bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-silico Screening ofOriganum vulgarePhytocompounds as Potential Drug Agents AgainstVp35Protein of the Ebola Virus
Authors: Saeed Malaika , Ashraf Aqeela , Sabir Burhan , Zafar Muhammad Osama , Raza Muhammad Hassan , Saif Rashid 
Published: March 2023

AbstractThe leading cause of the Ebola virus outbreak during 2013-16 in Western Africa was a lack of targeted anti- viral drug choices, a fast rate of mutations and the unavailability of many of the structural proteins and annotations within its genome. The surroundings of the Ebola River in DR-Congo fail to get rid of this endemic, the reason behind this was believed to be its origin from non-human primates, which made its risk assessment and tracing difficult. The Vp35 is a multifunctional protein with innate immune antagonistic properties and is considered one of the most suitable drug targets within this virus. The main motive of this study is to discover a potential anti-viral drug against the Ebola virus by targeting the aforementioned protein with different phytocompounds of oregano that have the lowest binding energies and qualifies over different simulation parameters, so firstly, molecular docking was performed on its 28 compounds using PyRx to get the best complexes with minimum binding energies e.g., -8.9Kcal/mol. Ligands with the best docking scores were gone through Lipinski’s rule of five for drug likeliness potential. For the drug affirmation, molecular dynamic simulation was also performed with the best two docked complexes using NAMD/VMD to find out their conformational stability through RMSD, RMSF, Rg, SASA and H-bond analyses. Current computer-generated prediction suggested that Ursolic acid and Oleanolic acid possess potential inhibitory effects against virus replication. Furthermore, paradigm shifts of usage of natural and herbal products for treating infectious diseases are being encouraged here, However, further wet-lab experiments and clinical trials are still needed to determine the robustness of these virtually tested phytocompounds against the Vp35 protein of the Ebola virus.
Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study
Authors: Itahashi Takashi , Yamashita Ayumu , Takahara Yuji , Yahata Noriaki , Aoki Yuta Y. , Fujino Junya , Yoshihara Yujiro , Nakamura Motoaki , Aoki Ryuta , Ohta Haruhisa , Sakai Yuki , Takamura Masahiro , Ichikawa Naho , Okada Go , Okada Naohiro , Kasai Kiyoto , Tanaka Saori C. , Imamizu Hiroshi , Kato Nobumasa , Okamoto Yasumasa , Takahashi Hidehiko , Kawato Mitsuo , Yamashita Okito , Hashimoto Ryu-ichiro 
Published: March 2023

AbstractAutism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites (U.S., Belgium, and Japan) and different developmental stages (children and adolescents). Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults (area under the curve [AUC] = 0.70) and Japanese adults (AUC = 0.81). The neuromarker demonstrated significant generalization for children (AUC = 0.66) and adolescents (AUC = 0.71; allP<0.05, family-wise-error corrected). We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. These FCs largely centered on social brain regions such as the amygdala, hippocampus, dorsomedial and ventromedial prefrontal cortices, and temporal cortices. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.
PRMT1 Inhibition Selectively Targets BNC1-Dependent Proliferation, but not Migration in Squamous Cell Carcinoma
Authors: Boudra Rafik , Patenall Bethany L. , King Sandra , Wang Diana , Best Sarah A. , Ko Joo Yeon , Xu Shuyun , Padilla Maria G. , Schmults Chrysalyne D. , Barthel Steven R. , Lian Christine G. , Ramsey Matthew R. 
Published: March 2023

