bluuebunny/crossref_metadata_2025 huggingface dataset:
Memory for the News: Does Event Transience Matter?
Authors: Nester Caroline O. , Malone Christopher , Munro Catherine , Madigan Nancy , Hoffschmidt Sara , Sweeney Joan , Zink Tyler , O’Connor Margaret
Published: January 2023

Background:

Health providers frequently probe patients’ recall of current and/or remote news events to determine the extent of memory loss. Impaired memory for transient events (ie, in the news for a circumscribed time) may provide information regarding the onset of cognitive impairment.

Objective:

To use the Transient News Events Test (TNET) to explore how memory changes over time in both older adults with cognitive impairment (CI) and noncognitively impaired (NCI) older adults. We also investigated the role of episodic and semantic memory on TNET performance.

Method:

Sixty-seven older adults completed the TNET as part of a comprehensive neuropsychological assessment. Analyses included t tests to evaluate group differences for TNET score and correlations between TNET and neuropsychological measures, including episodic and semantic memory tests.

Results:

NCI adults demonstrated better memory for TNET items than adults with CI. The NCI and CI groups did not differ regarding memory for remote events; however, the CI group exhibited worse memory for recent events. There was a significant association between TNET score and the capacity for episodic and semantic memory in the CI group. In the NCI group, TNET score was significantly associated with episodic memory.

Conclusion:

Findings support the use of transient news events to assess remote memories in older adults. Novel remote memory measures broaden the scope of memory assessment far beyond what is feasible with traditional neuropsychological assessment and may provide insight into the onset of memory changes.
Evolutionary analysis of p38 stress-activated kinases in unicellular relatives of animals suggests an ancestral function in osmotic stress
Authors: Shabardina Victoria , Charria Pedro Romero , Saborido Gonzalo Bercedo , Diaz-Mora Ester , Cuenda Ana , Ruiz-Trillo Iñaki , Sanz-Ezquerro Juan Jose
Published: January 2023

p38 kinases are key elements of the cellular stress response in animals. They mediate the cell response to a multitude of stress stimuli, from osmotic shock to inflammation and oncogenes. However, it is unknown how such diversity of function in stress evolved in this kinase subfamily. Here, we show that the p38 kinase was already present in a common ancestor of animals and fungi. Later, in animals, it diversified into three JNK kinases and four p38 kinases. Moreover, we identified a fifth p38 paralog in fishes and amphibians. Our analysis shows that each p38 paralog has specific amino acid substitutions around the hinge point, a region between the N-terminal and C-terminal protein domains. We showed that this region can be used to distinguish between individual paralogs and predict their specificity. Finally, we showed that the response to hyperosmotic stress in
Capsaspora owczarzaki
, a close unicellular relative of animals, follows a phosphorylation–dephosphorylation pattern typical of p38 kinases. At the same time,
Capsaspora
's cells upregulate the expression of GPD1 protein resembling an osmotic stress response in yeasts. Overall, our results show that the ancestral p38 stress pathway originated in the root of opisthokonts, most likely as a cell's reaction to salinity change in the environment. In animals, the pathway became more complex and incorporated more stimuli and downstream targets due to the p38 sequence evolution in the docking and substrate binding sites around the hinge region. This study improves our understanding of p38 evolution and opens new perspectives for p38 research.
Utilization of the ExactMPF package for solving a discrete analogue of the nonlinear Schrödinger equation by the inverse scattering transform method
Authors: Adukov V. M. , Mishuris G.
Published: January 2023

We are revisiting the problem of solving a discrete nonlinear Schrödinger equation by the inverse scattering transform method, by use of the recently developed ExactMPF package within MAPLE Software. ExactMPF allows for an
exact
Wiener–Hopf factorization of matrix polynomials regardless of the partial indices of the matrix. The package can be widely used in various problems, where Wiener–Hopf factorization as one of the effective mathematical tools is required, as its code has already been disclosed. The analysis presented in this paper contains not only numerical examples of its use, but is also supported by appropriate and accurate
a priori
estimations. The procedure itself guarantees that the ExactMPF package produces all computations arithmetically
exactly
, and a detailed numerical analysis of various aspects of the computational algorithm and approximation strategies is provided in the case of a finite initial impulse.
The shifting shelf task: a new, non-verbal measure for attentional set shifting
Authors: Reindl E. , Völter C. J. , Civelek Z. , Duncan L. , Lugosi Z. , Felsche E. , Herrmann E. , Call J. , Seed A. M.
Published: January 2023

