bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathoclinical associations between panic disorders and the brain-derived neurotrophic factor Val66Met polymorphism: an updated meta-analysis
Authors: Xia Yu , Song Xun , Wu Lijuan , Li Jun , Liu Nan , Cui Wenhui
Published: February 2023

Prior studies have indicated the pathological role of brain-derived neurotrophic factor (BDNF) gene polymorphism in panic disorders (PD). A functionally less active BDNF Val66Met mutant was previously detected in PD patients with different ethnic backgrounds. However, the results remain inconclusive or inconsistent. A meta-analysis was used to explore the consistency of the BDNF Val66Met mutant’s association with PD irrespective of the subject’s ethnicity. Relevant case-controlled full-length clinical and preclinical reports were retrieved by database searching, and 11 articles involving 2203 cases and 2554 controls were systematically selected per the standard inclusion criteria. Eleven articles were finally included that explored the relationship between the Val66Met polymorphism and PD risk susceptibility. Statistical analysis revealed a significant genetic association of the mutation, allele frequencies, and genotype distributions of BDNF with PD onset. Our findings demonstrated that the BDNF Val66Met is a susceptibility factor of PD.
Fructilactobacillus cliffordii sp. nov., Fructilactobacillus hinvesii sp. nov., Fructilactobacillus myrtifloralis sp. nov., Fructilactobacillus carniphilus sp. nov. and Fructobacillus americanaquae sp. nov., five novel lactic acid bacteria isolated from insects or flowers of Kangaroo Island, South Australia
Authors: Oliphant Scott A. , Watson-Haigh Nathan S. , Sumby Krista M. , Gardner Jennifer M. , Jiranek Vladimir
Published: February 2023

Six strains, KI11_D11T, KI4_B1, KI11_C11T, KI16_H9T, KI4_A6T and KI3_B9T, were isolated from insects and flowers on Kangaroo Island, South Australia. On the basis of 16S rRNA gene phylogeny, strains KI11_D11T, KI4_B1, KI11_C11T, KI16_H9T, KI4_A6T were found to be closely related to

Fructilactobacillus ixorae

Ru20-1T. Due to the lack of a whole genome sequence for this species, whole genome sequencing of

Fructilactobacillus ixorae

Ru20-1T was undertaken. KI3_B9T was found to be closely related to

Fructobacillus tropaeoli

F214-1T. Utilizing core gene phylogenetics and whole genome analyses, such as determination of AAI, ANI and dDDH, we propose that these six isolates represent five novel species with the names Fructilactobacillus cliffordii (KI11_D11T= LMG 32130T = NBRC 114988T), Fructilactobacillus hinvesii (KI11_C11T = LMG 32129T = NBRC 114987T), Fructilactobacillus myrtifloralis (KI16_H9T= LMG 32131T = NBRC 114989T) Fructilactobacillus carniphilus (KI4_A6T = LMG 32127T = NBRC 114985T) and Fructobacillus americanaquae (KI3_B9T = LMG 32124T = NBRC 114983T). Chemotaxonomic analyses detected no fructophilic characters for these strains of member of the genus

Fructilactobacillus

. KI3_B9T was found to be obligately fructophilic, similarly to its phylogenetic neighbours in the genus

Fructobacillus

. This study represents the first isolation, to our knowledge, of novel species in the family

Lactobacillaceae

from the Australian wild.
APRI score is not predictive of post-surgical outcomes in cholangiocarcinoma patients
Authors: Aslam Faaiq N , Loveday Tristan A , Uson Junior Pedro Luiz Serrano , Truty Mark , Smoot Rory , Bekaii-Saab Tanios , Ahn Daniel , Sonbol Mohamad Bassam , Wu Christina , Stucky Chee-Chee , Babiker Hani , Borad Mitesh J
Published: February 2023

Objective

To assess the utility of aminotransferase-platelet ratio index (APRI) score in prognosticating post-surgical outcomes in cholangiocarcinoma patients.

Methods

152 cholangiocarcinoma patients at the Mayo Clinic that underwent surgical resection were retrospectively analyzed. Statistical analyses were done to determine the relationship between APRI score and demographic factors, laboratory values, pathological features, and outcomes data.

Results

No relationship between APRI score and demographic factors was identified. There was a correlation between APRI score and ALT, albumin, and bilirubin, but the remaining laboratory parameters showed no correlation. APRI score did not prove to be useful as a prognostic tool as it did not correlate with tumor pathology features and did not correlate with post-surgical recurrence and mortality.

Conclusion

We found that APRI score was not a prognostic tool for post-surgical outcomes in cholangiocarcinoma patients.
Ethnic inequalities during clinical placement: a qualitative study of student nurses’ experiences within the London National Health Service
Authors: Walker Chenel R , Gunasinghe Cerisse , Harwood Hannah , Ehsan Annahita , Ahmed Farah , Dorrington Sarah , Onwumere Juliana , Meriez Paula , Stanley Nathan , Stoll Nkasi , Woodhead Charlotte , Hatch Stephani L , Rhead Rebecca
Published: February 2023

Aim

To understand how student nurse experiences on clinical placement, within NHS hospitals, differ for ethnic minority and White British groups.

