bluuebunny/crossref_metadata_2025_split huggingface dataset:
A feedback-loop between telomerase activity and stemness factors regulates PDAC stem cells
Authors: Walter Karolin , Rodriguez-Aznar Eva , Ventura Ferreira Monica S. , Frappart Pierre-Olivier , Dittrich Tabea , Tiwary Kanishka , Meessen Sabine , Lerma Laura , Daiss Nora , Schulte Lucas-Alexander , Arnold Frank , Usachov Valentyn , Azoitei Ninel , Erkan Mert , Lechel Andre , Brümmendorf Tim H. , Seufferlein Thomas , Kleger Alexander , Tabarés Enrique , Günes Cagatay , Beier Fabian , Sainz Bruno , Hermann Patrick C. 
Published: November 2020

AbstractTo date, it is still unclear how cancer stem cells (CSCs) regulate their stemness properties, and to what extent they share common features with normal stem cells. Telomerase regulation is a key factor in stem cell maintenance. In this study, we investigate how telomerase regulation affects cancer stem cell biology in pancreatic ductal adenocarcinoma (PDAC), and delineate the mechanisms by which telomerase activity and CSC properties are linked. Using primary patient-derived pancreatic cancer cells, we show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using geneticTERT-knockdown or pharmacological inhibitor (BIBR1532) resulted in CSC marker depletionin vitro, and reduced tumorigenicityin vivo. Furthermore, we identify a positive feedback loop between stemness factors (KLF4, SOX2, OCT3/4, NANOG) and telomerase, which is essential for the self-renewal of pancreatic CSCs. Disruption the balance between telomerase activity and stemness factors, eliminates CSCs via induction of DNA damage and apoptosis, opening future perspectives to avoid CSC driven therapy resistance and tumor relapse in PDAC patients.
Identification of Cross-Reactive CD8+T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants
Authors: Hu Chao , Shen Meiying , Han Xiaojian , Chen Qian , Li Luo , Chen Siyin , Zhang Jing , Gao Fengxia , Wang Wang , Wang Yingming , Li Tingting , Li Shenglong , Huang Jingjing , Wang Jianwei , Zhu Ju , Chen Dan , Wu Qingchen , Tao Kun , Pang Da , Jin Aishun 
Published: November 2020

ABSTRACTDespite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369(KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+T cellsex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.
Proprioception Has Limited Influence on Tactile Reference Frame Selection
Authors: Yizhar Or , Buchs Galit , Heimler Benedetta , Friedman Doron , Amedi Amir 
Published: November 2020

ABSTRACTPerceiving the spatial location and physical dimensions of objects that we touch is crucial for goal-directed actions. To achieve this, our brain transforms skin-based coordinates into a reference frame by integrating visual and proprioceptive cues, a process known as tactile remapping. In the current study, we examine the role of proprioception in the remapping process when information from the more dominant visual modality is withheld. We developed a new visual-to-touch sensory substitution device and asked participants to perform a spatial localization task in three different arm postures that included posture switches between blocks of trials. We observed that in the absence of visual information novel proprioceptive inputs can be overridden after switching postures. This behavior demonstrates effective top-down modulations of proprioception and points to the unequal contribution of different sensory modalities to tactile remapping.
Statistical Physics of DNA melting: Unveiling the artificial corrections for self-complementary sequences
Authors: Plata C. A. , Marni S. , Maritan A. , Bellini T. , Suweis S. 
Published: November 2020

