bluuebunny/crossref_metadata_2025_split huggingface dataset:
AtERF60,negatively regulatesABR1to modulate basal resistance response in Arabidopsis
Authors: Joshi Ashutosh , Phukan Ujjal J , Singh Neeti , Jeena Gajendra Singh , Kumar Sunil , Pandey Durgesh Kumar , Pandey Alok , Tripathi Vineeta , Shukla Rakesh Kumar 
Published: December 2021

AbstractAPETALA2 (AP2)/ERF family transcription factors (TFs) contribute an important function against various external cues. Our study reportsAtERF60, an AP2/ERF TF, which plays a key role in regulating theABR1gene, leading to an altered basal resistance response in Arabidopsis.AtERF60is induced in response to drought, salt, abscisic acid (ABA), salicylic acid (SA), and bacterial pathogenPstDC3000 infection.AtERF60interacts with DEHYDRATION RESPONSE ELEMENTS and GCC box, indicating its ability to regulate multiple responses. The overexpressing lines ofAtERF60demonstrated increased resistance toPstDC3000 infection, whereaserf60mutant lines showed increased susceptibility. Complementation of theerf60mutant background exhibits no significant difference towardsPstDC3000 infection compared with the WT Col-0. Microarray and qRT-PCR analysis of overexpression and mutant lines indicated thatAtERF60regulates stress-inducible genes. The induction of these differentially expressed transcripts was significantly increased inerf60mutant lines, whereas it was reversed in wild-type lines whenAtERF60was complemented.ABR1was one of the differentially expressed transcripts, and we discovered thatAtERF60interacts with the DREcis-elements in theABR1promoter. Further, qRT-PCR expression analysis after infection withPstDC3000 inAtERF60-OX,erf60and its complementation background suggest that the mutation inAtERF60upregulatesABR1activity, leading to the enhanced susceptibility towardsPstDC3000. Conversely,AtERF60overexpression suppressesABR1activity, strengthening the basal resistance responses of Arabidopsis.
Biomechanical and biochemical assessment of YB-1 expression in melanoma cells
Authors: Cykowska Anna , Hofmann Ulf Krister , Tiwari Aadhya , Kosnopfel Corinna , Riester Rosa , Danalache Marina 
Published: December 2021

AbstractMalignant melanoma is the most lethal form of skin cancer; its incidence has increased over the last five decades. Y-box binding protein 1 (YB-1) plays a prominent role in mediating metastatic behavior by promoting epithelial-to-mesenchymal transition (EMT) processes. Migratory melanoma cells exhibit two major phenotypes: elongated mesenchymal or rounded amoeboid. The actomyosin cytoskeleton is key in both phenotypes, but intermediate filaments also undergo a significant rearrangement process, switching from cytokeratin-rich to vimentin and nestin-rich network. In this study, we aimed to investigate to what extent YB-1 impacts the biomechanical (cell stiffness) and biochemical aspects of melanoma cells and their cytoskeleton. To this end, we subjected A375 YB-1 knock-out and parental cells to atomic force microscopy investigations (stiffness determination), immunolabelling, and proteome analysis. We found that YB-1 expressing cells were significantly stiffer compared to the corresponding YB-1 knock-out cell line. Proteomic analysis revealed that expression of YB-1 results in a strong co-expression of nestin, vimentin, fascin-1, and septin-9. In the YB-1 knock-out nestin was completely depleted, but zyxin was strongly upregulated. Collectively, our results showed that YB-1 knock-out acquires some characteristics of mesenchymal phenotype but lacks important markers of malignancy and invasiveness such as nestin or vimentin. We posit that there is an association of YB-1 expression with an amoeboid phenotype, which would explain the increased migratory capacity.
Subcellular dynamics and functional activity of the cleaved Na+channel β1 subunit intracellular domain
Authors: Haworth Alexander S. , Hodges Samantha L. , Capatina Alina L. , Isom Lori L. , Baumann Christoph G. , Brackenbury William J. 
Published: December 2021