Design

A qualitative thematic analysis with an inductive approach.

Methods

Data from semi-structured interviews with 21 London (United Kingdom) hospital-based student nurses were examined using thematic analysis. Participants were interviewed as part of theTackling Inequalities and Discrimination Experiences in health Services(TIDES) study and asked about their experiences during clinical placement.

Results

Five main themes were identified: 1) Role of mentors, 2) Discrimination and unfair treatment, 3) Speaking up/out, 4) Career progression, and 5) Consequences of adverse experiences. All themes were linked, with the social dynamics and workplace environment (referred to as ‘ward culture’) providing a context that normalises mistreatment experienced by nursing students. Students from ethnic minority backgrounds reported racism as well as cultural and/or religious microaggressions. While being valued for their race and ethnicity, White British students also experienced discrimination and inequity due to their age, sex, gender, and sexual orientation. Students from both White British and ethnic minority groups acknowledged that being treated badly was a barrier to career progression. Ethnic minority students also noted that the lack of diverse representation within senior nursing positions discouraged career progression within the UK National Health Service (NHS).

Conclusion

These initial experiences of inequality and discrimination are liable to shape a student’s perspective of their profession and ability to progress within nursing. The NHS is responsible for ensuring that student nurses’ developmental opportunities are equal, irrespective of ethnicity.

Impact

Ward culture is perpetuated through the action of others to normalise mistreatment and concurrently disadvantage ethnic minority students making them feel unvalued, which in turn impacts both staff retention and career progression within the NHS. Training assessors should be aware of the existing culture of discrimination within clinical placements and work to eradicate it.
Universal health coverage in the context of population ageing: Catastrophic health expenditure and unmet need for healthcare
Authors: Okamoto Shohei , Sata Mizuki , Rosenberg Megumi , Nakagoshi Natsuko , Kamimura Kazuki , Komamura Kohei , Kobayashi Erika , Sano Junko , Hirazawa Yuzuki , Okamura Tomonori , Iso Hiroyasu
Published: February 2023

Objectives

This study investigates the incidence/prevalence, determinants, and consequences of catastrophic health expenditure (CHE) and unmet need for healthcare and assesses the potential heterogeneity between younger (≤ 64 years) and older people (65 years≤).

Methods

Utilising an annual nationally representative survey of Japanese aged 20 years and over, we estimated the incidence of CHE and unmet need for healthcare using disaggregated estimates by household members’ age (i.e. ≤ 64 years vs. 65 years≤) between 2004–2020. Using a fixed-effects model, we assessed the determinants of CHE and unmet need along with the consequences of CHE. We also assessed the heterogeneity by age.

Results

Households with older members were more likely to have their healthcare needs met but experienced CHE more so than households without older members. The financial consequences of CHE were heterogeneous by age, suggesting that households with older members responded to CHE by reducing food and social expenditures more so than households without older members reducing expenditure on education. Households without older members experienced an income decline in the year following the occurrence of CHE, while this was not found among households with older members. A U-shaped relationship was observed between age and the probability of experiencing unmet healthcare need.

Conclusions

Households with older members are more likely to experience CHE with different financial consequences compared to those with younger members. Unmet need for healthcare is more common among younger and older members than among their middle-aged counterparts, though the health consequences of this unmet need could not be determined.
Genotype and Clinical Characteristics of Patients with Wolfram Syndrome and WFS1-related Disorders
Authors: Lee Evan M. , Verma Megha , Palaniappan Nila , Pope Emiko M. , Lee Sammie , Blacher Lindsey , Neerumalla Pooja , An William , Campbell Toko , Brown Cris , Hurst Stacy , Marshall Bess , Hershey Tamara , Nunes Virginia , de Heredia Miguel López , Urano Fumihiko
Published: February 2023

Objective

Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity and prognosis of Wolfram syndrome more accurately.

Approach

Patient data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and patient case reports were analyzed to select for patients with two recessive mutations in the WFS1 gene. Mutations were classified as being either nonsense/frameshift variants or missense/in-frame insertion/deletion variants and statistical analysis was performed using unpaired and paired t-tests and one- and two-way ANOVA with Tukey’s or Dunnett’s tests.

Results

A greater number of genotype variants correlated with earlier onset and a more severe presentation of Wolfram syndrome. Secondly, non-sense and frameshift variants had more severe phenotypic presentations than missense variants, as evidenced by optic atrophy emerging significantly earlier in patients with 2 nonsense/frameshift alleles compared with 0 missense transmembrane variants. In addition, the number of transmembrane in-frame variants demonstrated a statistically significant dose-effect on age of onset of diabetes mellitus and optic atrophy.