Attentional set shifting is a core ingredient of cognition, allowing for fast adaptation to changes in the environment. How this skill compares between humans and other primates is not well known. We examined performance of 3- to 5-year-old children and chimpanzees on a new attentional set shifting task. We presented participants with two shelves holding the same set of four boxes. To choose the correct box on each shelf, one has to switch attention depending on which shelf one is currently presented with. Experiment 1 (forty-six 3- to 5-year olds, predominantly European White) established content validity, showing that the majority of errors were specific switching mistakes indicating failure to shift attention. Experiment 2 (one hundred and seventy-eight 3- to 6-year olds, predominantly European White) showed that older children made fewer mistakes, but if mistakes were made, a larger proportion were switching mistakes rather than ‘random’ errors. Experiment 3 (52 chimpanzees) established suitability of the task for non-human great apes and showed that chimpanzees' performance was comparable to the performance of 3- and 4-year olds, but worse than 5-year olds. These results suggest that chimpanzees and young children share attentional set shifting capacities, but that there are unique changes in the human lineage from 5 years of age.
DNA methylation dynamics in a coastal foundation seagrass species under abiotic stressors
Authors: Pazzaglia Jessica , Dattolo Emanuela , Ruocco Miriam , Santillán-Sarmiento Alex , Marin-Guirao Lazaro , Procaccini Gabriele
Published: January 2023

DNA methylation (DNAm) has been intensively studied in terrestrial plants in response to environmental changes, but its dynamic changes in a temporal scale remain unexplored in marine plants. The seagrassPosidonia oceanicaranks among the slowest-growing and longest-living plants on Earth, and is particularly vulnerable to sea warming and local anthropogenic pressures. Here, we analysed the dynamics of DNAm changes in plants collected from coastal areas differentially impacted by eutrophication (i.e. oligotrophic, Ol; eutrophic, Eu) and exposed to abiotic stressors (nutrients, temperature increase and their combination). Levels of global DNAm (% 5-mC) and the expression of key genes involved in DNAm were assessed after one, two and five weeks of exposure. Results revealed a clear differentiation between plants, depending on environmental stimuli, time of exposure and plants' origin. % 5-mC levels were higher during the initial stress exposure especially in Ol plants, which upregulated almost all genes involved in DNAm. Contrarily, Eu plants showed lower expression levels, which increased under chronic exposure to stressors, particularly to temperature. These findings show that DNAm is dynamic inP. oceanicaduring stress exposure and underlined that environmental epigenetic variations could be implicated in the regulation of acclimation and phenotypic differences depending on local conditions.
Diagnosis of helminths depends on worm fecundity and the distribution of parasites within hosts
Authors: Crellen Thomas , Haswell Melissa , Sithithaworn Paiboon , Sayasone Somphou , Odermatt Peter , Lamberton Poppy H. L. , Spencer Simon E. F. , Déirdre Hollingsworth T.
Published: January 2023

Helminth transmission and morbidity are dependent on the number of mature parasites within a host; however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver flukeOpisthorchis viverrini, which infects approximately 10 million people across Southeast Asia, by analysing five epidemiological surveys (n= 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that greater than 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is nonlinear and strongly influenced by parasite aggregation.
Flavihumibacter fluminis sp. nov., a novel thermotolerant bacterium isolated from river silt
Authors: Guo Bai , Mu Weidong , Mao Sidi , Li Shucheng , Yang Shaomei , Liu Aijv , Wei Shuzhen , Li Xiuyun , Sang Feng , Deng Hongkuan , Dong Yuling , Liu Hongliang , Chen Zhiwei
Published: January 2023

A yellow, Gram-stain-positive, strictly aerobic, thermotolerant, non-motile and rod-shaped bacterial strain, designated RY-1T, was isolated from a silt sample of Fuyang River, Wuqiang County, Hengshui City, Hebei Province, PR China. Cells showed oxidase- and catalase-positive activities. Growth occurred at 20–45 °C (optimum, 37 °C) and pH 6.0–8.0 (optimum, pH 7.0), and in the presence of 0–1.5 % (w/v) NaCl (optimum, 0%). A phylogenetic tree based on 16S rRNA gene sequences revealed that strain RY-1T formed a phylogenetic lineage with

Flavihumibacter

members within the family

Chitinophagaceae

. A comparison of 16S rRNA gene sequences showed that strain RY-1T was most closely related to

Flavihumibacter cheonanensis

WS16T (98.6 %),

Flavihumibacter sediminis

CJ663T (97.7 %) and

Flavihumibacter solisilvae

3-3T (97.6 %). The genome size of strain RY-1T was 4.71 Mb, and the DNA G+C content was 44.3  %. The average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity values between strain RY-1T and reference strains were all lower than the threshold values for species delineation. Strain RY-1T contained menaquinone-7 and iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1G as the sole respiratory isoprenoid quinone and major cellular fatty acids (≥5 %), respectively. The major polar lipids consisted of phosphatidylethanolamine, three unidentified aminolipids and four unidentified lipids. According to the results of phenotypic, phylogenetic and chemotaxonomic characteristics, strain RY-1T represents a novel species of the genus

Flavihumibacter

, for which the name Flavihumibacter fluminis sp. nov. is proposed. The type strain is RY-1T (=GDMCC 1.2775T=JCM 34870T).
Streptomyces rhizoryzae sp. nov., isolated from paddy rhizosphere soil and formal proposal to reclassify Streptomyces albulus as a later heterotypic synonym of Streptomyces noursei
Authors: Butdee Waranya , Muangham Supattra , Chonudomkul Duenrut , Duangmal Kannika
Published: January 2023

