bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial transcriptomics
Authors: Avraham-Davidi Inbal , Mages Simon , Klughammer Johanna , Moriel Noa , Imada Shinya , Hofree Matan , Murray Evan , Chen Jonathan , Pelka Karin , Mehta Arnav , Boland Genevieve M. , Delorey Toni , Caplan Leah , Dionne Danielle , Strasser Robert , Lalakova Jana , Niesnerova Anezka , Xu Hao , Rouault Morgane , Tirosh Itay , Hacohen Nir , Chen Fei , Yilmaz Omer , Roper Jatin , Rozenblatt-Rosen Orit , Nitzan Mor , Regev Aviv
Published: October 2022

While advances in single cell genomics have helped to chart the cellular components of tumor ecosystems, it has been more challenging to characterize their specific spatial organization and functional interactions. Here, we combine single cell RNA-seq, spatial transcriptomics by Slide- seq, andin situmultiplex RNA analysis, to create a detailed spatial map of healthy and dysplastic colon cellular ecosystems and their association with disease progression. We profiled inducible genetic CRC mouse models that recapitulate key features of human CRC, assigned cell types and epithelial expression programs to spatial tissue locations in tumors, and computationally used them to identify the regional features spanning different cells in the same spatial niche. We find that tumors were organized in cellular neighborhoods, each with a distinct composition of cell subtypes, expression programs, and local cellular interactions. Comparing to scRNA-seq and Slide-seq data from human CRC, we find that both cell composition and layout features were conserved between the species, with mouse neighborhoods correlating with malignancy and clinical outcome in human patient tumors, highlighting the relevance of our findings to human disease. Our work offers a comprehensive framework that is applicable across various tissues, tumors, and disease conditions, with tools for the extrapolation of findings from experimental mouse models to human diseases.
Impact of acute complex exercise on inhibitory control and brain activation: a functional near-infrared spectroscopy study
Authors: Takahashi Shinji , Grove Philip M.
Published: October 2022

A growing body of literature demonstrates that a single bout of exercise benefits executive function. While the acute effect of simple exercises like walking, running, and cycling has been well investigated, it is less clear how complex exercise, which requires open skills and various motions, impacts executive function and brain activation. Therefore, we compared the acute effects of a complex exercise on inhibitory control and brain activation with those of a simple exercise using functional near-infrared spectroscopy (fNIRS). Twenty-four young right-hand dominant adults (9 women) completed three interventions: badminton, running, and a seated rest control condition for 10 min each. During each intervention, oxygen uptake and heart rate were monitored. A Stroop task composed of neutral and incongruent conditions was administrated before and after each intervention. An fNIRS system recorded hemodynamics in the prefrontal cortex to evaluate brain activation during the Stroop task. The intensities of badminton and running were comparable. Performance on the Stroop task was significantly improved after badminton, specifically in the incongruent condition relative to in the neutral condition. On the other hand, neither running nor seated rest affected performance in the Stroop task. The fNIRS measures indicated that badminton and running had no significant influence on brain activation. These results show that a single bout of complex exercise enhances inhibitory control without increasing brain activation compared to simple exercise, suggesting that an acute complex exercise induces neural efficiency.
Distribution of intraperitoneally administered D2O in AQP4-knockout mouse brain after MCA occlusion
Authors: Urushihata Takuya , Takuwa Hiroyuki , Takahashi Manami , Kershaw Je◻ , Shibata Sayaka , Nitta Nobuhiro , Tachibana Yasuhiko , Yasui Masato , Higuchi Makoto , Takayuki Obata
Published: October 2022

As the movement of water in the brain is known to be involved in neural activity and various brain pathologies, the ability to assess water dynamics in the brain will be important for the understanding of brain function and the diagnosis and treatment of brain diseases. Aquaporin-4 (AQP4) is a membrane channel protein that is highly expressed in brain astrocytes and is important for the movement of water molecules in the brain. In this study, we investigated the contribution of AQP4 to brain water dynamics by administering deuterium-labeled water (D2O) intraperitoneally to wild-type and AQP4 knockout (AQP4-ko) mice that had undergone surgical occlusion of the middle cerebral artery. Water dynamics in the infarct region and on either side of the anterior cerebral artery (ACA) was monitored with proton-density-weighted imaging (PDWI) performed on a 7T animal MRI. D2O caused a negative signal change quickly after administration. The AQP4-ko mice showed a delay of the time-to-minimum in both contralateral and ipsilateral ACA region compared to wild-type mice. Also, only the AQP4-ko mice showed a delay of the time-to-minimum in the ipsilateral ACA region compared to the contralateral side. In only the wild-type mice, the signal minimum in the ipsilateral ACA region was higher than that in the contralateral ACA region. In the infarct region, the signal attenuation was slower for the AQP4-ko mice in comparison to the wild-type mice. These results suggest that AQP4 loss affects water dynamics in the ACA region not only in the infarct region. Dynamic PDWI after D2O administration may be a useful tool for showing the effects of AQP4 in vivo.

Highlights

The measurement of brain water dynamics with D2O.

In vivo investigation of AQP4 loss and focal brain ischemia.