ABSTRACTDNA hybridization is at the heart of countless biological and biotechnological processes. Its theoretical modeling played a crucial role, since it has enabled extracting the relevant thermodynamic parameters from systematic measurements of DNA melting curves. However, in its current state, hybridization modelling requires introducing an extra entropic contribution in self-complementary sequences that lacks any biophysical meaning. In this article, we propose a framework based on statistical physics to describe DNA hybridization and melting in an arbitrary mixture of DNA strands. In particular, we are able to analytically derive closed expressions of the system partition functions for any numberNof strings, and explicitly calculate them in two paradigmatic situations: (i) a system made of self-complementary sequences and (ii) a system comprising two mutually complementary sequences. We derive the melting curve in the thermodynamic limit (N→ ∞) of our description, which differs from the expression commonly used to evaluate the melting of self-complementary systems in that it does not require correcting terms. We provide a thorough study comprising limit cases and alternative approaches showing how our framework can give a comprehensive view of hybridization and melting phenomena.SIGNIFICANCEIn this study, we provide a transparent derivation of the melting curves of DNA duplexes using basic tools of statistical mechanics. We find that in the case of self-complementary sequences, our expression differs from the one used in literature, which is generally amended by the introduction of a phenomenological correction which in our approach becomes unnecessary. By offering a clean formal description of DNA hybridization, our approach sharpens our understanding of DNA interactions and opens the way to study the pairing of DNA oligomers away from any thermodynamic limit.
Machine learning enabled phenotyping for GWAS and TWAS of WUE traits in 869 field-grown sorghum accessions
Authors: Ferguson John N. , Fernandes Samuel B. , Monier Brandon , Miller Nathan D. , Allan Dylan , Dmitrieva Anna , Schmuker Peter , Lozano Roberto , Valluru Ravi , Buckler Edward S. , Gore Michael A. , Brown Patrick J. , Spalding Edgar P. , Leakey Andrew D.B. 
Published: November 2020

ABSTRACTSorghum is a model C4 crop made experimentally tractable by extensive genomic and genetic resources. Biomass sorghum is also studied as a feedstock for biofuel and forage. Mechanistic modelling suggests that reducing stomatal conductance (gs) could improve sorghum intrinsic water use efficiency (iWUE) and biomass production. Phenotyping for discovery of genotype to phenotype associations remain bottlenecks in efforts to understand the mechanistic basis for natural variation ingsandiWUE. This study addressed multiple methodological limitations. Optical tomography and a novel machine learning tool were combined to measure stomatal density (SD). This was combined with rapid measurements of leaf photosynthetic gas exchange and specific leaf area (SLA). These traits were then the subject of genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) across 869 field-grown biomass sorghum accessions. SD was correlated with plant height and biomass production. Plasticity in SD and SLA were interrelated with each other, and productivity, across wet versus dry growing seasons. Moderate-to-high heritability of traits studied across the large mapping population supported identification of associations between DNA sequence variation, or RNA transcript abundance, and trait variation. 394 unique genes underpinning variation in WUE-related traits are described with higher confidence because they were identified in multiple independent tests. This list was enriched in genes whose orthologs in Arabidopsis have functions related to stomatal or leaf development and leaf gas exchange. These advances in methodology and knowledge will aid efforts to improve the WUE of C4 crops.
Selecting the most effective DBS contact in essential tremor patients based on individual tractography
Authors: Petry-Schmelzer Jan Niklas , Dembek Till A. , Steffen Julia K. , Jergas Hannah , Dafsari Haidar S. , Fink Gereon R. , Visser-Vandewalle Veerle , Barbe Michael T. 
Published: November 2020

AbstractPostoperative choice of the most effective DBS contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. It has been shown that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from the stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed contact-wise during test stimulation with 2mA. The individual DRTTs were identified from diffusion tensor imaging. Contacts were ranked by their overlap of the test stimulation with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT-overlap on tremor control. In 92.9 % of the cases, the contact with the best clinical effect was the contact with the highest or second-highest DRTT-overlap. On the group level, the DRTT-overlap explained 26.7% of the variance of the clinical outcome (p<0.001). To conclude, data suggest that the overlap with the DRTT based on individual tractography may serve as a marker to determine the most effective DBS contact in ET patients and reduce burdensome clinical testing in the future.
Safety, Tolerability, and Immunogenicity of COVID-19 Vaccines: A Systematic Review and Meta-Analysis
Authors: Yuan Ping , Ai Pu , Liu Yihan , Ai Zisheng , Wang Yi , Cao Weijun , Xia Xiaohuan , Zheng Jialin C. 
Published: November 2020