The taxonomic position of a novel actinomycete, designated strain RS10V-4T, was determined using a polyphasic approach. Strain RS10V-4T was isolated from paddy rhizosphere soil of rice plant (Oryzae sativa L.). The morphological, physiological and chemotaxonomic properties were consistent with its classification in the genus

Streptomyces

. On the basis of 16S rRNA gene sequence analysis, strain RS10V-4T belongs to the genus

Streptomyces

and had the highest sequence similarity to

Streptomyces noursei

NBRC 15452T (98.3 %). The G+C content of the genomic DNA was 73.8 %. Digital DNA–DNA hybridization and average nucleotide identity values between the genome sequences of strain RS10V-4T and S.noursei ATCC 11455T were lower than the recommendation threshold values for the recognition of species within the same genus. The whole-cell hydrolysates of strain RS10V-4 T contained
ll

-diaminopimelic acid as the diagnostic diamino acid and the whole-cell sugars were glucose and ribose. The predominant menaquinones were MK-9(H6) and MK-9(H8). The predominant cellular fatty acids (>10 %) were iso-C16 : 0, anteiso-C15 : 0, iso-C14 : 0 and iso-C15 : 0. The polar lipids of strain RS10V-4T contained diphosphatidylglycerol, hydroxyphosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol, an unidentified aminolipid, two unidentified lipids and an unidentified phospholipid. On the basis of these phenotypic and genotypic characteristics, it is supported that strain RS10V-4T represents a novel species of the genus

Streptomyces

, for which the name Streptomyces rhizoryzae sp. nov. is proposed. The type strain is RS10V-4T (=TBRC 15167T=NBRC 115345T). In addition, the comparison of the whole genome sequences and phenotypic features suggested that

S. noursei

and

S. albulus

belong to the same species. Therefore, it is proposed that

S. albulus

is reclassified as a later heterotypic synonym of

S. noursei

.
Adaptation of Pseudomonas aeruginosa biofilms to tobramycin and the quorum sensing inhibitor C-30 during experimental evolution requires multiple genotypic and phenotypic changes
Authors: Bové Mona , Kolpen Mette , Lichtenberg Mads , Bjarnsholt Thomas , Coenye Tom
Published: January 2023

In the present study we evaluated the fitness, antimicrobial susceptibility, metabolic activity, gene expression, in vitro production of virulence factors and in vivo virulence of experimentally evolved

Pseudomonas aeruginosa

PAO1. These strains were previously evolved in the presence of tobramycin and the quorum sensing inhibitor furanone C-30 (C-30) and carried mutations in mexT and fusA1. Compared to the wild-type (WT), the evolved strains show a different growth rate and different metabolic activity, suggesting they have an altered fitness. mexT mutants were less susceptible to C-30 than WT strains; they also show reduced susceptibility to chloramphenicol and ciprofloxacin, two substrates of the MexEF-OprN efflux pump. fusA1 mutants had a decreased susceptibility to aminoglycoside antibiotics, and an increased susceptibility to chloramphenicol. The decreased antimicrobial susceptibility and decreased susceptibility to C-30 was accompanied by a changed metabolic activity profile during treatment. The expression of mexE was significantly increased in mexT mutants and induced by C-30, suggesting that MexEF-OprN exports C-30 out of the bacterial cell. The in vitro production of virulence factors as well as virulence in two in vivo models of the strains evolved in the presence of C-30 was unchanged compared to the virulence of the WT. Finally, the evolved strains were less susceptible towards tobramycin (alone and combined with C-30) in an in vivo mouse model. In conclusion, this study shows that mutations acquired during experimental evolution of

P. aeruginosa

biofilms in the presence of tobramycin and C-30, are accompanied by an altered fitness, metabolism, mexE expression and in vitro and in vivo antimicrobial susceptibility.
Co-administration of prism adaptation and methylphenidate needs striatal integrity to alleviate spatial neglect
Authors: Beaudoin-Gobert Maude , Benistant Faustine , De Lanversin Maxence , Javouhay Jules , Jacquin-Courtois Sophie , Rode Gilles , Rossetti Yves , Luauté Jacques
Published: January 2023

Context

A previous study demonstrated a long-term functional improvement of spatial neglect after methylphenidate combined with prismatic adaptation in a group of patients suffering from left spatial neglect after a right stroke (RITAPRISM study).

Objective

we hypothesized that the functional improvement after MP combined with PA depends on striatal integrity in responders patients.

Methods

We conducted an MRI study in “MP+PA” program to identify lesional pattern in responders and non-responders patients in the RITAPRISM cohort. Using anatomical segmentation on morphological MRI, we compared lesional pattern in the striatum between responders and non-responders patients.

