bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-dependent extracellular matrix alterations of young tendons in response to stress relaxation: a model for the Ponseti method
Authors: Lee Mu-Huan , Tsai Hung-Pei , Lavy Chris , Mouthuy Pierre-Alexis , Czernuszka Jan
Published: May 2023

The Ponseti method corrects a clubfoot by manipulation and casting which causes stress relaxation on the tendons. Here, we examined the effect of long-term stress relaxation on tendon extracellular matrix (ECM) by (1) an
ex vivo
stress relaxation test, (2) an
in vitro
tenocyte culture with stress relaxation and (3) an
in vivo
rabbit study. Time-dependent tendon lengthening and ECM alterations including crimp angle reduction and cleaved elastin were observed, which illustrated the mechanism of tissue lengthening behind the treatment—a material-based crimp angle reduction resulted from elastin cleavage. Additionally,
in vitro
and
in vivo
results observed restoration of these ECM alterations along with increased elastin level after 7 days of treatment, and the existence of neovascularization and inflammation, indicating the recovery and adaptation from the tendon in reaction to the treatment. Overall, this study provides the scientific background and information that helps explain the Ponseti method.
Asymptotic analysis on charging dynamics for stack-electrode model of supercapacitors
Authors: Ji Lijie , Xu Zhenli , Zhou Shenggao
Published: May 2023

Supercapacitors are promising electrochemical energy storage devices due to their prominent performance in rapid charging/discharging rates, long cycle life, stability, etc. Experimental measurement and theoretical prediction on charging timescale for supercapacitors often have large differences. This work develops a matched asymptotic expansion method to derive the charging dynamics of supercapacitors with porous electrodes, in which the supercapacitors are described by the stack-electrode model. Coupling leading-order solutions between every two stacks by continuity of ionic concentration and fluxes leads to an ODE system, which is a generalized equivalent circuit model for zeta potentials, with the potential-dependent nonlinear capacitance and resistance determined by physical parameters of electrolytes, e.g. specific counterion valences for asymmetric electrolytes. Linearized stability analysis on the ODE system after projection is developed to theoretically characterize the charging timescale. The derived asymptotic solutions are numerically verified. Further numerical investigations on the biexponential charging timescales demonstrate that the proposed generalized equivalent circuit model, as well as companion linearized stability analysis, can faithfully capture the charging dynamics of symmetric/asymmetric electrolytes in supercapacitors with porous electrodes.
Shear wave transmissivity and wave-induced vorticity diffusion through conversion scattering to slow-shear diffusion wave
Authors: González Josué G. , Sahay Pratap N. , Müller Tobias M.
Published: May 2023

In the poroelasticity theory of de la Cruz and Spanos, fluid shearing within the viscous boundary layer, i.e. fluid vorticity, manifests as an independent process, namely the diffusive slow shear wave. Quantifying its impact on elastic wave propagation remains a research challenge. We analyse the transmissivity of a horizontally polarized shear wave travelling across a stack of porous fluid-saturated layers. The fluid shearing developed at each contact is captured, in a macroscopic sense, through conversion scattering into this diffusive slow shear wave. Generalizing the reflectivity method for elastic waves to the poroelastic case, we develop semi-analytical results for an arbitrary number of layers. We find that the conversion scattering into this diffusion wave reduces the shear wave amplitude, and this reduction accumulates with the number of layers. In the limit when the layer thickness corresponds to the pore diameter, the resulting wave quality factor is close to the predictions of previously reported attempts to capture the fluid vorticity. However, our approach is distinctively different since it is purely based on a wave-theoretic analysis of interacting waves, acknowledging vorticity diffusion as an independent process, thereby avoiding the problems arising when incorporating a pore-scale phenomenon in a macroscopic wave propagation theory.
Draft genome sequence of Enterobacter cloacae ST473 harbouring blaCMH-3 isolated from a human patient diagnosed with recurrent bacteriuria in Nigeria
Authors: David Ebuka Elijah , Igwenyi Ikechuku Okorie , Iroha Ifeanyichukwu Romanus , Martins Layla Farage , Uceda-Campos Guillermo , da Silva Aline Maria
Published: May 2023

Enterobacter cloacae is among the most frequently isolated species described in clinical infections and is commonly associated with a multidrug resistance (MDR) phenotype. We present the draft genome sequence of a MDR E. cloacae isolated in Nigeria from the urine sample of an adult male outpatient diagnosed with asymptomatic recurrent bacteriuria. The isolate was found to be resistant to ceftriaxone, cefotaxime, cefepime and levofloxacin. Genome analysis revealed the presence of the beta-lactamase chromosomal gene blaCMH-3 which may be responsible for the antibiotic resistance observed in the recurrent E. cloacae urinary tract infection.
Improving data archiving practices in ancient genomics
Authors: Bergström Anders
Published: May 2023