SummarySquamous Cell Carcinoma (SCC) develops in stratified epithelial tissues and demonstrates frequent alterations in transcriptional regulators. We sought to discover SCC-specific transcriptional programs and identified the transcription factor Basonuclin 1 (BNC1) as highly expressed in SCC compared to other tumor types. RNA-seq and ChIP-seq analysis identified pro-proliferative genes activated by BNC1 in SCC cells and keratinocytes. Inhibition of BNC1 in SCC cells suppressed proliferation and increased migration via FRA1. In contrast, BNC1 reduction in keratinocytes caused differentiation, which was abrogated by IRF6 knockdown, leading to increased migration. Protein interactome analysis identified PRMT1 as a co-activator of BNC1-dependent proliferative genes. Inhibition of PRMT1 resulted in a dose-dependent reduction in SCC cell proliferation without increasing migration. Importantly, therapeutic inhibition of PRMT1 in SCC xenografts significantly reduced tumor size, resembling functional effects of BNC1 knockdown. Together, we identify BNC1-PRMT1 as an SCC-lineage specific transcriptional axis that promotes cancer growth, which can be therapeutically targeted to inhibit SCC tumorigenesis.Abstract Figure
APOL1 kidney risk variants in glomerular diseases modeled in transgenic mice
Authors: Yoshida Teruhiko , Latt Khun Zaw , Santo Briana A. , Shrivastav Shashi , Zhao Yongmei , Fenaroli Paride , Chung Joon-Yong , Hewitt Stephen M. , Tutino Vincent M. , Sarder Pinaki , Rosenberg Avi Z. , Winkler Cheryl A. , Kopp Jeffrey B. 
Published: March 2023

AbstractAPOL1high-risk variants partially explain the high kidney disease prevalence among African ancestry individuals. Many mechanisms have been reported in cell culture models, but few have been demonstrated in mouse models. Here we characterize two models: (1) HIV- associated nephropathy (HIVAN) Tg26 mice crossed with bacterial artificial chromosome (BAC)/APOL1 transgenic mice and (2) interferon-ψ administered to BAC/APOL1 mice. Both models showed exacerbated glomerular disease in APOL1-G1 compared to APOL1-G0 mice. HIVAN model glomerular bulk RNA-seq identified synergistic podocyte-damaging pathways activated by the APOL1-G1 allele and by HIV transgenes. Single-nuclear RNA-seq revealed podocyte-specific patterns of differentially-expressed genes as a function of APOL1 alleles. Eukaryotic Initiation factor-2 pathway was the most activated pathway in the interferon-ψ model and the most deactivated pathway in the HIVAN model. HIVAN mouse model podocyte single-nuclear RNA-seq data showed similarity to human focal segmental glomerulosclerosis (FSGS) glomerular bulk RNA-seq data. Furthermore, single-nuclear RNA-seq data from interferon-ψ mouse model podocytes (in vivo) showed similarity to human FSGS single-cell RNA- seq data from urine podocytes (ex vivo) and from human podocyte cell lines (in vitro) using bulk RNA-seq. These data highlight differences in the transcriptional effects of theAPOL1-G1 risk variant in a model specific manner. Shared differentially expressed genes in podocytes in both mouse models suggest possible novel glomerular damage markers inAPOL1variant-induced diseases. Transcription factorZbtb16was downregulated in podocytes and endothelial cells in both models, possibly contributing to glucocorticoid-resistance. In summary, these findings in two mouse models suggest both shared and distinct therapeutic opportunities for APOL1 glomerulopathies.Significance statementCoding variants in APOL1, encoding apolipoprotein L1, contribute to kidney disease in individuals with African ancestry. The mechanisms for glomerular injury remain incompletely understood. We studied two transgenic mouse models, HIV-associated nephropathy and interferon-ψ administration. Using glomerular and single-nuclear RNA sequencing, we identified genes differentially expressed among mice with kidney risk alleles (G1) and the common variant (G0). Both models exhibited up-regulation of genes that indicated podocyte damage with risk alleles compared to the common variant. One gene down-regulated in both models was Zbtb16, encoding a transcription factor, that may contribute to glucocorticoid-resistance. Overall, the findings suggest both shared and distinct alterations in the two disease models.
Drivers of species knowledge across the Tree of Life
Authors: Mammola Stefano , Adamo Martino , Antić Dragan , Calevo Jacopo , Cancellario Tommaso , Cardoso Pedro , Chamberlain Dan , Chialva Matteo , Durucan Furkan , Fontaneto Diego , Gonçalves Duarte V. , Martínez Alejandro , Santini Luca , Rubio-López Iñigo , Sousa Ronaldo , Villegas-Ríos David , Verdes Aida , Correia Ricardo A. 
Published: March 2023