Results

The beneficial effect of MP+PA co-administration should require striatal integrity in neglect patients. More specifically, our results suggest that the short-term effect is mediated by the ventral striatum whereas the long-term effect is mediated by the posterior putamen.

Conclusion

Benefical effet of MP+PA could rely on reinforcement processes at early stage of the MP+PA program and visuospatial substrates at long-term.
Targeted Sequencing of Pancreatic Ductal Adenocarcinoma Tissue
Authors: Thailli Kiruthikah , Benzing Christian , Quaglia Alberto , Sarker Debashis , Wells Claire M
Published: January 2023

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer and the majority of patients present with metastatic disease. Metastatic spread requires a reorganisation of the actin cytoskeleton, a process that is dependent on the Rho family GTPases and their interaction with subsequent downstream effectors. The p21 activated kinases (also known as the PAKs) are effectors of Rho GTPases Cdc42 and Rac and play key roles in cell migration and survival. PAK4 is overexpressed in PDAC and can reciprocally activate the PI3K pathway. Hepatocyte growth factor (HGF), via c-Met, is an established activator of PAK4 and the PI3K pathway and may promote PDAC invasion. Next generation sequencing (NGS) was performed on 31 PDAC tissue using a pre-determined targeted panel to attempt to identify novel mutations in the PAK: PI3K pathway. Targeted NGS identified several recurrent mutations including 5 PAK4 mutations in PDAC tissue.
An efficient context-aware approach for whole slide image classification
Authors: Shen Hongru , Wu Jianghua , Shen Xilin , Hu Jiani , Liu Jilei , Zhang Qiang , Sun Yan , Chen Kexin , Li Xiangchun
Published: January 2023

Computational pathology for gigapixel whole slide images (WSIs) at slide-level is helpful in disease diagnosis and remains challenging. We propose a context-aware approach termedWSIInspection via Transformer (WIT) for slide-level classification via holistically modeling dependencies among patches on the WSI. WIT automatically learns feature representation of WSI by aggregating features of all image patches. We evaluate classification performance of WIT along with state-of-the-art baseline method. WIT achieved an accuracy of 82.1% (95% CI, 80.7% - 83.3%) in the detection of 32 cancer types on the TCGA dataset, 0.918 (0.910 - 0.925) in diagnosis of cancer on the CPTAC dataset and 0.882 (0.87 - 0.890) in the diagnosis of prostate cancer from needle biopsy slide, outperforming the baseline by 31.6%, 5.4% and 9.3%, respectively. WIT can pinpoint the WSI regions that are most influential for its decision. WIT represents a new paradigm for computational pathology, facilitating the development of effective tools for digital pathology.
AnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics
Authors: Mongia Aanchal , Saunders Diane C. , Wang Yue J. , Brissova Marcela , Powers Alvin C. , Kaestner Klaus H. , Vahedi Golnaz , Naji Ali , Schwartz Gregory W. , Faryabi Robert B.
Published: January 2023

Cellular composition and anatomical organization influence normal and aberrant organ functions. Emerging spatial single-cell proteomic assays such as Image Mass Cytometry (IMC) and Co-Detection by Indexing (CODEX) have facilitated the study of cellular composition and organization by enabling high-throughput measurement of cells and their localization directly in intact tissues. However, annotation of cell types and quantification of their relative localization in tissues remain challenging. To address these unmet needs, we developed AnnoSpat (Annotator and Spatial Pattern Finder) that uses neural network and point process algorithms to automatically identify cell types and quantify cell-cell proximity relationships. Our study of data from IMC and CODEX show the superior performance of AnnoSpat in rapid and accurate annotation of cell types compared to alternative approaches. Moreover, the application of AnnoSpat to type 1 diabetic, non-diabetic autoantibody-positive, and non-diabetic organ donor cohorts recapitulated known islet pathobiology and showed differential dynamics of pancreatic polypeptide (PP) cell abundance and CD8+T cells infiltration in islets during type 1 diabetes progression.
Study protocol - Ascertaining the career Intentions of UK Medical Students (AIMS) post-graduation: a cross-sectional survey
Authors: Ferreira Tomas , Collins Alexander M. , Horvath Rita
Published: January 2023

Background

Among doctors in the United Kingdom, there is growing sentiment regarding delaying specialist training, emigrating to practice medicine abroad, or leaving the profession altogether. This may have significant implications for the future of the profession in the UK. The extent to which this sentiment is also present in the medical student population is unknown.

Methods

The AIMS study is a national, multi-institution, cross-sectional study of all medical students at all medical schools in the United Kingdom. It will be administered via an online questionnaire and disseminated through a collaborative network recruited for this purpose. Our primary outcome is to determine current medical students’ career intentions after graduation and upon completing the Foundation Programme, and to establish the motivations behind these intentions. Secondary outcomes include determining which, if any, demographic factors alter the propensity to pursue different career paths available to a medical graduate, determining which specialties medical students plan on pursuing and understanding current views on the prospect of working in the National Health Service (NHS). Both quantitative analysis and thematic analysis will be used.