Summary / Conclusions

The results contribute to our current understanding of the genotype-phenotype relationship of Wolfram syndrome, suggesting that alterations in coding sequences result in significant changes in the presentation and severity of Wolfram. The impact of these findings is significant, as the results will aid clinicians in predicting more accurate prognoses and pave the way for personalized treatments for Wolfram syndrome.
Semi-conservative transmission of DNA N6-adenine methylation in a unicellular eukaryote
Authors: Sheng Yalan , Wang Yuanyuan , Yang Wentao , Wang Xue Qing , Lu Jiuwei , Pan Bo , Nan Bei , Liu Yongqiang , Li Chun , Song Jikui , Dou Yali , Gao Shan , Liu Yifan
Published: February 2023

While DNA N6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has generated great interest recently. Biochemical and genetic evidence supports that AMT1, a MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, 6mA transmission mechanism remains to be elucidated. Taking advantage of Single Molecule Real-Time Circular Consensus Sequencing (SMRT CCS), here we provide definitive evidence for semi-conservative transmission of 6mA, showcased in the unicellular eukaryoteTetrahymena thermophila. In wildtype (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); hemi-methylation (hemi-6mApT) is transiently present on the parental strand of newly replicated DNA. In ΔAMT1cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and likely processive, whilede novo6mA deposition in ΔAMT1cells is slow and sporadic. InTetrahymena, regularly spaced 6mA clusters coincide with linker DNA of the canonical nucleosome arrays in the gene body. Importantly,in vitromethylation of human chromatin by reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1’s intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semi-conservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independentde novomethylation, reveals a molecular pathway for 6mA transmission with striking similarity to 5-methyl cytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as abona fideeukaryotic epigenetic mark.
Downregulation of stromal syntenin sustains AML development
Authors: Leblanc Raphael , Ghossoub Rania , Goubard Armelle , Castellano Rémy , Fares Joanna , Camoin Luc , Audebert Stephane , Balzano Marielle , Bou-Tayeh Berna , Fauriat Cyril , Vey Norbert , Borg Jean-Paul , Collette Yves , Aurrand-Lions Michel , David Guido , Zimmermann Pascale
Published: February 2023

The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC), stromal syntenin deficiency, in turn, generating a pro-tumoral microenvironment. From serial transplantations in mice and co-culture experiments, we conclude that syntenin-deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro-tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, whichin transstimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML-stroma crosstalk and unsuspected tumor-suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.
Cancer Prevalence Across Vertebrates
Authors: Compton Zachary T. , Mellon Walker , Harris Valerie , Rupp Shawn , Mallo Diego , Kapsetaki Stefania E. , Wilmot Mallory , Kennington Ryan , Noble Kathleen , Baciu Cristina , Ramirez Lucia , Peraza Ashley , Martins Brian , Sudhakar Sushil , Aksoy Selin , Furukawa Gabriela , Vincze Orsolya , Giraudeau Mathieu , Duke Elizabeth G. , Spiro Simon , Flach Edmund , Davidson Hannah , Li Christopher , Zehnder Ashley , Graham Trevor A. , Troan Brigid , Harrison Tara M. , Tollis Marc , Schiffman Joshua D. , Aktipis Athena , Abegglen Lisa M. , Maley Carlo C. , Boddy Amy M.
Published: February 2023

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Peto’s Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.

Statement of Significance

Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes.
Actin Dysregulation Induces Neuroendocrine Plasticity and Immune Evasion: A Vulnerability of Small Cell Lung Cancer
Authors: Seo Yoojeong , Zhang Shengzhe , Jang Jinho , Ko Kyung-Pil , Kim Kee-Beom , Huang Yuanjian , Kim Dong-Wook , Kim Bongjun , Zou Gengyi , Zhang Jie , Jun Sohee , Chu Wonhong , Kirk Nicole A. , Hwang Ye Eun , Ban Young Ho , Dhar Shilpa S. , Chan Joseph M. , Lee Min Gyu , Rudin Charles M. , Park Kwon-Sik , Park Jae-Il
Published: February 2023

Small cell lung cancer (SCLC) is aggressive with limited therapeutic options. Despite recent advances in targeted therapies and immunotherapies, therapy resistance is a recurring issue, which might be partly due to tumor cell plasticity, a change in cell fate. Nonetheless, the mechanisms underlying tumor cell plasticity and immune evasion in SCLC remain elusive. CRACD, a capping protein inhibitor that promotes actin polymerization, is frequently inactivated in SCLC.Cracdknockout (KO) transforms preneoplastic cells into SCLC tumor-like cells and promotes in vivo SCLC development driven byRb1,Trp53, andRbl2triple KO.CracdKO induces neuroendocrine (NE) plasticity and increases tumor cell heterogeneity of SCLC tumor cells via dysregulated NOTCH1 signaling by actin cytoskeleton disruption. CRACD depletion also reduces nuclear actin and induces EZH2-mediated H3K27 methylation. This nuclear event suppresses the MHC-I genes and thereby depletes intratumoral CD8+T cells for accelerated SCLC tumorigenesis. Pharmacological blockade of EZH2 inhibits CRACD-negative SCLC tumorigenesis by restoring MHC-I expression and immune surveillance. Unsupervised single-cell transcriptomics identifies SCLC patient tumors with concomitant inactivation of CRACD and downregulated MHC-I pathway. This study defines CRACD, an actin regulator, as a tumor suppressor that limits cell plasticity and immune evasion and proposes EZH2 blockade as a viable therapeutic option for CRACD-negative SCLC.
A diverse repertoire of anti-defense systems is encoded in the leading region of plasmids
Authors: Samuel Bruria , Burstein David
Published: February 2023

