bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of upper limb training and analyzed muscles on estimate of physical activity during cereal grinding using saddle quern and rotary quern
Authors: Struška Michal , Hora Martin , Rocek Thomas R. , Sládek Vladimír 
Published: November 2020

AbstractExperimental grinding has been used to study the relationship between human humeral robusticity and cereal grinding in the early Holocene. However, such replication studies raise two questions regarding the robusticity of the results: whether female nonathletes used in previous research are sufficiently comparable to early agricultural females, and whether previous analysis of muscle activation of only four upper limb muscles is sufficient to capture the stress of cereal grinding on upper limb bones. We test the influence of both of these factors. Electromyographic activity of eight upper limb muscles was recorded during cereal grinding in an athletic sample of 10 female rowers and a nonathletic sample of 25 females and analyzed using both an eight- and four-muscle model. Athletes had lower activation than nonathletes in the majority of measured muscles, but most of these differences were non-significant. Furthermore, both athletes and nonathletes had lower muscle activation during saddle quern grinding than rotary quern grinding suggesting that the nonathletic sample can be used to model early agricultural females during saddle and rotary quern grinding.Similarly, in both eight- and four-muscle models, upper limb loading was lower during saddle quern grinding than during rotary quern grinding, suggesting that the upper limb muscles may be reduced to the previously used four-muscle model for evaluation of the upper limb loading during cereal grinding. Another implication of our measurements is to question the assumption that skeletal indicators of high involvement of the biceps brachii muscle can be interpreted as specifically indicative of saddle quern grinding.
Extending and repeating assessments is a key tool to reveal barriers to effective management of protected areas
Authors: Maes Marcos Eugênio , Giehl Eduardo L. Hettwer , Hanazaki Natalia 
Published: November 2020

AbstractHere we assessed protected area (PA) management effectiveness while also checking for potential barriers. We addressed 21 PAs of the State of Santa Catarina, southern Brazil. Out of these, we assessed 10 PAs under state level administration that lacked thus far a standardized assessment. For PAs under federal administration, we got assessment data from the government itself. We contrasted the PAs regarding the level of administration and collected a list of aspects that could result in differences in management effectiveness between PAs. We checked the relationship between PA aspects and mean effectiveness with linear models. The same aspects were also related to PA management elements, namely context, planning, inputs, processes, and outputs, using redundancy analysis. Management effectiveness and scores of management elements were found to be lower for PAs either with unresolved land tenure, lacking management plans, being under many pressures and threats, or being under state level administration. Our results call for extended assessments to reach the reality of the Brazilian PA network with different administration levels. Assessments must be carried out regularly since it is the only way to effectively flag a barrier, clear it, then find the next one to be tackled.
Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation
Authors: Wang Xiuye , Liu Liang , Whisnant Adam W. , Hennig Thomas , Djakovic Lara , Haque Nabila , Bach Cindy , Sandri-Goldin Rozanne M. , Erhard Florian , Friedel Caroline C. , Dölken Lars , Shi Yongsheng 
Published: November 2020

AbstractEukaryotic gene expression is extensively regulated by cellular stress and pathogen infections. We have previously shown that herpes simplex virus 1 (HSV-1) and several cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes and that the viral immediate early factor ICP27 plays an important role in HSV-1-induced DoTT. Here, we show that HSV-1 infection also leads to widespread changes in alternative polyadenylation (APA) of host mRNAs. In the majority of cases, polyadenylation shifts to upstream poly(A) sites (PAS), including many intronic PAS. Mechanistically, ICP27 contributes to HSV-1-mediated APA regulation. HSV-1- and ICP27-induced activation of intronic PAS is sequence-dependent and does not involve general inhibition of U1 snRNP. HSV1-induced intronic polyadenylation is accompanied by early termination of RNAPII. Finally, HSV-1-induced mRNAs polyadenylated at intronic PAS are exported into the cytoplasm while APA isoforms with extended 3’ UTRs are sequestered in the nuclei, both preventing the expression of the full-length gene products. Together with other recent studies, our results suggest that viral infection and cellular stresses induce a multi-faceted host shutoff response that includes DoTT and changes in APA profiles.
How to best evaluate applications for junior fellowships? Remote evaluation and face-to-face panel meetings compared
Authors: Bieri Marco , Roser Katharina , Heyard Rachel , Egger Matthias 
Published: November 2020

