bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRD: aDe novoDesign algorithm for prediction of Cognate Protein Receptors for small molecule ligands
Authors: Sankar Santhosh , Chandra Nagasuma 
Published: April 2023

AbstractWhile predicting a new ligand to bind to a protein is possible with current methods, the converse of predicting a receptor for a ligand is highly challenging, except for very closely-related known protein-ligand complexes. Predicting a receptor for any given ligand will be path-breaking in understanding protein function, mapping sequence-structure-function relationships and for several aspects of drug discovery including studying the mechanism of action of phenotypically discovered drugs, off-target effects and drug repurposing. We use a novel approach for predicting receptors for a given ligand throughde novodesign combined with structural bioinformatics. We have developed a new algorithm CRD, that has multiple modules which combines fragment-based sub-site finding, a machine learning function to estimate the size of the site, a genetic algorithm that encodes knowledge on protein structures and a physics-based fitness scoring scheme. CRD has a pseudo-receptor design component followed by a mapping component to identify possible proteins that house the site. CRD is designed to cater to ligands with known and unknown complexes. CRD accurately recovers sites and receptors for several known natural ligands including ATP, SAM, Glucose and FAD. It designs similar sites for similar ligands, yet to some extent distinguishes between closely related ligands. More importantly CRD correctly predicts receptor classes for several drugs such as penicillins and NSAIDs. We expect CRD to be a valuable tool in fundamental biology research as well as in the drug discovery and biotechnology industry.
Bradykinin receptor expression and bradykinin-mediated sensitization of human sensory neurons
Authors: Yi Jiwon , Bertels Zachariah , Del Rosario John Smith , Widman Allie J. , Slivicki Richard A. , Payne Maria , Susser Henry M. , Copits Bryan A. , Gereau Robert W. 
Published: April 2023

AbstractBradykinin is a peptide implicated in inflammatory pain in both humans and rodents. In rodent sensory neurons, activation of B1 and B2 bradykinin receptors induces neuronal hyperexcitability. Recent evidence suggests that human and rodent dorsal root ganglia (DRG), which contain the cell bodies of sensory neurons, differ in the expression and function of key GPCRs and ion channels; whether BK receptor expression and function are conserved across species has not been studied in depth. In this study, we used human DRG tissue from organ donors to provide a detailed characterization of bradykinin receptor expression and bradykinin-induced changes in the excitability of human sensory neurons. We found that B2 and, to a lesser extent, B1 receptors are expressed by human DRG neurons and satellite glial cells. B2 receptors were enriched in the nociceptor subpopulation. Using patch-clamp electrophysiology, we found that acute bradykinin increases the excitability of human sensory neurons, while prolonged exposure to bradykinin decreases neuronal excitability in a subpopulation of human DRG neurons. Finally, our analyses suggest that donor’s history of chronic pain and age may be predictors of higher B1 receptor expression in human DRG neurons. Together, these results indicate that acute BK-induced hyperexcitability, first identified in rodents, is conserved in humans and provide further evidence supporting BK signaling as a potential therapeutic target for treating pain in humans.
Lysosome transporter purification and reconstitution identifies Ypq1 pH-gated lysine transport and regulation
Authors: Arines Felichi Mae , Wielenga Aleksander , Burata Olive E. , Garcia Francisco Narro , Stockbridge Randy B. , Li Ming 
Published: April 2023

AbstractLysosomes achieve their function through numerous transporters that import or export nutrients across their membrane. However, technical challenges in membrane protein overexpression, purification, and reconstitution hinder our understanding of lysosome transporter function. Here, we developed a platform to overexpress and purify the putative lysine transporter Ypq1 using a constitutive overexpression system in protease- and ubiquitination-deficient yeast vacuoles. Using this method, we purified and reconstituted Ypq1 into proteoliposomes and showed lysine transport function, supporting its role as a basic amino acid transporter on the vacuole membrane. We also found that the absence of lysine destabilizes purified Ypq1 and causes it to aggregate, consistent with its propensity to be downregulatedin vivoupon lysine starvation. Our approach may be useful for the biochemical characterization of many transporters and membrane proteins to understand organellar transport and regulation.
CilioGenics: an integrated method and database for predicting novel ciliary genes
Authors: Pir Mustafa S. , Yenisert Ferhan , Karaman Aslı , Begar Efe , Tsiropoulou Sofia , Firat-Karalar Elif Nur , Blacque Oliver E , Oner Sukru S. , Doluca Osman , Cevik Sebiha , Kaplan Oktay I. 
Published: April 2023

