bluuebunny/crossref_metadata_2025 huggingface dataset:
Nocardioides palaemonis sp. nov. and Tessaracoccus palaemonis sp. nov., isolated from the gastrointestinal tract of lake prawn
Authors: Kim Do-Yeon , Jeong In-Chul , Lee So-Yeon , Jeong Yun-Seok , Han Jeong Eun , Tak Euon Jung , Lee June-Young , Kim Pil Soo , Hyun Dong-Wook , Bae Jin-Woo
Published: December 2022

Two novel Gram-stain-positive, non-motile and non-spore-forming bacterial strains, designated J2M5T and J1M15T, were isolated from the gastrointestinal tract of a lake prawn Palaemon paucidens. Strain J2M5T was an obligately aerobic bacterium that formed milky-coloured colonies and showed a rod–coccus cell cycle, while strain J1M15T was a facultatively aerobic bacterium that formed orangish-yellow-coloured colonies and showed rod-shaped cells. Strains J2M5T and J1M15T showed the highest 16S rRNA gene sequence similarity to

Nocardioides ganghwensis

JC2055T (98.63 %) and

Tessaracoccus flavescens

SST-39T (98.08 %), respectively. The whole-genome sequence of strain J2M5T was 4.52 Mbp in size and the genomic G+C content directly calculated from the genome sequence of strain J2M5T was 72.5 mol%. The whole-genome sequence of strain J1M15T was 3.20 Mbp in size and the genomic G+C content directly calculated from the genome sequence of strain J1M15T was 69.6mol %. Strains J2M5T and J1M15T showed high OrthoANI similarity to

N. ganghwensis

JC2055T (83.6 %) and

T. flavescens

(77.2 %), respectively. We analysed the genome sequences of strains J2M5T and J1M15T in terms of carbohydrate-active enzymes, antibiotic resistance genes and virulence factor genes. Strains J2M5T and J1M15T contained MK-8 (H4) and MK-9 (H4) as the predominant respiratory quinones, respectively. The major polar lipids of both strains were phosphatidylglycerol and diphosphatidylglycerol. Additionally, strain J2M5T possessed phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine. The cellular sugar components of strain J2M5T were ribose, mannose, glucose and galactose, and its cellular amino acid components were l-alanine and l-lysine. The cellular sugar components of strain J1M15T were rhamnose, ribose, mannose and glucose, and its cellular amino acid component was l-alanine. The major cellular fatty acids of strains J2M5T and J1M15T were iso-C16 : 0 and anteiso-C15 : 0, respectively. The multiple taxonomic analyses indicated that strains J2M5T and J1M15T represent novel species of the genus

Nocardioides

and

Tessaracoccus

, respectively. We propose the names Nocardioides palaemonis sp. nov. and Tessaracoccus palaemonis sp. nov. for strain J2M5T (=KCTC 49461T=CCUG 74767T) and strain J1M15T (=KCTC 49462T=CCUG 74766T), respectively.
The Radiogenomic and Spatiogenomic Landscapes of Glioblastoma, and their Relationship to Oncogenic Drivers
Authors: Kazerooni Anahita Fathi , Akbari Hamed , Hu Xiaoju , Bommineni Vikas , Grigoriadis Dimitris , Toorens Erik , Sako Chiharu , Mamourian Elizabeth , Ballinger Dominique , Sussman Robyn , Singh Ashish , Verginadis Ioannis I. , Dahmane Nadia , Koumenis Constantinos , Binder Zev A. , Bagley Stephen J. , Mohan Suyash , Hatzigeorgiou Artemis , O’Rourke Donald M. , Ganguly Tapan , De Subhajyoti , Bakas Spyridon , Nasrallah MacLean P. , Davatzikos Christos
Published: December 2022

Glioblastoma (GBM) is well-known for its molecular and spatial heterogeneity, which poses a challenge for precision therapies and clinical trial stratification. Here, in a comprehensive radiogenomics study of 358 GBMs, we investigated the associations between the imaging and spatial characteristics of the tumors with their cancer gene mutation status, as well as with the cross-sectionally inferred likely order of mutational events. We show that cross-validated machine learning analysis of multi-parametric MRI scans results in distinctivein vivoimaging signatures of several mutations, which are relatively more distinctive in homogeneous tumors which harbor only one of these mutations. These imaging signatures offer mechanistic insights into how various mutations influence the phenotype of the tumor and its surrounding infiltrated brain tissue via neovascularization and vascular leakage, increased cell density, invasion and migration, and other characteristics captured by respective imaging features. Furthermore, we found that spatial location and tumor distribution vary, depending on the GBM’s molecular characteristics. Finally, distinct imaging and spatial characteristics were associated with cross-sectionally estimated evolutionary trajectories of the tumors. Collectively, our study establishes a panel ofin vivoand clinically accessible imaging-AI biomarkers of GBM that reflect their molecular composition and oncogenic drivers.
Establishment of a novel set of vectors for transformation of the dinoflagellateAmphidinium carterae
Authors: Nimmo I.C. , Geisler K. , Barbrook A.C. , Kleiner F.H. , Scarampi A. , Kosmützky D. , Nisbet R.E.R. , Howe C.J.
Published: December 2022