The sequencing of ancient DNA from preserved biological remains is producing a rich record of past genetic diversity in humans and other species. However, unless the primary data is made available in public archives in an appropriate fashion, its long-term value will not be fully realised. I surveyed publicly archived data from 42 recent ancient genomics studies. I found that half of the studies archived incomplete subsets of the generated genomic data, preventing accurate replication and representing a loss of data of potential use for future research. None of the studies met all archiving criteria that could be considered best practice. Based on these results, I make six recommendations for data producers: 1) archive all sequencing reads, not just those that can be aligned to a reference genome, 2) archive read alignments as well, but as secondary analysis files linked to the underlying raw read files, 3) provide correct experiment metadata on how samples, libraries and sequencing runs relate to each other, 4) provide informative sample metadata in the public archives, 5) publish and archive data from screening, low-coverage, poorly performing and negative experiments, and 6) document data archiving choices in papers, and review these as part of peer review processes. Given the reliance on destructive sampling of finite material, I argue that ancient genomics studies have a particularly strong responsibility to ensure the longevity and reusability of generated data.
NLRP3 and NLRP1/CARD8 pathways differently contribute to pyroptosis of CD8+ T cells of ART-treated HIV patients
Authors: Roa Mariela EGV , Cambui Raylane AG , Yamada Suemy M , Leal Vinicius CN , Pontillo Alessandra
Published: May 2023

HIV-infected (HIV) patients exhibit immune dysregulation independently of antiretroviral therapy. The inflammasome, a cytosolic complex responsible for cleavage of the inflammatory cytokines IL -1β and IL -18 and pyroptosis, is highly activated in peripheral blood mononuclear cells of HIV patients, suggesting its involvement in leukocyte dysfunction. While monocytes, B cells, and CD4+ T cells have been studied, little is known about CD8+ T lymphocytes.

Therefore, we proposed to characterize the inflammasome activation in these cells, both the NLRP3 and NLRP1/CARD8 pathways, which are partially described in T cells. CD8+ T lymphocytes from non-HIV healthy donors (HD) and HIV patients were analyzedex vivoand stimulatedin vitrowith known activators of NLRP3 (α-CD3/α-CD28), NLRP1 and CARD8 (DPP9 inhibitor ValboroPro, VbP) to assess inflammasome activation. HIV CD8+ T cells present a constitutively activated caspase-1 which positively correlates with the cell activation state. HIV CD8+ T cells were more activated and more resistant to VbP-induced pyroptosis than HD. On the other way, HIV CD8+ T lymphocytes showed higher pyroptosis in response to α-CD3/α-CD28.

These findings suggest that the NLRP3 pathway is significantly dysregulated in those patients, and TCR stimulation may result in cell loss. At the same time, being HIV CD8+ T cells constitutively activated, other inflammasome pathways, such as NLRP1 or CARD8, present a delayed activation.
Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs
Authors: Whitworth Isabella T. , Knoener Rachel A. , Puray-Chavez Maritza , Halfmann Peter , Romero Sofia , Baddouh M’bark , Scalf Mark , Kawaoka Yoshihiro , Kutluay Sebla B. , Smith Lloyd M. , Sherer Nathan M.
Published: May 2023

Host RNA binding proteins recognize viral RNA and play key roles in virus replication and antiviral defense mechanisms. SARS-CoV-2 generates a series of tiered subgenomic RNAs (sgRNAs), each encoding distinct viral protein(s) that regulate different aspects of viral replication. Here, for the first time, we demonstrate the successful isolation of SARS-CoV-2 genomic RNA and three distinct sgRNAs (N, S, and ORF8) from a single population of infected cells and characterize their protein interactomes. Over 500 protein interactors (including 260 previously unknown) were identified as associated with one or more target RNA at either of two time points. These included protein interactors unique to a single RNA pool and others present in multiple pools, highlighting our ability to discriminate between distinct viral RNA interactomes despite high sequence similarity. The interactomes indicated viral associations with cell response pathways including regulation of cytoplasmic ribonucleoprotein granules and posttranscriptional gene silencing. We validated the significance of five protein interactors predicted to exhibit antiviral activity (APOBEC3F, TRIM71, PPP1CC, LIN28B, and MSI2) using siRNA knockdowns, with each knockdown yielding increases in viral production. This study describes new technology for studying SARS-CoV-2 and reveals a wealth of new viral RNA-associated host factors of potential functional significance to infection.
Confounders in the relationship between temporomandibular disorders and posture: a scoping review protocol
Authors: Diciolla Pier Claudio , Bizzarri Paolo
Published: May 2023

Background

The relationship between temporomandibular disorders (TMDs) and posture is widely discussed in literature. However, evidence to support this relationship is scarce, and little is known about their causal association.

Objectives

The aim of this scoping review is to provide an analysis on how much the potential confounders (craniofacial morphological elements, sleep apnea and/or psychological factors) are the real responsible for postural changes.

Methods

A search will be conducted through all publications written in English and Italian about this topic using Mediline (PubMed) database. Cross-sectional studies will be included concerning morphological (e.g. class II, class III, crossbite, etc.), respiratory (e.g. sleep apnea) and/or psychological (e.g. anxiety, depression) elements and postural patterns (lordosis, kyphosis, scoliosis, forward head position) in adults (≥18 years).

No restriction for the year of publication.