AbstractThe voltage-gated Na+channel β1 subunit, encoded bySCN1B, regulates cell surface expression and gating of α subunits, and participates in cell adhesion. β1 is cleaved by α/β and γ-secretases, releasing an extracellular domain and intracellular domain (ICD) respectively. AbnormalSCN1Bexpression/function is linked to pathologies including epilepsy, cardiac arrhythmia, and cancer. In this study, we sought to determine the effect of secretase cleavage on β1 function in breast cancer cells. Using a series of GFP-tagged β1 constructs, we show that β1-GFP is mainly retained intracellularly, particularly in the endoplasmic reticulum and endolysosomal pathway, and accumulates in the nucleus. Reduction in endosomal β1-GFP levels occurred following γ-secretase inhibition, implicating endosomes, and/or the preceding plasma membrane, as important sites for secretase processing. Using live-cell imaging, we report β1ICD-GFP accumulation in the nucleus. Furthermore, β1-GFP and β1ICD-GFP both increased Na+current, whereas β1STOP-GFP, which lacks the ICD, did not, thus highlighting that the β1-ICD was necessary and sufficient to increase Na+current measured at the plasma membrane. Importantly, although the endogenous Na+current expressed in MDA-MB-231 cells is TTX-resistant (carried by Nav1.5), the Na+current increased by β1-GFP or β1ICD-GFP was TTX-sensitive. In addition, β1-GFP increased mRNA levels of the TTX-sensitive α subunitsSCN1A/Nav1.1 andSCN9A/Nav1.7. Taken together, this work suggests that the β1-ICD is a critical regulator of α subunit function in cancer cells. Our data further highlight that γ-secretase may play a key role in regulating β1 function in breast cancer.
Biogenesis of mature piRNAs in Caenorhabditis elegans is dependent on orchestration between multiple ribonucleases and PRG-1
Authors: Samajdar Aniruddha , Chowdhury Tamoghna , Chatterjee Saibal 
Published: December 2021

AbstractPiwi-interacting RNAs (piRNAs) are an animal-specific class of germline-enriched small non-coding RNAs that shape transcriptome, as well as ensure genomic integrity and fertility by regulating transposons and other selfish genetic elements. In Caenorhabditis elegans mature piRNAs are 21-nucleotides long, begin with a monophosphorylated uridine, and they associate with PRG-1 to form piRISCs that scan the transcriptome for ‘non-self’ sequences. However, these piRNAs are born as longer 5’-capped transcripts, where PARN-1, a 3’-5’ exoribonuclease, contributes to the formation of the mature 3’-end. But, till date, the 5’-processing events remain elusive. We demonstrate that the recently identified endoribonuclease activity of XRN-2 is involved in the processing of the 5’-end of precursor piRNAs in worms. Depletion of XRN-2 results in reduced mature piRNA levels, with concomitant increase in levels of the 5’-capped precursors. We also reveal that the piRNAs born as longer precursor molecules (≥60 nt), prior to 5’-end processing, undergo ENDU-1-mediated endoribonucleolytic processing of their 3’-ends. Our in vitro RNA-protein interaction studies unravel the mechanistic interactions between XRN-2 and PRG-1 towards the formation of mature 5’-ends of piRNAs. In vivo experiments employing prg-1 mutant worms indicate that XRN-2 has the potential to perform clearance of precursors that are not bound and protected by PRG-1. Finally, we also demonstrate that XRN-2 is not only important for the generation of mature piRNAs and piRNA-dependent endo-siRNAs, but through yet unknown pathways, it also affects piRNA-independent endo-siRNAs that shape transcriptome, as well as contribute to genomic integrity via regulation of transposable elements.
Transcription Profile And Pathway Analysis Of The Endocannabinoid Receptor Inverse Agonist AM630 In The Core And Infiltrative Boundary Of Human Glioblastoma Cells
Authors: Williams Gareth , Chambers David , Rahman Ruman , Molina-Holgado Francisco 
Published: December 2021

AbstractBackgroundWe have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumor cell proliferation. To uncover the mechanism behind the anti-tumour effects we have performed a transcriptional analysis of AM630 activity both in the tumour core cells (U87) and the invasive margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease.ResultsThe core and invasive margin cells exhibited markedly different gene expression profiles and only the core cells had high expression of a potential AM630 target, the CB1 receptor. Both cell types had moderate expression of the HTR2B serotonin receptor, a reported AM630 target. We found that the AM630 driven transcriptional response was substantially higher in the central cells than in the invasive margin cells, with the former driving the up regulation of immune response and the down regulation of cell cycle and metastatic pathways and correlating with transcriptional responses driven by established anti-neoplastics as well as serotonin receptor antagonists.ConclusionOur results highlight the different responsiveness of the core and invasive margin cells. Taken together, whilst our findings identify AM630 as an anti-neoplastic drug, showing a high correlation with known anti-proliferative drugs, we find distinct drug sensitivies of the infiltrative margin relative to contrast-enhanced core regions of GBM upon which failed molecular targeted therapies to date have been predicated.
Shrimp draft genome contains independent clusters of ancient and current endogenous viral elements (EVE) of the parvovirus IHHNV
Authors: Taengchaiyaphum Suparat , Wongkhaluang Prapatsorn , Flegel Timothy W. , Sritunyalucksana Kallaya 
Published: December 2021