AbstractObjectivesTo test a simplified evaluation of fellowship proposals by analyzing the agreement of funding decisions with the official evaluation, and to examine the use of a lottery-based decision for proposals of similar quality.DesignThe study involved 134 junior fellowship proposals (Postdoc.Mobility). The official method used two panel reviewers who independently scored the application, followed by triage and discussion of selected applications in a panel. Very competitive/uncompetitive proposals were directly funded/rejected without discussion. The simplified procedure used the scores of the two panel members, with or without the score of an additional, third expert. Both methods could further use a lottery to decide on applications of similar quality close to the funding threshold. The same funding rate was applied, and the agreement between the two methods analyzed.SettingSwiss National Science Foundation (SNSF).ParticipantsPostdoc.Mobility panel reviewers and additional expert reviewers.Primary outcome measurePer cent agreement between the simplified and official evaluation method with 95% confidence intervals (95% CI).ResultsThe simplified procedure based on three reviews agreed in 80.6% (95% CI 73.9-87.3) with the official funding outcome. The agreement was 86.6% (95% CI 80.8-92.4) when using the two reviews of the panel members. The agreement between the two methods was lower for the group of applications discussed in the panel (64.2% and 73.1%, respectively), and higher for directly funded/rejected applications (range 96.7% to 100%). The lottery was used in eight (6.0%) of 134 applications (official method), 19 (14.2%) applications (simplified, three reviewers) and 23 (17.2%) applications (simplified, two reviewers). With the simplified procedure, evaluation costs could have been halved and 31 hours of meeting time saved for the two 2019 calls.ConclusionAgreement between the two methods was high. The simplified procedure could represent a viable evaluation method for the Postdoc.Mobility early career instrument at the SNSF.
Sub-millisecond conformational dynamics of the A2A adenosine receptor revealed by single-molecule FRET
Authors: Maslov Ivan , Volkov Oleksandr , Khorn Polina , Orekhov Philipp , Gusach Anastasiia , Kuzmichev Pavel , Gerasimov Andrey , Luginina Aleksandra , Coucke Quinten , Bogorodskiy Andrey , Gordeliy Valentin , Wanninger Simon , Barth Anders , Mishin Alexey , Hofkens Johan , Cherezov Vadim , Gensch Thomas , Hendrix Jelle , Borshchevskiy Valentin 
Published: November 2020

AbstractThe complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by their multi-state conformational dynamics. Single-molecule Förster Resonance Energy Transfer (smFRET) is well-suited to quantify dynamics for individual protein molecules, however, its application to GPCRs is challenging; therefore, smFRET has been limited to studies of interreceptor interactions in cellular membranes and receptors in detergent environments. Here, we performed smFRET experiments on functionally active human A2A adenosine receptor (A2AAR) molecules embedded in freely diffusing lipid nanodiscs to study their intramolecular conformational dynamics. We propose a dynamic model of A2AAR activation that involves a slow (>2 ms) exchange between the active-like and inactive-like conformations in both apo and antagonist-bound A2AAR, explaining the receptor’s constitutive activity. For the agonist-bound A2AAR, we detected faster (390±80 μs) ligand efficacy-dependent dynamics. This work establishes a general smFRET platform for GPCR investigations that can potentially be used for drug screening and/or mechanism-of-action studies.
Orthogonal targeting of KDM6A/B and HDACs mediates potent therapeutic effects in IDH1-mutant glioma
Authors: Kayabolen Alisan , Yilmaz Ebru , Sahin Gizem Nur , Seker-Polat Fidan , Cingoz Ahmet , Isik Bekir , Acar Simge , Wakimoto Hiroaki , Cahill Daniel P. , Solaroglu Ihsan , Cribbs Adam P , Oppermann Udo , Bagci-Onder Tugba 
Published: November 2020