The level of bias in the included studies will be assessed using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies.
Rapid detection of SARS-CoV-2 B.1.1.529 (Omicron BA.1) variant by SYBR Green□based RT□qPCR
Authors: Abdel-Sater Fadi , Makki Rawan , Khalil Alia , Hussein Nader , Borghol Nada , Khattar Ziad Abi , Hamade Aline , Khreich Nathalie , El Homsi Mahoumd , Kanaan Hussein , Raad Line , Skafi Najwa , Al-Nemer Fatima , Ghandour Zeinab , El-Zein Nabil , Abou-Hamdan Mohamad , Akl Haidar , Hamade Eva , Badran Bassam , Hamze Kassem
Published: May 2023

The COVID-19 pandemic is unceasingly spreading across the globe, and recently a highly transmissible Omicron SARS-CoV-2 variant (B.1.1.529) has been discovered in South Africa and Botswana. Rapid identification of this variant is essential for pandemic assessment and containment. However, variant identification is mainly being performed using expensive and time-consuming genomic sequencing. In this study we propose an alternative RT-qPCR approach for the detection of the Omicron BA.1 variant using a low-cost and rapid SYBR Green method. We have designed specific primers to confirm the deletion mutations in the spike (S Δ143-145) and the nucleocapsid (N Δ31-33) which are characteristics of this variant. For the evaluation, we used 120 clinical samples from patients with PCR-confirmed SARS-CoV-2 infections, and displaying an S-gene target failure (SGTF) when using TaqPath COVID-19 kit (Thermo Fisher Scientific, Waltham, USA) that included the ORF1ab, S, and N gene targets. Our results showed that all the 120 samples harbored S Δ143-145 and N Δ31-33, which was further confirmed by Whole genome sequencing (WGS) of 10 samples thereby validating our SYBR Green-based protocol. This protocol can be easily implemented to rapidly confirm the diagnosis of the Omicron BA.1 variant in COVID-19 patients and prevent its spread among populations, especially in countries with high prevalence of SGTF profile.
Environmental equity and COVID-19 experiences in the United States: Results from three survey waves of a nationally representative study conducted between 2020-2022
Authors: Anneser Elyssa , Stopka Thomas J. , Naumova Elena N. , Spangler Keith R. , Lane Kevin J. , Acevedo Andrea , Griffiths Jeffrey K. , Lin Yan , Levine Peter , Corlin Laura
Published: May 2023

Certain environmental exposures, such as air pollution, are associated with COVID-19 incidence and mortality. To determine whether environmental context is associated with other COVID-19 experiences, we used data from the nationally representative Tufts Equity in Health, Wealth, and Civic Engagement Study data (n=1785; three survey waves 2020-2022). Environmental context was assessed using self-reported climate stress and county-level air pollution, greenness, toxic release inventory site, and heatwave data. Self-reported COVID-19 experiences included willingness to vaccinate against COVID-19, health impacts from COVID-19, receiving assistance for COVID-19, and provisioning assistance for COVID-19. Self-reported climate stress in 2020 or 2021 was associated with increased COVID-19 vaccination willingness by 2022 (odds ratio [OR] = 2.35; 95% confidence interval [CI] = 1.47, 3.76), even after adjusting for political affiliation (OR = 1.79; 95% CI = 1.09, 2.93). Self-reported climate stress in 2020 was also associated with increased likelihood of receiving COVID-19 assistance by 2021 (OR = 1.89; 95% CI = 1.29, 2.78). County-level exposures (i.e., less greenness, more toxic release inventory sites, more heatwaves) were associated with increased vaccination willingness. Air pollution exposure in 2020 was positively associated with likelihood of provisioning COVID-19 assistance in 2020 (OR = 1.16 per µg/m3; 95% CI = 1.02, 1.32). Associations between certain environmental exposures and certain COVID-19 outcomes were stronger among those who identify as a race/ethnicity other than non-Hispanic White and among those who reported experiencing discrimination; however, these trends were not consistent. A latent variable representing a summary construct for environmental context was associated with COVID-19 vaccination willingness. Our results add to the growing body of literature suggesting that intersectional equity issues affecting likelihood of exposure to adverse environmental conditions are also associated with health-related outcomes.
Clonal Hematopoiesis of Indeterminate Potential is Associated with Acute Kidney Injury
Authors: Vlasschaert Caitlyn , Robinson-Cohen Cassianne , Kestenbaum Bryan , Silver Samuel A. , Chen Jian-Chun , Akwo Elvis , Bhatraju Pavan K , Zhang Ming-Zhi , Cao Shirong , Jiang Ming , Wang Yinqiu , Niu Aolei , Siew Edward , Kramer Holly J , Kottgen Anna , Franceschini Nora , Psaty Bruce M. , Tracy Russell P. , Alonso Alvaro , Arking Dan E. , Coresh Josef , Ballantyne Christie M , Boerwinkle Eric , Grams Morgan , Lanktree Matthew B. , Rauh Michael J. , Harris Raymond C. , Bick Alexander G.
Published: May 2023