AbstractDiscovering the entire list of human ciliary genes would help in the diagnosis of cilia-related human disorders known as ciliopathy, but at present the genetic diagnosis of many ciliopathies (over 30%) is far from complete (Bachmann-Gagescu et al., 2015; Knopp et al., 2015; Paff et al., 2018). In a theory, many independent approaches may uncover the whole list of ciliary genes, but 30% of the genes on the ciliary gene list are still ciliary candidate genes (van Dam et al., 2019; Vasquez et al., 2021). All of these cutting-edge techniques, however, have relied on a different single strategy to discover ciliary candidate genes. Because different methodologies demonstrated distinct capabilities with varying quality, categorizing the ciliary candidate genes in the ciliary gene list without further evidence has been difficult. Here, we present a method for predicting ciliary capacity of each human gene that incorporates diverse methodologies (single-cell RNA sequencing, protein-protein interactions (PPIs), comparative genomics, transcription factor (TF)-network analysis, and text mining). By integrating multiple approaches, we reveal previously undiscovered ciliary genes. Our method, CilioGenics, outperforms other approaches that are dependent on a single method. Our top 500 gene list contains 256 new candidate ciliary genes, with 31 experimentally validated. Our work suggests that combining several techniques can give useful evidence for predicting the ciliary capability of all human genes.
Machine Learning-aided Discovery of Novel Chemotype Antagonists for G Protein-coupled Receptors: The Case of the Adenosine A2AReceptor
Authors: Goßen Jonas , Ribeiro Rui Pedro , Bier Dirk , Neumaier Bernd , Carloni Paolo , Giorgetti Alejandro , Rossetti Giulia 
Published: April 2023

AbstractIdentifying the correct chemotype of ligands targeting receptors (i.e., agonist or antagonist) is a challenge forin silicoscreening campaigns. Here we present an approach that identifies novel chemotype ligands by combining structural data with a random forest agonist/antagonist classifier and a signal-transduction kinetic model. As a test case, we apply this approach to identify novel antagonists of the human adenosine transmembrane receptor type 2A, an attractive target against Parkinson’s disease and cancer. The identified antagonists were tested here in a radioligand binding assay. Among those, we found a promising ligand whose chemotype differs significantly from all so-far reported antagonists, with a binding affinity of 310±23.4 nM. Thus, our protocol emerges as a powerful approach to identify promising ligand candidates with novel chemotypes while preserving antagonistic potential and affinity in the nanomolar range.
Preclinical Screening of Splice-Switching Antisense Oligonucleotides in PDAC Organoids
Authors: Wan Ledong , Kral Alexander J. , Voss Dillon , Krainer Adrian R. 
Published: April 2023

AbstractAberrant alternative splicing is emerging as a cancer hallmark and a potential therapeutic target. It is the result of dysregulated splicing factors or genetic alterations in splicing-regulatorycis-elements. Targeting individual altered splicing events associated with cancer-cell dependencies is a potential therapeutic strategy, but several technical limitations need to be addressed. Patient-derived organoids (PDOs) are a promising platform to recapitulate key aspects of disease states and to facilitate drug development for precision medicine. Here, we report an efficient antisense-oligonucleotide (ASO) transfection method to systematically evaluate and screen individual splicing events as therapeutic targets in pancreatic ductal adenocarcinoma (PDAC) organoids. This optimized delivery method allows fast and efficient screening of ASOs that reverse oncogenic alternative splicing. In combination with advancements in chemical modifications and ASO-delivery strategies, this method has the potential to accelerate the discovery of anti-tumor ASO drugs that target pathological alternative splicing.
Assessing Microbial Diversity in Soil Samples Along the Potomac River: Implications for Environmental Health
Authors: Taraboletti Alexandra , King Alexus , Dixon Yasheka , Orr Oshane , Parnell Chevell , Watson Yasheika , Nash Bruce , Esimai Chimdimnma , Ude George 
Published: April 2023