AbstractWe aimed to summarize reliable medical evidence by the meta-analysis of all published clinical trials that investigated the safety, tolerability, and immunogenicity of vaccine candidates against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The PubMed, Cochrane Library, EMBASE, and medRxiv databases were used to select the studies. 7094 articles were identified initially and 43 were retrieved for more detailed evaluation. 5 randomized, double-blind, placebo-controlled trials were selected. A total of 1604 subjects with either vaccines or placebo infections were included in the meta-analysis within the scope of these articles. According to the results, there is an increase in total adverse events for subjects with either low (95% CI: 1.90-4.29) or high (CI: 2.65-5.63) dose vaccination. The adverse effects of COVID-19 vaccine are mainly local ones including pain, itching, and redness, and no significant difference was identified in the systemic reactions. All adverse effects were transient and resolved within a few days. Moreover, the neutralizing and IgG antibody levels post different dose vaccinations were all significantly increased at day 14/21 (P = 0.0004 and P = 0.0003, respectively) and day 28/35 (P < 0.00001) in vaccine groups compared to placebo controls. Besides, the levels of neutralizing and IgG antibodies were also elevated significantly at from day 14 to 35, versus day 0 (All P < 0.001). In conclusion, our analysis suggests that the current COVID-19 vaccine candidates are safe, tolerated, and immunogenic, which provides important information for further development, evaluation, and clinical application of COVID-19 vaccine.
The ACE2-binding interface of SARS-CoV-2 Spike inherently deflects immune recognition
Authors: Hattori Takamitsu , Koide Akiko , Panchenko Tatyana , Romero Larizbeth A. , Teng Kai Wen , Tada Takuya , Landau Nathaniel R. , Koide Shohei 
Published: November 2020

AbstractThe COVID-19 pandemic remains a global threat, and host immunity remains the main mechanism of protection against the disease. The spike protein on the surface of SARS-CoV-2 is a major antigen and its engagement with human ACE2 receptor plays an essential role in viral entry into host cells. Consequently, antibodies targeting the ACE2-interacting surface (ACE2IS) located in the receptor-binding domain (RBD) of the spike protein can neutralize the virus. However, the understanding of immune responses to SARS-CoV-2 is still limited, and it is unclear how the virus protects this surface from recognition by antibodies. Here, we designed an RBD mutant that disrupts the ACE2IS and used it to characterize the prevalence of antibodies directed to the ACE2IS from convalescent sera of 94 COVID19-positive patients. We found that only a small fraction of RBD-binding antibodies targeted the ACE2IS. To assess the immunogenicity of different parts of the spike protein, we performed in vitro antibody selection for the spike and the RBD proteins using both unbiased and biased selection strategies. Intriguingly, unbiased selection yielded antibodies that predominantly targeted regions outside the ACE2IS, whereas ACE2IS-binding antibodies were readily identified from biased selection designed to enrich such antibodies. Furthermore, antibodies from an unbiased selection using the RBD preferentially bound to the surfaces that are inaccessible in the context of whole spike protein. These results suggest that the ACE2IS has evolved less immunogenic than the other regions of the spike protein, which has important implications in the development of vaccines against SARS-CoV-2.
Retinal and cortical visual acuity in a common inbred albino mouse
Authors: Braha Michelle , Porciatti Vittorio , Chou Tsung-Han 
Published: November 2020