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown and to date no genetic mechanisms for AKI have been established. Clonal hematopoiesis of indeterminate potential (CHIP) is a recently recognized biological mechanism conferring risk of several chronic aging diseases including cardiovascular disease, pulmonary disease and liver disease. In CHIP, blood stem cells acquire mutations in myeloid cancer driver genes such asDNMT3A, TET2, ASXL1andJAK2and the myeloid progeny of these mutated cells contribute to end-organ damage through inflammatory dysregulation. We sought to establish whether CHIP causes acute kidney injury (AKI). To address this question, we first evaluated associations with incident AKI events in three population-based epidemiology cohorts (N = 442,153). We found that CHIP was associated with a greater risk of AKI (adjusted HR 1.26, 95% CI: 1.19–1.34, p<0.0001), which was more pronounced in patients with AKI requiring dialysis (adjusted HR 1.65, 95% CI: 1.24–2.20, p=0.001). The risk was particularly high in the subset of individuals where CHIP was driven by mutations in genes other thanDNMT3A(HR: 1.49, 95% CI: 1.37–1.61, p<0.0001). We then examined the association between CHIP and recovery from AKI in the ASSESS-AKI cohort and identified that non-DNMT3ACHIP was more common among those with a non-resolving pattern of injury (HR 2.3, 95% CI: 1.14–4.64, p = 0.03). To gain mechanistic insight, we evaluated the role ofTet2-CHIP to AKI in ischemia-reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) mouse models. In both models, we observed more severe AKI and greater post-AKI kidney fibrosis inTet2-CHIP mice. Kidney macrophage infiltration was markedly increased inTet2-CHIP mice andTet2-CHIP mutant renal macrophages displayed greater pro-inflammatory responses. In summary, this work establishes CHIP as a genetic mechanism conferring risk of AKI and impaired kidney function recovery following AKI via an aberrant inflammatory response in CHIP derived renal macrophages.
Analysis of the learning curve for Retzius-sparing Robot-assisted radical prostatectomy for a single surgeon
Authors: Hussein H , Maitra N , Tay J , Saxionis I , Makin R , Sivathasan S , Smart S , Warren A , Shah N , Lamb BW
Published: May 2023

Introduction

The learning curve for retzius sparing robotic radical prostatectomy is not fully understood. This study attempts to identify the learning-curve across the first 130 cases of a single surgeon.

Methods

All retzius sparing robotic radical prostatectomy cases performed by a single surgeon between April 2019 and July 2022 were included. Cases were divided chronologically into 3 groups.

Results

130 RS-RARP cases were identified. Statistically significant differences were found between groups in several areas. Median patient age increased between group 1 (59yrs) and Group 3 (66.5yrs) (P=0.04). Proportion of patients with stage >T2 increased between Group 1 (27.9%) and Group 2 (41.9%) (P=0.036). Median console time increased between Group 1 (120 mins) and Group 2 (150 mins,) (P=0.01). Median gland weight increased between Group 1 (28g) and Group 3 (35.5g) (P<0.001). Positive surgical margin rate fell between Group 1 (30.2%) and Group 3 (9.1%).

Conclusions

The complexity of cases increased over the learning curve, reflected in older patients, larger prostates and higher stage disease, but the positive surgical margin rate improved with experience. Safety and functional outcomes are excellent throughout. The learning curve might be facilitated by careful case selection favouring smaller prostates with less advanced disease.
Neutrophil-to-lymphocyte Ratio (NLR) as an Index of Response to Treatment in Patients with Hepatocellular Carcinoma after Receiving Trans-arterial Chemoembolization (TACE)
Authors: Shayegan Neda , Ayoobi Niloofar , Mohammadi Esmaeil , Saberi Hajir , Salahshour Faeze , Alborzi Forough , Sadighi Nahid , Taher Mohammad
Published: May 2023

Background

Trans-arterial chemoembolization (TACE) is commonly used for patients with large, un-resectable tumors or bridge therapy in patients with hepatocellular carcinoma (HCC) prior to liver transplantation. We evaluated the response to TACE treatment in patients with hepatocellular carcinoma according to modified RECIST criteria and determined the prognostic value of neutrophil-to-lymphocyte ratio (NLR).

Methods

Patients with definitive diagnosis of HCC referred for TACE were studied. The response rate to TACE treatment was assessed based on dynamic MRI 28-days after treatment according to modified RECIST. The NLR value was calculated and its prognostic value was evaluated to predict the response to treatment.

Results

Forty patients with HCC who underwent TACE were included in the study. The response to TACE treatment in included patients was: complete response (CR) in 6 patients (15%), partial response (PR) in 16 patients (40%) and stable disease (SD) in 18 patients (45%). No progressive disease (PD) was found. Responders (CR+PR) were 22 (55%) cases. The mean NLR after treatment in the non-responder group was significantly higher than the responder group (4.2 vs 2.4, P-value=0.026). NLR values greater than 2.6 after treatment had a sensitivity of 70.6% and a specificity of 77.3% in the diagnosis of non-responders with an Area Under the Curve of 0.73 [95% confidence interval 0.58–0.89], P-value=0.011).

Conclusion

Compared to responders, higher levels of NLR after treatment were observed in the non-responder group. NLR level more than 2.6 after treatment is believed to be able to discriminate non-responders as a moderate prognostication tool.
Cell source-derived variabilities in human juvenile chondrocyte-derived cell sheet cartilage regenerative effects in a nude rat chondral defect implantation model
Authors: Matsukura Keisuke , Kondo Makoto , Metzler Nicolas F. , Ford Adam J. , Maak Travis G. , Hutchinson Douglas T. , Wang Angela A. , Sato Masato , Grainger David W. , Okano Teruo
Published: May 2023

The authors have withdrawn their manuscript owing to the necessity of reallocating the data to another study. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Transcriptome profiling of human colonic cells exposed to the gut pathobiontStreptococcus gallolyticussubsp.gallolyticus
Authors: Ewa Pasquereau-Kotula , du Merle Laurence , Sismeiro Odile , Pietrosemoli Natalia , Varet Hugo , Legendre Rachel , Trieu-Cuot Patrick , Dramsi Shaynoor
Published: May 2023