Peridinin-containing dinoflagellate algae have a chloroplast genome formed from plasmid-like minicircles. This fragmented genome has allowed us to develop a genetic modification methodology involving the use of biolistics to introduce artificial minicircles inAmphidinium carterae(Nimmo et al., 2019). The previously reported artificial minicircles were based on native minicircles containing either thepsbAoratpBgene. Each artificial minicircle allowed expression of a single selectable marker instead ofpsbAoratpB. Here, we present two further artificial minicircles for use in transformation ofA. carterae. One is based on thepetDminicircle, allowing the expression of a single selectable marker. The second is based on the two-gene minicircle originally containingatpAandpetB, and allows the dual expression of a selectable marker and a gene of interest. Our research suggest that all of the 20 or so minicircles inA. carteraeare suitable for adaptation as artificial minicircles, allowing for the simultaneous introduction of multiple genes.
A receptor tyrosine kinase regulated by the transcription factor VAB-3/PAX6 pairs with a pseudokinase to trigger immune signalling upon oomycete recognition inC. elegans
Authors: Drury Florence , Grover Manish , Hintze Mark , Saunders Jonathan , Fasseas Michael K , Constantinou Charis , Barkoulas Michalis
Published: December 2022

Oomycetes were recently discovered as natural pathogens ofCaenorhabditis elegansand pathogen recognition alone was shown to be sufficient to activate a protective transcriptional program in the host characterised by the expression of multiplechitinase-like(chil) genes. However, the molecular mechanisms underlying oomycete recognition in animals remain fully unknown. We performed here a forward genetic screen to uncover regulators ofchilgene induction and found several independent loss-of-function alleles ofold-1andflor-1,which encode receptor tyrosine kinases belonging to theC. elegans-specific KIN-16 family. We present evidence that OLD-1 is an active kinase mounting the immune response, and FLOR-1 a pseudokinase that is also required for the response and regulates the distribution of OLD-1 at the epidermal membrane. Interestingly, theold-1locus is adjacent to thechilgenes in the nematode genome, thereby revealing a genetic cluster important for oomycete-resistance. Furthermore, we identify the VAB-3/PAX-6 transcription factor known for its role in visual system development to regulateold-1expression, and consequently the spatial pattern of the response to oomycete recognition. Taken together, our study reveals both conserved and species-specific factors shaping the response to oomycete recognition.
Interleukin 31 receptor alpha induces airway hyperresponsiveness in asthma
Authors: Akkenepally Santoshi , Yombo Dan JK , Yerubandi Sanjana , Geereddy Bhanuprakash R. , McCormack Francis X. , Madala Satish K
Published: December 2022

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Both Th1 and Th2 cytokines, including IFN-γ, IL-4, and IL-13 have been shown to induce asthma; however, the underlying mechanisms remain unclear. We observed a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31 during house dust mite- andSchistosoma mansonisoluble egg antigen-induced allergic asthma. In support of this, IFN-γ and Th2 cytokines, IL-4 and IL-13, upregulated IL-31RA but not IL-31 in airway smooth muscle cells (ASMC). Importantly, the loss of IL-31RA attenuated AHR but had no effects on inflammation and goblet cell hyperplasia in allergic asthma or mice treated with IL-13 or IFNγ. Mechanistically, we demonstrate that IL-31RA functions as a positive regulator of muscarinic acetylcholine receptor 3 (CHRM3) expression and calcium signaling involved in the contractility of ASMC. Together, these results identified a novel role for IL-31RA in ASMC contractility and AHR distinct from airway inflammation and goblet cell hyperplasia in asthma.

The study identified an important role for the IL-31RA-CHRM3 axis in inducing airway hyperresponsiveness with limited changes in inflammation in allergic asthma. IL-31RA, whose expression is regulated by both Th1 and Th2 cytokines, augments the CHRM3-dependent contractility of ASMC and AHR.
A microbial community growth model for dynamic phenotype predictions
Authors: Freiburger Andrew P. , Dewey Jeffrey A. , Foflonker Fatima , Babnigg Gyorgy , Antonopoulos Dionysios A. , Henry Christopher
Published: December 2022

1

Microbial communities are increasingly recognized as key drivers in animal health, agricultural productivity, industrial operations, and ecological systems. The abundance of chemical interactions in these complex communities, however, can complicate or evade experimental studies, which hinders basic understanding and limits efforts to rationally design communities for applications in the aforementioned fields. Numerous computational approaches have been proposed to deduce these metabolic interactions – notably including flux balance analysis (FBA) and systems of ordinary differential equations (ODEs) – yet, these methods either fail to capture the dynamic phenotype expression of community members or lack the abstractions required to fit or explain the diverse experimental omics data that can be acquired today.

