bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the efficacy of multiple myeloma cell lines as models for patient tumors via transcriptomic correlation analysis
Authors: Sarin Vishesh , Yu Katharine , Ferguson Ian D. , Gugliemini Olivia , Nix Matthew A. , Hann Byron , Sirota Marina , Wiita Arun P. 
Published: March 2020

AbstractMultiple myeloma (MM) cell lines are routinely used to model the disease. However, a long-standing question is how well these cell lines truly represent tumor cells in patients. Here, we employ a recently described method of transcriptional correlation profiling to compare similarity of 66 MM cell lines to 779 newly diagnosed MM patient tumors. We found that individual MM lines differ significantly with respect to patient tumor representation, with median R ranging from 0.35 to 0.54. ANBL-6 was the “best” line, markedly exceeding all others (p < 2.2e−16). Notably, some widely used cell lines (RPMI-8226, U-266) scored poorly in our patient similarity ranking (48 and 52 of 66, respectively). Lines cultured with interleukin-6 showed significantly improved correlations with patient tumor (p = 9.5e−4). When common MM genomic features were matched between cell lines and patients, only t(4;14) and t(14;16) led to increased transcriptional correlation. To demonstrate the utility of our top-ranked line for preclinical studies, we showed that intravenously implanted ANBL-6 proliferates in hematopoietic organs in immunocompromised mice. Overall, our large-scale quantitative correlation analysis, utilizing emerging datasets, provides a resource informing the MM community of cell lines that may be most reliable for modeling patient disease while also elucidating biological differences between cell lines and tumors.
XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary
Authors: Tamura Ryo , Yoshihara Kosuke , Nakaoka Hirofumi , Yachida Nozomi , Yamaguchi Manako , Suda Kazuaki , Ishiguro Tatsuya , Nishino Koji , Ichikawa Hiroshi , Homma Keiichi , Kikuchi Akira , Ueda Yutaka , Takei Yuji , Fujiwara Hiroyuki , Motoyama Teiichi , Okuda Shujiro , Wakai Toshifumi , Inoue Ituro , Enomoto Takayuki 
Published: March 2020

AbstractMolecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.
High-mobility group AT-hook 1 promotes cardiac dysfunction in diabetic cardiomyopathy via autophagy inhibition
Authors: Wu Qing-Qing , Liu Chen , Cai Zhulan , Xie Qingwen , Hu Tongtong , Duan Mingxia , Wu Haiming , Yuan Yuan , Tang Qizhu 
Published: March 2020

AbstractHigh-mobility group AT-hook1 (HMGA1, formerly HMG-I/Y), an architectural transcription factor, participates in a number of biological processes. However, its effect on cardiac remodeling (refer to cardiac inflammation, apoptosis and dysfunction) in diabetic cardiomyopathy remains largely indistinct. In this study, we found that HMGA1 was upregulated in diabetic mouse hearts and high-glucose-stimulated cardiomyocytes. Overexpression of HMGA1 accelerated high-glucose-induced cardiomyocyte inflammation and apoptosis, while HMGA1 knockdown relieved inflammation and apoptosis in cardiomyocytes in response to high glucose. Overexpression of HMGA1 in mice heart by adeno-associated virus 9 (AAV9) delivery system deteriorated the inflammatory response, increased apoptosis and accelerated cardiac dysfunction in streptozotocin-induced diabetic mouse model. Knockdown of HMGA1 by AAV9-shHMGA1 in vivo ameliorated cardiac remodeling in diabetic mice. Mechanistically, we found that HMGA1 inhibited the formation rather than the degradation of autophagy by regulating P27/CDK2/mTOR signaling. CDK2 knockdown or P27 overexpression blurred HMGA1 overexpression-induced deteriorating effects in vitro. P27 overexpression in mice heart counteracted HMGA1 overexpression-induced increased cardiac remodeling in diabetic mice. The luciferase reporter experiment confirmed that the regulatory effect of HMGA1 on P27 was mediated by miR-222. In addition, a miR-222 antagomir counteracted HMGA1 overexpression-induced deteriorating effects in vitro. Taken together, our data indicate that HMGA1 aggravates diabetic cardiomyopathy by directly regulating miR-222 promoter activity, which inhibits P27/mTOR-induced autophagy.
Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K
Authors: Petroni Giulia , Bagni Giacomo , Iorio Jessica , Duranti Claudia , Lottini Tiziano , Stefanini Matteo , Kragol Goran , Becchetti Andrea , Arcangeli Annarosa 
Published: March 2020