ABSTRACTBackgroundShrimp have the ability to accommodate viruses in long term, persistent infections without signs of disease. Endogenous viral elements (EVE) play a role in this process probably via production of negative-sense Piwi-interacting RNA (piRNA)-like fragments. These bind with Piwi proteins to dampen viral replication via the RNA interference (RNAi) pathway. We searched a draft genome of the giant tiger shrimp (Penaeus monodon)(GenBank record JABERT000000000) for the presence of EVE related to a shrimp parvovirus originally named infectious hypodermal and hematopoietic necrosis virus (IHHNV).ResultsThe shrimp draft genome contained 3 piRNA-like gene clusters containing scrambled IHHNV EVE. Two clusters were located distant from one another in linkage group 35 (LG35). Both LG35 clusters contained multiple DNA fragments with high homology (99%) to GenBank records DQ228358 and EU675312 that were both called “ non-infectious IHHNV Type A” (IHHNV-A) when originally discovered. However, our results and those from a recent Australian P. monodon genome assembly indicate that the relevant GenBank records for IHHNV-A are sequence-assembly artifacts derived from scrambled and fragmental IHHNV-EVE. Although the EVE in the two LG35 clusters showed high homology only to IHHNV-A, the clusters were separate and distinct with respect to the arrangement (i.e., order and reading direction) and proportional content of the IHHNV-A GenBank records. We conjecture that these 2 clusters may constitute independent allele-like clusters on a pair of homologous chromosomes. The third EVE cluster was found in linkage group 7 (LG7). It contained EVE with high homology (99%) only to GenBank record AF218266 with the potential to protect shrimp against infectious IHHNV.ConclusionsOur results suggested the possibility of viral-type specificity in EVE clusters. Specificity is important because whole EVE clusters for one viral type would be transmitted to offspring as collective hereditary units. This would be advantageous if one or more of the EVE within the cluster were protective against disease caused by the cognate virus. It would also facilitate gene editing for removal of non-protective EVE clusters or for transfer of protective EVE clusters to genetically improve existing shrimp breeding stocks that might lack them.
Regulation of Kidney Mitochondrial Function by Caloric Restriction
Authors: Serna Julian D. C. , Amaral Andressa G. , Caldeira da Silva Camille C. , Munhoz Ana C. , Menezes-Filho Sergio L. , Kowaltowski Alicia J. 
Published: December 2021

ABSTRACTCaloric restriction (CR) prevents obesity, promotes healthy aging, and increases resilience against several pathological stimuli in laboratory rodents. At the mitochondrial level, protection promoted by CR in the brain and liver is related to higher calcium uptake rates and capacities, avoiding Ca2+-induced mitochondrial permeability transition. Dietary restriction has also been shown to increase kidney resistance against damaging stimuli such as ischemia/reperfusion, but if these effects are related to similar mitochondrial adaptations had not yet been uncovered. Here, we characterized changes in mitochondrial function in response to six months of CR in rats, measuring bioenergetic parameters, redox balance and calcium homeostasis. CR promoted an increase in mitochondrial oxygen consumption rates under non-phosphorylating and uncoupled conditions. While CR prevents mitochondrial reactive oxygen species production in many tissues, in kidney we found that mitochondrial H2O2 release was enhanced, although levels of carbonylated proteins and methionine sulfoxide were unchanged. Surprisingly, and opposite to the effects observed in brain and liver, mitochondria from CR animals are more prone to Ca2+-induced mitochondrial permeability transition. CR mitochondria also displayed higher calcium uptake rates, which were not accompanied by changes in calcium efflux rates, nor related to altered inner mitochondrial membrane potentials or the amounts of the mitochondrial calcium uniporter (MCU). Instead, increased mitochondrial calcium uptake rates in CR kidneys correlate with a loss of MICU2, an MCU modulator. Interestingly, MICU2 is also modulated by CR in liver, suggesting it has a broader diet-sensitive regulatory role controlling mitochondrial calcium homeostasis. Together, our results highlight the organ-specific bioenergetic, redox, and ionic transport effects of CR. Specifically, we describe the regulation of the expression of MICU2 and its effects on mitochondrial calcium transport as a novel and interesting aspect of the metabolic responses to dietary interventions.
Investigating the in vivo biodistribution of extracellular vesicles isolated from various human cell sources using positron emission tomography
Authors: Rosenkrans Zachary T. , Thickens Anna S. , Kink John A. , Aluicio-Sarduy Eduardo , Engle Jonathan W. , Hematti Peiman , Hernandez Reinier 
Published: December 2021

