bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating different pattern of immunoregulation in BALB/c and C57BL/6 mice and their F1 progeny
Authors: Hartmann Wiebke , Blankenhaus Birte , Brunn Marie-Luise , Meiners Jana , Breloer Minka 
Published: January 2021

AbstractHelminths are large multicellular parasites that infect one quarter of the human population. To prolong their survival, helminths suppress the immune responses of their hosts. Strongyloides ratti delays its expulsion from the gut by induction of regulatory circuits in a mouse strain-specific manner: depletion of Foxp3+ regulatory T cells (Treg) improves the anti-S. ratti immunity in BALB/c but not in C57BL/6 mice. In the current study we compare the hierarchy of immunoregulatory pathways in BALB/c, C57BL/6 mice and their F1 progeny (BALB/c × C57BL/6). Using multicolor flow cytometry, we show that S. ratti induces a distinct pattern of inhibitory checkpoint receptors by Foxp3+ Treg and Foxp3− T cells. Intensity of expression was highest in C57BL/6 and lowest in BALB/c mice, while the F1 cross had an intermediate phenotype or resembled BALB/c mice. Treg subsets expanded during infection in all three mouse strains. Similar to BALB/c mice, depletion of Treg reduced intestinal parasite burden and increased mucosal mast cell activation in S. ratti-infected F1 mice. Our data indicate that Treg dominate the regulation of immune responses in BALB/c and F1 mice, while multiple regulatory layers exist in C57BL/6 mice that may compensate for the absence of Treg.
Connectivity-informed drainage network generation using deep convolution generative adversarial networks
Authors: Kim Sung Eun , Seo Yongwon , Hwang Junshik , Yoon Hongkyu , Lee Jonghyun 
Published: January 2021

AbstractStochastic network modeling is often limited by high computational costs to generate a large number of networks enough for meaningful statistical evaluation. In this study, Deep Convolutional Generative Adversarial Networks (DCGANs) were applied to quickly reproduce drainage networks from the already generated network samples without repetitive long modeling of the stochastic network model, Gibb’s model. In particular, we developed a novel connectivity-informed method that converts the drainage network images to the directional information of flow on each node of the drainage network, and then transforms it into multiple binary layers where the connectivity constraints between nodes in the drainage network are stored. DCGANs trained with three different types of training samples were compared; (1) original drainage network images, (2) their corresponding directional information only, and (3) the connectivity-informed directional information. A comparison of generated images demonstrated that the novel connectivity-informed method outperformed the other two methods by training DCGANs more effectively and better reproducing accurate drainage networks due to its compact representation of the network complexity and connectivity. This work highlights that DCGANs can be applicable for high contrast images common in earth and material sciences where the network, fractures, and other high contrast features are important.
SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
Authors: Lanjanian Hossein , Moazzam-Jazi Maryam , Hedayati Mehdi , Akbarzadeh Mahdi , Guity Kamran , Sedaghati-khayat Bahareh , Azizi Fereidoun , Daneshpour Maryam S. 
Published: January 2021

AbstractThe genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.
Striped bass (Morone saxatilis) migration timing driven by estuary outflow and sea surface temperature in the San Francisco Bay-Delta, California
Authors: Goertler Pascale , Mahardja Brian , Sommer Ted 
Published: January 2021

AbstractThe influence of climate on the timing of large-scale animal migrations is a major ecological and resource management concern. Anadromous fish migrations can have broad scale impacts on human communities and marine, aquatic and terrestrial food webs. However, isolating the effects of climate change on the timing of life stage transitions for anadromous fish species is challenging. Striped bass (Morone saxatilis) exhibit striking variation in migration patterns within their natural range, including migratory behaviors that change with latitude, and climate-induced temperature changes are predicted to drive future habitat and distribution changes. Here we explore the linkages between migration and multiple components of coastal and inland aquatic ecosystems impacted by climate change. By leveraging environmental and fisheries monitoring which began in 1969, we describe the upstream migration timing of non-native adult Striped bass influenced by estuary outflow and sea surface temperature in the San Francisco Bay-Delta, California. Striped bass migrated later in years when Delta outflow was greater and sea surface temperature was cooler. It is likely that temperature thresholds in the ocean during the springtime provide a cue for Striped bass to initiate migration, but sea surface temperature may also represent composite climatic trends influencing Striped bass. Further, the observed variation in migration timing of adult Striped bass has implications for predation risk on the seaward-migration of juvenile Chinook salmon.
Regulation of mitochondrial dynamics in 2-methoxyestradiol-mediated osteosarcoma cell death
Authors: Gorska-Ponikowska Magdalena , Bastian Paulina , Zauszkiewicz-Pawlak Agata , Ploska Agata , Zubrzycki Adrian , Kuban-Jankowska Alicja , Nussberger Stephan , Kalinowski Leszek , Kmiec Zbigniew 
Published: January 2021