ABSTRACTKnowledge of biodiversity is unevenly distributed across the Tree of Life. In the long run, such disparity in awareness unbalances our understanding of life on Earth, influencing policy decisions and the allocation of research and conservation funding. We investigated how humans accumulate knowledge of biodiversity by searching for consistent relationships between scientific (number of publications) and societal (number of views in Wikipedia) interest, and species-level morphological, ecological and socio-cultural factors. Across a random selection of 3,019 species spanning 29 Phyla/Divisions, we show that socio-cultural factors are the most important correlates of scientific and societal interest in biodiversity, including the fact that a species is useful or harmful to humans, has a common name and is listed in the IUCN Red List. Furthermore, large-bodied, broadly distributed and taxonomically unique species receive more scientific and societal attention, whereas colorfulness and phylogenetic proximity to humans correlates exclusively with societal attention. These results highlight a favoritism towards limited branches of the Tree of Life, and that scientific and societal priorities in biodiversity research broadly align. This suggests that we may be missing out on key species in our research and conservation agenda simply because they are not on our cultural radar.
Accurately estimating pathway activity in single cells for clustering and differential analysis
Authors: Davis Daniel , Wizel Avishai , Drier Yotam 
Published: March 2023

AbstractInferring which and how biological pathways and gene sets are changing is a key question in many studies that utilize single-cell RNA sequencing. Typically, these questions are addressed by quantifying the enrichment of known gene sets in lists of genes derived from global analysis. Here we offer SiPSiC, a new method to infer pathway activity in each cell. This allows more sensitive differential analysis and utilizing pathway scores to cluster cells and compute UMAP or other similar projections. We apply our method on datasets of COVID-19, lung adenocarcinoma and glioma, and demonstrate its utility. SiPSiC analysis is consistent with findings reported by previous analyses in many cases, but also reveals the differential activity of novel pathways, enabling us to suggest new mechanisms underlying the pathophysiology of these diseases and demonstrating SiPSiC’s high accuracy and sensitivity in detecting biological function and traits. In addition, we demonstrate how it can be used to better classify cells based on activity of biological pathways instead of single genes and its ability to overcome patient specific artifacts.
A rationally designed inactivatedSalmonellaTyphimurium vaccine induces strong and long-lasting immune responses in pigs
Authors: Lentsch Verena , Aslani Selma , Echtermann Thomas , Preet Swapan , Barazzone Elisa Cappio , Hoces Daniel , Moresi Claudia , Kuemmerlen Dolf , Slack Emma 
Published: March 2023

AbstractSalmonella entericasubspeciesentericaserovar Typhimurium (S.Tm) poses a considerable threat to public health due to its zoonotic potential. Human infections are mostly foodborne, and pork and pork products are ranked among the top culprits for transmission. In addition, the high percentage of antibiotic resistance, especially in monophasicS.Tm, limits treatment options when needed. BetterS.Tm control would therefore be of benefit both for farm animals and for safety of the human food chain.A promising pre-harvest intervention is vaccination. In this study we tested safety and immunogenicity of an oral inactivatedS.Tm vaccine, which has been recently shown to generate an “evolutionary trap” and to massively reduceS.Tm colonization and transmission in mice. We show that this vaccine is highly immunogenic and safe in post-weaning pigs and that administration of a single oral dose results in a strong and long-lasting serum IgG response. This has several advantages over existing – mainly live – vaccines againstS.Tm, both in improved seroconversion and reduced risk of vaccine-strain persistence and reversion to virulence.
Transcriptional regulation of the synthesis and secretion of farnesol in the fungusCandida albicans:Examination of the Homann transcription regulator knockout collection
Authors: Gutzmann Daniel J. , Kramer Jaxon J. , Toomey Brigid M. , Boone Cory H. T. , Atkin Audrey L. , Nickerson Kenneth W. 
Published: March 2023