ABSTRACTBackgroundIDH1/2-mutant gliomas are primary brain tumors for which curative treatments are lacking. Mutant IDH-dependent 2-hydroxyglutarate (2-HG) accumulation leads to DNA and histone hypermethylation. Based on this distinct phenotype, we interrogated epigenetic dependencies of IDH-mutant glioma that can be targeted therapeutically.MethodsWe conducted a chemical screen targeting chromatin modifiers in patient derived IDH1-mutant GBM cells. We investigated mechanisms of action of compound hits and their combinations through cell-based functional assays, live-cell imaging, Western blot, CRISPR knockout, RNA-seq and ChIP experiments. The therapeutic concept was validated in vivo using chemical inhibitors GSK-J4 and Belinostat in an orthotopic GBM model.ResultsWe identified the H3K27me3 demethylase (KDM6) inhibitor GSK-J4 and histone deacetylase inhibitor Belinostat as potent, genotype-selective agents against IDH1-mutant glioma. RNA-sequencing on paired wild-type and IDH1R132H cells revealed inhibition of cholesterol biosynthesis and activation of cellular stress in IDH1R132H cells, which were reversible with a mutant IDH1 inhibitor. GSK-J4 caused further repression of cholesterol biosynthesis pathway genes through H3K27me3 deposition and exacerbated the ATF4-mediated integrated stress response. Belinostat inhibited anti-apoptotic pathways through activation of TGF-β signaling and induced cell cycle arrest. Together, the GSK-J4 and Belinostat combination activated DDIT3/CHOP-dependent apoptosis in IDH1-mutant cells and extended survival in an IDH1-mutant orthotopic model in vivo.ConclusionsThese results provide a possible therapeutic approach that exploits epigenetic vulnerabilities of IDH-mutant gliomas.Key points-Combination of GSK-J4 and Belinostat selectively targets IDH1-mutant cells.-GSK-J4 downregulates cholesterol biosynthesis and activates an ATF4-mediated stress response.-Belinostat activates the TGFβ pathway, induces G2/M arrest and inhibits anti-apoptotic pathways.Importance of the studyIDH1/2 genes are frequently mutated in low grade glioma and secondary glioblastoma. These tumors exhibit a distinct epigenomic signature with increased DNA and histone methylation; therefore, identifying and exploiting their epigenetic vulnerabilities may lead to effective therapies. We discovered that targeting of KDM6A/6B together with HDACs provides a promising therapeutic approach for IDH1-mutant glioma.
Tumor irradiation combined with vascular-targeted photodynamic therapy enhances anti-tumor effects in preclinical prostate cancer
Authors: Sjoberg Hanna T , Philippou Yiannis , Magnussen Anette L , Tullis Iain DC , Bridges Esther , Chatrian Andrea , Loefebvre Joel , Tam Ka Ho , Murphy Emma A , Rittscher Jens , Preise Dina , Agemy Lilach , Yechezkel Tamar , Smart Sean C , Kinchesh Paul , Gilchrist Stuart , Allen Danny P , Scheiblin David A , Lockett Stephen J , Wink David A , Lamb Alastair D , Mills Ian G , Harris Adrian , Muschel Ruth J , Vojnovic Boris , Scherz Avigdor , Hamdy Freddie C , Bryant Richard J 
Published: November 2020

AbstractRationaleThere is an important clinical need to improve the treatment of high risk localized and locally advanced prostate cancer (PCa), and to reduce the side effects of these treatments. We hypothesized that multi-modality therapy combining radiotherapy and vascular-targeted photodynamic therapy (VTP) could PCa tumour control compared against monotherapy with each of these treatments alone. This could provide proof-of-concept to take to the clinic. VTP is a focal therapy for localized PCa, which rapidly destroys targeted tumors through vascular disruption. Tumor vasculature is characterized by vessel immaturity, increased permeability, aberrant branching and inefficient flow. Fractionated radiotherapy (FRT) alters the tumor microenvironment and promotes transient vascular normalization.ObjectiveWe investigated whether sequential delivery of FRT followed by VTP 7 days later improves PCa tumor control compared to monotherapy with FRT or VTP alone.FindingsFRT induced vascular normalization changes in PCa flank tumor allografts, improving vascular function as demonstrated using dynamic contrast enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumor growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP alone, and improved overall survival.ConclusionTaken together, these results suggest that combining FRT and VTP could become a promising multimodal clinical strategy in PCa therapy. This provides proof-of-concept for this multi-modality therapy approach to take forward to early phase clinical trials.
Investigation of heterochromatin protein 1 function in the malaria parasitePlasmodium falciparumusing a conditional domain deletion and swapping approach
Authors: Bui Hai T. N. , Passecker Armin , Brancucci Nicolas , Voss Till S. 
Published: November 2020

