd with the 5th and also with the 6th period resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid October 2020 a weighted overall seroprevalence of 4.2% (95% CrI 3.1-5.2).

During lockdown, an initial small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.
SARS-CoV-2 in first trimester pregnancy – does it affect the fetus?
Authors: Cour Freiesleben Nina la , Egerup Pia , Römmelmayer Hviid Kathrine Vauvert , Severinsen Elin Rosenbek , Kolte Astrid Marie , Westergaard David , Olsen Line Fich , Prætorius Lisbeth , Zedeler Anne , Christiansen Ann-Marie Hellerung , Nielsen Josefine Reinhardt , Bang Didi , Berntsen Sine , Ollé-López Joaquim , Ingham Andreas , Bello-Rodríguez Judith , Storm Ditte Marie , Ethelberg-Findsen Jeppe , Hoffmann Eva R , Wilken-Jensen Charlotte , Jørgensen Finn Stener , Westh Henrik , Løvendahl Jørgensen Henrik , Nielsen Henriette Svarre
Published: June 2020

Background

Several viral infections are known to be harmful to the fetus in the first trimester of pregnancy and can cause increased nuchal translucency thickness and pregnancy loss. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies.

Methods

Cohort 1 included pregnant women with a double test taken between Feb. 17 and Apr. 23, 2020, during the SARS-CoV-2 epidemic peak in Denmark. The double test was taken as part of the first trimester risk assessment. Cohort 2 included women with a first trimester pregnancy loss before double test. Serum from the double test or from a blood sample, in case of pregnancy loss, was analyzed for SARS-CoV-2 antibodies. The results were correlated to the nuchal translucency thickness and the number of pregnancy losses.

Results

In total, 1,019 pregnant women with double test and 36 women with pregnancy loss participated in the study. Thirty (2.9%) women had SARS-CoV-2 antibodies in the serum from the double test. All women with pregnancy loss prior to the double test were negative for SARS-CoV-2 antibodies. There were no significant differences in nuchal translucency thickness for women testing positive (n=14) versus negative (p=0.20) or grey zone (n=16) versus negative (p=0.28). In total, 54 women experienced a pregnancy loss of whom two had grey zone or positive SARS-CoV-2 antibodies.

Conclusion

Maternal SARS-CoV-2 infection did not seem harmful in first trimester pregnancies. Infection had no effect on the nuchal translucency thickness and women with SARS-CoV-2 antibodies were not overrepresented among women with pregnancy loss.
Quantifying hospital flows and occupancy due to COVID-19 outbreak in France. Was French lockdown effective?
Authors: Ternant David
Published: June 2020

Context

The spread of SARS-CoV-2 led to a rapid and deadly pandemic which reached almost all countries in the world in a few months. In most countries, rigorous measures of mitigation, including national or subnational lockdowns were established. The present work aimed at quantifying the effect of national lockdown in France on hospital occupancy.

Methods

A compartmental model describing patient hospital flows was developed, where the effect of lockdown was quantified on the hospitalization rate. Model parameters were estimated using nonlinear mixed-effects (NLME) modelling.

Results

French lockdown led to a hospitalization rate decreased by thrice from 12 days after its beginning. However, lockdown may not to have decreased either hospital occupancy or deaths in hospital, which would have been both decreased by 30% and 85% in average if lockdown was started 20 and 30 days before this date, respectively.

Conclusion

The present work showed an intrinsic effect of lockdown to decrease hospital burden, but its efficacy on hospital burden may have been increased if established sooner.
Two N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamides as disordered ethanol monosolvates
Authors: Harish Chinthal Chayanna , Yathirajan Hemmige S. , Kadambar Anish Kumar , Kalluraya Balakrishna , Foro Sabine , Glidewell Christopher
Published: June 2020

Two new N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formylsydnones and N-[(4-amino-5-sulfanylidene-1H-1,2,4-triazol-3-yl)methyl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O (I), and N-({4-[3-(4-methylphenyl)-4-sydnonylideneamino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl}methyl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O (II), differ only in the presence of a methyl group for (II) instead of a hydrogen atom for (I), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in (I), and 0.906 (6) and 0.094 (6) in (II). Combinations of O—H...O and N—H...O hydrogen bonds link the molecules into cyclic, centrosymmetric four-molecule aggregates. Comparisons are made with the structures of some related compounds.
Psychological ownership in social media influencer marketing
Authors: Pick Mandy
Published: June 2020

Purpose

Social media, especially social media-based influencer marketing, has become an important factor in consumer decision-making. Studies have recently begun investigating how influencers affect consumer behaviour. Despite the increasing interest, the purpose of this study is to examine influencers’ evaluation impact on consumer behaviour are scarce.

Design/methodology/approach

An online study undertook research to gain further understanding. Specifically, the study examines the following: firstly, the impact of consumers’ perceived influencer credibility (IC), using the source credibility model in respect of purchase intention, attitude towards advertising and product; secondly, the impact of the organizational behaviour concept psychological ownership (PO) on consumer behaviour by showing that the concept has significant positive effects on attitude towards the product and purchase intention like in prior research; thirdly, the perceived connection and relationship between the influencer and consumer to understand the relations.

