bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of alpha-cyclodextrin on postprandial glucose excursions, a systematic meta analysis Alpha-cyclodextrin and Blood Glucose
Authors: Wittkowski Knut M. 
Published: September 2022

Alpha-cyclodextrin (αCD) is a natural bacterial product that is widely used as a food ingredient. In the EU, αCD is regulated as a “dietary fiber” with an authorized health claim “for contributing to the reduction of postprandial glycemic responses”. In the US, αCD is generally recognized as save (GRAS), but on April 25, 2022, the U.S. Food and Drug Administration (FDA) rejected the inclusion of αCD in the list of “dietary fibers” because “the strength of the scientific evidence does not support a finding of a beneficial effect of αCD on postprandial blood glucose …”.This meta-analysis reviews clinical trials conducted to test the effect of αCD on blood glucose and insulin levels during three hours after consumption of a meal comprising carbohydrates, fats, and proteins.Several issues related to the standardization of the outcomes, the choice of the statistical methods in the cross-over studies conducted, and the choice of methods for the aggregation of P-values are discussed. In conclusion, the EU decision is confirmed and extended. The administration of αCD not only reduces the postprandial glycemic responses, but the absence of an increase in insulin levels suggests that αCD acts independent of increasing insulin production and, thus, their beneficial effect is not affected by insulin resistance.
Integrated human-machine interface for closed-loop stimulation using implanted and wearable devices
Authors: Sladky Vladimir , Kremen Vaclav , McQuown Kevin , Mivalt Filip , Brinkmann Benjamin H. , Van Gompel Jamie , Miller Kai J. , Denison Timothy , Worrell Gregory A. 
Published: September 2022

AbstractRecent development in implantable devices for electrical brain stimulation includes sensing and embedded computing capabilities that enable adaptive stimulation strategies. Applications include stimulation triggered by pathologic brain activity and endogenous rhythms, such as circadian rhythms. We developed and tested a system that integrates an electrical brain stimulation & sensing implantable device with embedded computing and uses a distributed system with commercial electronics, smartphone and smartwatch for patient annotations, extensive behavioral testing, and adaptive stimulation in subjects in their natural environments. The system enables precise time synchronization of the external components with the brain stimulating device and is coupled with automated analysis of continuous streaming electrophysiology synchronized with patient reports. The system leverages a real-time bi-directional interface between devices and patients with epilepsy living in their natural environment.
Establishment and characterization of a tumoroid biobank derived from dog patients’ mammary tumors for translational research
Authors: Raffo-Romero Antonella , Aboulouard Soulaimane , Bouchaert Emmanuel , Rybicka Agata , Tierny Dominique , Hajjaji Nawale , Fournier Isabelle , Salzet Michel , Duhamel Marie 
Published: September 2022

AbstractBreast cancer is the most frequent cancer among women causing the greatest number of cancer-related deaths. Cancer heterogeneity is a main obstacle to therapies. Around 96% of the drugs fail from discovery to the clinical trial phase probably because of the current unreliable preclinical models. New models emerge such as companion dogs who develop spontaneous mammary tumors resembling human breast cancer in many clinical and molecular aspects. The present work aimed at developing a robust canine mammary tumor model in the form of tumoroids which recapitulate the tumor diversity and heterogeneity. We conducted a complete characterization of these canine mammary tumoroids through histologic, molecular and proteomic analysis, demonstrating their strong similarity to the primary tumor. We demonstrated that these tumoroids can be used as a drug screening model. In fact, we showed that Paclitaxel, a human chemotherapeutic, could killed canine tumoroids with the same efficacy as human tumoroids with 0.1 to 1 μM of drug needed to kill 50% of the cells. Due to easy tissue availability, canine tumoroids can be produced at larger scale and cryopreserved to constitute a biobank. We have demonstrated that cryopreserved tumoroids keep the same histologic and molecular features (ER, PR and HER2 expression) as fresh tumoroids. Two techniques of cryopreservation were compared demonstrating that tumoroids made from frozen tumor material allowed to maintain a higher molecular diversity. These findings revealed that canine mammary tumoroids can be easily generated at large scale and can represent a more reliable preclinical model to investigate tumorigenesis mechanisms and develop new treatments for both veterinary and human medicine.
Longitudinal characterization of circulating extracellular vesicles and small RNA during simian immunodeficiency virus infection and antiretroviral therapy
Authors: Huang Yiyao , Liao Zhaohao , Dang Phuong , Queen Suzanne , Abreu Celina Monteiro , Zheng Lei , Witwer Kenneth W. 
Published: September 2022