AbstractIn this study, we investigated the microbial diversity and community composition of soil samples collected from various sites along the Potomac River within an urbanized region. Our findings revealed the presence of both typical marine soil bacteria and bacterial taxa indicative of urbanization and waste runoff. We observed significant variations in microbial community structure and diversity across different sampling sites, highlighting the influence of environmental factors on microbial abundance and diversity. Through taxon set analysis, we identified shared taxa strongly associated with agricultural pollution, organochlorine pesticide contamination, and bromochloromethane pollution. Additionally, the study revealed potential disparities in human impact, water retention, and tidal/current effects among the soil samples. These insights carry significant implications for understanding the consequences of urbanization on soil microbial communities along the Potomac River and can inform strategies for managing and preserving these ecosystems. Further research is warranted to elucidate the effects of soil health and microbial diversity in this region.
Sex-specific age-related changes in glymphatic function assessed by resting-state functional magnetic resonance imaging
Authors: Han Feng , Liu Xufu , Yang Yifan , Liu Xiao 
Published: April 2023

SummaryThe glymphatic system that clears out brain wastes, such as amyloid-β (Aβ) and tau, through cerebrospinal fluid (CSF) flow may play an important role in aging and dementias. However, a lack of non-invasive tools to assess the glymphatic function in humans hindered the understanding of the glymphatic changes in healthy aging. The global infra-slow (<0.1 Hz) brain activity measured by the global mean resting-state fMRI signal (gBOLD) was recently found to be coupled by large CSF movements. This coupling has been used to measure the glymphatic process and found to correlate with various pathologies of Alzheimer’s disease (AD), including Aβ pathology. Using resting-state fMRI data from a large group of 719 healthy aging participants, we examined the sex-specific changes of the gBOLD-CSF coupling, as a measure of glymphatic function, over a wide age range between 36-100 years old. We found that this coupling index remains stable before around age 55 and then starts to decline afterward, particularly in females. Menopause may contribute to the accelerated decline in females.
Oxaliplatin Inhibits RNA Polymerase I via DNA Damage Signaling Targeted to the Nucleolus
Authors: Nechay Misha , Kleiner Ralph E. 
Published: April 2023

ABSTRACTPlatinum (Pt) compounds are an important class of anti-cancer therapeutics, but outstanding questions remain regarding their mode of action. In particular, emerging evidence indicates that oxaliplatin, a Pt drug used to treat colorectal cancer, kills cells by inducing ribosome biogenesis stress rather than through DNA damage generation, but the underlying mechanism is unknown. Here, we demonstrate that oxaliplatin-induced ribosomal RNA (rRNA) transcriptional silencing and nucleolar stress occur downstream of DNA damage signaling involving ATM and ATR. We show that NBS1 and TOPBP1, two proteins involved in the nucleolar DNA damage response (n-DDR), are recruited to nucleoli upon oxaliplatin treatment. However, we find that rRNA transcriptional inhibition by oxaliplatin does not depend upon NBS1 or TOPBP1, nor does oxaliplatin induce substantial amounts of nucleolar DNA damage, distinguishing it from previously characterized n-DDR pathways. Taken together, our work indicates that oxaliplatin induces a distinct DDR signaling pathway that functionsin transto inhibit Pol I transcription in the nucleolus, demonstrating how nucleolar stress can be linked to DNA damage signaling and highlighting an important mechanism of Pt drug cytotoxicity.
The decision to present comparative financial statements in a mandatory IFRS adoption setting
Authors: Sánchez Francisco , Giner Begoña , Gill-de-Albornoz Belén 
Published: April 2023