AQP4 loss affects water dynamics in the ACA region not only in the infarct region.
Vascular tortuosity quantification as an outcome metric of the oxygen-induced retinopathy model of ischemic retinopathy
Authors: Marra Kyle V. , Chen Jimmy S. , Robles-Holmes Hailey K. , Miller Joseph , Wei Guoqin , Aguilar Edith , Ideguchi Yoichiro , Ly Kristine B. , Prenner Sofia , Erdogmus Deniz , Ferrara Napoleone , Campbell J. Peter , Friedlander Martin , Nudleman Eric
Published: October 2022

The murine oxygen-induced retinopathy (OIR) model is one of the most widely used animal models of ischemic retinopathy, mimicking hallmark pathophysiology of initial vaso-obliteration (VO) resulting in ischemia that drives neovascularization (NV). In addition to NV and VO, human ischemic retinopathies including Retinopathy of Prematurity (ROP) are characterized by increased vascular tortuosity. Vascular tortuosity is an indicator of disease severity, need to treat, and treatment response in ROP. Current literature investigating novel therapeutics in the OIR model report their effects on NV and VO, but no standardized quantification of vascular tortuosity exists to date despite this metric’s relevance to human disease in clinics. The current proof-of-concept study applied a computer-based image analysis algorithm capable of calculating standardized measurements of vascular tortuosity. Quantification of vascular tortuosity correlated with disease activity in OIR analogously to that observed in infants with ROP. Treatment of OIR mice with anti-Vascular Endothelial Growth Factor (aflibercept) rescued vascular tortuosity in the model. Altogether, these data demonstrated that vascular tortuosity is a quantifiable feature of the OIR model and may be used as an outcome measurement in future studies investigating new treatment modalities for retinal ischemia.
Megakaryocyte and erythroblast DNA in plasma and platelets
Authors: Moss Joshua , Ben-Ami Roni , Shai Ela , Kalish Yosef , Klochender Agnes , Cann Gordon , Glaser Benjamin , Arad Ariela , Shemer Ruth , Dor Yuval
Published: October 2022

Circulating cell-free DNA (cfDNA) fragments are a biological analyte with extensive utility in diagnostic medicine. Understanding the source of cfDNA and mechanisms of release is crucial for designing and interpreting cfDNA-based liquid biopsy assays. Using cell type-specific methylation markers as well as genome-wide methylation analysis, we determined that megakaryocytes, the precursors of anuclear platelets, are major contributors to cfDNA (∼26%), while erythroblasts contribute 1-4% of cfDNA in healthy individuals. Surprisingly, we discovered that platelets contain genomic DNA fragments originating in megakaryocytes, contrary to the general understanding that platelets lack genomic DNA. Megakaryocyte-derived cfDNA is increased in pathologies involving increased platelet production (Essential Thrombocythemia, Idiopathic Thrombocytopenic Purpura) and decreased upon reduced platelet production due to chemotherapy-induced bone marrow suppression. Similarly, erythroblast cfDNA is reflective of erythrocyte production and is elevated in patients with Thalassemia. Megakaryocyte- and erythroblast-specific DNA methylation patterns can thus serve as novel biomarkers for pathologies involving increased or decreased thrombopoiesis and erythropoiesis, which can aid in determining the etiology of aberrant levels of erythrocytes and platelets.

GRAPHICAL ABSTRACT
Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates
Authors: Verstegen Niels J.M. , Pollastro Sabrina , Unger Peter-Paul A. , Marsman Casper , Elias George , Jorritsma Tineke , Streutker Marij , Baβler Kevin , Händler Kristian , Rispens Theo , Schultze Joachim L. , ten Brinke Anja , Beyer Marc , van Ham S. Marieke
Published: October 2022

Differentiation of B cells into antibody-secreting cells (ASCs) is a key process to generate protective humoral immunity. A detailed understanding of the cues controlling ASC differentiation is important to devise strategies to modulate antibody formation. Here, we dissected differentiation trajectories of human naive B cells into ASCs using single-cell RNA sequencing. By comparing transcriptomes of B cells at different stages of differentiation from an in vitro model with ex vivo B cells and ASCs, we uncovered a novel pre-ASC population present ex vivo in lymphoid tissues. For the first time, a germinal-center-like population is identified in vitro from human naive B cells and possibly progresses into a memory B cell population through an alternative route of differentiation, thus recapitulating in vivo human GC reactions. Our work allows further detailed characterization of human B cell differentiation into ASCs or memory B cells in both healthy and diseased conditions.
Chronically elevated corticosterone impairs dopaminergic transmission in the dorsomedial striatum by sex-divergent mechanisms
Authors: Holloway Ashley L. , Schaid Michael D. , Lerner Talia N.
Published: October 2022

Background

Major depressive disorder (MDD) is a leading cause of disability worldwide. Individuals with MDD exhibit decreased motivation and deficits in reward processing along with chronically elevated levels of the ‘stress hormone,’ cortisol. However, the mechanistic relationship between chronically elevated cortisol and behavioral deficits in motivation and reward processing remains unclear. Given that women are diagnosed with MDD at twice the rate of men, it is important to understand whether the mechanisms linking chronically elevated cortisol to the symptoms of MDD differ by sex.