Discussion

Doctors’ career satisfaction within the NHS is a well-researched topic, however, there is a shortage of high-powered studies able to offer insight into medical students’ outlook on their future careers. It is anticipated that the results from this study will bring clarity to this issue. Identified areas of improvement in medical training or within the NHS could be targeted to improve doctors’ working conditions and help retain medical graduates. Results may also aid future workforce planning efforts.

Trial Registration

Not Applicable.
Covid-19 affects taste independently of smell: results from a combined chemosensory home test and online survey from a global cohort (N=10,953)
Authors: Nguyen Ha , Albayay Javier , Höchenberger Richard , Bhutani Surabhi , Boesveldt Sanne , Busch Niko A. , Croijmans Ilja , Cooper Keiland W. , de Groot Jasper H. B. , Farruggia Michael C. , Fjaeldstad Alexander W. , Hayes John E. , Hummel Thomas , Joseph Paule V. , Laktionova Tatiana K. , Thomas-Danguin Thierry , Veldhuizen Maria G. , Voznessenskaya Vera V. , Parma Valentina , Pepino M. Yanina , Ohla Kathrin
Published: January 2023

People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with ten household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 3,356 self-reported a positive and 602 a negative COVID-19 diagnosis (COVID+ and COVID-, respectively); 1,267 were awaiting test results (COVID?). The rest reported no respiratory illness and were grouped by symptoms: sudden smell/taste changes (STC, N=4,445), other symptoms excluding smell or taste loss (OthS, N=832), and no symptoms (NoS, N=416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% Confidence Interval (CI): 15-28%), 47% in smell (95%-CI: 37-56%), and 17% in oral irritation (95%-CI: 10-25%) intensity. In all groups, perceived intensity of smell (r=0.84), taste (r=0.68), and oral irritation (r=0.37) was correlated. Our findings suggest most reports of taste dysfunction with COVID-19 were genuine and not due to misinterpreting smell loss as taste loss (i.e., a classical taste-flavor confusion). Assessing smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and helps to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.
EEF2-inactivating toxins engage the NLRP1 inflammasome and promote epithelial barrier disruption uponPseudomonasinfection
Authors: Pinilla Miriam , Mazars Raoul , Vergé Romain , Gorse Leana , Santoni Karin , Robinson Kim Samirah , Toh Gee Ann , Prouvensier Laure , LeonIcaza Stephen Adonai , Hessel Audrey , Péricat David , Murris Marlène , Henras Anthony , Buyck Julien , Cougoule Céline , Ravet Emmanuel , Zhong Franklin L. , Planès Rémi , Meunier Etienne
Published: January 2023

The intracellular inflammasome complex have been implicated in the maladaptive tissue damage and inflammation observed in chronicPseudomonas aeruginosainfection. Human airway and corneal epithelial cells, which are critically altered during chronic infections mediated byP. aeruginosa, specifically express the inflammasome sensor NLRP1. Here, together with a companion study, we report that the NLRP1 inflammasome detects Exotoxin A (EXOA), a ribotoxin released byP. aeruginosaType 2 Secretion System (T2SS) during chronic infection. Mechanistically, EXOA-driven Eukaryotic Elongation Factor 2 (EEF2) ribosylation and covalent inactivation promotes ribotoxic stress and subsequent NLRP1 inflammasome activation, a process shared with other EEF2-inactivating toxins, Diphtheria Toxin and Cholix Toxin. Biochemically, irreversible EEF2 inactivation triggers ribosome stress-associated kinases ZAKα- and P38-dependent NLRP1 phosphorylation and subsequent proteasome-driven functional degradation. Finally, Cystic Fibrosis cells from patients exhibit exacerbated P38 activity and hypersensitivity to EXOA-induced ribotoxic stress-dependent NLRP1 inflammasome activation, a process inhibited by the use of ZAKα inhibitors. Altogether, our results show the importance ofP. aeruginosavirulence factor EXOA at promoting NLRP1-dependent epithelial damage and identify ZAKα as a critical sensor of virulence-inactivated EEF2.

KEY POINTS

P. aeruginosainduces NLRP1-dependent pyroptosis in human corneal and nasal epithelial cells

P. aeruginosaExotoxin A (EXOA) and other EEF2-inactivating bacterial exotoxins activate the human NLRP1 inflammasome

EEF2 inactivation promotes ribotoxic stress response and ZAKα kinase-dependent NLRP1 inflammasome activation.