PurposeThis study analyzes the factors behind the decisions made by the largest listed Chilean companies that mandatorily adopted the International Financial Reporting Standards (IFRS) in 2009 to present comparative IFRS financial statements that year. The authors focus on the role of the expected impact of the change in the accounting standards on a company's financial position as a determinant of this decision.Design/methodology/approachThe sample comprises 105 nonfinancial companies, of which 57 decided to present comparative IFRS financial statements (full adoption) and 48 did not (proforma adoption). Logistic regression is employed to model the decision of interest.FindingsThe decision for full adoption is positively associated with the company's expectation that the change in the accounting standards would improve its financial position, albeit only up to a certain threshold, as evidenced by their inverse U-shaped association.Originality/valueIFRS adoption in Chile creates a unique scenario that allows us to contribute to the literature on the determinants of voluntary disclosure by focusing on a specific case in which the decision to disclose comparative financial statements is associated with mandatory IFRS adoption. The present study provides evidence that opportunistic behavior influences this decision.
Quality factor based transducer power gain expression
Authors: Şengül Metin 
Published: April 2023

Purpose
In the literature, while designing broadband matching networks, transducer power gain (TPG) is used to measure the transferred power. Generally, in TPG expressions, load and back-end impedances of the matching network are used. This study aims to derive a new quality factor-based TPG expression.

Design/methodology/approach
In deriving the new expression, narrowband L type-matching network design approach is used and the new expression in terms of back-end quality factor, load quality factor and output port quality factor is obtained. Then, a broadband-matching network design approach using the derived TPG expression is proposed.

Findings
Two broadband double-matching networks are designed by using the proposed design approach using the derived TPG expression. Performances of the designed-matching networks are compared with the performances of the matching networks designed by means of simplified real frequency technique which is a well-known technique in the literature, and it is shown that they are nearly the same.

Originality/value
In broadband-matching problems, generally an impedance-based TPG expression is used, and it must be satisfied by the designed broadband-matching networks. But, in the literature, there is no quality factor-based TPG expression that can be used in broadband-matching problems. So, this gap in the literature has been filled by this paper.
Green finance: between commitment and illusion
Authors: Chenguel Mohamed Bechir , Mansour Nadia 
Published: April 2023

Purpose
After almost 10 years, people wonder if green finance has been able to attain its objectives in terms of controlling climate change. Persistent global warming and climate deregulation manifested by melting glaciers, droughts and floods, are all of these determinants that have called into question the efficiency of green finance.

Design/methodology/approach
Green finance is a way to support climate action through investments. It has proven that this is a viable financial instrument and that it can be used by governments and private companies to plan for the future of our planet.

Findings
Based on an analysis of articles published in top international journals from 2016 to 2022, about the relationship between green technology and financial services in China, this paper aims to present an overview of green finance, its importance for the planet, its objectives and its instruments.

Research limitations/implications
This study’s contribution is to shed light on the aspects that may have limited its effectiveness, such as the absence of incentives, the absence of climate costs and above all the absence of finance green standards.

Originality/value
The results have shown that there is still a significant gap in green finance before inclusive green growth can be achieved. Inclusive green growth. All stakeholders need to increase the level of investment in green finance. The green investment financing gap is the result of inconsistencies in sustainability and policies. Therefore, governments must intervene to impose appropriate policies and regulations to compel the financial sector to engage in sustainable development. All of these factors make the concept of green finance just an illusion.
Developing a prediction model for improving bifurcated garment fit for mass customization
Authors: Galada Aditi , Baytar Fatma 
Published: April 2023

