bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seasonality but not photoperiodism affects susceptibility of the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae) to pesticides
Authors: Yang Zhenguo , Wang Zinan , Ni Jing , Da Aisi , Xie Daoyan , Chung Henry , Luo Yanjie 
Published: March 2022

AbstractUnderstanding how endogenous and exogenous factors such as annual seasonal rhythm and photoperiodism affect the toxicity of pesticides can help design integrated pest management strategies. The two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae), a worldwide phytophagous pest species distributed in areas with different time zones, is a good model to explore how the photoperiodism and seasonality affect the pesticide toxicity. In this study, we conducted a laboratory experiment from March 2017 to November 2018 where spider mites were reared at three photoperiod regimes in environmentally controlled incubators. The toxicities of two acaricides, propargite and diafenthiruon, were measured on T. urticae every month. To determine potential mechanisms underlying the changes in the acaricide toxicity, we measured body size and total GSTs activity with the toxicity measurements in 2018. Our results showed that the toxicities of the two acaricides were not significantly different among the three photoperiod regimes. However, both had a consistent trend along the season which increased in the spring and summer and decreased in the winter in all photoperiod regimes for two consecutive years, suggesting seasonality be an endogenous factor affecting the susceptibility of the spider mites to pesticide. Pearson’s correlation analyses showed only the body size had a weak negative correlation with the acaricide toxicities, suggesting a minor contribution to the higher toxicity from the smaller size of T. urticae. Our study is the first to show that seasonality can have an endogenous effect on the pesticide toxicity, and the results can inform practical insights into the pest management strategies.
Cell-surface PD-L1 expression identifies a sub-population of distal epithelial cells enriched in idiopathic pulmonary fibrosis
Authors: Ahmadvand Negah , Carraro Gianni , Jones Matthew R. , Shalashova Irina , Wilhelm Jochen , Baal Nelli , Kosravi Farhad , Chen Chengshui , Zhang JinSan , Ruppert Clemens , Guenther Andreas , Wasnick Roxana , Bellusci Saverio 
Published: March 2022

AbstractIdiopathic lung fibrosis (IPF) is a fatal lung disease characterized by chronic epithelial injury and exhausted repair capacity of the alveolar compartment, associated with the expansion of cells with intermediate alveolar epithelial cell (AT2) characteristics. Using SftpcCreERT2/+: tdTomatoflox/flox mice, we previously identified a lung population of quiescent injury activated alveolar epithelial progenitors (IAAPs) marked by low expression of the AT2 lineage trace marker tdTomato (Tomlow), and characterized by high levels of Pd-l1 (Cd274) expression. This led us to hypothesize that a population with similar properties exists in the human lung. To that end, we used flow cytometry to characterize the CD274 cell surface expression in lung epithelial cells isolated from donor and end-stage IPF lungs. The identity and functional behavior of these cells were further characterized by qPCR analysis, in vitro organoid formation, and ex vivo precision-cut lung slices (PCLS). Our analysis led to the identification of a population of CD274pos cells expressing intermediate levels of SFTPC, which was expanded in IPF lungs. While donor CD274pos cells initiated clone formation, they did not expand significantly in 3D organoids in AT2-supportive conditions. However, an increased number of CD274pos cells was found in cultured PCLS. In conclusion, we demonstrate that, similar to the IAAPs in the mouse lung, a population of CD274 expressing cells exists in the normal human lung and this population is expanded in the IPF lung and in an ex vivo PCLS assay, suggestive of progenitor cell behavior.
Differential Activity of Repurposed Drugs as Receptor Binding Domain Antagonists for Omicron and Native Strains of SarsCov2
Authors: Meher Kranti , K Saranya , Reddy Arpitha , Kadiyala Gopi , Iyer Subra , Vangala Subhramanyam , Chandran Satish , Saxena Uday 
Published: March 2022