Streptococcus gallolyticus sp. gallolyticus (SGG)is a gut pathobiont involved in the development of colorectal cancer (CRC). To decipher the contribution ofSGGin tumor initiation and/or acceleration respectively, a global transcriptome was performed in normal colonic cells (FHC) and in tumoral colonic cells (HT29). To identifySGG-specific alterations, we chose the phylogenetically closest relative,Streptococcus gallolyticussubsp.macedonicus(SGM)as the control bacterium. We show thatSGM,a bacterium generally considered as safe, did not induce any transcriptional changes on the two human colonic cells. The transcriptional reprogramming induced bySGGwas significantly different in FHC and HT29 cells, with most of the up- and down-regulated genes associated with cancer disease. Top up-regulated genes related to cancer were: (i)IL-20, CLK1, SORBS2, ERG1, PIM1, SNORD3Afor normal FHC cells and (ii)TSLP, BHLHA15, LAMP3, ZNF27B, KRT17, ATF3for cancerous HT29 cells.SGGinduces much stronger transcriptional changes in cancerous than in normal colonic cells (2,090vs128 genes being affected, respectively). Gene set enrichment analysis reveals thatSGG-induced strong ER- (endoplasmic reticulum) stress and UPR- (unfolded protein response) activation in colonic epithelial cells. Our results suggest thatSGGinduces a pro-tumoral shift in human colonic cells, particularly in transformed cells potentially accelerating tumor development in the colon.
TheToxoplasmaOxygen Sensing Protein, TgPhyA, Is Required for Resistance to Interferon-gamma Mediated Nutritional Immunity
Authors: Cordonnier Charlotte , Mandalasi Msano , Gigley Jason , Wohlfert Elizabeth A. , West Christopher M. , Blader Ira J
Published: May 2023

AsToxoplasma gondiidisseminates through its host, the parasite must sense and adapt to its environment and scavenge nutrients. Oxygen (O2) is one such environmental factor and cytoplasmic prolyl 4-hydroxylases (PHDs) are evolutionarily conserved O2cellular sensing proteins that regulate responses to changes in O2availability.Toxoplasmaexpresses two PHDs. One of them, TgPHYa hydroxylates SKP1, a subunit of the SCF-E3 ubiquitin ligase complex.In vitro,TgPHYa is important for growth at low O2levels. However, studies have yet to examine the role that TgPHYa or any other pathogen encoded PHD plays in virulence and disease. Using a type II ME49ToxoplasmaTgPHYa knockout, we report that TgPHYa is important for Toxoplasma virulence and brain cyst formation in mice. We further find that while TgPHYa mutant parasites can establish an infection in the gut they are unable to efficiently disseminate to peripheral tissues because the mutant parasites are unable to survive within recruited immune cells. Since this phenotype abrogated in IFNγ knockout mice, we studied how TgPHYa mediates survival in IFNγ-treated cells. We find that TgPHYa is not required for release of parasite-encoded effectors into host cells that neutralize anti-parasitic processes induced by IFNγ. In contrast, we find that TgPHYa is required for the parasite to scavenge tryptophan, which is an amino acid whose levels are decreased after IFNγ upregulates the tryptophan-catabolizing enzyme, indoleamine dioxygenase (IDO). We further find that relative to wild-type mice that IDO knockout mice display increased morbidity when infected with TgPHYa knockout parasites. Together, these data identify the first parasite mechanism for evading IFNγ-induced nutritional immunity and highlight a novel role that oxygen sensing proteins play in pathogen growth and virulence.
Neurog1 and Olig2 integrate patterning and neurogenesis signals in development of zebrafish dopaminergic and glutamatergic dual transmitter neurons
Authors: Altbürger Christian , Rath Meta , Driever Wolfgang
Published: May 2023

Dopaminergic neurons develop in distinct neural domains by integrating local patterning and neurogenesis signals. While the proneural proteins Neurog1 and Olig2 have been previously linked to development of dopaminergic neurons, their dependence on local prepatterning and specific contributions to dopaminergic neurogenesis are not well understood. Here, we show that both transcription factors are differentially required for the development of defined dopaminergic glutamatergic subpopulations in the zebrafish posterior tuberculum, which are homologous to A11 dopaminergic neurons in mammals. Both Olig2 and Neurog1 are expressed inotpaexpressing progenitor cells and appear to act upstream of Otpa during dopaminergic neurogenesis. Our epistasis analysis confirmed that Neurog1 acts downstream of Notch signaling, while Olig2 acts downstream of Shh, but upstream and/or in parallel to Notch signaling. Furthermore, we identified Olig2 to be an upstream regulator ofneurog1in dopaminergic neurogenesis. This regulation occurs through Olig2-dependent repression of the proneural repressor and Notch target geneher2. Our study reveals how Neurog1 and Olig2 integrate local patterning signals, including Shh, with Notch neurogenic selection signaling, to specify the progenitor population and initiate neurogenesis and differentiation of A11-type dopaminergic neurons.
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
Authors: Hawkins Sophie , Mondaini Alexandre , Namboori Seema C. , Javed Asif , Bhinge Akshay
Published: May 2023