ABSTRACTObjectivesLatent infection by human immunodeficiency virus (HIV) hinders viral eradication despite effective antiretroviral treatment (ART), Amongst proposed contributors to viral latency are cellular small RNAs that have also been proposed to shuttle between cells in extracellular vesicles (EVs). Thus, we profiled EV small RNAs during different infection phases to understand the potential relationship between these EV-associated small RNAs and viral infection.DesignA well characterized simian immunodeficiency virus (SIV)/macaque model of HIV was used to profile EV-enriched blood plasma fractions harvested during pre-infection, acute infection, latent infection/ART treatment, and rebound after ART interruption.MethodsMeasurement of EV concentration, size distribution, and morphology was complemented with qPCR array for small RNA expression, followed by individual qPCR validations. Iodixanol density gradients were used to separate EV subtypes and virions.ResultsPlasma EV particle counts correlated with viral load and peaked during acute infection. However, SIV gag RNA detection showed that virions did not fully explain this peak. EV microRNAs miR-181a, miR-342-3p, and miR-29a decreased with SIV infection and remained downregulated in latency. Interestingly, small nuclear RNA U6 had a tight association with viral load peak.ConclusionsThis study is the first to monitor how EV concentration and EV small RNA expression change dynamically in acute viral infection, latency, and rebound in a carefully controlled animal model. These changes may also reveal regulatory roles in retroviral infection and latency.
Identifying medications underlying communication atypicalities in psychotic and affective disorders: A pharmacovigilance study within the FDA Adverse Event Reporting System
Authors: Fusaroli Michele , Simonsen Arndis , Borrie Stephanie A. , Low Daniel M. , Parola Alberto , Raschi Emanuel , Poluzzi Elisabetta , Fusaroli Riccardo 
Published: September 2022

AbstractPurposeCommunication atypicalities are considered promising markers of a broad range of clinical conditions. However, little is known about the mechanisms and confounders underlying them. Medications might have a crucial, relatively unknown role both as potential confounders and offering an insight on the mechanisms at work. The integration of regulatory documents with disproportionality analyses provides a more comprehensive picture to account for in future investigations of communication-related markers. The aim of the current study was to identify a list of drugs potentially associated with communicative atypicalities within psychotic and affective disorders.MethodWe developed a query using the Medical Dictionary for Regulatory Activities (MedDRA) to search for communicative atypicalities within the FDA Adverse Event Reporting System (FAERS, updated June 2021). A Bonferroni corrected disproportionality analysis (Reporting Odds Ratio) was separately performed on spontaneous reports involving psychotic, affective, and non-neuropsychiatric disorders, to account for the confounding role of different underlying conditions. Drug adverse event associations not already reported in the SIDER database of labeled adverse drug reactions (unexpected) were subjected to further robustness analyses to account for expected biases.ResultsA list of 291 expected and 91 unexpected potential confounding medications was identified, including drugs that may irritate (inhalants) or desiccate (anticholinergics) the larynx, impair speech motor control (antipsychotics), induce nodules (acitretin) or necrosis (VEGFR-inhibitors) on vocal cords, sedatives and stimulants, neurotoxic agents (antiinfectives), and agents acting on neurotransmitter pathways (dopamine agonists).ConclusionsWe provide a list of medications to account for in future studies of communication-related markers in affective and psychotic disorders. The current test case illustrates rigorous procedures for digital phenotyping, and the methodological tools implemented for large scale disproportionality analyses can be considered a roadmap for investigations of communication-related markers in other clinical populations.
A Multithreaded Model for Cancer Tissue Heterogeneity: An Application
Authors: Chaudhuri Anik , Choudhury Shabnam , Mohanty Anwoy Kumar , Satpathy Manoranjan , Shell M. , Doe J. 
Published: September 2022