Methods

We used subcutaneous implants to chronically elevate free plasma corticosterone (rodent homolog of cortisol; ‘CORT’) in male and female mice and examined changes in behavior and dopamine system function. We used operant training to assay reward-guided motivation and high-performance liquid chromatography to quantify striatal dopamine content. We assessed dopamine transporter (DAT) function using ex vivo slice imaging and in vivo fiber photometry in combination with a fluorescent dopamine sensor, dLight1.3b. We further quantified DAT expression and phosphorylation using western blot.

Results

We found that chronic CORT treatment impaired reward-seeking in both sexes. In female but not male mice, CORT treatment reduced dopamine content in the dorsomedial striatum (DMS). In male but not female mice, the function of the dopamine transporter (DAT) was impaired in DMS.

Conclusions

Chronic elevation of CORT impairs reward-seeking by impairing dopaminergic transmission in the DMS, but via different mechanisms in male and female mice. A better understanding of these sex-specific mechanisms could lead to new directions in MDD diagnosis and treatment.
A cnidarian phylogenomic tree fitted with hundreds of 18S leaves
Authors: DeBiasse Melissa B. , Buckenmeyer Ariane , Macrander Jason , Babonis Leslie S. , Bentlage Bastian , Cartwright Paulyn , Prada Carlos , Reitzel Adam M. , Stampar Sergio N. , Collins Allen G. , Daly Marymegan , Ryan Joseph F.
Published: October 2022

Cnidarians are critical members of aquatic communities and have been an experimental system for a diversity of research areas ranging from development to biomechanics to global change biology. Yet we still lack a well-resolved, taxonomically balanced, cnidarian tree of life to place this research in appropriate phylogenetic context. To move towards this goal, we combined data from 26 new anthozoan transcriptomes with 86 previously published cnidarian and outgroup datasets to generate two 748-locus alignments containing 123,051 (trimmed) and 449,935 (untrimmed) amino acids. We estimated maximum likelihood phylogenies for both matrices under partitioned and unpartitioned site-homogeneous and site-heterogenous models of substitution. We used the resulting topology to constrain a phylogenetic analysis of 1,814 small subunit ribosomal (18S) gene sequences from GenBank. Our results confirm the position of Ceriantharia (tube-dwelling anemones), a historically recalcitrant group, as sister to the rest of Hexacorallia across all phylogenies regardless of data matrix or model choice. We also find unanimous support for the sister relationship of Endocnidozoa and Medusozoa and propose the name Operculozoa for the clade uniting these taxa. Our 18S hybrid phylogeny provides insight into relationships of 15% of extant taxa. Together these data are an invaluable resource for comparative cnidarian research and provide perspective to guide future refinement of cnidarian systematics.
MarR-Dependent Transcriptional Regulation of mmpSL5 induces Ethionamide Resistance in Mycobacterium abscessus
Authors: Rodriguez Ronald , Campbell-Kruger Nick , Camba Jesus Gonzalez , Berude John , Fetterman Rachel , Stanley Sarah
Published: October 2022

Mycobacterium abscessus (Mabs) is an emerging non-tuberculosis mycobacterial (NTM) pathogen responsible for a wide variety of respiratory and cutaneous infections that are difficult to treat with standard antibacterial therapy. Mabs has a high degree of both innate and acquired antibiotic resistance to most clinically relevant drugs, including standard anti-mycobacterial agents. Ethionamide (ETH), an inhibitor of mycolic acid biosynthesis is currently utilized as a second-line agent for treating multidrug resistant tuberculosis (MDR-TB) infections. Here, we show that ETH has activity against clinical strains of Mabs in vitro at concentrations that are therapeutically achievable. Using transposon mutagenesis and whole genome sequencing of spontaneous drug-resistant mutants, we identified marR (MAB_2648c) as a genetic determinant of ETH sensitivity in Mabs. The gene marR encodes a transcriptional regulator of the TetR family of regulators. We show that MarR represses expression of MAB_2649 (mmpS5) and MAB_2650 (mmpL5). Further, we show that de-repression of these genes in marR mutants confers resistance to ETH, but not other antibiotics. To identify determinants of resistance that may be shared across antibiotics, we also performed Tn-Seq during treatment with amikacin and clarithromycin, drugs currently used clinically to treat Mabs. We found very little overlap in genes that modulate the sensitivity of Mabs to all three antibiotics, suggesting a high degree of specificity for resistance mechanisms in this emerging pathogen.