Bronchial epithelial cells from Cystic Fibrosis patients show extreme sensitivity to ribotoxic stress-dependent NLRP1 inflammasome activation in response to Exotoxin A

P38 and ZAKα inhibition protects Cystic Fibrosis epithelial cell from EXOA-induced pyroptosis
Conditional, tissue-specific CRISPR/Cas9 vector system in zebrafish reveal the role of neuropilin-1b in heart regeneration
Authors: Angom Ramcharan Singh , Wang Ying , Wang Enfeng , Dutta Shamit , Mukhopadhyay Debabrata
Published: January 2023

CRISPR/Cas9 technology-mediated genome editing has significantly improved the targeted inactivation of genesin vitroandin vivoin many organisms. In this study, we have reported a novel CRISPR-based vector system for conditional tissue-specific gene ablation in zebrafish. Specifically, the cardiac-specificcardiac myosins light chain 2 (cmlc2) promoter drives Cas9 expression to silence theneuropilin-1(nrp1) gene in cardiomyocytes in a heat-shock inducible manner. This vector system establishes a unique tool to regulate the gene knockout in both the developmental and adult stages and hence, widens the possibility of loss-of-function studies in zebrafish at different stages of development and adulthood. Using this approach, we investigated the role of neuropilin isoformsnrp1aandnrp1bin response to cardiac injury and regeneration in adult zebrafish hearts. We observed that both the isoforms (nrp1aandnrp1b) are upregulated after the cryoinjury. Interestingly, thenrp1b-knockout significantly altered heart regeneration and impaired cardiac function in the adult zebrafish, demonstrated by reduced heart rate (ECG), ejection fractions, and fractional shortening. In addition, we show that the knockdown ofnrp1bbut notnrp1ainduces activation of the cardiac remodeling genes in response to cryoinjury. To our knowledge, this is the first study where we have reported a heat shock-mediated conditional knockdown ofnrp1aandnrp1bisoforms using CRISPR/Cas9 technology in the cardiomyocyte in zebrafish, and furthermore have identified a crucial role fornrp1bisoform in zebrafish cardiac remodeling and eventually heart function in response to injury.
Coordinated multiple cellular processes in tongue development
Authors: Kawasaki Maiko , Kawasaki Katsushige , Sari Finsa Tisna , Kudo Takehisa , Nihara Jun , Kitamura Madoka , Nagai Takahiro , Utama Vanessa , Ishida Yoko , Meguro Fumiya , Nishimura Takayuki , Kogure Yuan , Maruyama Satoshi , Tanuma Jun-ichi , Kakihara Yoshito , Maeda Takeyasu , Ghafoor Sarah , Khonsari Roman H. , Corre Pierre , Sharpe Paul T. , Cobourne Martyn T. , Franco Brunella , Ohazama Atsushi
Published: January 2023

Dysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested migration of other mesoderm-derived cells and CNCC. Some aberrant CNCC abnormally differentiated into osteoblasts due to the lack of Hh signal, which migrated into tongue to form ectopic bone. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations in CNCC to disturb cellular processes which were disrupted in mutant mice. Thus, tongue development requires coordinated multiple cellular processes (cell-cell contact, migration and differentiation). Our results provide hints for possible future treatment in ciliopathies.
Dissecting the basis for differential substrate specificity of ADAR1 and ADAR2
Authors: Zambrano-Mila Marlon S. , Witzenberger Monika , Uzonyi Anna , Nir Ronit , Ben-Aroya Shay , Levanon Erez Y. , Schwartz Schraga
Published: January 2023

Millions of adenosines are deaminated throughout the transcriptome by ADAR1 and ADAR2, modulating double-stranded RNA (dsRNA) immunogenicity and recoding mRNA. The high variability in the susceptibility of different adenosines to editing begs the question of what are the determinants of substrate specificity. Here, we systematically monitor how secondary structure modulates ADAR2 vs ADAR1 substrate selectivity, on the basis of systematic probing of thousands of synthetic sequences transfected into ADAR1-deleted cell lines exogenously expressing either ADAR2 or ADAR1. In both cases, structural disruptions gave rise to symmetric, strand-specific induced editing at a fixed offset, but of varying length: -26 nt for ADAR2, and -35 nt for ADAR1. We dissect the basis for the differences in offset between ADAR1 and ADAR2 via diverse mutants, domain-swaps, and ADAR evolutionary homologs, and reveal that it is encoded by the differential RNA binding domain architecture. We demonstrate that this offset-enhanced editing can allow an improved design of ADAR2-recruiting therapeutics, with proof-of-concept experiments suggestive of increased on-target and potentially decreased off-target editing. Our findings provide novel insight into the determinants guiding ADAR2 substrate selectivity and into the roles of the RNA binding domains of ADAR1 and ADAR2 in mediating differential targeting, and should facilitate the design of improved ADAR-recruiting therapeutics.
Microtubule-associated proteins MAP7 and MAP7D1 promote DNA double strand break repair in the G1 cell cycle phase
Authors: Dullovi Arlinda , Ozgencil Meryem , Rajvee Vinothini , Tse Wai Yiu , Cutillas Pedro R , Martin Sarah A , Hořejší Zuzana
Published: January 2023