AbstractWe have studied how the macrolide antibiotic Clarithromycin (Cla) regulates autophagy, which sustains cell survival and resistance to chemotherapy in cancer. We found Cla to inhibit the growth of human colorectal cancer (CRC) cells, by modulating the autophagic flux and triggering apoptosis. The accumulation of cytosolic autophagosomes accompanied by the modulation of autophagic markers LC3-II and p62/SQSTM1, points to autophagy exhaustion. Because Cla is known to bind human Ether-à-go-go Related Gene 1 (hERG1) K+channels, we studied if its effects depended on hERG1 and its conformational states. By availing of hERG1 mutants with different gating properties, we found that fluorescently labelled Cla preferentially bound to the closed channels. Furthermore, by sequestering the channel in the closed conformation, Cla inhibited the formation of a macromolecular complex between hERG1 and the p85 subunit of PI3K. This strongly reduced Akt phosphorylation, and stimulated the p53-dependent cell apoptosis, as witnessed by late caspase activation. Finally, Cla enhanced the cytotoxic effect of 5-fluorouracil (5-FU), the main chemotherapeutic agent in CRC, in vitro and in a xenograft CRC model. We conclude that Cla affects the autophagic flux by impairing the signaling pathway linking hERG1 and PI3K. Combining Cla with 5-FU might be a novel therapeutic option in CRC.
Intra- and interspecific diversity analyses in the genus Eremurus in Iran using genotyping-by-sequencing reveal geographic population structure
Authors: Hadizadeh Hanieh , Bahri Bochra A. , Qi Peng , Wilde H. Dayton , Devos Katrien M. 
Published: March 2020

AbstractEremurusspecies, better known as ‘Foxtail Lily’ or ‘Desert Candle’, are important worldwide in landscaping and the cut-flower industry. One of the centers of highest diversity of the genusEremurusis Iran, which has seven species. However, little is known about the genetic diversity within the genusEremurus. With the advent of genotyping-by-sequencing (GBS), it is possible to develop and employ single nucleotide polymorphism (SNP) markers in a cost-efficient manner in any species, regardless of its ploidy level, genome size or availability of a reference genome. Population structure and phylogeographic analyses of the genusEremurusin Iran using a minimum of 3002 SNP markers identified either at the genus level or at the species level from GBS data showed longitudinal geographic structuring at the country scale for the genus and for the speciesE. spectabilisandE. luteus, and at the regional scale forE. olgae. Our analyses furthermore showed a close genetic relatedness betweenE. olgaeandE. stenophyllusto the extent that they should be considered subspecies within anE. olgae/stenophyllusspecies complex. Their close genetic relatedness may explain why crosses between these two (sub)species have been found in the wild and are exploited extensively as ornamentals. Last, current species identification, while robust, relies on flower morphology. A subset of seven SNPs with species-specific (private) alleles were selected that differentiate the sevenEremurusspecies. The markers will be especially useful for cultivar protection and in hybrid production, where true hybrids could be identified at the seedling stage.
Quantum non-demolition readout of an electron spin in silicon
Authors: Yoneda J. , Takeda K. , Noiri A. , Nakajima T. , Li S. , Kamioka J. , Kodera T. , Tarucha S. 
Published: March 2020

AbstractWhile single-shot detection of silicon spin qubits is now a laboratory routine, the need for quantum error correction in a large-scale quantum computing device demands a quantum non-demolition (QND) implementation. Unlike conventional counterparts, the QND spin readout imposes minimal disturbance to the probed spin polarization and can therefore be repeated to extinguish measurement errors. Here, we show that an electron spin qubit in silicon can be measured in a highly non-demolition manner by probing another electron spin in a neighboring dot Ising-coupled to the qubit spin. The high non-demolition fidelity (99% on average) enables over 20 readout repetitions of a single spin state, yielding an overall average measurement fidelity of up to 95% within 1.2 ms. We further demonstrate that our repetitive QND readout protocol can realize heralded high-fidelity (>99.6%) ground-state preparation. Our QND-based measurement and preparation, mediated by a second qubit of the same kind, will allow for a wide class of quantum information protocols with electron spins in silicon without compromising the architectural homogeneity.
Quantitative models reveal the organization of diverse cognitive functions in the brain
Authors: Nakai Tomoya , Nishimoto Shinji 
Published: March 2020

AbstractOur daily life is realized by the complex orchestrations of diverse brain functions, including perception, decision-making, and action. The essential goal of cognitive neuroscience is to reveal the complete representations underlying these functions. Recent studies have characterised perceptual experiences using encoding models. However, few attempts have been made to build a quantitative model describing the cortical organization of multiple active, cognitive processes. Here, we measure brain activity using fMRI, while subjects perform 103 cognitive tasks, and examine cortical representations with two voxel-wise encoding models. A sparse task-type model reveals a hierarchical organization of cognitive tasks, together with their representation in cognitive space and cortical mapping. A cognitive factor model utilizing continuous, metadata-based intermediate features predicts brain activity and decodes tasks, even under novel conditions. Collectively, our results show the usability of quantitative models of cognitive processes, thus providing a framework for the comprehensive cortical organization of human cognition.
Efficient strain modulation of 2D materials via polymer encapsulation
Authors: Li Zhiwei , Lv Yawei , Ren Liwang , Li Jia , Kong Lingan , Zeng Yujia , Tao Quanyang , Wu Ruixia , Ma Huifang , Zhao Bei , Wang Di , Dang Weiqi , Chen Keqiu , Liao Lei , Duan Xidong , Duan Xiangfeng , Liu Yuan 
Published: March 2020