AbstractNoninvasive imaging is a powerful tool for understanding the in vivo behavior of drug delivery systems and successfully translating promising platforms into the clinic. Extracellular vesicles (EVs), nano-sized vesicles with a lipid bilayer produced by nearly all cell types, are emerging platforms for drug delivery. To date, the biodistribution of EVs has been insufficiently investigated, particularly using nuclear imaging-based modalities such as positron emission tomography (PET). Herein, we developed positron-emitting radiotracers to investigate the biodistribution of EVs isolated from various human cell sources using PET imaging. Chelator conjugation did not impact EVs size and subsequent radiolabeling was found to be highly efficient and stable with Zr-89 (t1/2 = 78.4 h). In vivo tracking of EVs isolated from bone marrow-derived mesenchymal stromal cells (BMSCs EVs), primary human macrophages (Mϕ EVs), and a melanoma cell line (A375 EVs) were performed in immunocompetent ICR mice. Imaging studies revealed excellent in vivo circulation for all EVs, with a half-life of approximately 12 h. Significantly higher liver uptake was observed for Mϕ EVs, evidencing the tissue tropism of EV and highlighting the importance of carefully choosing EVs cell sources for drug delivery applications. Conversely, the liver, spleen, and lung uptake of the BMSC EVs and A375 EVs was relatively low. We also investigated the impact of immunodeficiency on the biodistribution of BMSC EVs using NSG mice. The spleen uptake drastically increased in NSG mice, which could confound results of therapeutic studies employing this mouse models. Lastly, PET imaging studies in a melanoma tumor model demonstrated efficient tumor uptake of BMSC EVs following intravenous injection. Overall, these imaging studies evidenced the potential of EVs as carriers to treat a variety of diseases, such as cancer or in regenerative medicine applications, and the necessity to understand EVs tropism to optimize their therapeutic deployment.
Subgenomic SARS-CoV-2 replicon and reporter replicon cell lines enable ultrahigh throughput antiviral screening and mechanistic studies with antivirals, viral mutations or host factors that affect COVID-19 replication
Authors: Lan Shuiyun , Tedbury Philip R. , Ong Yee Tsuey , Shah Raven , Slack Ryan L. , Cilento Maria E. , Zhang Huanchun , Du Haijuan , Lulkin Nicole , Le Uyen , Kirby Karen A. , Melcak Ivo , Cantara William A. , Boggs Emerson A. , Sarafianos Stefan G. 
Published: December 2021

ABSTRACTReplicon-based technologies were used to develop reagents and assays for advanced drug discovery efforts against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and for examining all facets of the SARS-CoV-2 replication cycle at reduced biocontainment level. Specifically: a) 21 replicons were cloned in bacterial artificial chromosomes (BACs) and delivered as transfectable plasmid DNA or transcribed RNA in various cell types. Replicons carrying mutations that affect the activity or antiviral susceptibility of SARS-CoV-2 enzymes were used to establish utility for mechanistic studies while reducing the community risks associated with gain-of-function studies in fully infectious virus. b) A BHK-21 stable cell line harboring SARS-CoV-2 replicon was generated and characterized in robust high/ultra-high throughput assays of antiviral efficacy with orthogonal SARS-CoV-2 replication reporter genes (Nano luciferase and enhanced green fluorescent protein-eGFP); the estimated antiviral potencies in the fully infectious SARS-CoV-2 system and in the transient or stable replicon systems were similar. HEK293 and Calu1 stable cell lines expressing SARS-CoV-2 replicon have also been prepared. Finally, c) we generated trans-encapsidated replicons by co-expression with SARS-CoV-2 structural proteins, thus producing single-round infectious SARS-CoV-2 virus-like particles that are able to transduce susceptible cell types and have expanded utility to enable study of virion assembly and entry into target cells. Hence, these SARS-CoV-2 replicon-based reagents include a novel approach to replicon-harboring cell line generation and are valuable tools that can be used at lower biosafety level (BSL2) for drug discovery efforts, characterization of SARS-CoV-2 and variant evolution in the COVID-19 pandemic, mechanisms of inhibition and resistance, and studies on the role of SARS-CoV-2 genes and host dependency factors.
Research on robust adaptive sliding film fault-tolerant control under nonlinear distortion of signal transmission in amorphous flat air-to-ground wireless ad-hoc network system
Authors: Wang Zhifang , Yu Jianguo , Lin Shangjing 
Published: December 2021