AbstractOsteosarcoma (OS) is one of the most malignant tumors of childhood and adolescence. Research on mitochondrial dynamics (fusion/fission) and biogenesis has received much attention in last few years, as they are crucial for death of cancer cells. Specifically, it was shown that increased expression of the cytoplasmic dynamin-related protein 1 (Drp1) triggers mitochondrial fission (division), which activates BAX and downstream intrinsic apoptosis, effectively inhibiting OS growth. In the presented study, human OS cells (metastatic 143B OS cell line) were incubated with 2-methoxyestradiol (2-ME) at both physiologically and pharmacologically relevant concentrations. Cell viability was determined by the MTT assay. Confocal microscopy and western blot methods were applied to examine changes in Drp1 and BAX protein levels. Mitochondrial Division Inhibitor 1, MDIVI-1, was used in the study to further examine the role of Drp1 in 2-ME-mediated mechanism of action. To determine quantitative and qualitative changes in mitochondria, electron microscopy was used. 2-ME at all used concentrations increased mitochondrial fission and induced autophagy in OS cells. At the concentration of 1 µM 2-ME increased the area density of mitochondria in OS cells. Subsequent, upregulated expression of Drp1 and BAX proteins by 2-ME strongly suggests the activation of the intrinsic apoptosis pathway. We further observed 2-ME-mediated regulation of glycolytic state of OS cells. Therefore, we suggest that changes of mitochondrial dynamics may represent a novel mechanism of anticancer action of 2-ME. This finding may open new approaches to improve the efficacy of chemotherapy in the treatment of OS, however, it has to be confirmed by in vivo studies.
A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
Authors: Duran-Trio Lara , Fernandes-Pires Gabriella , Simicic Dunja , Grosse Jocelyn , Roux-Petronelli Clothilde , Bruce Stephen J. , Binz Pierre-Alain , Sandi Carmen , Cudalbu Cristina , Braissant Olivier 
Published: January 2021

AbstractCreatine is an organic compound used as fast phosphate energy buffer to recycle ATP, important in tissues with high energy demand such as muscle or brain. Creatine is taken from the diet or endogenously synthetized by the enzymes AGAT and GAMT, and specifically taken up by the transporter SLC6A8. Deficit in the endogenous synthesis or in the transport leads to Cerebral Creatine Deficiency Syndromes (CCDS). CCDS are characterized by brain creatine deficiency, intellectual disability with severe speech delay, behavioral troubles such as attention deficits and/or autistic features, and epilepsy. Among CCDS, the X-linked creatine transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different mouse models of CTD were generated by doing long deletions in the Slc6a8 gene showing reduced brain creatine and cognitive deficiencies or impaired motor function. We present a new knock-in (KI) rat model of CTD holding an identical point mutation found in patients with reported lack of transporter activity. KI males showed brain creatine deficiency, increased urinary creatine/creatinine ratio, cognitive deficits and autistic-like traits. The Slc6a8Y389C KI rat fairly enriches the spectrum of CTD models and provides new data about the pathology, being the first animal model of CTD carrying a point mutation.
High-speed and high-precision PbSe/PbI2 solution process mid-infrared camera
Authors: Dortaj Hannaneh , Dolatyari Mahboubeh , Zarghami Armin , Alidoust Farid , Rostami Ali , Matloub Samiye , Yadipour Reza 
Published: January 2021