AbstractWhile albino mice are widely used in research which includes the use of visually guided behavioral tests, information on their visual capability is scarce. We compared the spatial resolution (acuity) of albino mice (BALB/c) with that of pigmented mice (C57BL/6J). We used a high-throughput pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) method for objective assessment of retinal and cortical acuity, as well as optomotor head-tracking response/ reflex (OMR). We found that PERG, PVEP, and OMR acuities of C57BL/6J mice were all in the range of 0.5-0.6 cycles/degree (cyc/deg). BALB/c mice had PERG and PVEP acuities in the range of 0.1-0.2 cyc/deg but were unresponsive to OMR stimulus. Results indicate that retinal and cortical acuity can be reliably determined with electrophysiological methods in BALB/c mice, although PERG/PVEP acuities are lower than those of C57BL/6J mice. The reduced acuity of BALB/c mice appears to be primarily determined at retinal level.
Reduced Nicotinamide Mononucleotide (NMNH) Potently Enhances NAD+, Suppresses Glycolysis, TCA Cycle and Cell Growth
Authors: Liu Yan , Luo Chengting , Li Ting , Zhang Wenhao , Zong Zhaoyun , Liu Xiaohui , Deng Haiteng 
Published: November 2020

AbstractIn the present study, we developed a chemical method to produce dihydro nicotinamide mononucleotide (NMNH), which is the reduced-form of nicotinamide mononucleotide (NMN). We demonstrated that NMNH was a better NAD+enhancer compared to NMN bothin vitroandin vivomediated by NMNAT. Additionally, NMNH increased the reduced NAD (NADH) levels in cells and in mouse liver. Metabolomic analysis revealed that NMNH inhibited glycolysis and TCA cycle.In vitroexperiments demonstrated that NMNH induced cell cycle arrest and suppressed cell growth. Nevertheless, NMNH treatment did not cause observable difference in mice. Taken together, our work demonstrates that NMNH is a potent NAD+enhancer, and suppresses glycolysis, TCA cycle and cell growth.
The effectiveness of sensory integration intervention on the emotional-behavioral problems of children with autism spectrum disorder
Authors: Hemati Alamdarloo Ghorban , Mradi Hasan 
Published: November 2020

PurposeAutism spectrum disorder is a kind of neurodevelopmental disorder characterized by persistent deficits in social communication and interaction across multiple contexts, and restricted, repetitive patterns of behavior, interests or activities. The purpose of this paper is to determine the effectiveness of sensory integration intervention on emotional-behavioral problems in children with autism spectrum disorder.Design/methodology/approachThis research was conducted in a pretest-posttest design with control group. The participants were 30 children with autism spectrum disorder (6–11 years old) who were selected through convenience sampling from among children with autism spectrum disorder in Zeinab center of Isfahan and were randomly divided into two groups of 15 subjects. The children of the experimental group received 14 sessions of sensory integration intervention while the control group did not receive this intervention. To measure emotional-behavioral problems, the Behavior Assessment System for Children-Second Edition was used. To analyze the data, ANCOVA and MANCOVA tests were used.FindingsThe results showed that sensory integration intervention improves emotional-behavioral problems and its subscales (hyperactivity, aggression, behavioral problems, anxiety, depression, somatization, attention problems, learning difficulties, atypicality and withdrawal) in children with autism spectrum disorder.Research limitations/implicationsTherefore, it can be concluded that sensory integration intervention can be a suitable treatment for reducing sensory problems and improving emotional-behavioral problems in children with autism spectrum disorder.Originality/valueThe study of the effect of sensory integration on emotional-behavioral problems in children with autism spectrum disorder is necessary as a simple and non-side-effect educational and therapeutic method, both as a step to fill the research gap in this field, besides being a cheap and affordable way for improving the various skills of children with autism spectrum disorder for professionals, teachers, parents and educators.
Impact of marketization process on China's forestry economic growth – based on the statistical yearbook data from 1978 to 2016
Authors: Qiao Dan , Ke Shuifa , Zhang Xiaoxiao , Feng Qiya 
Published: November 2020