Purpose
To solve the above problems and ensure the stability of the ad hoc network node topology in the process of wireless signal transmission, this paper aims to design a robust adaptive sliding film fault-tolerant controller under the nonlinear distortion of signal transmission in an amorphous flat air-to-ground wireless ad hoc network system.

Design/methodology/approach
This paper designs a robust adaptive sliding film fault-tolerant controller under the nonlinear distortion of signal transmission in an amorphous flat air-to-ground wireless ad hoc network system.

Findings
The simulation results show that the amorphous flat wireless self-organizing network system has good nonlinear distortion fault-tolerant correction ability under the feedback control of the designed controller, and the system has the asymptotically stable convergence ability; the test results show: the node topology of the self-organizing network structural stability is significantly improved, which provides a foundation for the subsequent realization of long-distance transmission of ad hoc network nodes.

Research limitations/implications
Because of the chosen research approach, the research results may lack generalizability. Therefore, researchers are encouraged to test the proposed propositions further.

Originality/value
The controller can extract the fault information caused by nonlinear distortion in the wireless signal transmission process, and at the same time, its feedback matrix K can gradually converge the generated wireless signal error to zero, to realize the stable transmission of the wireless signal.
Conformal transformation of Douglas space of second kind with special (α, β)-metric
Authors: Ranjan Rishabh , Pandey P.N. , Paul Ajit 
Published: December 2021

PurposeIn this paper, the authors prove that the Douglas space of second kind with a generalised form of special (α, β)-metric F, is conformally invariant.Design/methodology/approachFor, the authors have used the notion of conformal transformation and Douglas space.FindingsThe authors found some results to show that the Douglas space of second kind with certain (α, β)-metrics such as Randers metric, first approximate Matsumoto metric along with some special (α, β)-metrics, is invariant under a conformal change.Originality/valueThe authors introduced Douglas space of second kind and established conditions under which it can be transformed to a Douglas space of second kind.
RE-engineered factory acceptance testing under the new normal
Authors: Peiris Sanduni , De Silva Nayanthara 
Published: December 2021

PurposeFactory acceptance testing (FAT) in the construction industry has been severely hampered due to restrictions in cross-border travel resulting from the COVID-19 pandemic. Consequently, virtual FAT (vFAT) became a popular substitute for physical FAT. However, the credibility of vFAT is being questioned because it was adopted without much scrutiny. Hence, this study is aimed at investigating vFATs and re-engineering the FAT process to suit an effective vFAT environment.Design/methodology/approachA comprehensive literature search on FAT procedures was followed by two stages of expert interviews with eight leading subject experts and a case study. The findings were analysed using code-based content analysis on NVivo software.FindingsStrengths of vFATs include “reduction in cost and time consumed”, “flexibility for more participants” and “faster orders”. Most emphasized weaknesses include “lack of reliability” and “lack of technology transfer”. vFAT has mostly increased test reliability by “improving accessibility” and has decreased reliability by “restricting physical touch and feel observation of the equipment”. A four-step vFAT process was developed with a noteworthy additional step called “Pre-FAT Meeting”.Research limitations/implicationsThe scope of this study is limited to the Sri Lankan construction industry. Expansion of the geographical area of focus is recommended for future studies.Originality/valueThe findings of this study unveil a vFAT process, which is timely and beneficial for construction practitioners to optimize and enhance the effectiveness of vFATs which are currently conducted in a disarranged manner.