AbstractInfrared (IR) cameras based on semiconductors grown by epitaxial methods face two main challenges, which are cost and operating at room temperature. The alternative new technologies which can tackle these two difficulties develop new and facile material and methods. Moreover, the implementation of high speed camera, which makes high resolution images with normal methods, is very expensive. In this paper, a new nanostructure based on a cost-effective solution processed technology for the implementation of the high-speed mid-infrared light camera at room temperature is proposed. To this end, the chemically synthesized PbSe–PbI2 core–shell Quantum Dots (QDs) are used. In this work, a camera including 10 × 10 pixels is fabricated and synthesized QDs spin-coated on interdigitated contact (IDC) and then the fabricated system passivated by epoxy resin. Finally, using an electronic reading circuit, all pixels are converted to an image on the monitor. To model the fabricated camera, we solved Schrodinger–Poisson equations self consistently. Then output current from each pixel is modeled based on semiconductor physics and dark and photocurrent, as well as Responsivity and Detectivity, are calculated. Then the fabricated device is examined, and dark and photocurrents are measured and compared to the theoretical results. The obtained results indicate that the obtained theoretical and measured experimental results are in good agreement together. The fabricated detector is high speed with a rise time of 100 ns. With this speed, we can get 10 million frames per second; this means we can get very high-resolution images. The speed of operation is examined experimentally using a chopper that modulates input light with 50, 100, 250, and 500 Hz. It is shown that the fabricated device operates well in these situations, and it is not limited by the speed of detector. Finally, for the demonstration of the proposed device operation, some pictures and movies taken by the camera are attached and inserted in the paper.
WASP: a software package for correctly characterizing the topological development of ribbon structures
Authors: Sierzega Zachary , Wereszczynski Jeff , Prior Chris 
Published: January 2021

AbstractWe introduce the Writhe Application Software Package (WASP) which can be used to characterisze the topology of ribbon structures, the underlying mathematical model of DNA, Biopolymers, superfluid vorticies, elastic ropes and magnetic flux ropes. This characterization is achieved by the general twist–writhe decomposition of both open and closed ribbons, in particular through a quantity termed the polar writhe. We demonstrate how this decomposition is far more natural and straightforward than artificial closure methods commonly utilized in DNA modelling. In particular, we demonstrate how the decomposition of the polar writhe into local and non-local components distinctly characterizes the local helical structure and knotting/linking of the ribbon. This decomposition provides additional information not given by alternative approaches. As example applications, the WASP routines are used to characterise the evolving topology (writhe) of DNA minicircle and open ended plectoneme formation magnetic/optical tweezer simulations, and it is shown that the decomponsition into local and non-local components is particularly important for the detection of plectonemes. Finally it is demonstrated that a number of well known alternative writhe expressions are actually simplifications of the polar writhe measure.
The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent
Authors: Cheng Yinwen , Borcherding Nicholas , Ogunsakin Ayomide , Lemke-Miltner Caitlin D. , Gibson-Corley Katherine N. , Rajan Anand , Choi Allen B. , Wongpattaraworakul Wattawan , Chan Carlos H. F. , Salem Aliasger K. , Weiner George J. , Simons Andrean L. 
Published: January 2021

AbstractThe Toll-like receptor 8 (TLR8) agonist VTX-2337 (motolimod) is an anti-cancer immunotherapeutic agent that is believed to augment natural killer (NK) and dendritic cell (DC) activity. The goal of this work is to examine the role of TLR8 expression/activity in head and neck squamous cell carcinoma (HNSCC) to facilitate the prediction of responders to VTX-2337-based therapy. The prognostic role of TLR8 expression in HNSCC patients was assessed by TCGA and tissue microarray analyses. The anti-tumor effect of VTX-2337 was determined in SCCVII/C3H, mEERL/C57Bl/6 and TUBO-human EGFR/BALB/c syngeneic mouse models. The effect of combined VTX-2337 and cetuximab treatment on tumor growth, survival and immune cell recruitment was assessed. TLR8 expression was associated with CD8+ T cell infiltration and favorable survival outcomes. VTX-2337 delayed tumor growth in all 3 syngeneic mouse models and significantly increased the survival of cetuximab-treated mice. The anti-tumor effects of VTX-2337+ cetuximab were accompanied by increased splenic lymphoid DCs and IFNγ+ CD4+ and tumor-specific CD8+ T cells. Depletion of CD4+ T cells, CD8+ T cells and NK cells were all able to abolish the anti-tumor effect of VTX-2337+ cetuximab. Altogether, VTX-2337 remains promising as an adjuvant for cetuximab-based therapy however patients with high TLR8 expression may be more likely to derive benefit from this drug combination compared to patients with low TLR8 expression.
The dual effect of social ties on COVID-19 spread in Japan
Authors: Fraser Timothy , Aldrich Daniel P. 
Published: January 2021