AbstractOmicron strain is the latest variant of concern of SarsCov2 virus. The mutations in this strain in the S protein Receptor Binding domain (RBD) enable it to be more transmissible as well as escape neutralizing activity by antibodies in response to vaccine. Thus, Omicron specific strategies are need to counter infection by this strain.We investigated a collection of approved drugs shown to antagonize the binding of native strain RBD to human ACE2, for their ability to antagonize binding to Omicron strain RBD.While most of the drugs the drugs that antagonize binding to native RBD are also active for Omicron RBD but some were inactive, namely drugs that contain iodine are completely inactive against Omicron RBD. Our data strongly indicate that presence of a single iodine molecule in the drug renders it inactive against Omicron strain. Thus, there is molecular specificity of drugs for antagonizing Omicron strain RBD versus native strain RBD of this virus. Such information will pave way for specific drugs for Omicron. A pragmatic message from our data is that the often-used iodine containing mouth wash and rises may be ineffective in antagonizing receptor binding of Omicron strain.
An ultra-high-throughput method for measuring biomolecular activities
Authors: Tu Boqiang , Sundar Vikram , Esvelt Kevin M. 
Published: March 2022

AbstractLarge datasets of biomolecular activities are crucial for protein engineering, yet their scarcity due to limited experimental throughput hampers progress. We introduce Direct High-throughput Activity Recording and Measurement Assay (DHARMA), an innovative method enabling ultra-high-throughput measurement of biomolecular activities. DHARMA employs molecular recording techniques to link activity directly to editing rates of DNA segments contiguous with the coding sequence of biomolecule of interest. Leveraging a Bayesian inference-based denoising model, we mapped the fitness landscape of TEV protease across 160,000 variants. Using these datasets, we benchmarked popular protein models and showed the impact of data size on model performance. We also developed circuit self-optimization strategies and demonstrated DHARMA’s capability to measure a wide range of biomolecular activities. DHARMA represents a leap forward, offering the machine learning community unparalleled datasets for accurate protein fitness prediction and enhancing our understanding of sequence-to-function relationships.Abstract Figure
Phospholipase Cβ2 Promotes Vascular Endothelial Growth Factor Induced Vascular Permeability
Authors: Phoenix Kathryn N. , Yue Zhichao , Yue Lixia , Cronin Chunxia G. , Liang Bruce T. , Hoeppner Luke H. , Claffey Kevin P. 
Published: March 2022

AbstractBackgroundRegulation of vascular permeability (VP) is critical to maintaining tissue metabolic homeostasis. Vascular endothelial growth factor (VEGF) is a key stimulus of VP in acute and chronic diseases including ischemia reperfusion injury, sepsis and cancer. Identification of novel regulators of VP would allow for the development of effective targeted therapeutics for patients with unmet medical need.MethodsIn vitro and in vivo models of VEGFA-induced vascular permeability, pathological permeability, quantitation of intracellular calcium release and cell entry, and PIP2 levels were evaluated with and without modulation of PLCβ2.ResultsGlobal knock-out of PLCβ2 in mice resulted in blockade of VEGFA-induced vascular permeability in vivo and trans-endothelial permeability in primary lung endothelial cells. Further work in an immortalized human microvascular cell line modulated with stable knock-down of PLCβ2 recapitulated the observations in the mouse model and primary cell assays. Additionally, loss of PLCβ2 limited both intracellular release and extracellular entry of calcium following VEGF stimulation as well as reduced basal and VEGFA-stimulated levels of PIP2 compared to control cells. Finally, loss of PLCβ2 in both a hyperoxia induced lung permeability model and a cardiac ischemia:reperfusion model resulted in improved animal outcomes when compared to WT controls.ConclusionsThe results implicate PLCβ2 as a key positive regulator of VEGF-induced VP through regulation of both calcium flux and PIP2 levels at the cellular level. Targeting of PLCβ2 in a therapeutic setting may provide a novel approach to regulating vascular permeability in patients.Graphic AbstractHighlightsPLCβ2 promotes VEGFA induced vascular permeability.Loss of PLCβ2 prevents VEGFA vascular permeability via repression of cellular calcium flux and membrane PIP2 levels.Loss of PLCβ2 reduces vascular permeability and improves outcomes in a hyperoxic lung damage model and a cardiac ischemia:reperfusion model in vivo.Targeting PLCβ2 inhibition may lead to a novel therapeutic for diseases such as stroke and myocardial infarction.
Performance of the cobas® HBV RNA Automated Investigational Assay for the Detection and Quantification of Circulating HBV RNA in Chronic HBV Patients
Authors: Scholtès Caroline , Hamilton Aaron T. , Plissonnier Marie-Laure , Charre Caroline , Scott Beth , Wang Ling , Berby Françoise , French Janine , Testoni Barbara , Blair Alan , Subic Miroslava , Hoppler Matthias , Lankenau Andreas , Grubenmann Andreas , Levrero Massimo , Heil Marintha L. , Zoulim Fabien 
Published: March 2022