Plasmids are an important source of antibiotic-resistance genes that mobilize horizontally between bacteria, including many human pathogens. Bacteria express various defense mechanisms, such as CRISPR-Cas, restriction-modification systems, and SOS-response genes, to prevent the invasion of mobile elements. Yet, plasmids efficiently and robustly overcome these defenses during conjugation. Here, we show that the leading region of plasmids, which is the first to enter recipient cells, is a hotspot for an extensive repertoire of anti-defense systems, encoding anti-CRISPR, anti-restriction, anti-SOS, and other counter-defense proteins. We further demonstrate that focusing on these specific functional regions can lead to the discovery of diverse anti-defense genes. Promoters known to allow expression from ssDNA were prevalent in the leading regions, potentially facilitating rapid protection against bacterial immunity in the early stages of plasmid invasion. These findings reveal a new facet of plasmid dissemination and provide theoretical foundations for developing conjugative delivery systems for natural microbial communities.
Fish microbiota repels ovipositing mosquitoes
Authors: Shteindel Nimrod , Gerchman Yoram , Silberbush Alon
Published: February 2023

The mere presence of predators causes prey organisms to enact predation-avoidance strategies. This presence is often reveled through predator-released kairomones. It was previously suggested that in many cases, the predator’s microbiota composition plays an important role in the release of these kairomones, however this mechanism is still poorly understood. Ovipositing mosquito females of several species are repelled by kairomones released from larvivorous fish. In this study we looked into the effects of the microbiota originated byGambusia affinis(Baird and Girard) on the ovipisition behavior of gravid mosquito females in an outdoor mesocosm experiment. We show that interference with the fish microbiota significantly reduces its repellant effect. We further show that the bacteriumPantoea pleurotiisolated from the skin of the fish repels oviposition ofCulex laticinctus(Edwards) andCuliseta longiareolataMacquart mosquitoes similarly to the effect of live fish. These results highlight the importance of bacteria in the interspecies interactions of their hosts and the potential conflict of interests in this system, where bacteria may benefit from the absence of the bacterivore mosquito larvae, but the fish loose access to prey.
Clustering rare diseases within an ontology-enriched knowledge graph
Authors: Sanjak Jaleal , Zhu Qian , Mathé Ewy A.
Published: February 2023

Structured Abstract

Objective

Identifying sets of rare diseases with shared aspects of etiology and pathophysiology may enable drug repurposing and/or platform based therapeutic development. Toward that aim, we utilized an integrative knowledge graph-based approach to constructing clusters of rare diseases.

Materials and Methods

Data on 3,242 rare diseases were extracted from the National Center for Advancing Translational Science (NCATS) Genetic and Rare Diseases Information center (GARD) internal data resources. The rare disease data was enriched with additional biomedical data, including gene and phenotype ontologies, biological pathway data and small molecule-target activity data, to create a knowledge graph (KG). Node embeddings were used to convert nodes into vectors upon which k-means clustering was applied. We validated the disease clusters through semantic similarity and feature enrichment analysis.

Results

A node embedding model was trained on the ontology enriched rare disease KG and k-means clustering was applied to the embedding vectors resulting in 37 disease clusters with a mean size of 87 diseases. We validate the disease clusters quantitatively by looking at semantic similarity of clustered diseases, using the Orphanet Rare Disease Ontology. In addition, the clusters were analyzed for enrichment of associated genes, revealing that the enriched genes within clusters were shown to be highly related.

Discussion

We demonstrate that node embeddings are an effective method for clustering diseases within a heterogenous KG. Semantically similar diseases and relevant enriched genes have been uncovered within the clusters. Connections between disease clusters and approved or investigational drugs are enumerated for follow-up efforts.