AbstractStudying the heterogeneity in cancerous tissue is challenging in cancer research. It is vital to process the real-world data efficiently to understand the heterogeneous nature of cancer tissue. GPU compatible models, which can estimate the subpopulation of cancerous tissue, are fast if the size of input data, i.e., the number of qPCR (quantitative polymerase chain reaction) gene expression reading is extensive. In the real world, we rarely get that much data to reap the benefits of a GPU’s parallelism. Real experimental data from fibroblasts are much less, and models using those data on a GPU are slower than the CPU multithreaded application. This paper will show a method to run GPU-compatible models for cancer tissue heterogeneity on a multithreaded CPU. Further, we also show that the model running on a multithreaded CPU is faster than the model running on a GPU with real experimental data.
Base Editing for Reprogramming Cyanobacterium Synechococcus elongatus
Authors: Wang Shu-Yan , Li Xin , Wang Shu-Guang , Xia Peng-Fei 
Published: September 2022

AbstractGlobal climate change demands carbon-negative innovations to reduce the concentration of atmospheric carbon dioxide (CO2). Cyanobacteria can fix CO2 from the atmosphere and can be genetically reprogrammed for the production of biofuels, chemicals and food products, making an ideal microbial chassis for carbon-negative biotechnology. However, the progress seems to be slowed down due to the lagging-behind synthetic biology toolkits, especially the CRISPR-Cas-based genome-editing tools. As such, we developed a base-editing tool based on the CRISPR-Cas system and deamination for cyanobacterium Synechococcus elongatus. We achieved efficient and precise genome editing at a single-nucleotide resolution, and identified the pure population of edited cells at the first round of selection without extra segregation. By using the base-editing tool, we successfully manipulated the glycogen metabolic pathway via the introduction of premature STOP codons to inactivate the corresponding genes. We demonstrated multiplex base editing by editing two genes at once, obtaining a nearly two-fold increase in the glycogen content. We present here the first report of base editing in the phylum of cyanobacteria, and a paradigm for applying CRISPR-Cas systems in bacteria. We believe that this work will accelerate the synthetic biology of cyanobacteria and drive more innovations to alleviate global climate change.
Copy number variations shape the structural diversity of Arabidopsis metabolic gene clusters and are associated with the climatic gradient
Authors: Marszalek-Zenczak Malgorzata , Satyr Anastasiia , Wojciechowski Pawel , Zenczak Michal , Sobieszczanska Paula , Brzezinski Krzysztof , Iefimenko Tetiana , Figlerowicz Marek , Zmienko Agnieszka 
Published: September 2022

AbstractMetabolic gene clusters (MGCs) encode at least three different enzymes for a common biosynthetic pathway. Comparative genome analyses highlighted the role of duplications, deletions and rearrangements in MGC formation. We hypothesized that these mechanisms also contribute to MGC intraspecies diversity and play a role in adaptation. We assessed copy number variations (CNVs) of four Arabidopsis thaliana MGCs in a population of 1,152 accessions, with experimental and bioinformatic approaches. The MGC diversity was lowest in marneral gene cluster (one private deletion CNV) and highest in the arabidiol/baruol gene cluster where 811 accessions had gene gains or losses, however, there were no presence/absence variations of the entire clusters. We found that the compact version of thalianol gene cluster was predominant in A. thaliana and more conserved than the noncontiguogus version. In arabidiol/baruol cluster we found a large insertion in 35% of analyzed accessions, that contained duplications of the reference genes CYP705A2 and BARS1. The BARS1 paralog, which we named BARS2, encoded a novel oxidosqualene synthase. Unexpectedly, in accessions with the insertion, the arabidiol/baruol gene cluster was expressed not only in roots but also in leaves. Additionally, they presented different root growth dynamics and were associated with warmer climates compared to the reference-like accessions. We also found that paired genes encoding terpene synthases and cytochrome P450 oxidases had higher copy number variability compared to non-paired ones. Our study highlights the importance of intraspecies variation and nonreference genomes for dissecting secondary metabolite biosynthesis pathways and understanding their role in adaptation and evolution.
The injury-induced circular RNA circGLIS3 activates dermal fibroblasts to promote wound healing
Authors: Toma Maria A. , Wang Qizhang , Li Dongqing , Xiao Yunting , Niu Guanglin , Geara Jennifer , Vij Manika , Piipponen Minna , Liu Zhuang , Zhang Letian , Bian Xiaowei , Wang Aoxue , Sommar Pehr , Xu Landén Ning 
Published: September 2022