PurposeThe paper aims to explore the impact of marketization on forestry economic growth. Firstly, the development process of forestry marketization was summarized. Secondly, from the three dimensions of forestry production factor marketization, production marketization and product marketization, the framework of marketization is constructed by the authors.Design/methodology/approachBased on the yearbook data from 1978 to 2016, the relationship between forestry marketization and forestry growth was demonstrated through multiple regression and Granger test in this paper.FindingsThe results showed that forestry marketization was one of the important driving factors that impacted on China's forestry economic growth. Since the reform and opening up, China's forestry marketization degree has been constantly strengthened, but there is still room for improvement. China has provided an important model as forestry marketization reform and development sample for the world.Social implicationsMany useful references and inspirations have been provided from China such as gradually promoting market-oriented reforms; paying attention to the important role of reform and opening up in the construction of market mechanism; dynamic coordination of market and government relations; developing and connecting the relationship between domestic and international market; and coordinating the development of forestry state-owned economy, private economy and mixed ownership economy.Originality/valueThis paper creates a measure index of forestry marketization from three dimensions of forestry production factor marketization, production marketization and product marketization.
Measuring user experiences with e-sourcing platforms: the development of the e-sourcing experience index
Authors: Li Xintong , Zhao Li , Lee Stacy H. 
Published: November 2020

PurposeGrounded in two primary theories such as (1) the triangular alignment model and (2) the technology–organization–environment framework, this paper aims to develop appropriate scales to measure the e-sourcing experience index (EEI).Design/methodology/approachThe sample includes a total of 630 e-sourcing platform users in the US and India who have already utilized e-commerce platforms. Item response theory and factor analysis were used for the psychometric analysis. Measurement invariance was established between the Indian and US participants, indicating similar conceptualization of the items across the two cultures.FindingsThe study's results demonstrated that users have a better experience when online sourcing platforms provide adequate resources for making sourcing decisions, finding potential buyers and managing sourcing activities more efficiently. From the perspective of e-sourcing platforms, suppliers' performance and users' experiences can be improved when businesses address the concerns indicated in the five factors.Research limitations/implicationsThe study's objective was to develop the EEI in order to assess suppliers' experiences with e-sourcing platforms. Due to the diffusion of innovation theory (DOI), different stages of adaptation may cause varied experiences and relationships with buyers.Originality/valueFrom a theoretical perspective, this study is one of the few to combine triangular alignment model (TAM) and technology–organization–environment (TOE) theories and to develop a reliable and valid scale (EEI) for user experiences with online sourcing platforms. Based on the previous scales, the EEI was found to be well in line with the established theories on traditional apparel sourcing, and, at the same time, considered the particulars of e-sourcing practices.
Interactive research: concepts, contributions and challenges
Authors: Ellström Per-Erik , Elg Mattias , Wallo Andreas , Berglund Martina , Kock Henrik 
Published: November 2020

PurposeThis paper introduces interactive research as an emerging approach within a broad family of collaborative research approaches in management and organization research. Interactive research is a way to contribute to the dual tasks of long-term theory development and innovation and change processes in organizations. One of the distinguishing features of interactive research is a focus on continuous joint learning processes between the researchers and the involved practitioners.Design/methodology/approachThe basic concepts, contributions and challenges of the interactive research approach are presented and illustrated in the present paper through a practical case, the HELIX Centre.FindingsInteractive research is a way to advance scientific knowledge about the development of new types of work organizations and the development of sustainable operations. The multi-disciplinary and interactive research approach at HELIX has made it possible to reach a high degree of both rigour and relevance in research questions and projects. The authors identified five principles from the HELIX case that were instrumental in accomplishing the dual tasks of interactive research.Originality/valueThe interactive research approach is a powerful method of collaboration between different stakeholders throughout the research process. This type of research makes it possible to interact at various levels of research, from the programme level, to research and development projects, to the individual level. The results from interactive research should not only be considered traditionally valid but also valid in relation to organizational and societal needs.