RNA processing is a fundamental mode of gene regulation that is perturbed in a variety of diseases including cancer and neurodegenerative disorders. RNA-binding proteins (RBPs) regulate key aspects of RNA processing including alternative splicing, mRNA degradation and localization by physically binding RNA molecules. Current methods to map these interactions, such as CLIP, rely on purifying single proteins at a time. We have developed a new method (ePRINT) to map RBP-RNA interaction networks on a global scale without purifying individual RBPs. ePRINT allows precise mapping of the 5’ end of the RBP binding site, and can uncover direct and indirect targets of an RBP of interest. Importantly, ePRINT can also uncover RBPs that are differentially activated between cell fate transitions, for instance, as neural progenitors differentiate into neurons. Given its versatility, ePRINT has vast application potential as an investigative tool for RNA regulation in development, health and disease.
Impact of inter-species interactions between flower microbiota commensals and a floral pathogen on disease incidence and pathogen activity
Authors: Hassani M. Amine , Cui Zhouqi , LaReau Jacquelyn , B. Huntley Regan , Steven Blaire , Zeng Quan
Published: May 2023

Flowers are colonized by a diverse community of microorganisms that alter plant health and interact with floral pathogens.Erwinia amylovorais a flower-inhabiting bacterium and a pathogen that infects different plant species, includingMalus × domestica(apple). Previously, we showed that the co-inoculation of two bacterial strains,PseudomonasandPantoeanatural inhabitants of apple flowers, reduced disease incidence caused by this floral pathogen. Here, we decipher the ecological interactions between these two flower-associated bacteria andE. amylovorain field experimentation andin vitroco-cultures. The two flower microbiota strains did not competitively excludeE. amylovorafrom the stigma habitat, as both commensal bacteria and the pathogen co-existed on the apple flowers, proscribing microbial antibiosis or niche exclusion as predominant mechanisms of host protection. Inspection of the total and the active microbiota populations on flowers revealed that strain co-inoculations altered microbiota activity. Using synthetic stigma exudation medium, tripartite co-culture of the bacterial strains strongly acidified the growth milieu and led to a substantial alteration of gene expression in both the pathogen and the two microbiota members. Our study emphasizes the critical role of emergent properties mediated by inter-species interactions within the plant holobiont and their impact on plant health and pathogen behavior.

Importance

Fire blight, caused byErwinia amylovora, is one of the most important plant diseases of pome fruits. Plant-associated microbiota can influence plant disease occurrence through inter-species interactions. Previous studies have shown that plant microbiota commensals could suppress disease mainly by antagonizing of the pathogen growth, however, whether plant-associated microbiota could alter pathogen activity and behavior have not been well studied. Here, we show that the co-inoculation of two bacterial strains that naturally colonize the apple flowers reduce disease pressure. We further demonstrate that the interactions between these two microbiota commensals and the floral pathogen lead to a strong alteration of the pH and to the emergence of new gene expression patterns that may alter the pathogen behavior. Our findings emphasize the critical role of emergent properties mediated by inter-species interactions between plant microbiota and plant pathogens and their impact on plant health.
Automated model building and protein identification in cryo-EM maps
Authors: Jamali Kiarash , Käll Lukas , Zhang Rui , Brown Alan , Kimanius Dari , Scheres Sjors H.W.
Published: May 2023

Interpreting electron cryo-microscopy (cryo-EM) maps with atomic models requires high levels of expertise and labour-intensive manual intervention. We present ModelAngelo, a machine-learning approach for automated atomic model building in cryo-EM maps. By combining information from the cryo-EM map with information from protein sequence and structure in a single graph neural network, ModelAngelo builds atomic models for proteins that are of similar quality as those generated by human experts. For nucleotides, ModelAngelo builds backbones with similar accuracy as humans. By using its predicted amino acid probabilities for each residue in hidden Markov model sequence searches, ModelAngelo outperforms human experts in the identification of proteins with unknown sequences. ModelAngelo will thus remove bottlenecks and increase objectivity in cryo-EM structure determination.
The curious case of cyanobacteria: a tale of light and darkness
Authors: Lee Victoria , Zheng Sally , Meza-Padilla Isaac , Nissimov Jozef I.
Published: May 2023

Toxic algal bloom-forming cyanobacteria are a persistent problem globally for many aquatic environments. Their occurrence is attributed to eutrophication and rising temperatures due to climate change. The result of these blooms is often loss in biodiversity, economic impacts on tourism and fisheries, and risks to human and animal health. Of particular concern is the poorly understood interplay between viruses and toxic species that form blooms because viruses may exacerbate their harmful effects. Concurrently, cyanobacteria are also a source of bioactive compounds other than toxins, which makes them good candidates for drug discovery. We show that virus infection of the cyanobacteriumMicrocystis aeruginosa, results in as high as a 40-fold increase in the toxin microcystin two days post virus infection (dpi), and predict that microcystin levels may remain high in a body of water up to 7 dpi, long after water discoloration and cell lysis. This implicates viruses as major contributors to toxin release from cyanobacteria and emphasizes the importance of taking them into account in predictive models and in the assessment of water safety. We also show that bioactive compounds ofM. aeruginosainhibit and delay infection of single stranded DNA and single stranded RNA viruses. This highlights the potential of cyanobacteria as an excellent source for the discovery of novel antiviral compounds, and the ease with which screening for cyanobacterial antivirals can be achieved.
Native-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer’s disease pathology
Authors: Kumar Prateek , Goettemoeller Annie M , Espinosa-Garcia Claudia , Tobin Brendan R. , Tfaily Ali , Nelson Ruth S. , Natu Aditya , Dammer Eric B. , Santiago Juliet V. , Malepati Sneha , Cheng Lihong , Xiao Hailian , Duong Duc , Seyfried Nicholas T. , Wood Levi B. , Rowan Matthew JM , Rangaraju Srikant
Published: May 2023