AbstractThe human malaria parasitePlasmodium falciparumencodes a single ortholog of heterochromatin protein 1 (PfHP1) that plays a crucial role in the epigenetic regulation of various survival-related processes. PfHP1 is essential for parasite proliferation and the heritable silencing of genes linked to antigenic variation, host cell invasion and sexual conversion. Here, we employed CRISPR/Cas9-mediated genome editing combined with the DiCre/LoxP system to investigate how the PfHP1 chromodomain (CD), hinge domain and chromoshadow domain (CSD) contribute to overall PfHP1 function. We show that the C-terminal 76 residues are responsible for targeting PfHP1 to the nucleus. Furthermore, we reveal that each of the three functional domains of PfHP1 are required for heterochromatin formation, gene silencing and mitotic parasite proliferation. Finally, we discovered that the hinge and CSD domains of HP1 are functionally conserved betweenP. falciparumandP. berghei, a related malaria parasite infecting rodents. In summary, our study provides new insights into PfHP1 function and offers a tool for further studies on epigenetic regulation and life cycle decision in malaria parasites.
Archaeogenomics of a ~2,100-year-old Egyptian leaf provides a new timestamp on date palm domestication
Authors: Pérez-Escobar Oscar A. , Bellot Sidonie , Gros-Balthazard Muriel , Flowers Jonathan M. , Nesbitt Mark , Ryan Philippa , Gutaker Rafal M. , Wells Tom , Schley Rowan , Bogarín Diego , Przelomska Natalia , Dodsworth Steven , Diaz Rudy , Lehmann Manuela , Petoe Peter , Eiserhardt Wolf L. , Preick Michaela , Hofreiter Michael , Hajdas Irka , Antonelli Alexandre , Leitch Ilia J. , Gravendeel Barbara , Torres Maria Fernanda , Chomicki Guillaume , Renner Susanne S. , Papadopulos Alexander S.T. , Purugganan Michael , Baker William J. 
Published: November 2020

AbstractThe date palm (Phoenix dactylifera) has been a cornerstone of Middle Eastern and North African agriculture for millennia. It is presumed that date palms were first domesticated in the Persian Gulf and subsequently introduced into North Africa, where their evolution in the latter region appears to have been influenced by gene flow from the wild relativeP. theophrasti, which is restricted to Crete and Turkey. However, the timing of gene flow fromP. theophrastitoP. dactyliferaremains unknown due to the limited archaeobotanical evidence ofP. theophrastiand their exclusion from population genomic studies.We addressed this issue by investigating the relatedness and ancestry of a ~2,100-year-oldP. dactyliferaleaf from Saqqara (Egypt), combining genome sequencing of this ancient specimen with a broad sample of date palm cultivars and closely related species.The ancient Saqqara date palm shares close genetic ancestry with North African date palm populations. We find clear genomic admixture between the Saqqara date palm,P. theophrastiand the closest known relativeP. sylvestris.Our study highlights that gene flow fromP. theophrastiandP. sylvestristo North African date palms had already occurred at least ~2,100 years ago, providing a minimum timestamp for hybridisation between species.
Centromere drive and suppression by parallel pathways for recruiting microtubule destabilizers
Authors: Kumon Tomohiro , Ma Jun , Stefanik Derek , Nordgren Erik C. , Akins R. Brian , Kim Junhyong , Levine Mia T. , Lampson Michael A. 
Published: November 2020