AbstractDelayed skin wound healing and excessive scarring are consequences of an impaired healing process and represent a major health and economic burden worldwide. Current intervention strategies lack efficacy and suffer from high recurrence rates necessitating the investigation into alternative treatment modalities like circular RNAs (circRNAs). By RNA sequencing, we profiled circRNA expression changes during human skin wound healing as well as in keratinocytes and fibroblasts isolated from donor-matched skin and acute wounds. CircGLIS3 was found to be transiently upregulated in the dermal fibroblasts upon skin injury, which was at least partially due to the activated IL-1 signaling. Similarly, overabundant circGLIS3 expression was detected in human keloid lesions compared to the surrounding healthy skin. We found that circGLIS3 resided mainly in the cytoplasm, where it interacted with and stabilized Procollagen C-endopeptidase enhancer 1 (PCPE-1) protein to enhance TGF-β signaling, fibroblast activation, and production of extracellular matrix – important biological processes required for wound repair. Accordingly, knockdown of circGLIS3 in humanex vivowounds potently reduced wound contraction and delayed re-epithelialization. Collectively, we have identified a previously uncharacterized circRNA regulator of human skin wound healing that may open an avenue for circRNA-based therapeutics for abnormal scarring or nonhealing wounds.One Sentence SummaryTransient increase of the circular RNA circGLIS3 promotes the wound fibroblast activation and extracellular matrix production to facilitate wound closure.
Dual control of lysogeny and phage defense by a phosphorylation-based toxin/antitoxin system
Authors: Guo Yunxue , Tang Kaihao , Sit Brandon , Gu Jiayu , Chen Ran , Lin Jianzhong , Lin Shituan , Liu Xiaoxiao , Wang Weiquan , Gao Xinyu , Nie Zhaolong , Liu Tianlang , Waldor Matthew K. , Wang Xiaoxue 
Published: September 2022

SUMMARYRegulatory systems that maintain prophage quiescence integrate phage and host gene expression with environmental conditions1,2. In the opportunistic bacterial pathogenPseudomonas aeruginosa, Pf filamentous bacteriophages play critical roles in biofilm formation and virulence3-5, but mechanisms governing Pf prophage activation in biofilms are largely unknown. Here, we report a new type of prophage regulatory module in a widely-distributedP. aeruginosalineage that not only controls virion production of co-resident Pf prophages, but also mediates defense against diverse lytic phages. By comparing two lineages of the prototypeP. aeruginosastrain PAO1 that harbor different Pf prophages, we identified a prophage-encoded kinase-kinase-phosphatase (KKP) system that controls Pf production in biofilms. KKP components exhibit dynamic stoichiometry, where high kinase levels in planktonic conditions maintain phosphorylation of the host H-NS protein MvaU, repressing prophage activation. During biofilm formation, phosphatase expression is heightened, leading to MvaU dephosphorylation and alleviating repression of prophage gene expression. KKP clusters are present in hundreds of diverse temperate prophages and other mobile elements across Gram-negative bacteria. Characterization of KKP modules from different species revealed that, in addition to regulating Pf phage lysogeny, KKP functions as a tripartite toxin-antitoxin system that mediates host defense from predatory lytic phages. KKP represents a new phosphorylation-based mechanism for prophage regulation and for phage defense. The dual function of this module raises the question of whether other newly described phage defense systems6-9also regulate intrinsic prophage biology in diverse hosts.
A translational repression reporter assay for the analysis of RNA-binding protein consensus sites
Authors: Nowacki Jessica , Malenica Mateo , Schmeing Stefan , Schiller Damian , Buchmuller Benjamin , ‘t Hart Peter 
Published: September 2022