AbstractStrain engineering is a promising method to manipulate the electronic and optical properties of two-dimensional (2D) materials. However, with weak van der Waals interaction, severe slippage between 2D material and substrate could dominate the bending or stretching processes, leading to inefficiency strain transfer. To overcome this limitation, we report a simple strain engineering method by encapsulating the monolayer 2D material in the flexible PVA substrate through spin-coating approach. The strong interaction force between spin-coated PVA and 2D material ensures the mechanical strain can be effectively transferred with negligible slippage or decoupling. By applying uniaxial strain to monolayer MoS2, we observe a higher bandgap modulation up to ~300 meV and a highest modulation rate of ~136 meV/%, which is approximate two times improvement compared to previous results achieved. Moreover, this simple strategy could be well extended to other 2D materials such as WS2 or WSe2, leading to enhanced bandgap modulation.
Information flow in finite flocks
Authors: Brown J. , Bossomaier T. , Barnett L. 
Published: March 2020

AbstractWe explore information flow in finite active matter flocks by simulating the canonical Vicsek model and estimating the flow of information as a function of noise (the variability in the extent to which each animal aligns with its neighbours). We show that the global transfer entropy for finite flocks not only fails to peak near the phase transition, as demonstrated for the canonical 2D Ising model, but remains constant from the transition throughout the entire ordered regime to very low noise values. This provides a foundation for future study regarding information flow in more complex models and real-world flocking data.
Genome-scale exploration of transcriptional regulation in the nisin Z producer Lactococcus lactis subsp. lactis IO-1
Authors: Poorinmohammad Naghmeh , Hamedi Javad , Masoudi-Nejad Ali 
Published: March 2020

AbstractTranscription is of the most crucial steps of gene expression in bacteria, whose regulation guarantees the bacteria’s ability to adapt to varying environmental conditions. Discovering the molecular basis and genomic principles of the transcriptional regulation is thus one of the most important tasks in cellular and molecular biology. Here, a comprehensive phylogenetic footprinting framework was implemented to predict maximal regulons of Lactococcus lactis subsp. lactis IO-1, a lactic acid bacterium known for its high potentials in nisin Z production as well as efficient xylose consumption which have made it a promising biotechnological strain. A total set of 321 regulons covering more than 90% of all the bacterium’s operons have been elucidated and validated according to available data. Multiple novel biologically-relevant members were introduced amongst which arsC, mtlA and mtl operon for BusR, MtlR and XylR regulons can be named, respectively. Moreover, the effect of riboflavin on nisin biosynthesis was assessed in vitro and a negative correlation was observed. It is believed that understandings from such networks not only can be useful for studying transcriptional regulatory potentials of the target organism but also can be implemented in biotechnology to rationally design favorable production conditions.
Adaptive fitness of Sapindus emarginatus Vahl populations towards future climatic regimes and the limiting factors of its distribution
Authors: Kumar Pal Ashish , Vaishnav Vivek , Meena Baleshwar , Pandey Nalini , Singh Rana Tikam 
Published: March 2020

AbstractSapindus emarginatus Vahl (Sapindaceae) also known as ‘Indian Soap nut’ is significantly important for saponin content in its fruits. However, its current population in India is heavily fragmented due to a lack of sustainable harvesting practices. Moreover, changing climatic regimes may further limit its distribution and possibly compromise the survival of the species in nature. The aim of the present study was to: predict the future distribution range of S. emarginatus; identify the bioclimatic variables limiting this distribution and to evaluate its adaptive fitness and genomic resilience towards these variables. To determine future species distribution range and identify limiting bioclimatic variables, we applied two different ecological niche models (ENMs; BioClim and MaxEnt) on real occurrence data (n = 88 locations). The adaptive fitness of the species was evaluated by quantifying the genetic variability with AFLP markers and marker-environmental associations, using AFLP-associated Bayesian statistics. We found 77% overlap between the baseline (2030) and predicted (2100) species distribution ranges, which were primarily determined by maximum temperature (TMAX) and mean annual precipitation (MAP). The TMAX and MAP contributed 43.1% and 27.1%, respectively to ENM model prediction. Furthermore, AFLP loci significantly associated with bioclimatic variables, and TMAX and MAP represent the lowest proportion (6.15%), confirming to the severe response of the species genome towards these variables. Nevertheless, the very low Linkage disequilibrium (LD) in these loci (4.54%) suggests that the current sensitivity to TMAX and MAP is subject to change during recombination. Moreover, a combination of high heterozygosity (0.40–0.43) and high within-population variability (91.63 ± 0.31%) confirmed high adaptive fitness to maintain reproductive success. Therefore, the current populations of S. emarginatus have substantial genomic resilience towards future climate change, albeit significant conservation efforts (including mass multiplication) are warranted to avoid future deleterious impacts of inbreeding depression on the fragmented populations.
RETRACTED ARTICLE: Conditioned place preference reveals ongoing pain in calves 3 weeks after disbudding
Authors: Adcock Sarah J. J. , Tucker Cassandra B. 
Published: March 2020