We therefore developed a dynamic model (CommPhitting) that deduces phenotype abundances and growth kinetics for each community member, concurrent with metabolic concentrations, by coupling flux profiles for each phenotype with experimental growth and -omics data of the community. These data are captured as variables and coefficients within a mixed integer linear optimization problem (MILP) designed to represent the associated biological processes. This problem finds the globally optimized fit to all experimental data of a trial, thereby most accurately computing aspects of the community: (1) species and phenotype abundances over time; (2) a linearized growth kinetic constant for each phenotype; and (3) metabolite concentrations over time. We exemplify CommPhitting by applying it to study batch growth of an idealized two-member community of the model organisms (Escherichia coliandPseudomonas flourescens) that exhibits cross-feeding in maltose media. Measurements of this community from our accompanying experimental studies – including total biomass, species biomass, and metabolite abundances over time – were parameterized into a CommPhitting simulation. The resultant kinetics constants and biomass proportions for each member phenotype would be difficult to ascertain experimentally, yet are important for understanding community responses to environmental perturbations and therefore engineering applications: e.g. for bioproduction. We believe that CommPhitting – which is generalized for a diversity of data types and formats, and is further available and amply documented as a Python API – will augment basic understanding of microbial communities and will accelerate the engineering of synthetic communities for diverse applications in medicine, agriculture, industry, and ecology.
Search for Medical Information and Treatment Options for Musculoskeletal Disorders through an Artificial Intelligence Chatbot: Focusing on Shoulder Impingement Syndrome
Authors: Kim Jun-hee
Published: December 2022

Background

The ChatGPT is an artificial intelligence chatbot that processes natural language text learned through reinforcement learning based on the GPT-3.5 architecture, a large-scale language model. Natural language processing models are being used in various fields and are gradually expanding their use in the medical field.

Purpose

This study aimed to investigate the medical information and treatment options that ChatGPT can provide for SIS.

Method

Using ChatGPT, which is provided as a free beta test, messages related to SIS were entered, and responses to medical information and treatment options were received and analyzed.

Result

ChatGPT not only provided answers to the definition, prevalence, and risk factors of SIS, but also symptoms, diseases with similar symptoms, and orthopedic tests according to the messages input. Additionally, a list of treatment options and exercises were provided.

Conclusion

ChatGPT will be able to provide overall useful medical information and treatment options to patients unfamiliar with SIS. However, caution is required as it contains content that may be biased or inappropriate information for patients with SIS. Nevertheless, if natural language processing technology develops further, it is expected to be able to express more detailed medical information and treatment options.
Association of Graph-based Spatial Features with Overall Survival Status of Glioblastoma Patients
Authors: Lee Joonsang , Narang Shivali , Martinez Juan , Rao Ganesh , Rao Arvind
Published: December 2022

Background and purpose

Glioblastoma multiforme (GBM) is the most common malignant brain tumor with less than 15 months median survival. To aid prognosis, there is a need for decision tools that leverage diagnostic modalities such as MRI to inform survival. In this study, we examine higher-order spatial proximity characteristics from habitats and propose two graph-based methods (minimum spanning tree and graph run-length matrix) to characterize spatial heterogeneity over tumor MRI-derived intensity habitats and assess their relationships with overall survival as well as immune signature status of patients with GBM.

Material and methods

A data set of 74 patients was studied based on the availability of post-contrast T1-weighted and T2-weighted fluid attenuated inversion recovery (FLAIR) image data in The Cancer Image Archive (TCIA). We assessed the predictive value of MST- and GRLM-derived features from 2D images for prediction of 12-month survival status and immune signature status of patients with GBM via a receiver operating characteristic curve analysis.

Results

For 12-month survival prediction using MST-based method, sensitivity and specificity were 0.82 and 0.79 respectively. For GRLM-based method, sensitivity and specificity were 0.73 and 0.77 respectively. For immune status, sensitivity and specificity were 0.91 and 0.69, respectively, for the GRLM-based method with an immune effector.

Conclusion

Our results show that the proposed MST- and GRLM-derived features are predictive of 12-month survival status as well as the immune signature status of patients with GBM. To our knowledge, this is the first application of MST- and GRLM-based proximity analyses for the study of radiologically-defined tumor habitats in GBM.
Understanding the impact of mobility on COVID-19 spread: a hybrid gravity-metapopulation model of COVID-19
Authors: Iyaniwura Sarafa A. , Ringa Notice , Adu Prince A. , Mak Sunny , Janjua Naveed Z. , Irvine Michael A. , Otterstatter Michael
Published: December 2022

The outbreak of the severe acute respiratory syndrome coronavirus 2 started in Wuhan, China, towards the end of 2019 and spread worldwide. The rapid spread of the disease can be attributed to many factors including its high infectiousness and the high rate of human mobility around the world. Although travel/movement restrictions and other non-pharmaceutical interventions aimed at controlling the disease spread were put in place during the early stages of the pandemic, these interventions did not stop COVID-19 spread. To better understand the impact of human mobility on the spread of COVID-19 between regions, we propose a hybrid gravity-metapopulation model of COVID-19. Our model explicitly incorporates time-dependent human mobility into the disease transmission rate, and has the potential to incorporate other factors that affect disease transmission such as facemasks, physical distancing, contact rates, etc. An important feature of this modeling framework is its ability to independently assess the contribution of each factor to disease transmission. Using a Bayesian hierarchical modeling framework, we calibrate our model to the weekly reported cases of COVID-19 in thirteen local health areas in metro Vancouver, British Columbia (BC), Canada, from July 2020 to January 2021. We consider two main scenarios in our model calibration: using a fixed distance matrix and time-dependent weekly mobility matrices. We found that the distance matrix provides a better fit to the data, whilst the mobility matrices have the ability to explain the variance in transmission between regions. This result shows that the mobility data provides more information in terms of disease transmission than the distances between the regions.
Chromatin phase separated nanoregions regulated by cross-linkers and explored by single particle trajectories
Authors: Papale A , Holcman D.
Published: December 2022