Findings

The results show that perceived IC serves as a significant criterion, determining purchase intention, attitude towards advertising and product, while contributing an instrument for transferring convincing messages, which increase the perceived connection to the influencer and the PO feeling for a product and, thus, influence consumer behaviour positively.

Originality/value

Theories on source credibility and a connection to the PO concept allowed to develop a framework to assess the importance of IC and its influence on consumers’ perception of the products that influencers advertise to better understand the interactions in the influencer marketing context.
GDPR compliance: proposed technical and organizational measures for cloud provider
Authors: Georgiopoulou Zafeiroula , Makri Eleni-Laskarina , Lambrinoudakis Costas
Published: June 2020

Purpose

The purpose of this paper is to give a brief guidance on what a cloud provider should consider and what further actions to take to comply with General Data Protection Regulation (GDPR).

Design/methodology/approach

This paper presents in detail the requirements for GDPR compliance of cloud computing environments, presents the GDPR roles (data controller and data processor) in a cloud environment and discusses the applicability of GDPR compliance requirements for each cloud architecture (Infrastructure as a Service, Platform as a Service, Software as a Service), proposes countermeasures for satisfying the aforementioned requirements and demonstrates the applicability of the aforementioned requirements and countermeasures to a PaaS environment offering services for building, testing, deploying and managing applications through cloud managed data centers. The applicability of the method has been demonstrated on in a PaaS environment that offers services for building, testing, deploying and managing applications through cloud managed data centers.

Findings

The results of the proposed GDPR compliance measures for cloud providers highlight the effort and criticality required from cloud providers to achieve compliance.

Originality/value
The effectiveness of management accounting systems in SMEs: a multidimensional measurement approach
Authors: Pedroso Elsa , Gomes Carlos F.
Published: June 2020

Purpose

The purpose of this paper is to present and validate a multidimensional approach to measure the effectiveness of management accounting systems.

Design/methodology/approach

Based on an extensive literature review, the most appropriate information dimensions were identified. To validate the multidimensional tool, survey data were obtained from 284 chief financial officers of Portuguese small- and medium-sized enterprises (SMEs). A structural equation model, evaluating the influence on the managerial performance, was used to verify the nomological validity of this new construct.

Findings

The results of this study suggest that the effectiveness of management accounting systems can be measured using a second-order construct. This construct includes 14 items, covering four dimensions of the management information characteristics.

Research limitations/implications

Although contributing to the advancement of knowledge, it is, however, limited to the Portuguese organizational environment and culture. Therefore, further studies should be carried out in other organizational contexts and cultures, to test and validate this multidimensional tool.

Practical implications

The multidimensional tool presented and validated in this study can be used by executives of SMEs for assessing the effectiveness of their management accounting systems, which can help to improve SMEs' performance measurement and benchmarking processes.

Originality/value

On the best of our knowledge, this is the first study wherein the management accounting system is modeled as a second-order construct from the perspective of multidimensional information characteristics. This second-order approach recognizes the contribution and retains the distinctive nature of each first-order construct, representing the management accounting system. This multidimensional construct could be very important for future research by allowing to capture synergies resulting from the balanced development of its four information dimensions, and consequently, offer new contributions to management accounting knowledge.
Psychometric examination of the Connor–Davidson resilience scale (CD-RISC-10) among Vietnamese students
Authors: Minh-Uyen Vu Thi , Im Seongah
Published: June 2020

Purpose

This study examined psychometric properties of the ten-item Connor–Davidson resilience scale (CD-RISC-10) among university undergraduate students in Vietnam.

Design/methodology/approach

The study followed a cross-sectional design using a sample of 414 students from multiple universities in Southern Vietnam. Three bilingual experts back-translated the provided scale to verify its content. Factor analyses were used to explore and confirm the scale structure, and item response theory (IRT) model for polytomous responses was selected to further examine individual items and the entire scale.

Findings

Factor analyses confirmed a single-dimensional structure of the CD-RISC-10. IRT analysis demonstrated that individual items and the entire scale reliably measured resilience. However, probabilities to endorse the lowest category were particularly low for most of the items, suggesting a potential to modify the number of the response categories. The overall results indicated that the CD-RISC-10 in Vietnamese was a reliable and accurate tool to measure a range of university students' resilience levels.

Research limitations/implications

Convenience sampling method, the use of self-reported survey and the inclusion of only university students were limitations of the study. However, using IRT to thoroughly examine the CD-RISC-10 was an important contribution to the work of validating research instruments.

Practical implications

The CD-RISC-10 could be a valid, reliable and convenient assessment tool for school psychologists and psychiatrists to use in trainings, counseling services or resilience intervention programs.

Originality/value

While many studies have investigated psychometric properties of the CD-RISC-10 in other languages, none has been conducted in Vietnamese.