AbstractBackgroundThe amount of HBV RNA in peripheral blood may reflect HBV covalently closed circular DNA (cccDNA) transcriptional activity within infected hepatocytes. Quantification of circulating HBV RNA (cirB-RNA) is thus a promising biomarker for monitoring antiviral treatment.ObjectivesWe evaluated the performance of an automated, prototype quantitative HBV RNA assay for use on the Roche cobas® 6800/8800 systems.Study DesignThe sensitivity, specificity, linearity, and potential interference by HBV DNA of the cobas® HBV RNA assay were assessed using synthetic HBV armored RNA and clinical specimens.Resultscobas® HBV RNA results were linear between 10 and 107 copies/mL in clinical samples of several HBV genotypes, and up to 109 copies/mL with synthetic RNA. Precision and reproducibility were excellent, with standard deviation below 0.15 log10 copies/mL and coefficients of variation below 5% throughout the linear range. The presence of HBV DNA had minimal (<0.3 log10 copies/mL) impact on HBV RNA quantification at DNA:RNA ratios of up to approximately one million. In a panel of 36 untreated patient samples, cirB-RNA concentrations were approximately 200-fold lower than HBV DNA. cirB-RNA was detected in all 13 HBeAg-positive patients (mean 6.0 log10 copies/mL), and in 20 of 23 HBeAg-negative patients (mean of quantifiable samples 2.2 log10 copies/mL). Finally, cirB-RNA was detected in 12 of 20 nucleoside analog-treated patients (mean of quantifiable samples 3.4 log10 copies/mL).ConclusionsThe cobas® 6800/8800 investigational HBV RNA assay is a high throughput, sensitive and inclusive assay to evaluate the clinical relevance of cirB-RNA quantification in patients with chronic hepatitis B.
Cohesin erases genomic-proximity biases to drive stochastic Protocadherin expression for proper neural wiring
Authors: Kiefer Lea , Servito Gabrielle Isabelle F. , Rajkumar Sandy M. , Langen Jennifer , Chiosso Anna , Buckley Alexander , Cha Elizabeth S. , Horta Adan , Mui Michael H. , Canzio Daniele 
Published: March 2022

ABSTRACTClustered Protocadherin (Pcdh) proteins act as cell-surface recognition barcodes for neural circuit formation. Neurites expressing the same barcode repel each other, but this mechanism is deployed in two different ways. For instance, convergence of olfactory sensory neuron (OSN) projections requires stochastic expression of distinct Pcdh isoforms in individual cells, while tiling of neural arbors of serotonergic neurons (5-HTs) requires expression of the same isoform, Pcdhαc2. Despite their essential role, however, the molecular mechanisms of cell-type specific Pcdh barcoding remain a mystery. Here, we uncover a new role of cohesin: that of regulating distance-independent enhancer-promoter interactions to enable random Pcdh isoform choice via DNA loop extrusion in OSNs. Remarkably, this step mediates DNA demethylation of Pcdh promoters and their CTCF binding sites, thus directing CTCF to the chosen promoter. In contrast, the uniform pattern of Pcdh expression in 5-HTs is achieved through conventional cohesin-independent, distance-dependent enhancer/promoter interactions, that favor choice of the nearest isoform. Thus, cell-type specific cohesin deployment converts a distance-dependent and deterministic regulatory logic into a distance-independent and stochastic one. We propose that this mechanism provides an elegant strategy to achieve distinct patterns of Pcdh expression that generate wiring instructions to meet the connectivity requirements of different neural classes.
Extracellular prostaglandins E1 and E2 and inflammatory cytokines are regulated by the senescence program in potentially premalignant oral keratinocytes
Authors: Karen-Ng Lee Peng , Ahmad Usama Sharif , Gomes Luis , Hunter Keith David , Wan Hong , Hagi-Pavli Eleni , Parkinson Eric Kenneth 
Published: March 2022