Importance

Antibiotic resistant infections caused by Mycobacterium abscessus (Mabs) have been increasing in prevalence and treatment is often unsuccessful. Success rates range from 30-50%, primarily due to the high intrinsic resistance of Mabs to most clinically useful antibiotics. New therapeutic strategies, including repurposing of existing antibiotics, are urgently needed to improve treatment success rates. Here, we show that the anti-TB antibiotic ethionamide (ETH) has repurposing potential against Mabs, displaying bacteriostatic activity and delaying emergence of drug resistance when combined with clinically relevant antibiotics currently used against Mabs in vitro. We identified genes that modulated susceptibility of Mabs to ETH. marR encodes a transcriptional regulator that when deleted, confers ETH resistance. Our collective findings can be used to further explore the function of other genes that contribute to ETH susceptibility and help design the next generation of antibacterial regimens against Mabs that may potentially include ETH.
Remarkable improvement in detection of readthrough downstream-of-gene transcripts by semi-extractable RNA-sequencing
Authors: Iwakiri Junichi , Tanaka Kumiko , Chujo Takeshi , Yamazaki Tomohiro , Terai Goro , Asai Kiyoshi , Hirose Tetsuro
Published: October 2022

The mammalian cell nucleus contains dozens of membrane-less nuclear bodies that play significant roles in various aspects of gene expression. Several nuclear bodies are nucleated by specific architectural noncoding RNAs (arcRNAs) acting as structural scaffolds. We have reported that a minor population of cellular RNAs exhibits an unusual semi-extractable feature upon using the conventional procedure of RNA preparation and that needle shearing or heating of cell lysates remarkably improves extraction of dozens of RNAs. Because semi-extractable RNAs, including known arcRNAs, commonly localize in nuclear bodies, this feature may be a hallmark of arcRNAs. Using the semi-extractability of RNA, we performed genome-wide screening of semi-extractable long non-coding RNAs to identify new candidate arcRNAs for arcRNA under hyperosmotic and heat stress conditions. After screening stress-inducible and semi-extractable RNAs, hundreds of readthrough downstream-of-gene (DoG) transcripts over several hundreds of kilobases, many of which were not detected among RNAs prepared by the conventional extraction procedure, were found to be stress-inducible and semi-extractable. We further characterized some of the abundant DoGs and found that stress-inducible transient extension of the 3’-UTR made DoGs semi-extractable. Furthermore, they were localized in distinct nuclear foci that were sensitive to 1,6-hexanediol. These data suggest that semi-extractable DoGs exhibit arcRNA-like features and our semi-extractable RNA-seq is a powerful tool to extensively monitor DoGs that are induced under specific physiological conditions.
142 telomere-to-telomere assemblies reveal the genome structural landscape inSaccharomyces cerevisiae
Authors: O’Donnell Samuel , Yue Jia-Xing , Saada Omar Abou , Agier Nicolas , Caradec Claudia , Cokelaer Thomas , Chiara Matteo De , Delmas Stéphane , Dutreux Fabien , Fournier Téo , Friedrich Anne , Kornobis Etienne , Li Jing , Miao Zepu , Tattini Lorenzo , Schacherer Joseph , Liti Gianni , Fischer Gilles
Published: October 2022

As population genomics is transitioning from single reference genomes to pangenomes, major improvements in terms of genome contiguity, phylogenetic sampling, haplotype phasing and structural variant (SV) calling are required. Here, we generated theSaccharomyces cerevisiaeReference Assembly Panel (ScRAP) comprising 142 reference-quality genomes from strains of various geographic and ecological origins that faithfully represent the genomic diversity and complexity of the species. The ca. 4,800 non-redundant SVs we identified impact the expression of genes near the breakpoints and contribute to gene repertoire evolution through disruptions, duplications, fusions and horizontal transfers. We discovered frequent cases of complex aneuploidies, preferentially involving large chromosomes that underwent large SVs. We also characterized the evolutionary dynamics of complex genomic regions that classically remain unassembled in short read-based projects, including the 5 Ty families and the 32 individual telomeres. Overall, the ScRAP represents a crucial step towards establishing a high-quality, unified and complete S. cerevisiae pangenome.
Molecular basis of the TRAP complex function in ER protein biogenesis
Authors: Jaskolowski Mateusz , Jomaa Ahmad , Gamerdinger Martin , Shrestha Sandeep , Leibundgut Marc , Deuerling Elke , Ban Nenad
Published: October 2022

The Translocon Associated Protein (TRAP) complex resides in the endoplasmic reticulum (ER) membrane and interacts with the Sec translocon and the translating ribosome to facilitate biogenesis of secretory and membrane proteins1–4. TRAP is essential for the secretion of many hormones, and its key role in the production of the hormone peptide insulin has been particularly well established5,6. The mechanism by which TRAP engages ribosomes and the translocon to facilitate translocation of protein clients in the secretory pathway is not clear. Here, we reveal the molecular architecture of the mammalian TRAP complex and how it engages the translating ribosome associated with Sec61 translocon on the ER membrane. The TRAP complex is anchored to the ribosome via a long tether and its position relative to the ribosome and the translocon is further stabilized by a finger-like loop. This spatial arrangement positions a cradle-like lumenal domain of TRAP below the protein conducting pore of the translocon for interactions with translocated nascent chains. The biological importance of these key interactions is evident by structure-guided TRAP mutations in C. elegans that lead to growth deficits associated with increased ER stress and defects in insulin secretion. Our findings elucidate the molecular basis of the TRAP complex in the biogenesis and translocation of proteins at the ER.
A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection
Authors: Kulsuptrakul Jessie , Turcotte Elizabeth A. , Emerman Michael , Mitchell Patrick S.
Published: October 2022