AbstractCandida albicansis an efficient colonizer of human gastrointestinal tracts and skin and is an opportunistic pathogen.C. albicansexhibits morphological plasticity and the ability to switch between yeast and filamentous morphologies is associated with virulence. One regulator of this switch is the quorum sensing molecule farnesol which is produced byC. albicansthroughout growth. However, the synthesis, secretion, regulation, and turnover of farnesol is not fully understood. To address this, we used our improved farnesol assay to screen a transcription regulator knockout library of 164 mutants for farnesol accumulation in whole cultures, pellets, and supernatants. All mutants produced farnesol and they averaged 9.2X more farnesol in the pellet than the supernatant. Nineteen mutants had significant differences with ten mutants producing more farnesol than their SN152+parent while nine produced less. Seven mutants exhibited greater secretion of farnesol while two exhibited less. We examined the time course for farnesol accumulation in six mutants with the greatest accumulation differences and found that those differences persisted throughout growth and they were not time dependent. Significantly, two high accumulating mutants did not exhibit the decay in farnesol levels during stationary phase characteristic of wild typeC. albicans, suggesting that a farnesol modification/degradation mechanism is absent in these mutants. Identifying these transcriptional regulators provides new insight into farnesol’s physiological functions regarding cell cycle progression, white-opaque switching, yeast-mycelial dimorphism, and response to cellular stress.
Variation of wine preference amongst consumers is influenced by the composition of salivary proteins
Authors: Luo Jiaqiang , Ruan Xinwei , Ang Ching-Seng , Nolvachai Yada , Marriott Philip J. , Zhang Pangzhen , Howell Kate 
Published: March 2023

ABSTRACTThe preferences of consumers for different flavours and aromas in wine are varied and may be explained by inherent factors such as cultural background, wine education and personal taste of the wine consumer. Wine flavour as perceived in the mouth includes aroma compounds released through the retronasal pathway which are shaped by interactions with saliva. Saliva and wine interactions could provide an explanation as to why wine tasters express different preferences for wine. To test this hypothesis, 13 Western and 13 Chinese experienced wine tasters were recruited. Sensory evaluation was performed in formal surroundings to acquire free description-based and perceived sensory intensity data using the Pivot®Profile and continuous scale assessment, respectively. Participants’ saliva samples were collected before the sensory evaluation and spiked into a wine sample to investigate the impact on the wine volatile release using GC×GC−MS. Saliva samples were subjected to enzyme activity assays and protein composition profiling by Tandem Mass Tag (TMT) quantitative proteomics. The wine tasters showed differences in wine flavour perception, which was supported by the difference in wine volatile release resulting from the addition of saliva. The two groups of participants did not have significant differences in total salivary protein concentrations or the amounts of esterase and α-amylase. However, statistically significant variations in the concentrations of specific proteins (proline-rich proteins (PRPs) and lipocalin-1 (LCN-1);p< 0.01) were found between the two groups. Significant correlations between perceived intensities of wine attributes and concentrations of PRPs and LCN-1 were observed. These results indicate that the composition of proteins in saliva are a factor that influences wine perception and preference. Our results provide a biochemical basis to understanding preference for food based on interactions between aroma compounds and salivary proteins and could be used to suggest foods or beverages to particular cultural groups.
Site-specific Effector Protein Functionalization to Create Bead-based Avidity Model Systems
Authors: Hackl Markus , Jayachandran Dharanidaran , Ramdin Khovesh , Zhong Tong , Chundawat Shishir P.S. 
Published: March 2023