The DNA-damage response is a complex signalling network that guards genomic integrity. The microtubule cytoskeleton is involved in the repair of DNA double-strand breaks; however, little is known about which cytoskeleton-related proteins are involved in DNA repair and how. Using quantitative proteomics, we discovered that microtubule associated proteins MAP7 and MAP7D1 interact with several DNA repair proteins including DNA double-strand break repair proteins RAD50, BRCA1 and 53BP1. We observed that downregulation of MAP7 and MAP7D1 leads to increased phosphorylation of p53 after γ- irradiation. Moreover, we determined that the downregulation of MAP7D1 leads to a strong G1 arrest and that the downregulation of MAP7 and MAP7D1 in cells arrested in G1 negatively affects DNA repair, recruitment of RAD50 to chromatin and localisation of 53BP1 to the sites of damage. These findings describe for the first time a novel function of MAP7 and MAP7D1 in cell cycle regulation and cellular response to DNA double-strand breaks.
Illumination of the complement receptors C3aR and C5aR signaling by anaphylatoxins
Authors: Wang Yue , Liu Weiyi , Xu Youwei , Yuan Qingning , He Xinheng , Luo Ping , Fan Wenjia , Zhu Jinpeng , Zhang Xinyue , Cheng Xi , Jiang Yi , Xu H. Eric , Zhuang Youwen
Published: January 2023

The complement receptors C3aR and C5aR, whose signaling are selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR signaling lead to multiple inflammatory disorders, including sepsis, asthma, and acute respiratory distress syndrome (ARDS). The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understandings of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders.
Early root phenotyping in sweetpotato (Ipomoea batatasL.) uncovers insights into root system architecture variability
Authors: Duque Luis O.
Published: January 2023

Background

We developed a novel, non-destructive, expandable, ebb and flow soilless phenotyping system to deliver a capable way to study early root system architectural traits in stem derived adventitious roots of sweetpotato (Ipomoea batatasL.). The platform was designed to accommodate up to 12 stems in a relatively small area for root screening. This platform was designed with inexpensive materials and equipped with an automatic watering system.

Methods

To test this platform, we designed a screening experiment for root traits using two contrasting sweetpotato genotypes, ‘Covington’ and ‘NC10-275’. We monitored and imaged root growth, architecture, and branching patterns every five days up to 20 days.

Results

We observed significant differences in both architectural and morphological root traits for both genotypes tested. After 10 days, root length, surface root area, and root volume were higher in ‘NC10-275’ compared to ‘Covington’. However, average root diameter and root branching density were higher in ‘Covington’.

Conclusion

These results validated the effective and efficient use of this novel root phenotyping platforming for screening root traits in early stem-derived adventitious roots. This platform allowed for monitoring and 2D imaging root growth over time with minimal disturbance and no destructive root sampling. This platform can be easily tailored for abiotic stress experiments, permit root growth mapping and temporal and dynamic root measurements of primary and secondary adventitious roots. This phenotyping platform can be a suitable tool for examining root system architecture and traits of clonally propagated material for a large set of replicates in a relatively small space.

Subjects

Plant Science, Agricultural Science
Understanding networking dynamics in born global firms’ internationalization: balancing the mix of physical and virtual networking in B2B markets
Authors: Tobiassen Anita Ellen , Pettersen Inger Beate
Published: January 2023

Purpose

This paper aims to explore how born global firms (BGs) in business to business (B2B) markets balance the mix of physical and virtual networking through social media to gain access to resources throughout their internationalization process. Further, the research seeks to understand these firms’ network dynamics in their continual adaptation to changing resource requirements throughout the internationalization process.

Design/methodology/approach

This research adopts a multiple case study approach based on in-depth interviews with founders and key informants in BGs in the software industry, supplemented with extensive secondary data.

Findings

Results reveal that networking through social media is efficient and can be used to access vital resources and to build trusting relationships in a B2B context, yet in combination with physical networking. This research found several boundary conditions related to the mix of physical and virtual networking, i.e. the relationship culture in the industry, strategic importance of partner/customer, type of product complexity and managers’ perceptions of the usefulness of social media in a B2B context. These conditions could evolve over time.

Originality/value

This research contributes to enhanced understanding of how resource-constrained BGs balance the mix of physical and virtual networking through social media in a B2B context, influenced by boundary conditions, achieving a network dynamic to advance internationalization.
Using social media to create real time online networks of school leaders
Authors: Miller Dustin , Tilak Shantanu , Evans Marvin , Glassman Michael
Published: January 2023

Purpose

School leaders work in a fast-paced job that requires critical decision-making, often without the luxury of time. Additionally, problems may be new and leave school leaders feeling isolated and ill-equipped to adequately address situations. To that end, this study introduced the use of Reddit, a social media platform, to connect school leaders with colleagues who can provide real time support when pressing issues arise.

Design/methodology/approach

This mixed methods study used hierarchical regressions, linguistic analysis of online discussions and qualitative analysis of focus group interviews to understand if online collective efficacy led to higher technology acceptance and principal efficacy for school leaders when discussing work-related and sociocultural issues online.