Inflammasomes are cytosolic innate immune complexes that play a critical role in host defense against pathogens but can also contribute to inflammatory pathogenesis. Here, we find that the human inflammasome-forming sensor CARD8 senses HIV-1 infection via site-specific cleavage of the CARD8 N-terminus by the HIV protease (HIV-1PR). HIV-1PR cleavage of CARD8 induces pyroptotic cell death and the release of pro-inflammatory cytokines from infected cells, processes that we find are dependent on Toll-like receptor stimulation prior to viral infection. Our evolutionary analyses reveal that the HIV-1PR cleavage site in CARD8 is unique to humans, and that chimpanzee CARD8 does not recognize proteases from HIV or simian immunodeficiency viruses from chimpanzees (SIVcpz). In contrast, SIVcpz does cleave human CARD8, suggesting that SIVcpz was poised to activate the human CARD8 inflammasome prior to its cross-species transmission into humans and implicating the CARD8 inflammasome as a potential driver of HIV pathogenesis.
Discovery of novel papillomaviruses in the critically-endangered Malayan and Chinese pangolins
Authors: Barreat Jose Gabriel Nino , Kamada Anselmo Jiro , de Souza Charles Reuben , Katzourakis Aris
Published: October 2022

Pangolins are scaly and toothless mammals which are distributed across Africa and Asia. Currently, the Malayan, Chinese and Philippine pangolins are all designated as critically-endangered species. Although few pangolin viruses have been described, their viromes have received more attention following the discovery that they harbour sarbecoviruses related to SARS-CoV-2. Using a large-scale genome mining strategy, we discovered novel lineages of papillomaviruses infecting the Malayan and Chinese pangolins. We were able to assemble 3 complete circular papillomavirus genomes with an intact coding capacity, and 5 additional L1 genes encoding the major capsid protein. Phylogenetic analysis revealed that 7 out of 8 L1 sequences formed a monophyletic group which is the sister lineage to the Tree shrew papillomavirus 1, isolated from Yunnan province in China. Additionally, a single L1 sequence assembled from a Chinese pangolin was placed in a clade closer to alpha- and omegapapillomaviruses. Examination of the SRA data from 95 re-sequenced genomes revealed that 49.3% Malayan pangolins and 50% Chinese pangolins, were positive for papillomavirus reads. Our results indicate that pangolins in South East Asia are the hosts to diverse and highly prevalent papillomaviruses, which may have implications for pangolin health and conservation.
NuMA deficiency causes micronuclei via checkpoint-insensitive k-fiber minus-end detachment from mitotic spindle poles
Authors: van Toorn Marvin , Gooch Amy , Boerner Susan , Kiyomitsu Tomomi
Published: October 2022

Micronuclei resulting from improper chromosome segregation foster chromosomal instability in somatic cell division cycles. To prevent micronuclei formation, bundled kinetochore-microtubules called k-fibers must be properly connected to all sister kinetochores on chromosomes via their plus-ends, whereas k-fiber minus-ends must be clustered at the two opposing spindle poles throughout mitosis. The bipolar attachment between sister kinetochores and k-fiber plus-ends is carefully monitored by the spindle assembly checkpoint and further promoted by error-correction mechanisms. However, how k-fiber minus-end clustering is maintained and monitored remains poorly understood. Here, we show that degradation of the Nuclear Mitotic Apparatus (NuMA) protein by auxin-inducible degron technologies in human cells results in micronuclei formation through k-fiber minus-end detachment from focused spindle poles during metaphase. Importantly, this k-fiber minus-end detachment creates misaligned chromosomes that maintain chromosome biorientation and do not activate the mitotic checkpoint, resulting in lagging chromosomes in anaphase. Moreover, we find that NuMA depletion causes centrosome clustering defects in tetraploid cells, leading to an increased frequency of multipolar divisions. Together, our data indicate that NuMA-mediated minus-end clustering of k-fibers and spindle microtubules is critical for faithful chromosome segregation. Similar to erroneous merotelic kinetochore attachments, detachment of k-fiber minus-ends from metaphase spindle poles evades spindle checkpoint surveillance and may therefore be a source of genomic instability in dividing cells.
Huntingtin is essential for synaptic plasticity in the adult hippocampus
Authors: Barron Jessica C. , Nafar Firoozeh , Parsons Matthew P.
Published: October 2022