Conclusion

Our study lays out a method for clustering rare diseases using the graph node embeddings. We develop an easy to maintain pipeline that can be updated when new data on rare diseases emerges. The embeddings themselves can be paired with other representation learning methods for other data types, such as drugs, to address other predictive modeling problems. Detailed subnetwork analysis and in-depth review of individual clusters may lead to translatable findings. Future work will focus on incorporation of additional data sources, with a particular focus on common disease data.
Functional networks in the infant brain during sleep and wake states
Authors: Yates Tristan S. , Ellis Cameron T. , Turk-Browne Nicholas B.
Published: February 2023

Functional brain networks are assessed differently early in development than at maturity: infants are almost universally scanned during sleep, whereas adults are typically scanned awake while resting or performing tasks. Observed differences between infant and adult functional networks may thus reflect these differing states of consciousness rather than or in addition to developmental changes. We explore this question by comparing functional networks in fMRI scans acquired from infants during natural sleep and awake movie-watching. As a reference, we also acquired fMRI scans in adults during awake rest and awake movie-watching. Whole-brain functional connectivity was more similar within-state (sleep-sleep, wake-wake) than across-state (sleep-wake) in infants, demonstrating that movies elicit a different network configuration than typical sleep acquisitions. Indeed, a classifier trained on patterns of functional connectivity during infant sleep versus wake robustly decoded the state of additional infants and even generalized to decode rest versus movie in adults; interestingly, a classifier trained on rest versus movie in adults did not generalize nearly as well to sleep versus wake in infants. Moreover, the overall level of similarity between infant and adult functional connectivity was modulated by adult state (stronger for movie than rest) but not infant state (equivalent for sleep and wake). Nevertheless, the network connections that drove similarity between infants and adults, particularly in frontoparietal network, were modulated by infant state. In sum, infant functional connectivity can differ between sleep and wake states, highlighting the potential value of awake data for studying the early development of functional brain networks.

Significance statement

Functional networks in the infant brain provide a foundation for early cognitive abilities and act as a marker of brain maturation and developmental disorders. What we know about these networks comes from fMRI data acquired during sleep, given the challenges of awake infant fMRI. This contrasts with the dominant approach in older populations of assessing networks during awake rest or tasks. These differing levels of consciousness cloud the interpretation of developmental changes. Here we show that whole-brain functional connectivity differs between sleeping and awake infants, and that the similarity of these infant states to adults loads on dissociable network connections. This research suggests that a full understanding of early functional brain networks will benefit from complementary insights in awake infants.
Construction of Fosmid-based SARS-CoV-2 replicons for antiviral drug screening and replication analyses in biosafety level 2 facilities
Authors: Takazawa Shunta , Kotaki Tomohiro , Nakamura Satsuki , Utsubo Chie , Kameoka Masanori
Published: February 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Δorf2-8, Δorf2.4, and Δorf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the Δorf2-8 and Δorf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the Δorf2.4-puro replicon by inserting a puromycin-resistant gene into the Δorf2.4 replicon. We observed the more sustained replication of the Δorf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.
Molecular basis for potent B cell responses to antigen displayed on particles of viral size
Authors: Brooks Jeremy F. , Riggs Julianne , Mueller James L. , Mathenge Raisa , Wholey Wei-Yun , Yoda Sekou-Tidiane , Vykunta Vivasvan S. , Cheng Wei , Zikherman Julie
Published: February 2023

Although it has long been appreciated that multivalent antigens – and particularly viral epitope display – produce extremely rapid, robust, and T-independent humoral immune responses, the biochemical basis for such potency has been incompletely understood. Here we take advantage of a set of neutral liposomes of viral size that are engineered to display affinity mutants of the model antigen (Ag) hen egg lysozyme at precisely varied density. We show that particulate Ag display by liposomes induces highly potent B cell responses that are dose-and density-dependent but affinity-independent. Titrating dose of particulate, but not soluble, Ag reveals bimodal Erk phosphorylation and cytosolic calcium increases. Particulate Ag induces signal amplification downstream of the B cell receptor (BCR) by selectively evading LYN-dependent inhibitory pathways, butin vitropotency is independent of CD19. Importantly, Ag display on viral-sized particles signals independently of MYD88 and IRAK1/4, but activates NF-κB robustly in a manner that mimics T cell help. Together, such biased signaling by particulate Ag promotes MYC expression and reduces the threshold required for B cell proliferation relative to soluble Ag. These findings uncover a molecular basis for highly sensitive B cell response to viral Ag display and remarkable potency of virus-like particle vaccines that is not merely accounted for by avidity and BCR cross-linking, and is independent of the contribution of B cell nucleic acid-sensing machinery.
The mitochondrial regulation of smooth muscle cell proliferation in type 2 diabetes
Authors: Koval Olha M. , Nguyen Emily K. , Mittauer Dylan J. , Ait-Aissa Karima , Chinchankar William , Qian Lan , Madesh Muniswamy , Dai Dao-Fu , Grumbach Isabella M.
Published: February 2023

Background

Type 2 diabetes (T2D) is associated with a strongly increased risk for restenosis after angioplasty driven by proliferation of vascular smooth muscle cells (VSMCs). Here, we sought to determine whether and how mitochondrial dysfunction in T2D drives VSMC proliferation with a focus on ROS and intracellular [Ca2+] that both drive cell proliferation, occur in T2D and are regulated by mitochondrial activity.