Findings

Findings revealed that (1) school leaders build collective efficacy among their peers and are willing to engage more freely in online communities, (2) school leaders are willing to embrace the use of technology if provided time and exposure to such communities and (3) seasoned school leaders are more likely to interact openly with colleagues in online discussions versus their less-experienced peers on how online communities can support school leaders in challenging, ever-changing aspects of their work.

Originality/value

We recommend both school district and educational leadership professional associations consider creating easily accessible online communities as spaces where school leaders have opportunities to engage confidentially with their colleagues over important work-related issues. Future studies should also continue to investigate the impact of school leader online communities through both quantitative and qualitative methodologies.
The role of narcissism in entrepreneurial activity: a systematic literature review
Authors: Burger Bastian , Kanbach Dominik K. , Kraus Sascha
Published: January 2023

Purpose

Recent years have seen a meteoric rise in the study of narcissism in entrepreneurship, although little consolidation has occurred in this area. The purpose of this paper is the development of an integrative framework to harmonise the academic discussion and serve as a structured foundation for future research.

Design/methodology/approach

The authors conducted an artificial intelligence-aided, structured literature review focused on content analysis of concepts and contexts to map out current findings and research gaps in startup narcissism research.

Findings

According to the findings of this study, narcissistic tendencies have the potential to positively influence startup success early on in an entrepreneur's journey, but after a certain point in the process, the influence of narcissism on success becomes predominantly negative.

Research limitations/implications

The research field is currently not very harmonised regarding research measures, research subjects and key research terms. Further research must use a standardised approach to add value to the research body.

Practical implications

Narcissism is a two-sided sword for founders. In the early stages of a company, many of the founder’s tasks can benefit from narcissistic tendencies. In the later stages of a company, that might shift to overwhelmingly negative effects of narcissism.

Originality/value

Methodically, this study is the first one to establish an artificial intelligence component to add value to the results of a review paper to the best of the authors’ knowledge. The results of this study provide a clear framework of entrepreneurial intention, entrepreneurial activity and entrepreneurial performance to give researchers the opportunity of a more differentiated way of organising work.
Biologics in pediatric psoriasis
Authors: Wang Wen‐Ming , Jin Hong‐Zhong
Published: January 2023

Psoriasis is a chronic inflammatory skin disorder with a chronic relapsing course. Biologics have revolutionized the treatment of adult psoriasis with higher efficacy and favorable safety profile. Recently, more studies have focused on the use of biologics in pediatric psoriasis, and several biologics have been approved for use therein. This review is divided into two sections: the first part focuses on real‐world studies on the use of biologics in pediatric psoriasis and the second part summarizes the findings of other clinical trials related to biologics in pediatric psoriasis. Case reports have been excluded from this review. Several biologics were used for treating pediatric psoriasis and the efficacy is encouraging. According to the studies included in this review, anti‐IL‐12/23 and anti‐IL‐17A for treating pediatric psoriasis might have a better efficacy than anti‐TNF‐α, but more data are needed.
Harry and Meghan Shine a Light on Monarchy, and its Demands
Authors: Hazell Robert
Published: January 2023

The Netflix documentary Harry and Meghan conveys the impression that they have been uniquely victimised. But the difficulties they have faced are shared by all the royal families of Europe. It is monarchy which is unique, in the extraordinary demands which it makes of close members of the royal family. They lack freedoms which ordinary citizens take for granted: privacy; free choice of career; freedom of speech; freedom to marry whom they like; freedom of religion; and freedom to travel. It is not surprising if individual royals wish to escape the gilded cage. But as Harry and Meghan have shown, opting out is easier said than done.
Spatial analysis of resources and environmental carrying capacity in Iran
Authors: Karami Hossein , Sayahnia Romina , Mahmoudi Hossein , Azadi Hossein , Salehi Sadegh
Published: January 2023

Urbanization and mass movement of the population from rural areas and small cities to megacities have led to environmental, economic, and social problems in Iran. In dealing with these challenges, assessing resource and environmental carrying capacity (RECC) is considered an effective method to leverage space and capital to achieve sustainable development. This study aimed to rank the provincial RECC in Iran. Toward this purpose, environmental indices were generated from remotely sensed and statistical census data. Then, the provinces were scored in terms of environmental, economic, and infrastructural carrying capacities, and RECC using the mean variance analysis method. Results demonstrated that in most areas, there is no relationship between economic and infrastructural capacities and development. Statistically, a correlation coefficient of −0.53 between economic and environmental carrying capacities indicated excessive use of environmental capacities. Moreover, the spatial distribution pattern of environmental, economic, and infrastructural carrying capacity was entirely heterogeneous between the provinces; there was a northeast–southwest pattern in terms of infrastructural capacity and an economic pattern from north to south. The distribution pattern of RECC is most consistent with the environmental capacity, pointing at the high weight of the indicators of the RECC model. In conclusion, this research offers a new vision for policymakers and provides a theoretical and applicable framework for implementing sustainable strategies in land‐use planning. It is recommended that the RECC concept and tools can be used not only for planning but also for measuring the efficiency of spatial development programs and establishing land balances in the region.