Huntingtin (HTT), an exceptionally large protein with hundreds of interacting partners within the central nervous system, has been extensively studied due to its role in Huntington’s disease (HD) pathology. HD is a monogenic disorder caused by a polyglutamine repeat expansion in the HTT gene, which results in the production of a pathogenic mutant huntingtin (mHTT) protein, and toxic effects of this mutant protein in the context of HD have been well-established. Less-established, however, is the role of wild type HTT (wtHTT) in the adult brain, particularly in areas outside the corticostriatal pathway. wtHTT has previously been suggested to play a vital role in cellular functions that promote synapse homeostasis, such as fast axonal transport of synaptic cargo, vesicle replenishment and receptor localization and stability. Synaptic dysfunction precedes and predicts cell death in many neurodegenerative diseases including HD (termed synaptopathies) and whether proper synaptic transmission can be maintained without wtHTT in extrastriatal brain areas such as the hippocampus remains unknown. Consequences of wtHTT reduction in the adult brain are of particular importance as clinical trials for many non-selective HTT-lowering therapies for HD are underway, which are unable to distinguish between mHTT and wtHTT, and therefore reduce levels of both proteins. We investigated the consequences of wtHTT loss of function in the CA3-CA1 pathway of the adult hippocampus using a conditional knockout mouse model and found that 1-2 month deletion of wtHTT in excitatory hippocampal neurons inhibits post-tetanic potentiation and completely abolishes NMDA receptor-dependent long-term potentiation in these animals. These data reveal a novel role of wtHTT as an essential regulator of short- and long-term plasticity in the adult hippocampus.
Securing ADS-B data transmissions using blockchain: a comprehensive survey and analysis
Authors: Pennapareddy Swathi , Natarajan K.
Published: October 2022

Purpose

The purpose of this paper is to study the various solutions and recommendations provided by researchers in applying the blockchain concept to different problems in aviation industry. It will discuss and highlight the specific approaches that leverages blockchain to mitigate the automatic dependent surveillance-broadcast (ADS-B) security issues. Furthermore, it introduces an innovative design and method to secure ADS-B data using a tamper-resistant distributed public ledger of authenticated flight plans and validates the position and other parameters of the associated aircraft identifier against the flight paths/routes that are stored in the blockchain ledger.

Design/methodology/approach

ADS-B is the key technology that is mandated by Federal Aviation Administration in USA by 2020. However, ADS-B data is neither encrypted nor authenticated. This paper proposes a novel solution using blockchain to secure the ADS-B data communications and in-depth analysis of existing solutions covering the following aspects: classification of various possible attacks on ADS-B. Presents various solutions proposed by different researchers regarding use of blockchain in aviation industry. Discuss a new solution to secure ADS-B using blockchain. Discuss the high-level architectural framework of the proposed and patented solution. Finally, presents the conclusions and future work scope.

Findings

While the main intention of this paper is to bring together all the existing solutions using blockchain to secure aviation and ADS-B data at one place, the proposed novel solution could contribute to maintaining security and privacy for aircrafts flying in the airspace at any point in time. Continuously securing the ADS-B data transmissions based upon the filed flight plans in real time can provide a mechanism to identify spoofed aircraft messages and communicate the same to ground stations for authentication of existence of such a malicious aircraft. Thus, this solution also differs from all the existing ones.

Practical implications

As aviation industry is in its infancy stage in implementing blockchain-based solutions, practical implementation of the proposed concept might take longer.

Originality/value

This paper is a comprehensive survey and review paper. To the best of the authors’ knowledge, this is the first of its kind that presents various use cases for usage of blockchain in aviation industry along with a detailed review of existing proposed or implemented solutions using blockchain to secure ADS-B data. This can serve as an invaluable reference for the future researchers on this topic in both industry and academia.
On the micro-foundations of corporate social responsibility: a perspective based on dynamic managerial capabilities
Authors: Chen Yantai , Guo Yanlin , Hu Xuhui
Published: October 2022

Purpose

This study proposes that the three core underpinnings of dynamic managerial capabilities (DMCs) – managerial cognition, managerial human capital and managerial social capital – represent individual-level micro-foundations that influence corporate social responsibility (CSR). It further explores the interaction mechanism between the three underpinnings in influencing CSR, and their influence depends on the technological turbulence caused by big-data-related technologies.

Design/methodology/approach

This study uses a quantitative research method and partial least squares structural equation modelling (PLS-SEM) to test the relationship between latent factors based on a sample of 270 Chinese top managers.

Findings

The three core underpinnings of DMCs are positively related to CSR. Managerial human capital and managerial social capital mediate the relationship between managerial cognition and CSR. Technological turbulence's moderating effects are also tested. Specifically, technological turbulence amplifies the positive relationship between managerial cognition, managerial human capital and CSR but negatively moderates the relationship between managerial social capital and CSR.

Originality/value

Why are some firms more willing to participate in CSR than others mainly depend on the fact that the actual participants of CSR are the top managers who formulate strategies and implement CSR plans. This study, grounded in the DMCs framework and the upper echelons perspective, is arguably the first to link DMCs' three core underpinnings and CSR, and further explore the multiple drivers' mechanisms and boundary conditions. This study contributes to individual micro-foundation of CSR literature, and advances the understanding of whether and how top managers influence CSR engagement.
Preparation and tribological performance of MoS2 nanoparticles supported on fly ash microparticles
Authors: Hu Kunhong , Miao Yan , Lu Ziyan
Published: October 2022

Purpose

This paper aims to explore the preparation and tribological performance of MoS2 nanoparticles supported on fly ash (FA) microparticles.

Design/methodology/approach

FA was activated by NaOH, oleic acid and HCl to obtain three modified FA samples. Nano-MoS2 was deposited on them to form MoS2/FA additives for poly-α-olefin (PAO) modification. Tribological tests were conducted on a reciprocating rig through the ball-on-disk friction manner. Using X-ray diffraction, scanning electron microscope, energy dispersive spectrometer, Raman spectrometer and element analyzers, the products and their lubrication mechanisms were characterized.