Methods

Using a diet-induced mouse model of T2D, the inhibition of the mitochondrial Ca2+/calmodulin-dependent kinase II (mtCaMKII), a regulator of Ca2+entry via the mitochondrial Ca2+uniporter selectively in VSMCs, we performed in vivo phenotyping after mechanical injury and established the mechanisms of excessive proliferation in cultured VSMCs.

Results

In T2D, the inhibition of mtCaMKII reduced both neointima formation after mechanical injury and the proliferation of cultured VSMCs. VSMCs from T2D mice displayed accelerated proliferation, reduced mitochondrial Ca2+entry and membrane potential with elevated baseline [Ca2+]cytocompared to cells from normoglycemic mice. Accelerated proliferation after PDGF treatment was driven by activation of Erk1/2 and its upstream regulators. Hyperactivation of Erk1/2 was Ca2+-dependent rather than mitochondrial ROS-driven Ca2+-dependent and included the activation of CaMKII in the cytosol. The inhibition of mtCaMKII exaggerated the Ca2+imbalance by lowering mitochondrial Ca2+entry and increasing baseline [Ca2+]cyto, further enhancing baseline Erk1/2 activation. With inhibition of mtCaMKII, PDGF treatment had no additional effect on cell proliferation. Inhibition of activated CaMKII in the cytosol decreased excessive Erk1/2 activation and reduced VSMC proliferation.

Conclusions

Collectively, our results provide evidence for the molecular mechanisms of enhanced VSMC proliferation after mechanical injury by mitochondrial Ca2+entry in T2D.
Start codon-associated ribosomal frameshifting mediates nutrient stress adaptation
Authors: Mao Yuanhui , Jia Longfei , Dong Leiming , Shu Xin Erica , Qian Shu-Bing
Published: February 2023

A translating ribosome is typically thought to follow the reading frame defined by the selected start codon. Using super-resolution ribosome profiling, here we report pervasive out-of-frame translation immediately from the start codon. The start codon-associated ribosome frameshifting (SCARF) stems from the slippage of ribosomes during the transition from initiation to elongation. Using a massively paralleled reporter assay, we uncovered sequence elements acting as SCARF enhancers or repressors, implying that start codon recognition is coupled with reading frame fidelity. This finding explains thousands of mass spectrometry spectra unannotated from human proteome. Mechanistically, we find that the eukaryotic initiation factor 5B (eIF5B) maintains the reading frame fidelity by stabilizing initiating ribosomes. Intriguingly, amino acid starvation induces SCARF by proteasomal degradation of eIF5B. The stress-induced SCARF protects cells from starvation by enabling amino acid recycling and selective mRNA translation. Our findings illustrate a beneficial effect of translational “noise” in nutrient stress adaptation.
Dominant and Genome-Wide Formation of DNA:RNA Hybrid G-Quadruplexes in Living Yeast Cells
Authors: Ren Chen-xia , Duan Rui-fang , Wang Jia , Hao Yu-hua , Tan Zheng
Published: February 2023

Guanine-rich nucleic acids form G-quadruplex (G4) structures that play a critical role in cellular processes. Previous studies have mostly focused on monomeric intramolecular G4s with four consecutive guanine tracts (G-tracts) from a single strand. However, this structural form has never been confirmed in eukaryotic cells. Here, we report the formation of hybrid G4s (hG4s), consisting of G-tracts from both DNA and RNA, in the genome of living yeast cells. Analysis of Okazaki fragment syntheses and G4-specific probing reveals that hG4s can efficiently form with as few as a single DNA guanine-guanine (GG) tract due to the participation of G-tracts from RNA. This finding increases the number of G4-forming sites in the yeast genome from 38 to 587,694, a more than 15,000-fold increase. Interestingly, hG4s still form and even dominate at genomic G4 sites that are theoretically capable of forming the monomeric intramolecular DNA G4s by themselves. Compared to DNA G4s (dG4s), hG4s exhibit a wider range of kinetics, higher prevalence, and greater structural diversity and stability. Most importantly, hG4 formation is tightly coupled to transcription through the involvement of RNA, allowing hG4s to function in a transcription-dependent manner. Overall, our study establishes hG4s as the overwhelmingly dominant G4 species in the yeast genome and emphasizes a renewal of the current perception of the structural form, formation mechanism, prevalence, and functional role of G4s in eukaryotic genomes. It also provides a sensitive and currently the only method for detecting the structural form of G4s in living cells.