AbstractThe cooperative effect of multiple affinity binding interactions creating a stable bond, known as avidity, is particularly important in assessing the potency of potential drugs such as monoclonal antibodies, CAR T, or NK cells to treat cancer. However, predicting avidity based onin vitrosingle affinity interactions has limitations and often fails to describe the avidity effects observedin vivo. Acoustic force-based assays have recently emerged as a reliable method for direct avidity measurements, expressed as adhesion forces, which positively correlate with drug efficacy. However, to better understand avidity, in particular for cell-cell interactions and correlate it with affinity, a cell model system with controlled avidity-related properties is needed. This study presents a method for producing a cell model system using “effector beads” that can be used in acoustic force spectroscopy-based avidity assays or any other bead-based avidity assay. The protein of interest is biotinylatedin vivoinE.coli, purified and subsequently mixed with streptavidin coated beads to create effector beads. The results demonstrate the dependency of rupture force on the receptor surface density and force loading rate, thus providing valuable information for designing future effector bead assays as well as cell avidity measurements for screening and characterization purposes.
Sustainable and healthy purchasing behaviors towards palm oil-based food in Italy
Authors: Baldassarre Fabrizio Flavio , Santovito Savino , Campo Raffaele , Dilorenzo Giacomo 
Published: March 2023

PurposePalm oil is widely used in the food industry; however, there are two main controversies connected to its use, namely, its nutritional value and the environmental consequences deriving from its crop. In Italy, the use of palm oil has recently been criticized, insomuch that some important bakery companies decided to substitute it, creating a real food marketing case. Through a focus on biscuits, this study is aimed at profiling consumers with regard to palm oil issue to better comprehend if the presence of this ingredient truly influences their food purchases and if they care about the nutritional and environmental aspects, highlighting the impact of the Covid-19 pandemic on consumers' consumption.Design/methodology/approachA questionnaire was administered to 243 subjects in Italy, in order to apply a cluster analysis.FindingsThe findings show the presence of three main kinds of consumers: (1) compromise finders (sensitive to cost savings but trying to privilege palm-oil free food), (2) brand-loyal consumers (palm oil does not influence their preferences) and (3) healthsensitives (the presence of palm oil profoundly affects their choices), who represent the majority of our sample. The results and implications are discussed.Originality/valueResearch on palm oil is essentially focused on chemistry, natural sciences or on its industrial uses: this study analyzes the consumer point of view by applying a different methodology compared to existing studies.
Rising to the challenge: adult student perceptions of institutional supports to increase access to careers in biotechnology
Authors: Portnoy Lindsay , Sadler Ash , Zulick Elizabeth 
Published: March 2023

PurposeAmidst continued calls for the democratization of access to higher education for historically underrepresented populations alongside the first global health crisis in a century lies the opportunity to address persistent societal needs: increasing access for underrepresented minority students to educational pathways that lead to careers in lucrative fields of science, technology, engineering and math (STEM).Design/methodology/approachStudent participants enrolled in the biotechnology pathway Associates, Bachelors and Masters programs share programmatic experience in an accelerated biotechnology program through a bi-annual survey grounded in the central tenets of social-cognitive career theory aimed at understanding requisite academic, social and financial support for student success.FindingsThe pathway program described in this paper emerged to address the need to support underrepresented students in degree attainment and taking on roles in the growing field of biotechnology through a novel, multi-degree, multi-institutional pathway to STEM degree attainment and career success.Social implicationsThis work has advanced understanding about how to effectively align higher education institutions with each other and with evolving STEM labor market demands while documenting the impact of essential academic, career and social supports recognized in the literature as high impact practices in broadening participation and increasing retention of underrepresented minority students in lucrative STEM careers.Originality/valuePathway programs which best support student success include robust mentoring, experiential learning and robust student scholarship support, part of the design of this unique pathway program. The authors share how this program utilizes high impact practices to provide low-income, underrepresented minority students with supportive, accelerated biotechnology degrees in preparation for success in the job market. What's more, of all our BS-level graduates thus far, 100% are employed and 93% within the biotechnology field. For many, the opportunity to raise their family out of poverty via a stable, high paying job is directly tied to their successes within this program.