Findings

At 1.5 Wt.%, nano-MoS2 and MoS2/FA could remarkably improve the tribological properties of PAO. The nano-MoS2 deposited on the HCl-activated FA presented better lubrication performance than nano-MoS2. It could reduce friction and wear by approximately 27% and approximately 66%, respectively. The lubrication of MoS2/FA can be attributed to the formation of MoS2 and carbon containing lubricating film.

Originality/value

FA was applied as a supporter to prepare MoS2/FA lubricants. The reuse of FA, a solid waste, is important for environmental protection. Moreover, MoS2/FA is more economical than nano-MoS2 as a lubricant, because it contains approximately 71% of low-cost FA.
Foreign market entry modes for servitization under diverse macroenvironmental conditions: taxonomy and propositions
Authors: Agnihotri Arpita , Bhattacharya Saurabh , Yannopoulou Natalia , Thrassou Alkis
Published: October 2022

Purpose

The article explores how servitization influences firms' foreign market entry mode decisions. This relationship is researched under the contingent effect of macroenvironmental factors in the host country, namely, market attractiveness, institutional environment and national culture differences between the home and host country.

Design/methodology/approach

The study employs a conceptual framework typology that interrelates, contextualizes and conceptualizes extant knowledge to develop explicit propositions.

Findings

Based on the extant literature, using a 2 × 2 matrix, the authors delineate the influence of two dimensions of servitization on entry mode decisions: customer relationship focus and digitalization focus. They conceptualize that relationship management and digitalization-based servitization have an antagonistic effect on the need for entry mode resource commitments, and macroenvironmental factors' favorability moderates this tension.

Research limitations/implications

The study extends and incorporates the servitization literature into the context of international marketing by exploring the combined effect of the two most significant dimensions of servitization, i.e. investment in customer relations versus investment in digitalization on entry mode, thus delivering valuable new insights and perspectives, as well as explicit propositions toward empirical testing.

Practical implications

The authors’ framework increases foreign market managers' awareness of how servitization drives entry mode decisions of firms in international markets. Also, the framework explicates how the host country's market attractiveness, institutional environment and difference with the home country's national culture tangibly influence the relationship.

Originality/value

The study provides novel insights into the implications of servitization on international marketing, particularly regarding foreign market entry mode. The study also elucidates the combined effect of two servitization dimensions, i.e. customer relations and digitalization – a critical research area in which the literature is scant.
Microclimatic variation affects developmental phenology, synchrony and voltinism in an insect population
Authors: Greiser Caroline , von Schmalensee Loke , Lindestad Olle , Gotthard Karl , Lehmann Philipp
Published: October 2022

Temperature influences the rate of most biological processes. Nonlinearities in the thermal reaction norms of such processes complicate intuitive predictions of how ectothermic organisms respond to naturally fluctuating temperatures, and by extension, to climate warming. Additionally, organisms developing close to the ground experience a highly variable microclimate landscape that often is poorly captured by coarse standard climate data.

Using a butterfly population in central Sweden as a model, we quantified the consequences of small‐scale temperature variation on phenology, emergence synchrony and number of annual reproductive cycles (voltinism). By combining empirical microclimate and thermal performance data, we project development of individual green‐veined white butterflies (Pieris napi) across 110 sites in an exceptionally high‐resolved natural microclimate landscape.

We demonstrate that differences among microclimates just meters apart can have large impacts on the rate of development and emergence synchrony of neighbouring butterflies. However, when considering the full development from egg to adult, these temporal differences were reduced in some scenarios, due to negative correlations in development times among life stages. The negative correlations were caused by temperatures at some sites beginning to exceed the optimum for development as the season progressed. Indeed, which sites were optimal for fast development could change across the lifetimes of individual butterflies, that is, ‘fast’ sites could become ‘slow’ sites. Thus, from a thermal point of view, there seem to be no consistently optimal microsites. Importantly, the fast sites were not always the warmest sites. We showed that such unintuitive effects could play an important role in the regulation of phenological synchrony and voltinism in insects, as most sites consistently favoured two generations. The results were generally robust across years and three different egg‐laying dates.

Using high‐resolved empirical climate data on organism‐relevant temporal and spatial scales and considering nonlinear responses to temperature, we demonstrated the large and unintuitive population‐level consequences of locally and temporarily high temperatures. We suggest to—whenever possible—incorporate species‐ and life stage‐specific nonlinear responses to temperature when studying the effects of natural microclimate variation and climate change on organisms.