Significance

The identification of hybrid G-quadruplexes (hG4s) has disclosed a previously unrecognized structural form of G4s as the most common and abundant G4 species in the yeast genome. It reveals not only a dominant rule governing the formation of G4s in eukaryotic genomes, but also a unique genotype that allows G4-mediated transcriptional regulation to take feedback from the output as input, thus allowing the creation of feedback loops at the transcriptome scale.
SNP profile for quantitative trait nucleotide in populations with small effective size and its impact on mapping and genomic predictions
Authors: Misztal Ignacy , Pocrnic Ivan , Lourenco Daniela
Published: February 2023

In animal populations, increasing the SNP density by incorporating sequence information only marginally increases prediction accuracies. To find out why, we used statistical models and simulations to investigate the profile or distribution of SNP around Quantitative Trait Nucleotides (QTN) in populations with small effective population size (Ne). A QTN profile created by averaging SNP solutions around each QTN was similar to the shape of expected pairwise linkage disequilibrium (PLD) based on Neand genetic distance between SNP, with a distinct peak for the QTN. Populations with smaller Neshowed lower but wider QTN profiles; however, adding more genotyped individuals with phenotypes dragged the profile closer to the QTN; the QTN profile was higher and narrower for populations with larger compared to smaller Ne. Assuming the PLD curve for the QTN profile, 80% of the additive genetic variance explained by each QTN is contained in 8 “Stam” segments (one segment = 1/4NeMorgans), corresponding to 1.6 Mb in cattle, and 5 Mb in pigs and broiler chickens. With such large segments, identifying QTN is difficult even if all of them are in the data and the assumed genetic architecture is simplistic. Additional complexity in QTN detection arises from confounding of QTN profiles with signals due to relationships, overlapping profiles with closely-spaced QTN, and spurious signals due to imputation errors. However, small Neallows for accurate prediction with large data even without QTN identification because QTN are accounted for by QTN profiles if SNP density is sufficient to saturate the segments.
Animal detection using thermal imaging and a UAV
Authors: Frąckowiak Rafał , Goraj Zdobysław Jan
Published: February 2023

Purpose

This study aims to test a multirotor unmanned aerial vehicle (UAV) paired with a thermal imaging camera for detecting big game species such as Eurasian elk, red deer, European roe deer and Eurasian wild boar.

Design/methodology/approach

The research work was carried out in the Czarna Bialostocka Forest District (Podlaskie Voivodeship, Poland). A thermal imaging camera E20Tvx Yuneec with a view angle of 33° × 26.6° and a thermal sensor resolution of 640 × 512 pixels was selected for the research. The Yuneec H520E hexacopter was chosen as the lifting vehicle. The flights for the study were conducted between the autumn of 2021 and the winter of 2022. The UAV was flown at two different altitudes, 120 and 80 m above ground level, which provided a ground sampling distance of 11 and 7 cm, respectively.

Findings

The results so far have shown the potential of commercially available thermal imaging cameras for detecting and identifying big game species, such as Eurasian elk and red deer. Moreover, in the winter season of 2022 on the 7th and 13th of March, it was also possible to determine the sex of red deer distinguishing between males and females. The results of the survey made with the thermal camera were compared to the assessment from the standard method for the determination of the game population in the Czarna Bialostocka sub-district. In the case of red deer, the results of the research carried out during the winter exceed five times the numbers obtained as a result of the traditional inventory. That is most likely due to the gregarious occurrence of this species in the winter season.

Originality/value

The use of thermovision to estimate the population and sex of animals is a relatively new issue, especially in Poland, where the use of thermal imaging is not the official method of research of big game species yet.
Design and implementation of a hardware-in-the-loop simulation platform for a tail-sitter UAV
Authors: Zou Xu , Liu Zhenbao , Zhao Wen , Wang Lina
Published: February 2023

Purpose

A high-fidelity simulation platform helps to verify the feasibility of the controller and reduce the cost of subsequent experiments. Therefore, this paper aims to design a high-fidelity hardware-in-the-loop (HIL) simulation platform for the tail-sitter vehicles.

Design/methodology/approach

The component breakdown approach is used to develop a more reliable model. Thruster dynamics and ground contact force are also modeled. Accurate aerodynamic coefficients are obtained through wind tunnel tests. This simulation system adopts a mode transition method to achieve continuous simulation for all flight modes.

Findings

Simulation results are in good agreement with the flight log and successfully predict the state of the vehicle.

Originality/value

First, the effects of the propeller slipstream are considered. Second, most researchers ignore the parasitic drag caused by the landing gear and other appendages, which is discussed in this study. Third, a ground contact model is implemented to allow a realistic simulation of the takeoff and landing phases. Fourth, complete wind tunnel tests are conducted to obtain more accurate aerodynamic coefficients. Finally, a mode transition method is deployed in the HIL simulation system to achieve continuous simulation for all flight modes.
First impressions matter: evaluating the importance of online reputation in social networking sites for initial trust in virtual work partners
Authors: Martinelli Watanuki Hugo , de Oliveira Moraes Renato
Published: February 2023

Purpose

The purpose of this paper is to identify the practices that owners of public profiles in social networking sites can leverage to actively build online reputation and to evaluate the impact of the adoption of such practices on the initial formation of trust toward these individuals when they are presented as new virtual work partners.

Design/methodology/approach

A theoretical model was developed and an experiment with 233 participants was utilized to assess the model using partial least squares structural equation modeling.