One of the earliest pathophysiological perturbations in Alzheimer’s Disease (AD) may arise from dysfunction of fast-spiking parvalbumin (PV) interneurons (PV-INs). Defining early protein-level (proteomic) alterations in PV-INs can provide key biological and translationally relevant insights. Here, we use cell-type-specific in vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state proteomes of PV interneurons. PV-INs exhibited proteomic signatures of high metabolic, mitochondrial, and translational activity, with over-representation of causally linked AD genetic risk factors. Analyses of bulk brain proteomes indicated strong correlations between PV-IN proteins with cognitive decline in humans, and with progressive neuropathology in humans and mouse models of Aβ pathology. Furthermore, PV-IN-specific proteomes revealed unique signatures of increased mitochondrial and metabolic proteins, but decreased synaptic and mTOR signaling proteins in response to early Aβ pathology. PV-specific changes were not apparent in whole-brain proteomes. These findings showcase the first native state PV-IN proteomes in mammalian brain, revealing a molecular basis for their unique vulnerabilities in AD.
Sequence-assignment validation in protein crystal structure models with checkMySequence
Authors: Chojnowski Grzegorz
Published: May 2023

Sequence-register shifts remain one of the most elusive errors in experimental macromolecular models. They may affect model interpretation and propagate to newly built models from older structures. In a recent publication, it was shown that register shifts in cryo-EM models of proteins can be detected using a systematic reassignment of short model fragments to the target sequence. Here, it is shown that the same approach can be used to detect register shifts in crystal structure models using standard, model-bias-corrected electron-density maps (2mF
o − DF
c). Five register-shift errors in models deposited in the PDB detected using this method are described in detail.
Cruise ship safety measures and their influence on passenger sense of security and purchase intention
Authors: Bahattab Shadi , Chen McCain Shiang-Lih , Lolli Jeffrey
Published: May 2023

Purpose

The purpose of this study is to investigate whether customers perceive current cruise ship safety measures provided as meeting a sense of security and their influence on purchase intention. Three types of potential risks associated with cruise lines evaluated were external/internal attacks, malfunctions/accidents and onboard medical/health issues.

Design/methodology/approach

A survey used 12 safety measures questions to examine how cruise ships handle the above three risks, three questions to measure a sense of security and three questions to measure purchase intention. A seven-point Likert scale was applied. Convenience sampling was used. There were 163 valid responses collected.

Findings

All three safety measures evaluated in this study had a direct and positive effect on passengers' Sense of Security. Also, Safety Measure (SM) 2 and Sense of Security had direct and positive effects on purchase intention. Finally, SM1 and SM3 have only indirect impacts on Purchase Intentions via Sense of Security.

Research limitations/implications

Because of the small sample size and the convenience sampling method, the results of this study may lack generalizability.

Practical implications

Cruise managers should be aware that merely providing safety measures that are regulated by guidelines is not sufficient, and passengers must personally see and experience safety measures.

Originality/value

This study evaluated not only customers’ perceptions of safety measures on a cruise ship but also their impact on a sense of security and how that played a moderating role in purchase intention.
Connecting international and domestic dots: how conflict entanglement informs resolution and escalation
Authors: Melin Molly M. , Grigorescu Alexandru V.
Published: May 2023

Purpose

This paper aims to seek to and understand how civil conflict and international claims inform one another. Does the existence of ongoing civil and international conflicts affect how a government addresses an international claim? The paper builds on existing literature that link international and domestic conflict. However, it suggests that the logic behind civil conflicts may be different from that for international ones as states decide how to deal with any one claim.

Design/methodology/approach

The paper posits that states faced with domestic conflicts and additional international claims are more likely to seek to resolve an international claim than those without similar conflicts. It develops a series of hypotheses about the likelihood of claim escalation and peaceful settlement attempts and proceed to test them quantitatively using the Issue Correlates of War data combined with the uppsala conflict data program/peace research institute oslo Armed Conflict Data.

Findings

On the one hand, the paper finds support for the argument regarding the difficulty states are faced with when seeking to resolve multiple international claims. On the other hand, it finds that the presence of civil conflicts incentivizes states to resolve international claims either by force or peacefully, suggesting internal violence can both lead to diversionary behavior and attempts at conflict resolution.

Research limitations/implications

The findings have important implications for work considering the complexity of domestic and international conflict linkages.