Phase separated domains (PSDs) are ubiquitous in cell biology, representing nanoregions of high molecular concentration. PSDs appear at diverse cellular domains, such as neuronal synapses but also in eukaryotic cell nucleus, limiting the access of transcription factors and thus preventing gene expression. We study here the properties of PSDs and in particular how they can be generated by polymers. We show that increasing the number of cross-linkers generate a polymer condensation, preventing the access of diffusing molecules. To investigate how the PSDs restrict the motion of diffusing molecules, we estimate the mean residence and first escaping times. Finally, by computing the mean square displacement of single particle trajectories, we can reconstruct the properties of PSDs in term of a continuum range of anomalous exponents. To conclude, PSDs can result from a condensed chromatin, where the number of cross-linkers control the molecular access.
Prewhitening and Normalization Help Detect a Strong Cross-Correlation Between Daily Wastewater SARS-CoV-2 RNA Abundance and COVID-19 Cases in a Community
Authors: Jeon Min Ki , Li Bo , Di Doris Yoong Wen , Yan Tao
Published: December 2022

Wastewater surveillance is a promising technology for real-time tracking and even early detection of COVID-19 infections in communities. Although correlation analysis between wastewater surveillance data and the daily clinical COVID-19 case numbers has been frequently conducted, the importance of stationarity of the time-series data has not been well addressed. In this study, we demonstrated that strong yet spurious correlation could arise from non-stationary time-series data in wastewater surveillance, and data prewhitening to remove trends helped to reveal distinct cross-correlation patterns between daily clinical case numbers and daily wastewater SARS-CoV-2 concentration during a lockdown period in 2020 in Honolulu, Hawaii. Normalization of wastewater SARS-CoV-2 concentration by the endogenous fecal viral markers in the same samples significantly improved the cross-correlation, and the best correlation was detected at a two-day lag of the daily clinical case numbers. The detection of a significant correlation between daily wastewater SARS-CoV-2 RNA abundance and clinical case numbers also suggests that disease burden fluctuation in the community should not be excluded as a contributor to the often observed weekly cyclic patterns of clinical cases.

Water impact

Wastewater surveillance represents an emerging water technology with significant human health benefits. The study demonstrated that non-stationary time-series data could lead to spurious correlation, highlighting the need for prewhitening. Normalization strategies could alleviate variations in sample collection and analyses, which is useful for detecting actual underlying relationships between wastewater surveillance data and clinical data.
Perinuclear force regulates SUN2 dynamics and distribution on the nuclear envelope for proper nuclear mechanotransduction
Authors: Niu Jiahao , Wang Xiaotian , Zhao Wenxue , Wang Yao , Qin Yizhi , Huang Xiaoshuai , Xue Boxin , Li Cheng , Sun Yujie
Published: December 2022

The trans-luminal LINC (Linker of Nucleoskeleton and Cytoskeleton) complex plays a central role in nuclear mechanotransduction by coupling the nucleus with cytoskeleton. High spatial density and active dynamics of LINC complex have hindered its precise characterization for the understanding of underlying mechanisms how the linkages sense and respond to mechanical stimuli. In this study, we focus on SUN2, a core component of LINC complex interconnecting the nuclear lamina and actin cytoskeleton and apply single molecule super-resolution imaging to reveal how SUN2 responds to actomyosin contractility. Using stochastic optical reconstruction microscopy (STORM), we quantitated the distribution pattern and density of SUN2 on the basal nuclear membrane. We found that SUN2 undergoes bidirectional translocation between ER and nuclear membrane in response to actomyosin contractility, suggesting that dynamic constrained force on SUN2 is required for its proper distribution. Furthermore, single molecule imaging unveils interesting dynamics of SUN2 molecules that are regulated by both actomyosin contractility and laminA/C network, whereas SUN2 oligomeric states are not affected by actomyosin contractility. Lastly, the mechanical response of SUN2 to actomyosin contractility was found to regulate expression of mechano-sensitive genes located in lamina-associated domains (LADs) and perinuclear heterochromatin. Taken together, our results reveal how SUN2 responds to mechanical cues at the single-molecule level, providing new insights into the mechanism of nuclear mechanotransduction.
Selenium Silk Nanostructured Films for Antifungal and Antibacterial Treatments
Authors: Toprakcioglu Zenon , Wiita Elizabeth G. , Jayaram Akhila K. , Gregory Rebecca C. , Knowles Tuomas P. J.
Published: December 2022

The rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. An orthogonal approach, therefore, is to explore biomaterials with physical modes of action which have the potential to generate antimicrobial activity and in some cases even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and non-cytotoxic towards mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a two-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials.
The episodic resurgence of highly pathogenic avian influenza H5 virus
Authors: Xie Ruopeng , Edwards Kimberly M. , Wille Michelle , Wei Xiaoman , Wong Sook-San , Zanin Mark , El-Shesheny Rabeh , Ducatez Mariette , Poon Leo L. M. , Kayali Ghazi , Webby Richard J. , Dhanasekaran Vijaykrishna
Published: December 2022

Highly pathogenic avian influenza (HPAI) H5N1 activity has intensified globally since 2021, replacing the dominant clade 2.3.4.4 H5N8 virus. H5N1 viruses have spread rapidly to four continents, causing increasing reports of mass mortality in wild birds and poultry. The ecological and virological properties required for future mitigation strategies are unclear. Using epidemiological, spatial and genomic approaches, we demonstrate changes in the source of resurgent H5 HPAI and reveal significant shifts in virus ecology and evolution. Outbreak data indicates key resurgent events in 2016/17 and 2020/21 that contributed to the panzootic spread of H5N1 in 2021/22, including an increase in virus diffusion velocity and persistence in wild birds. Genomic analysis reveals that the 2016/17 epizootics originated in Asia, where HPAI H5 reservoirs are documented as persistent. However, in 2020/21, 2.3.4.4b H5N8 viruses emerged in domestic poultry in Africa, featuring several novel mutations altering the HA structure, receptor binding, and antigenicity. The new H5N1 virus emerged from H5N8 through reassortment in wild birds along the Adriatic flyway around the Mediterranean Sea. It was characterized by extensive reassortment with low pathogenic avian influenza in domestic and wild birds as it spread globally. In contrast, earlier outbreaks of H5N8 were caused by a more stable genetic constellation, highlighting dynamic changes in HPAI H5 genomic evolution. These results suggest a shift in the epicenter of HPAI H5 beyond Asia to new regions in Africa, the Middle East, Europe, and North and South America. The persistence of HPAI H5 with resurgence potential in domestic birds indicates that elimination strategies remain a high priority.
Ongoing emergence of M1UKlineage among invasive group A streptococcus isolates in 2020 and use of allele-specific PCR
Authors: Zhi Xiangyun , Li Ho Kwong , Li Hanqi , Loboda Zuzanna , Charles Samson , Vieira Ana , Huse Kristin , Jauneikaite Elita , Coelho Juliana , Lamagni Theresa , Sriskandan Shiranee
Published: December 2022

Background

An increasing burden of invasive group A streptococcal infections is reported in multiple countries, notably England, where scarlet fever cases are also abundant. In England, increased scarlet fever and invasive infections have been associated with emergence of a sublineage ofemm1Streptococcus pyogenesthat expresses increased SpeA scarlet fever erythrogenic toxin. Wider surveillance for toxigenicStreptococcus pyogeneslineage M1UKis much needed however, to date, lineage assignment has required genome sequencing limiting surveillance to those centres with access to such facilities.

Methods

To circumvent the requirement for genome sequencing, an allele-specific PCR was developed to distinguish M1UKfrom otheremm1 strains. Additional PCR assays were developed to distinguish M1UKfrom two intermediate lineages that were detected previously. The assay was evaluated using DNA from genome-sequenced upper respiratory tractemm1S. pyogenesstrains and a further set of 16 genome-sequenced invasiveS. pyogenesisolates that included the two intermediate lineages. The assay was then applied to DNA from all 305 invasiveemm1 isolates that had been submitted to the reference laboratory in the one pear period Jan 1-Dec 31 2020, in order to assign lineage.

Results

The allele specific PCR was 100% accurate when compared with genome sequencing, correctly identifying M1UK, two intermediate sublineages, and otheremm1 strains. The assay demonstrated the M1UKlineage to be dominant amongemm1 invasive isolates in England, representing 278/305 (91%) of invasiveemm1 isolates by end of 2020.

Implications

Emm1S. pyogeneshave a prominent role in invasive infections; anyemm1 lineage that demonstrates enhanced fitness within the population is of public health concern. The allele specific PCR provides a readily available method to subtypeemm1 isolates and does not require access to complex sequencing facilities. The data confirm that the M1UKlineage has persisted and further expanded in England underlining the importance of wider global surveillance.
Extracellular vesicles improve GABAergic transmission in Huntington’s disease iPSC-derived neurons
Authors: Beatriz Margarida , Rodrigues Ricardo , Vilaça Rita , Egas Conceição , Pinheiro Paulo , Daley George Q. , Schlaeger Thorsten M. , Rego A. Cristina , Lopes Carla
Published: December 2022

Extracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs. In both Huntington’s disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation were reported. Recently, the use of EV cargo to reverse phenotypic alterations in disease models with synaptopathy as the end-result of the pathophysiological cascade has become an interesting possibility. Here, we assessed the contribution of EVs to GABAergic synaptic alterations using a human HD model and studied the miRNA content of isolated EVs. After differentiating HD human induced-pluripotent stem cells into electrophysiologically active striatal-like GABAergic neurons, we found that HD-derived neurons displayed reduced density of inhibitory synapse markers and of GABA receptor-mediated ionotropic signaling. Treatment with EVs secreted by control (CTR) fibroblasts reversed the deficits in GABAergic synaptic transmission and increased the density of inhibitory synapses on HD-neuron cultures, while EVs from HD-derived fibroblasts had the opposite effects on CTR-neurons. Moreover, analysis of miRNAs from purified EVs identified a set of differentially expressed miRNAs between manifest HD, premanifest and CTR lines with predicted synaptic targets. The EVs-mediated reversal of the abnormal GABAergic phenotype in HD-derived neurons reinforces the potential role of EVs-miRNAs on synapse regulation.
Novel uAUG creating variants in the 5’UTR of ENG causing Hereditary Hemorrhagic Telangiectasia
Authors: Soukarieh Omar , Tillet Emmanuelle , Proust Carole , Dupont Charlène , Jaspard-Vinassa Béatrice , Soubrier Florent , Goyenvalle Aurélie , Eyries Mélanie , Trégouët David-Alexandre
Published: December 2022

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular disorder causing abnormal vessel formation and characterized by autosomal dominant transmission. The associated considerable variability in symptoms and clinical severity complicate the management of the disease. In clinical routine, 3 main genes,ACVRL1(also known asALK1),ENGandSMAD4are screened for pathogenic variants at the origin of HHT. About 80% of HHT cases are caused by pathogenic coding variants inACVRL1andENG. However, at least 15% remain with no molecular explanations in the 3 main genes. We here report the identification of 2 never reported variants, c.-79C>T and c.-68G>A, in the 5’UTR ofENGin 2 unrelated HHT patients. These 2 variants are predicted to create upstream AUGs (uAUGs) in the 5’UTR, which are in frame with a stop codon located within the CoDing Sequence (CDS), thus generating Overlapping upstream Open reading frames (uoORFs). In other cases, uAUGs can lead to fully upstream ORFs (uORFs) when associated with stop codons located within the 5’UTR or to elongated CDS (eCDS) when in frame with the CDS and associated with the main stop codon.

In order to assess the pathogenicity of theseENGvariants, we performedin vitrofunctional assays based on the expression of wild-type and mutant constructs in human cells. We found that these 5’UTRENGvariants were associated with a decrease of protein levels in HeLa and HUVEC cells. They were also associated with a decreased ability to activate BMP9-stimulated ALK1 receptor in a BMP-response element (BRE) assay. This assay is a mandatory element before providing a definitive molecular diagnosis and has been so far applied only on codingENGvariants. We applied the same experimental workflow on 3 additional uoORF-creating variants (c.-142A>T, c.-127C>T and c.-10C>T) and one eCDS-creating variant (c.-9G>A) in the 5’UTR ofENGpreviously reported in HHT patients. We found that all the analysed uoORF-creating variants alter endoglin levels and function. A comparison of our experimental results with patients’ clinical characteristics suggests that uoORF-creating variants leading to ENG protein levels ≤ 40%in vitrowould be associated with HHT. Additional experiments relying on an artificial deletion in our mutated constructs show that created uAUGs predicted to create uoORFs are able to initiate the translation indicating that the associated effect is likely caused by an alteration of the translation mechanism.

Overall, we here identified two never reported 5’UTRENGvariations in HHT patients and shed new lights on the role of upstream ORFs on ENG regulation. Our findings contribute to the amelioration of molecular diagnosis in HHT.
Association of the 609 C/T NAD(P)H: quinone oxidoreductase (NQO1) polymorphism with development of cutaneous malignant melanoma
Authors: Naghynajadfard Maryam , Hodges Nikolas J , Towler Adam , Lee Amanda J , Norman Joanna , Doran Ryan , David Rhiannon M , Pheasant Anne E , Marsden Jerry , Chipman James K
Published: December 2022

Cutaneous Malignant Melanoma (CMM) is a life threatening disease whose incidence and mortality rates have risen rapidly in the White Caucasian population in recent decades. The aim of the current study was to investigate the association between polymorphisms in genes involved in DNA-repair and detoxification of reactive metabolites and the development of CMM. The patient cohort consisted of 69 individuals while the control population consisted of 100 individuals. We found a statistically significant association between the presence of the wild type NQO1 C allele, MDHFR C667T, TS1494del6, TSER polymorphisms and development of CMM [P= 0.04; odds ratio = 2.35]. The NQO1 CC genotype was more strongly associated with CMM development [P= 0.016; odds ratio = 2.92]. The NQO1 gene codes for a protein that has been widely considered to be protective through its ability to detoxify quinones. However recent studies have also linked it to an important source of reactive oxygen and to NF-κB-dependent proliferation of cultured melanoma cells. In conclusion these results link molecular epidemiology and experimental evidence for the role of the NQO1 gene product in development of CMM. MDHFR and TS in Folic acid metabolism are responsible for methylation of methyl group. Two important roles of folate ‘related to this study’ are the conversion of homocysteine to methionine and the generation of thymidylate (dTMP) which is required for DNA synthesis (Hayward, 2003). According to many studies done at this area, folate deficiency has been associated with chromosome strand breaks (Blountet al, 1997), impaired DNA repair (Hayward, 2003), DNA hypomethylation and hypermethylation all of which have been associated with cancer cell formation (Simonettaet al2001) (Dong-Hyun K. 2007). The result of study shows, MTHFR C677T and TS 6bp deletion/insertion are not related to increased risk of CMM and therefore have no effect on an individual’s susceptibility.
Inhibition stabilization and paradoxical effects in recurrent neural networks with short-term plasticity
Authors: Wu Yue Kris , Gjorgjieva Julijana
Published: December 2022