AbstractWe investigate why some communities experience worse COVID-19 outcomes than others. Past studies have linked the resilience of communities against crisis to social vulnerability and the capacity of local governments to provide public goods and services like health care. Disaster studies, which frequently examine the effect of social ties and mobility, may better help illuminate the current spread of COVID-19. We analyze Japan’s 47 prefectures from February 12 to August 31 using 62,722 individual confirmed cases of COVID-19, paired with daily tallies of aggregate Facebook user movement among neighborhoods. Controlling for mobility levels, health care systems, government finance, gender balance, age, income, and education levels of communities, our analysis indicates that areas with strong linking social ties see no or far lower levels of COVID-19 case rates initially. However, case fatality rates rise in such communities once the disease enters as they lack horizontal (bonding) ties which can mitigate its health impacts. We anticipate this study to be a starting point for broader studies of how social ties and mobility influence COVID-19 outcomes worldwide along with shining a light on how different types of social relationships play different roles as a crisis or disaster progresses.
Simultaneous determination of spirodiclofen, spiromesifen, and spirotetramat and their relevant metabolites in edible fungi using ultra-performance liquid chromatography/tandem mass spectrometry
Authors: Tian Fajun , Qiao Chengkui , Wang Caixia , Luo Jing , Guo Linlin , Pang Tao , Li Jun , Wang Ruiping , Pang Rongli , Xie Hanzhong 
Published: January 2021

AbstractA fast, sensitive, and reliable analytical method was developed and validated for simultaneous identification and quantification of spirodiclofen, spiromesifen, and spirotetramat and their relevant metabolites in edible fungi by ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC–MS/MS). First, sample extraction was done with acetonitrile containing 1% formic acid followed by phase separation with the addition of MgSO4:NaOAc. Then, the supernatant was purified by primary secondary amine (PSA), octadecylsilane (C18), and graphitized carbon black (GCB). The linearities of the calibrations for all analytes were excellent (R2 ≥ 0.9953). Acceptable recoveries (74.5–106.4%) for all analytes were obtained with good intra- and inter- relative standard deviations of less than 14.5%. The limit of quantification (LOQs) for all analytes was 10 μg kg−1. For accurate quantification, matrix-matched calibration curve was applied to normalize the matrix effect. The results indicated that the method was suitable for detecting the three acaricides and their relevant metabolites in edible fungi.
CD14+ monocytes repress gamma globin expression at early stages of erythropoiesis
Authors: Heshusius Steven , Heideveld Esther , von Lindern Marieke , van den Akker Emile 
Published: January 2021