Originality/value

While many studies of claim militarization and peaceful attempts focus on dyadic and international characteristics, this paper creates a more nuanced understanding of the complexities of this foreign policy decision process.
Students with emotional and behavioural difficulties in Irish post-primary schools: a role for occupational therapy
Authors: O’Donnell Shóna , O’Reilly Aishling , Robinson Katie , Ní Riain Eimer , Pettigrew Judith
Published: May 2023

Purpose

Higher levels of participation in school are linked to greater academic performance, better health and well-being and positive long-term outcomes for young people. Evidence shows that for students with emotional and behavioural difficulties (EBD), participation in school-based occupations is often restricted in comparison to their peers. Given the recent advancements towards introducing a new model of school-based occupational therapy in Ireland, this paper aims to discuss how occupational therapy can support students with EBD to increase their participation within the post-primary school context. The opinions in this paper are derived from the authors’ experience in the development of this practice in the Republic of Ireland.

Design/methodology/approach

The authors reviewed current literature and reflected on current practice to describe the unique role of occupational therapy in supporting students with EBD in the school environment.

Findings

Occupational therapists have potential to play a key role in school-based support for students with EBD. The authors describe how occupational therapists can promote whole school understanding of EBD and enable skill development, self-regulation, participation and school belonging, among youths with EBD. There is a significant lack of literature guiding practice in this area. Further research is required to explore professional issues and identify best practice.

Originality/value

This paper aims to provoke consideration of how school-based occupational therapists can play a crucial role in supporting students with EBD who are otherwise at risk of occupational injustice.
The quality of the Argentinean Malbec and the weather in the Mendoza region
Authors: Charlin Ventura , Cifuentes Arturo
Published: May 2023

Purpose

The climate in Mendoza is significantly different from the climate in most global wine-making regions. This paper aims to explore the relationship between the quality of the Malbec wine from the Mendoza region and its weather.

Design/methodology/approach

This study uses a multivariate regression model with fixed effects to assess how weather variations relate to wine quality. The Wine Spectator ratings are used as a measure of wine quality and to build a longitudinal data set of Malbec wine ratings from 1995 to 2020. The weather is described with several variables based on temperature, rainfall, humidity and cloudiness data from the Mendoza region. The model controls for wineries which are treated as fixed effects.

Findings

The results of this study indicate that the weather has a modest explanatory power when it comes to the quality of Mendoza’s Malbec. Additionally, the analyses show that the wineries are more important than the weather to explain quality differences in the wines. These findings are in agreement with previous studies carried out in regions with stable weather such as California and Australia.

Practical implications

The quality of Mendoza’s Malbec depends more on the winery of origin than the year-to-year weather variations. Therefore, consumers should focus more on the winery and less on the vintage when making purchasing decisions. Additionally, given the relevance of the winery in relation to quality, the findings of this study indicate that future research efforts should focus on directly linking the wine ratings to quality-drivers behind the winery effects.

Originality/value

To the best of the authors’ knowledge, this is the first study that explores the relationship between wine quality assessed through wine ratings and the weather in the Mendoza (Argentina) region. Most such studies have been done in connection with northern hemisphere wines.
No big deal: how leader self-deprecating humor influences subordinate learning from failure
Authors: Wang Xi , Yang Fu , Liu Songbo , Feng Wen
Published: May 2023

Purpose

Based on social information processing theory, this paper aims to explore how and when leader self-deprecating humor may spark subordinate learning from failure. The authors cast perspective taking as a novel explanatory mechanism for this indirect effect, and further consider leader–member exchange as a boundary condition of the relationship.

Design/methodology/approach

The authors tested the hypotheses by conducting a multiwave and multisource survey of 604 members from 152 teams in a Chinese high-technology company.

Findings

Results of multilevel path analyses demonstrate that leader self-deprecating humor positively influences subordinate learning from failure via perspective taking. Further, this mediation effect is stronger at higher levels of leader–member exchange.

Research limitations/implications

This study contributes to the theoretical understanding of the relationship between leader self-deprecating humor and subordinate learning from failure. However, the research design was not longitudinal or experimental, and thus the authors were unable to make strong inferences about absolute causality.

Practical implications

The work yields useful insights for practitioners aiming to encourage subordinates to learn from failure.

Originality/value

This study provides evidence that leader self-deprecating humor can stimulate subordinate learning from failure via perspective taking, and the indirect effect is further strengthened by leader–member exchange. The findings offer new directions for research on leader self-deprecating humor and learning from failure.
Hell for consumer addiction?: thematic analysis of COVID-19 narratives in a gambling support forum
Authors: Brownlow Luke , Li En
Published: May 2023

Purpose

The COVID-19 pandemic resulted in public health measures which unintentionally made unfortunate individual-, community- and system-level impacts. People experiencing gambling harm have distinctive vulnerabilities that are exacerbated during this period of uncertainty, physical distancing, self-isolation and changes to treatment services. This paper aims to investigate narratives of gambling harm to understand unmet needs in a COVID-19 context.

Design/methodology/approach

A leading international gambling support forum was mined for all posts associated with COVID-19 during 2020 and thematically analyzed.

Findings

A series of themes and subthemes that gamblers responded to the pandemic with a series of adaptive and maladaptive behaviors in line with the integrative theoretical framework of maladaptive consumption. Additionally, people experiencing gambling harm are disproportionately impacted by the COVID-19 pandemic, and the standard public health notices do not meet their unique needs.

Originality/value

This research builds upon knowledge of the antecedents and consequences of maladaptive consumption behavior. Further, the findings show that the lack of preventative measures, such as targeted and timely information to combat adverse outcomes, and reflexive support services has made this time more challenging.