Inhibition stabilization is considered a ubiquitous property of cortical networks, whereby inhibition controls network activity in the presence of strong recurrent excitation. In networks with fixed connectivity, an identifying characteristic of inhibition stabilization is that increasing (decreasing) excitatory input to the inhibitory population leads to a decrease (increase) in inhibitory firing, known as the paradoxical effect. However, population responses to stimulation are highly nonlinear, and drastic changes in synaptic strengths induced by short-term plasticity (STP) can occur on the timescale of perception. How neuronal nonlinearities and STP affect inhibition stabilization and the paradoxical effect is unclear. Using analytical calculations, we demonstrate that in networks with STP the paradoxical effect implies inhibition stabilization, but inhibition stabilization does not imply the paradoxical effect. Interestingly, networks with neuronal nonlinearities and STP can transition non-monotonically between inhibition-stabilization and non-inhibition-stabilization, and between paradoxically- and non-paradoxically-responding regimes with increasing excitatory activity. Furthermore, we generalize our results to more complex scenarios including networks with multiple interneuron subtypes and any monotonically increasing neuronal nonlinearities. In summary, our work reveals the relationship between inhibition stabilization and the paradoxical effect in the presence of neuronal nonlinearity and STP, yielding several testable predictions.
When background music in audiovisual advertisements can boost the perceived competence of the advertised brands – an empirical study from South Korea
Authors: Hong You Jeong , Choi Beomjoon , Lee Kyogu
Published: December 2022

Purpose

The authors aim to explore whether and how variations on pitch levels of background music in audiovisual commercials affect consumers' judgments of the competence of the advertised brands and for which group of consumers such changes in ad backgrounds are more influential.

Design/methodology/approach

Consumers are presented with an audiovisual advertisement in which the pitch of background music is lowered or raised. They are subsequently asked to evaluate the music and traits of the advertised brand and indicate their predisposed styles of thinking.

Findings

Consumers tend to judge a brand in an audiovisual commercial as possessing a higher level of competence traits when the brand is accompanied by lower-pitched (vs higher-pitched) background music, which is mediated by levels of powerfulness they perceive from the background music. Consumers with holistic (vs analytic) thinking styles, who are known to devote more focused attention to background information, tend to be more (vs less) susceptible to the changes in pitch.

Research limitations/implications

The current research approaches thinking styles as predisposed individual differences as in prior works in marketing. Provided that the predisposed thinking styles can be influenced by individuals' cultural backgrounds, the authors suggest cross-cultural studies as an approach to further validate the present findings.

Practical implications

Given the recent trends that consumers are increasingly exposed to audiovisual ads with the rapid growth of various video-based platforms (e.g. YouTube) and mobile advertising, this empirical study may assist contemporary marketers in considering an acoustic strategy for brand communication using the audiovisual advertisement. This study suggests that the pitch of ad background music can serve as a manageable strategic tool that can assist in establishing an image of a competent brand.

Originality/value

This research highlights a seemingly-trivial element in audiovisual advertisements, the pitch of background music, as a crucial determinant of the perceived competence of an advertised brand upon which further brand evaluations (e.g. brand trust, purchase intention) are based. An important yet overlooked effect of ad recipients' predisposed thinking styles on how consumers respond to the changes of background cues in audiovisual commercials is also proposed.
Adoption of e-government services at different maturity levels: a qualitative study in India
Authors: Kumar Rajiv , Sachan Amit , Mukherjee Arindam
Published: December 2022

Purpose

The purpose of this study is to determine the factors that enable citizens to adopt e-government services at different maturity levels: information, two-way communication, transaction and political participation.

Design/methodology/approach

The study uses a grounded approach by conducting semi-structured interviews.

Findings

The study reveals that the factors influencing the adoption of e-government services vary at different levels. It identifies 27 influencing factors. In total, 13 of these factors influence adoption at the information level; 13 at the two-way communication level; 25 at the transactional level; and 16 at the political participation level. Auxiliary facilities, connectedness, corruption avoidance, transparency and fairness, customer support and forced adoption, not commonly discussed as influencing factors for e-government adoption in the extant literature, have been revealed in this study.

Research limitations/implications

This study uses qualitative research and rather than generalization, the focus is explicitly on obtaining an in-depth understanding. Although the sampling used is sufficient for the purpose of this study and allows reasonable conclusions to be drawn; however, it cannot be considered representative of a vast country like India. Academicians and information systems researchers can use these findings for further research.