PurposeThe purpose of the present study was to improve the fit of women’s bifurcated garments by developing an equation that can predict the crotch length accurately by using a few basic body measurements. This equation could provide a simple mass-customization approach to the design of bifurcated garments.Design/methodology/approachDemographic characteristics and easy-to-record body measurements available in the size USA database were used to predict the crotch length. Different methodologies including best subset regression, lasso regression and principal components regression were experimented with to identify the most important predictor variables and establish a relationship between the significant predictors and crotch length.FindingsThe lasso regression model provided the highest accuracy, required only five body dimensions and dealt with multicollinearity. The preliminary pattern preparation and garment fit tests indicated that by utilizing the proposed equation, patterns of customized garments could be successfully altered to match the crotch length of the customer, thereby, improving the precision and efficiency of the pattern making process.Originality/valueCrotch length is a crucial measurement as it determines bifurcated garment comfort as well as aesthetic fit. The crotch length is usually estimated arbitrarily based on non-scientific methods while drafting patterns, and this increases the likelihood of dissatisfaction with the fit of the lower-body garments. The present study suggested an algorithm that could predict crotch length with 90.53% accuracy using the body dimensions height, hips, waist height, knee height and arm length.
Effectiveness of online teaching and learning in Indian universities during the COVID-19 pandemic
Authors: Khan Mohsin , Viswanathan Rajeesh 
Published: April 2023

PurposeThis study aims to analyze the effectiveness of online teaching and learning in the higher education sector during the COVID-19 pandemic and thereby design and formulate strategies to overcome the lacunas, if any, to enhance teaching effectiveness.Design/methodology/approachA survey was conducted to analyze how far students were able to adapt to online teaching and learning, access teaching platforms and afford it. It was also studied whether they were able to grasp and apply the concepts learned. A total of 600 questionnaires were given, and 372 complete responses were received. Structural equation modeling is employed to test the hypothesis. Confirmatory factor analysis (CFA) was conducted to test the model fit and measurement model.FindingsThis study is first of its kind in India which aims to analyze the effectiveness of online teaching and learning environments. This research model is designed to identify the determinants of effective online learning and to overcome the lacunas existing in the prevailing online teaching methods. It can be applied not just during crises like the pandemic but also during normal times to make teaching and learning more economical, innovative and impactful. The present study examined the impact of five major determinants—adaptability, affordability, bandwidth, grasping and interaction—on online learning and its effectiveness during COVID-19. It was observed that all the determinants positively influence online learning effectiveness.Research limitations/implicationsThe scope of the study was restricted to three centrally funded Indian Universities. Other institutions were not part of the study.Originality/valueThis study is the first of its kind done in the current COVID-19 scenario, and the outcome would help overcome the lacunas in the prevailing online teaching scenario across the globe and make it more effective.
Examining user-generated content, service failure recovery and customer–brand relationships: an exploration through commitment-trust theory
Authors: Ozuem Wilson , Willis Michelle , Howell Kerry , Ranfagni Silvia , Rovai Serena 
Published: April 2023

PurposeUser-generated content (UGC) and service failure have attracted considerable marketing inquiry over the last two decades. Previous studies primarily focused on the outcome of service failure and the impact of UGC on perceived failure severity. This article departs from previous studies as it examines the moderating role of UGC on the relationship between service failure recovery (SFR) and customer–brand relationship.Design/methodology/approachBuilding on commitment-trust theory and from a phenomenological hermeneutical perspective, this article explores this phenomenon through the interpretation of 60 in-depth interviews with millennials from three European countries: Italy, France and the UK. An analysis of the data was conducted using a qualitative approach to understand the main constructs and relationships derived from the data.FindingsThis study conceptualises four distinct moderating characteristics of UGC in the SFR process: satisfaction with experience and brand, dissatisfaction with experience and brand, satisfaction with brand and dissatisfaction with brand. The insights from the responsiveness, empathetic response, counterfactual thinking and brand salience (RECB) framework contribute to research on UGC and shed light on the relationship between SFR and consumer–brand relationships in the fashion industry.Originality/valueOverall, this study demonstrates that customer interactions with UGC significantly affect their responses to, and relationships with, a brand. The proposed framework opens up interesting avenues for future research on the moderating role of UGC on the relationship between SFR and customer–brand relationships.