AbstractPotentially pre-malignant lesions (PPOLs) are composed of keratinocytes that are either mortal (MPPOL) or immortal (IPPOL) in vitro. We report here that MPPOL, but not generally IPPOL keratinocytes upregulate various extracellular tumor promoting cytokines (interleukins 6 and 8) and prostaglandins E1 (ePGE1) and E2 (ePGE2) relative to normal oral keratinocytes (NOKs). ePGE upregulation in MPPOL was independent of PGE receptor status, associated with some but not all markers of cellular senescence. Nevertheless, ePGE upregulation was dependent on the senescence program, cyclo-oxygenase 2 (COX2) and p38 mitogen-activated protein kinase and partially regulated by hydrocortisone. Following senescence in the absence of p16INK4A ePGEs accumulated in parallel with a subset of tumor promoting cytokine and metalloproteinase (MMP) transcripts all of which were ablated by ectopic telomerase. Surprisingly, ataxia telangiectasia mutated (ATM) function was not required for ePGE upregulation and actually increased in expression in IPPOL keratinocytes in line with its recently reported role in telomerase function. Only ePGE1 was dependent on p53 function suggesting that ePGEs 1 and 2 are regulated differently in oral keratinocytes. We show here that ePGE2 stimulates IPPOL keratinocyte proliferation in vitro. Therefore, we propose that MPPOL keratinocytes promote the progression of IPPOL to oral SCC in a pre-cancerous field by supplying PGEs, interleukins and MMPs in a paracrine manner. Our results suggest that the therapeutic targeting of COX-2 might be enhanced by strategies that target keratinocyte senescence.Simple SummaryThe early treatment of oral cancer is a high priority, as improvements in this area could lead to greater cure rates and reduced disability due to extensive surgery. Oral cancer is very difficult to detect in over 70% of cases as it develops unseen until quite advanced, sometimes rapidly. It has become apparent that there are at least two types of epithelial cells (keratinocytes) found in oral tissue on the road to cancer (premalignant). One type secretes molecules called prostaglandins but the other does not and the former may stimulate the latter to progress to malignancy, either by stimulating their proliferation or encouraging the influx of blood vessels to feed them. Additionally, we have identified regulators of prostaglandin secretion in premalignant oral cells that could be targeted in future therapies such as inducers of cellular senescence, drugs which kill senescent cells (senolytics), steroid metabolism, cyclo-oxygenase 2 (COX2) and p38 mitogen-activated protein kinase.
CRISPR-Cas12a targeting of ssDNA plays no detectable role in immunity
Authors: Marino Nicole D. , Pinilla-Redondo Rafael , Bondy-Denomy Joseph 
Published: March 2022

ABSTRACTCRISPR-Cas12a (Cpf1) is a bacterial RNA-guided nuclease that cuts double-stranded DNA (dsDNA) at sites specified by a CRISPR RNA (crRNA) guide. Additional activities have been ascribed to this enzyme in vitro: site-specific (cis) single-stranded DNA (ssDNA) cleavage and indiscriminate (trans) degradation of ssDNA, RNA, and dsDNA after activation by a complementary target. The ability of Cas12a to cleave nucleic acids indiscriminately has been harnessed for many applications, including diagnostics, but it remains unknown if it contributes to bacterial immunity. Here, we provide evidence that cleavage of ssDNA in cis or in trans by Cas12a is insufficient to impact immunity. Using LbCas12a expressed in either Pseudomonas aeruginosa or Escherichia coli, we observed that cleavage of dsDNA targets did not elicit cell death or dormancy, suggesting insignificant levels of collateral damage against host RNA or DNA. Canonical immunity against invasive dsDNA also had no impact on the replicative fitness of co-infecting ssDNA phage or plasmid in trans. Lastly, crRNAs complementary to invasive ssDNA did not provide protection, suggesting that ssDNA cleavage does not occur in vivo or is insignificant. Overall, these results suggest that CRISPR-Cas12a immunity predominantly occurs via canonical targeting of dsDNA, and that the other activities are in vitro irregularities.
Structural relationship between food quality, usefulness, ease of use, convenience, brand trust and willingness to pay: the case of Starbucks
Authors: Moon Joonho , Song Myungkeun , Lee Won Seok , Shim Ji Min 
Published: March 2022