AbstractIn β-hemoglobinopathies, reactivation of gamma- at the expense of beta-globin is a prominent therapeutic option. Expression of the globin genes is not strictly intrinsically regulated during erythropoiesis, supported by the observation that fetal erythroid cells switch to adult hemoglobin expression when injected in mice. We show cultured erythroblasts are a mix of HbA restrictive and HbA/HbF expressing cells and that the proportion of cells in the latter population depends on the starting material. Cultures started from CD34+ cells contain more HbA/HbF expressing cells compared to erythroblasts cultured from total peripheral blood mononuclear cells (PBMC). Depletion of CD14+ cells from PBMC resulted in higher HbF/HbA percentages. Conversely, CD34+ co-culture with CD14+ cells reduced the HbF/HbA population through cell–cell proximity, indicating that CD14+ actively repressed HbF expression in adult erythroid cultures. RNA-sequencing showed that HbA and HbA/HbF populations contain a limited number of differentially expressed genes, aside from HBG1/2. Co-culture of CD14+ cells with sorted uncommitted hematopoietic progenitors and CD34-CD36+ erythroblasts showed that hematopoietic progenitors prior to the hemoglobinized erythroid stages are more readily influenced by CD14+ cells to downregulate expression of HBG1/2, suggesting temporal regulation of these genes. This possibly provides a novel therapeutic avenue to develop β-hemoglobinopathies treatments.
Early stability and late random tumor progression of a HER2-positive primary breast cancer patient-derived xenograft
Authors: Landuzzi Lorena , Palladini Arianna , Ceccarelli Claudio , Asioli Sofia , Nicoletti Giordano , Giusti Veronica , Ruzzi Francesca , Ianzano Marianna L. , Scalambra Laura , Laranga Roberta , Balboni Tania , Arigoni Maddalena , Olivero Martina , Calogero Raffaele A. , De Giovanni Carla , Dall’Ora Massimiliano , Di Oto Enrico , Santini Donatella , Foschini Maria Pia , Cucchi Maria Cristina , Zanotti Simone , Taffurelli Mario , Nanni Patrizia , Lollini Pier-Luigi 
Published: January 2021

AbstractWe established patient-derived xenografts (PDX) from human primary breast cancers and studied whether stability or progressive events occurred during long-term in vivo passages (up to 4 years) in severely immunodeficient mice. While most PDX showed stable biomarker expression and growth phenotype, a HER2-positive PDX (PDX-BRB4) originated a subline (out of 6 studied in parallel) that progressively acquired a significantly increased tumor growth rate, resistance to cell senescence of in vitro cultures, increased stem cell marker expression and high lung metastatic ability, along with a strong decrease of BCL2 expression. RNAseq analysis of the progressed subline showed that BCL2 was connected to three main hub genes also down-regulated (CDKN2A, STAT5A and WT1). Gene expression of progressed subline suggested a partial epithelial-to-mesenchymal transition. PDX-BRB4 with its progressed subline is a preclinical model mirroring the clinical paradox of high level-BCL2 as a good prognostic factor in breast cancer. Sequential in vivo passages of PDX-BRB4 chronically treated with trastuzumab developed progressive loss of sensitivity to trastuzumab while HER2 expression and sensitivity to the pan-HER tyrosine kinase inhibitor neratinib were maintained. Long-term PDX studies, even though demanding, can originate new preclinical models, suitable to investigate the mechanisms of breast cancer progression and new therapeutic approaches.
Mycobacterium tuberculosis Rv3160c is a TetR-like transcriptional repressor that regulates expression of the putative oxygenase Rv3161c
Authors: Tükenmez Hasan , Sarkar Souvik , Anoosheh Saber , Kruchanova Anastasiia , Edström Isabel , Harrison Gregory A. , Stallings Christina L. , Almqvist Fredrik , Larsson Christer 
Published: January 2021

AbstractTuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a major health threat listed among the top 10 causes of death worldwide. Treatment of multidrug-resistant Mtb requires use of additional second-line drugs that prolong the treatment process and result in higher death rates. Our team previously identified a 2-pyridone molecule (C10) that blocks tolerance to the first-line drug isoniazid at C10 concentrations that do not inhibit bacterial growth. Here, we discovered that the genes rv3160c and rv3161c are highly induced by C10, which led us to investigate them as potential targets. We show that Rv3160c acts as a TetR-like transcriptional repressor binding to a palindromic sequence located in the rv3161c promoter. We also demonstrate that C10 interacts with Rv3160c, inhibiting its binding to DNA. We deleted the rv3161c gene, coding for a putative oxygenase, to investigate its role in drug and stress sensitivity as well as C10 activity. This Δrv3161c strain was more tolerant to isoniazid and lysozyme than wild type Mtb. However, this tolerance could still be blocked by C10, suggesting that C10 functions independently of Rv3161c to influence isoniazid and lysozyme sensitivity.