Practical implications

This study advances the understanding of e-government adoption. The findings have potential implications for public administrators and policymakers in successfully designing, developing and implementing e-government services at different maturity levels.

Originality/value

Existing e-government adoption theories are of limited scope and do not capture and specify the complete essence of citizens’ adoption characteristics at different levels of e-government services. Hence, a theoretical gap exists, which this study aims to fill.
Organization culture types and the replication of transferred human resource management practices in multinational subsidiaries in Nigeria
Authors: Oseghale Raphael Oriaghe , Pepple Dennis , Ifere Simeon Emezana , Amaugo Amarachi Ngozi
Published: December 2022

Purpose

Given that institutional and cultural factors affect the transfer of HRM practices between multinational companies (MNCs) and their subsidiaries, the paper set out to investigate the explanatory mechanism for the replication of transferred HRM practices and the factors likely to influence the choice of transfer mechanisms.

Design/methodology/approach

Using an exploratory qualitative approach, 40 interviews were conducted with senior managers and employees in two MNC subsidiaries located in the alcoholic beverage and oil industries in Nigeria.

Findings

The findings suggest that organizational culture (OC) was the mechanism for MNC HRM replication and inhibition. In addition to explaining the mechanisms for HRM practice replication, the authors developed a conceptual framework to explain how clan and hierarchical OC influence the extent to which human resource (HR) practices are replicated or inhibited and how institutional and cultural factors influence the choice of OC.

Originality/value

The study uncovered that MNCs deploy hierarchical OC to oversee the replication of transferred practices. Interestingly, the authors found that institutional and cultural environments were key factors that influenced the choice of mechanism for overseeing the replication of HR practices. The conceptual framework can help managers of MNCs to understand how to replicate transferred HRM practices in developing countries.
Disentangling the performance implications of new venture status: competitive vulnerability, resource scarcity or strategic flexibility?
Authors: Wang Lucas Liang , Dai Qing , Gao Yan
Published: December 2022

Purpose

New venture status is the most prominent feature of entrepreneurial startups, but its performance implications have remained under-studied. This study aims to bridge this knowledge void and offer precise guidelines for startup managers in boosting performance.

Design/methodology/approach

The study develops and tests a multi-perspective model on the linkage between new venture status and firm performance by integrating I/O economics, resource-based view and dynamic capability perspective. The arguments from the first two perspectives point to an adverse effect of new venture status, which is contingent, respectively, on business differentiation and resource endowments. The third perspective grounds a positive relationship between new venture status and performance, which is more pronounced for firms with weaker dynamic capabilities.

Findings

Quantitative evidence from a sample of new and established firms in China shows that the direct effect of new venture status is negative but insignificant. Neither business differentiation nor dynamic capabilities moderate the relationship. Low resource endowments, however, reinforce the negative influence of new venture status. New venture status, thus, shapes firm performance through resource scarcity from resource-based view rather than competitive vulnerability from I/O economics or strategic flexibility from dynamic capability perspective.

Originality/value

Newness and new venture performance have both been extensively examined in literature. But the relationship between them has remained largely omitted. The multi-perspective model and the findings in this study help clarify the confusion as to whether newness is good or bad in the context of an emerging market and reveals the subtle mechanism the effect of newness unfolds.
Reconsidering learning in a socio-material world. A response to Fischer et al.'s contribution
Authors: Cerratto Pargman Teresa
Published: December 2022

Purpose

The purpose of this commentary is to comment on Fischer's et al. (2022)

Design/methodology/approach

This commentary responds to Fischer's et al. (2022) call on envisioning alternate conceptualizations of learning for the digital era. In doing so, the author argues for reconsidering learning in its socio-material condition, situated and made of a web of social and technological relations. In this context, the author takes a relational lens on learning to interrogate taken-for-granted views of (1) personalizing data increasingly used for student learning, (2) emerging educational infrastructures for higher education and (3) the student–teacher relationship mediated by data and algorithms.

Findings

In this commentary, the author suggested unpacking assumptions about learning that get reflected in the design and discourses about socio-technical arrangements and transformations in education. Taking the example of personalized learning, the author has illustrated a relational mode of thinking that leads the author to argue that, renewed definitions of learning must be discussed multidimensionally and, most importantly, situated in the material world that learning is already part of.

Research limitations/implications

Following Fischer et al. (2022, this issue), the author agrees that the focus should be on finding “new ways of organizing learning by exploring opportunities for radically new conceptualizations and practices.” In order to do that it is of utmost importance to problematize the social and material conditions that actively configure learning today and infrastructure tomorrow's learning. Hopefully, these observations will entice others to discuss further the educational transformations at stake in the age of datafication and algorithmic decision-making.

Originality/value

The author argues for reconsidering learning in its socio-material condition, which is situated and made of a web of social and technological relations. In this context, the author argues that any attempt to reconceptualize learning from a transformational perspective in the 21st century, as mentioned by Fischer et al. (2022), needs to interrogate views and assumptions about the socio-technical relationships researchers, practitioners and educators are contributing to via their practices and discourses.