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Y‐STR mixture deconvolution by single‐cell analysis
Authors: Huffman Kaitlin , Hanson Erin , Ballantyne Jack
Published: October 2022

Since Y‐STR typing only amplifies male Y chromosomal DNA, it can simplify the interpretation of some DNA mixtures that contain female DNA. However, if there are multiple male contributors, mixed Y‐STR DNA profiles will often be obtained. Y‐STR mixture analysis cases are particularly challenging though as, currently, there are no validated probabilistic genotyping (PG) software solutions commercially available to aid in their interpretation. One approach to fully deconvoluting these challenging mixtures into their individual donors is to conduct single‐cell genotyping by isolating individual cells from a mixture prior to conducting DNA typing. In this work, a physical micromanipulation technique involving a tungsten needle and direct PCR with decreased reaction volume and increased cycle number was applied to equimolar 2‐ and 3‐person buccal cell male DNA mixtures and a mock touch DNA case scenario involving the consecutive firing of a handgun by two males. A consensus DNA profiling approach was then utilized to obtain YFiler™ Plus Y‐STR haplotypes. Buccal cells were used to optimize and test the direct single‐cell subsampling approach, and 2–3 person male buccal cell mixtures were fully deconvoluted into their individual donor Y‐STR haplotypes. Single‐cell (or agglomerated cell clump) subsampling from the gun's trigger recovered single‐source Y‐STR profiles from both individuals who fired the gun, the owner, and the other unrelated male. Only the non‐owner's DNA was found in the cells recovered from the handle. In summary, direct single‐cell subsampling as described represents a potential simple way to analyze and interpret Y‐STR mixtures.
Accuracy of comparison decisions by forensic firearms examiners
Authors: Monson Keith L. , Smith Erich D. , Peters Eugene M.
Published: October 2022

This black box study assessed the performance of forensic firearms examiners in the United States. It involved three different types of firearms and 173 volunteers who performed a total of 8640 comparisons of both bullets and cartridge cases. The overall false‐positive error rate was estimated as 0.656% and 0.933% for bullets and cartridge cases, respectively, while the rate of false negatives was estimated as 2.87% and 1.87% for bullets and cartridge cases, respectively. The majority of errors were made by a limited number of examiners. Because chi‐square tests of independence strongly suggest that error probabilities are not the same for each examiner, these are maximum‐likelihood estimates based on the beta‐binomial probability model and do not depend on an assumption of equal examiner‐specific error rates. Corresponding 95% confidence intervals are (0.305%, 1.42%) and (0.548%, 1.57%) for false positives for bullets and cartridge cases, respectively, and (1.89%, 4.26%) and (1.16%, 2.99%) for false negatives for bullets and cartridge cases, respectively. The results of this study are consistent with prior studies, despite its comprehensive design and challenging specimens.
Accuracy and clinical use of biliary point‐of‐care ultrasound: A retrospective cohort study
Authors: Archer Juliette , Beck Sierra
Published: October 2022

Objectives

To assess the utilisation and diagnostic accuracy of biliary point‐of‐care ultrasounds (POCUS) performed and archived in a single New Zealand ED.

Methods

A retrospective cohort study of clinically indicated biliary POCUS, archived from 1 October 2019 to 20 May 2020. POCUS interpretation was compared to expert review and radiology imaging when available. The clinician interpretations, diagnostic imaging results and surgical referrals were extracted from electronic medical records. Archived POCUS images were retrospectively reviewed by an expert to determine diagnostic quality, sonographic findings and imaging errors.

Results

A total of 133 ultrasounds were included; 118 (90%) archived images were of diagnostic quality. The presence or absence of gallstones was documented in 124 (93%), and other sonographic findings were less consistently documented. There was almost perfect agreement with expert review for gallstones (κ = 0.82, 95% confidence interval 0.72–0.93) and substantial agreement for wall thickening (κ = 0.63, 95% confidence interval 0.42–0.83). For patients discharged following negative POCUS without radiology imaging or surgical review no patients returned and received a diagnosis of cholecystitis over 6 months of follow‐up. Imaging errors included failure to visualise the gallbladder neck, misinterpretation of artefacts and technical errors in measurement of the gallbladder wall.

Conclusion

Biliary POCUS was primarily utilised for and was accurate for the detection of gallstones. Further quality assurance and training could be directed at earlier credentialing to address technical errors and improved documentation of POCUS findings.
Refractance window drying in the production of instant baker's yeast and its effect on the quality characteristics of bread
Authors: Arslan‐Tontul Sultan , Çetin‐Babaoğlu Hümeyra , Aslan Mine , Tontul İsmail
Published: October 2022

The study aimed to produce instant dried baker's yeast (BY) by conventional or infrared‐assisted refractance window drying (RWD or InfraRWD, respectively) and compare their bakery performance with commercial BY. According to the findings of the study, the total yeast count was higher than 9.60 log cfu/g in all dried BY samples, and the lowest viability was obtained in BY dried by InfraRWD at 50°C. In general, BY produced by RWD increased the physical quality parameters of bread such as specific volume, total cell count, and the number of cell areas of bread crumbs. Moreover, bread leavened by BY dried by RWD slowed down the staling rate of bread, while infrared assistance accelerated the staling. Sensorial analysis showed that bread produced by refractance window dried BY was more acceptable than commercial BY. In a conclusion, RWD can be an effective alternative to the production of instant baker's yeast, but the most quality features of BY has negatively affected by infrared assistance.

Practical Application

In the drying of baker's yeast, promising advantages can be obtained by refractance window drying. The higher specific volume and superior bread crumb with a retarded staling rate were determined when bread was produced by the refractance window. This is the first time that RWD and InfraRWD have been used for the production of instant baker's yeast and it has several practical applications for bread quality.