ABSTRACTRNA-binding proteins are essential regulators of RNA processing and function. Translational repression assays can be used to study how they interact with specific RNA sequences by insertion of such a consensus sequence into the 5’ untranslated region of a reporter mRNA and measuring reporter protein translation. The straightforward set-up of these translational repression assays avoids the need for the isolation of the protein or the RNA providing speed, robustness, and a low-cost method. Here we report the optimization of the assay to function with linear RNA sequences instead of the previously reported hairpin type sequences to allow the study of a wider variety of RNA-binding proteins. Multiplication of a consensus sequence strongly improves the signal allowing analysis by both fluorescence intensity measurements and fluorescence activated cell sorting.
Scavenger receptor B1 facilitates the endocytosis of Escherichia coli via TLR4 signaling in mammary gland infection
Authors: Taban Qamar , Ahmad Syed Mudasir , Mumtaz Peerzada Tajamul , Bhat Basharat , Haq Ehtishamul , Magray Suhail , Saleem Sahar , Shabir Nadeem , Muhee Amatul , Kashoo Zahid Amin , Zargar Mahrukh Hameed , Malik Abrar A. , Ganai Nazir A. , Shah Riaz A. 
Published: September 2022

AbstractSCARB1 belongs to class B of Scavenger receptors (SRs) that are known to be involved in binding and endocytosis of various pathogens. SRs have emerging role in regulating innate immunity and host-pathogen interactions by acting in co-ordination with Toll-like receptors. Little is known about the function of SCARB1 in milk-derived mammary epithelial cells (MECs). This study reports the role of SCARB1 in infection and its potential association in TLR4 signaling on bacterial challenge in Goat mammary epithelial cells (GMECs). The novelty in the establishment of MEC culture lies in the method that aims to enhance the viability of the cells with intact characteristics upto a higher passage number. We represent MEC culture to be used as a potential infection model for deeper understanding of animal physiology especially around the mammary gland. On E.coli challenge the expression of SCARB1 was significant in induced GMECs at 6 h. Endoribonuclease-esiRNA based silencing of SCARB1 affects the expression of TLR4 and its pathways i.e. MyD88 and TRIF pathways on infection. Knockdown also affected the endocytosis of E.coli in GMECs demonstrating that E.coli uses SCARB1 function to gain entry in cells. Furthermore, we predict 3 unique protein structures of uncharacterized SCARB1 (Capra hircus) protein. Overall, we highlight SCARB1 as a main participant in host defence and its function in antibacterial advances to check mammary gland infections.
Transgressive and parental dominant gene expression and cytosine methylation during seed development inBrassica napushybrids
Authors: Orantes-Bonilla Mauricio , Wang Hao , Lee HueyTyng , Golicz Agnieszka A. , Hu Dandan , Li Wenwen , Zou Jun , Snowdon Rod J. 
Published: September 2022

AbstractThe enhanced performance of hybrids though heterosis remains a key aspect in plant breeding, however the underlying mechanisms are still not fully elucidated. To investigate the potential role of transcriptomic and epigenomic patterns in early expression of hybrid vigour, we investigated gene expression, small RNA abundance and genome-wide methylation in hybrids from two distantBrassica napusecotypes during seed and seedling developmental stages using next-generation sequencing technologies. A total of 71217, 773, 79518 and 31825 differentially expressed genes, microRNAs, small interfering RNAs and differentially methylated regions were identified, respectively. Approximately 70% of the differential expression and methylation patterns observed could be explained due to parental dominance levels. Via gene ontology enrichment and microRNA-target association analyses during seed development we found copies of reproductive, developmental and meiotic genes with transgressive and paternal dominance patterns. Interestingly, maternal dominance was more prominent in hypermethylated and downregulated features during seed formation. This contrasts to the general maternal gamete demethylation reported during gametogenesis in most plant species. Associations between methylation and gene expression allowed identification of putative epialleles with diverse pivotal biological functions during seed formation. Furthermore, most differentially methylated regions, differentially expressed siRNAs and transposable elements were found in regions flanking genes that had no differential expression. This suggests that differential expression and methylation of epigenomic features may help maintain expression of pivotal genes in a hybrid context. Differential expression and methylation patterns during seed formation in an F1 hybrid provide novel insight into genes and mechanisms with a potential role in early heterosis.Key messageTranscriptomic and epigenomic profiling of gene expression and small RNAs during seed and seedling development reveals expression and methylation dominance levels with implications on early stage heterosis in oilseed rape.