Findings

The results suggest that individuals can build their online reputations in public profiles of social networking sites via a series of practices of self-disclosure of information and that the adoption of these practices has significant effects on the initial formation of trust toward the profile owner in virtual work contexts. Categorization mechanisms such as stereotyping, unit grouping and reputation categorization have been found to contribute to the initial formation of trust, both from an affect and cognition-based perspectives.

Originality/value

Little is known about the information disclosure practices in public profiles of social networking sites that new work partners can adopt to facilitate the formation of trust between them before they start working together. This study has contributed to the existing body of literature by clarifying these practices and the relative importance of online reputation to the initial formation of trust during the outset of a new virtual work relationship.
Rhetorical structure parallels research topic in LIS articles: a temporal bibliometrics examination
Authors: Lou Wen , He Jiangen , Xu Qianqian , Zhu Zhijie , Lu Qiwen , Zhu Yongjun
Published: February 2023

Purpose

The effectiveness of rhetorical structure is essential to communicate key messages in research articles (RAs). The interdisciplinary nature of library and information science (LIS) has led to unclear patterns and practice of using rhetorical structures. Understanding how RAs are constructed in LIS to facilitate effective scholarly communication is important. Numerous studies investigated the rhetorical structure of RAs in a range of disciplines, but LIS articles have not been well studied.

Design/methodology/approach

In this study, the authors encoded rhetorical structures to 2,216 articles in the Journal of the Association for Information Science and Technology covering a period from 2001 to 2018 with the approaches of co-word analysis and visualization. The results show that the predominant rhetorical structures used by LIS researchers follow the sequence of Introduction-Literature Review-Methodology-Result-Discussion-Conclusion (ILMRDC).

Findings

The authors' temporal examination reveals the shifts of evolutionary pattern of rhetorical structure in 2008 and 2014. More importantly, the authors' study demonstrates that rhetorical structures have varied greatly across research areas in LIS community. For example, scholarly communication and scientometrics studies tend to exclude literature review in articles.

Originality/value

The present paper offers a first systematic examination of how rhetorical structures are used in a representative sample of a LIS journal, especially from a temporal perspective.
The effects of brand collaboration with the online game on customer equity and purchase intention: moderating effect of fashion brand type
Authors: Kim Sang Jin , Yoo Jiwon , Ko Eunju
Published: February 2023

Purpose

This study aims to investigate the relationship between collaboration product attributes, consumption value, customer equity and purchase intention – specifically, the moderating effect of fashion brand type (luxury and sports).

Design/methodology/approach

Online game and fashion (luxury and sports) brands were selected and online game items showing items' logos were used as stimuli. A total of 328 South Korea consumers answered a survey. The hypotheses were tested using a structural equation model (SEM).

Findings

Collaboration product attributes influence consumption value, which links to customer equity. Customer equity increases purchase intention. The multi-group analysis confirmed the difference between variables according to the brand.

Research limitations/implications

Research on collaboration with the online environment is limited. This study provides theoretical background for future research and suggests multiple items to measure collaboration product attributes.

Practical implications

Fashion brands can utilize online games to extend target markets. However, consumers perceive collaboration products differently depending on the brand types. Thus, companies should consider brand characteristics or identity when designing collaboration products with online games.

Originality/value

This study focuses on collaboration of fashion brands in the online environment. The results will help fashion brands establish relevant brand extension strategies.
Managing food security using blockchain-enabled traceability system
Authors: Gupta Rachita , Shankar Ravi
Published: February 2023

Purpose

Food insecurity is a major concern for developing economies. Operational inadequacies get introduced with unorganized interactions among stakeholders in the food supply chain, affecting social, economic, environmental and operational (SEEO) aspects of a nation. This study analyzes India's largest food safety net program, Public Distribution System (PDS) and develops a perception-based model, mapping the root causes (of food insecurity) with possible solutions. The novelty lies in leveraging blockchain in the implementation of food traceability system.

Design/methodology/approach

Soft system methodology (SSM) is used to identify and analyze problems in PDS, leveraging the learning and inquiry process. It relies on system thinking and action research to create a defendable and rational model, which helps in proposing recommendations for addressing the problem.

Findings

Blockchain-enabled food traceability system increases transparency, thus enabling the fulfillment of basic food necessities for beneficiaries.

Practical implications

The proposed model enables policymakers to build a profound understanding of existing operational issues and provides insightful recommendations for making informed decisions to deal with the grave issue of food insecurity.

Originality/value

Unlike previous studies, this research attempts to understand operational inefficiencies during interactions among stakeholders. It proposes a perception-based conceptual model for the final implementation at the ground level. It also reveals significance of three systems: a delivery system, an enabling system empowering delivery system and a criteria system to control and monitor processes. This study thus bridges an important gap in the literature by proposing a blockchain-driven traceability system, under the control of criteria system, through the integration of system-thinking and action-research approach.