Abstract
Hot-iron disbudding, a routine procedure that prevents horn bud growth
through cauterization, is painful for calves. The resulting burns remain sensitive
to touch for weeks, but it is unknown whether calves experience ongoing, non-evoked
pain. We evaluated conditioned place preference for analgesia in 44 calves disbudded
or sham-disbudded 6 hours (Day 0) or 20 days (Day 20) before testing
(n = 11/treatment). Calves were conditioned to associate the effects of a lidocaine
cornual nerve block with the location and pattern of a visual stimulus, and a
control injection of saline with the contrasting stimulus. On Day 0, disbudded
calves tended to prefer the lidocaine-paired stimulus over the saline-paired one,
suggesting that they found analgesia rewarding. On Day 20, sham calves avoided the
lidocaine-paired stimulus, consistent with humans’ experience of this drug being
painful. Disbudded calves on Day 20 did not show this aversion, suggesting that they
traded off the short-term pain of the lidocaine with the longer-term analgesia
provided. Day 0 sham calves did not avoid the lidocaine-paired stimulus, likely
because they received less than half the dose of Day 20 calves during conditioning.
Thus, higher doses of lidocaine are aversive to uninjured animals, but disbudded
calves are willing to engage in this cost. We conclude that calves experience
ongoing pain 3 weeks after disbudding, raising additional welfare concerns about
this procedure.
A dynamic perfusion based blood-brain barrier model for cytotoxicity testing and drug permeation
Authors: Elbakary Basma , Badhan Raj K. S. 
Published: March 2020

AbstractThe blood-brain barrier (BBB) serves to protect and regulate the CNS microenvironment. The development of an in-vitro mimic of the BBB requires recapitulating the correct phenotype of the in-vivo BBB, particularly for drug permeation studies. However the majority of widely used BBB models demonstrate low transendothelial electrical resistance (TEER) and poor BBB phenotype. The application of shear stress is known to enhance tight junction formation and hence improve the barrier function. We utilised a high TEER primary porcine brain microvascular endothelial cell (PBMEC) culture to assess the impact of shear stress on barrier formation using the Kirkstall QuasiVivo 600 (QV600) multi-chamber perfusion system. The application of shear stress resulted in a reorientation and enhancement of tight junction formation on both coverslip and permeable inserts, in addition to enhancing and maintaining TEER for longer, when compared to static conditions. Furthermore, the functional consequences of this was demonstrated with the reduction in flux of mitoxantrone across PBMEC monolayers. The QV600 perfusion system may service as a viable tool to enhance and maintain the high TEER PBMEC system for use in in-vitro BBB models.
Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening
Authors: Murphy Nicholas M. , Samarasekera Tanya S. , Macaskill Lisa , Mullen Jayne , Rombauts Luk J. F. 
Published: March 2020

AbstractWhole-genome sequencing of preimplantation human embryos to detect and screen for genetic diseases is a technically challenging extension to preconception screening. Combining preconception genetic screening with preimplantation testing of human embryos facilitates the detection of de novo mutations and self-validates transmitted variant detection in both the reproductive couple and the embryo’s samples. Here we describe a trio testing workflow that involves whole-genome sequencing of amplified DNA from biopsied embryo trophectoderm cells and genomic DNA from both parents. Variant prediction software and annotation databases were used to assess variants of unknown significance and previously not described de novo variants in five single-gene preimplantation genetic testing couples and eleven of their embryos. Pathogenic variation, tandem repeat, copy number and structural variations were examined against variant calls for compound heterozygosity and predicted disease status was ascertained. Multiple trio testing showed complete concordance with known variants ascertained by single-nucleotide polymorphism array and uncovered de novo and transmitted pathogenic variants. This pilot study describes a method of whole-genome sequencing and analysis for embryo selection in high-risk couples to prevent early life fatal genetic conditions that adversely affect the quality of life of the individual and families.