PurposeThis study aims to explore the structural relationship among food quality, usefulness, ease of use, convenience, brand trust and willingness to pay. The technology acceptance model was used as the theoretical foundation of this work.Design/methodology/approachAmazon Mechanical Turk was used to recruit survey participants, and 436 valid observations were ultimately used for the analysis. In the data analysis, the structural relationships between variables were explored through structural equation modeling.FindingsThe results of hypothesis testing show that ease of use positively affects the usefulness of the Starbucks mobile application. Usefulness also exerts positive impacts on both brand trust and convenience. Moreover, brand trust is positively associated with food quality. Finally, willingness to pay is positively influenced by both convenience and brand trust.Originality/valueThis study contributes to the literature by not only validating the technology acceptance model using the Starbucks mobile application but also proposing food quality-related attributes in the domain of the café business.
Keep dreaming: how personality traits affects the recognition and exploitation of entrepreneurial opportunities in the agritourism industry
Authors: Leonelli Simona , Iaia Lea , Masciarelli Francesca , Vrontis Demetris 
Published: March 2022

PurposeThis paper analyses how entrepreneurs recognise and exploit entrepreneurial opportunities following a sustainable approach that respects the equilibrium among environmental, social and commercial purposes, and how their personality affects this process. The main personality traits focused in this study are narcissism, locus of control and sustainability orientation.Design/methodology/approachThis single case study involves Essentia Dimora Rurale, a small agritourism business, located in Molise (Italy), characterised by a sustainable business model that generates value for the local environment, thus revitalising abandoned territories. Data are collected using qualitative and quantitative methods and are analysed using the Gioia methodology.FindingsThe Essentia Dimora Rurale's approach is rooted in the concept of sustainability and the development of tourism in the territory. The preservation of traditional values and the creation of a network allow the firm to prosper and survive. The personalities of the two sibling entrepreneurs fuel the process, and the authors show that each personality trait plays a different role in each phase of the firm's growth.Research limitations/implicationsFrom a theoretical point of view, the study contributes to entrepreneurial, sustainability and personality literature. However, using a single case study can represent a limit for the research.Practical implicationsVarious practical implications are recognised concerning several stakeholders, such as the owners and the entities linked to the regional promotion and tourism sectors.Originality/valueThe novelty of the research relies on the importance of entrepreneur opportunity identification, particularly in sustainable firms. Moreover, the authors fill the literature gap investigating the impact of three personality traits in this process.
WHO’s first scientific review of medicinal Cannabis: from global struggle to patient implications
Authors: Riboulet-Zemouli Kenzi , Krawitz Michael Alan 
Published: March 2022

Background
“Cannabis” and “cannabis resin” are derived from the Cannabis plant, used as herbal medications, in traditional medicine and as active pharmaceutical ingredients. Since 1961, they have been listed in Schedule IV, the most restrictive category of the single convention on narcotic drugs. The process to scientifically review and reschedule them was launched by the World Health Organisation (WHO) on 2 December 2016; it survived a number of hindrances until finally being submitted to a delayed and sui generis vote by the UN Commission on Narcotic Drugs on 2 December 2020, withdrawing “cannabis” and “cannabis resin” from Schedule IV.

Design/methodology/approach
To evaluate WHO’s scheduling recommendations, the process leading to the Commission vote and subsequent implications at global, national and patient/clinician levels. Narrative account of the four-year proceedings; review of the practical implications of both rejected and accepted recommendations.

Findings
The process was historically unprecedented, of political relevance to both medical Cannabis and evidence-based scheduling generally. Procedural barriers hampered the appropriate involvement of civil society stakeholders. The landscape resulting from accepted and rejected recommendations allow countries to continue creating decentralised, non-uniform systems for access to and availability of “cannabis” and “cannabis resin” for medical purposes.

Originality/value
Perspective of accredited observers; highlight of institutional issues and the lay of the land; contrast of stakeholders’ interpretations and engagement.