SummarySelfish centromere DNA sequences bias their transmission to the egg in female meiosis. Evolutionary theory suggests that centromere proteins evolve to suppress costs of this “centromere drive”. In hybrid mouse models with genetically different maternal and paternal centromeres, selfish centromere DNA exploits a kinetochore pathway to recruit microtubule-destabilizing proteins that act as drive effectors. We show that such functional differences are suppressed by a parallel pathway for effector recruitment by heterochromatin, which is similar between centromeres in this system. Disrupting heterochromatin by CENP-B deletion amplifies functional differences between centromeres, whereas disrupting the kinetochore pathway with a divergent allele of CENP-C reduces the differences. Molecular evolution analyses using newly sequenced Murinae genomes identify adaptive evolution in proteins in both pathways. We propose that centromere proteins have recurrently evolved to minimize the kinetochore pathway, which is exploited by selfish DNA, relative to the heterochromatin pathway that equalizes centromeres, while maintaining essential functions.
Internet reporting, social media strategy and firm characteristics – an Australian study
Authors: Xiang Yi , Birt Jacqueline L. 
Published: November 2020

Purpose
This paper aims to investigate internet reporting and social media strategies by Australian firms. This study looks at the extent of internet reporting and considers firm characteristics associated with disclosing information on the internet. This research is timely as in the past decade, this paper has witnessed the rapid growth of technologies such as the internet and social media and their subsequent impact on business and the economy.

Design/methodology/approach
This paper constructs a disclosure index featuring a wide range of both financial and non-financial disclosures including social media strategy. This study then investigates the firm characteristics associated with the level of internet disclosure.

Findings
This paper finds that a firm’s internet reporting is associated with firm size, financial performance and analysts’ coverage but not associated with the percentage of independent board members. A firm’s social media strategy is associated with firm size and its environmental, social and corporate governance (ESG) ranking.

Practical implications
The findings can help firms improve their internet reporting disclosures by providing a comprehensive list of disclosures that could benefit users of financial reports. It also helps standard setters and regulators understand some of the firm factors related to internet reporting and provide guidance for standard setters to consider in developing best practice internet reporting standards.

Originality/value
The research features the top 100 Australian companies’ internet disclosures in 2018 and also includes social media strategy. The results highlight that there is room for improvement with firms’ internet disclosure. By constructing a comprehensive index, this study provides guidance for standard setters to consider in developing best practice internet reporting standards.
Diagnosis of brushless synchronous generator using numerical modeling
Authors: Rahnama Mehdi , Vahedi Abolfazl , Mohammad-Alikhani Arta , Takorabet Noureddine 
Published: November 2020

Purpose
On-time fault diagnosis in electrical machines is a critical issue, as it can prevent the development of fault and also reduce the repairing time and cost. In brushless synchronous generators, the significance of the fault diagnosis is even more because they are widely used to generate electrical power all around the world. Therefore, this study aims to propose a fault detection approach for the brushless synchronous generator. In this approach, a novel extension of Relief feature selection method is developed.

Design/methodology/approach
In this paper, by taking the advantages of the finite element method (FEM), a brushless synchronous machine is modeled to evaluate the machine performance under two conditions. These conditions include the normal condition of the machine and one diode open-circuit of the rotating rectifier. Therefore, the harmonic behavior of the terminal voltage of the machine is obtained under these situations. Then, the harmonic components are ranked by using the extension of Relief to extract the most appropriate components for fault detection. Therefore, a fault detection approach is proposed based on the ranked harmonic components and support vector machine classifier.

Findings
The proposed diagnosis approach is verified by using an experimental test. Results show that by this approach open-circuit fault on the diode rectifier can effectively be detected by the accuracy of 98.5% and by using five harmonic components of the terminal voltage [1].

Originality/value
In this paper, a novel feature selection method is proposed to select the most effective FFT components based on an extension of Relief method, and besides, FEM modeling of a brushless synchronous generator for normal and one diode open-circuit fault.
The impact of information and communication technology and internal market orientation blending on organisational performance in small and medium enterprises
Authors: Kazakov Sergey , Ruiz-Alba José L. , Muñoz María M. 
Published: November 2020

PurposeThe present study examines the concept of internal market orientation (IMO) and its effects on organisational performance comprising job satisfaction and employees' loyalty in the small and medium enterprises (SMEs) research context. Rooted in administrative theory, human relations theory, conventional theories of IMO and internal marketing, this study develops a novel iIMO theoretical framework that evinces the proliferation of ICTs in SMEs.Design/methodology/approachThe proposed concept was empirically investigated by means of surveying 316 SME employees with the application of a multi-stage sampling procedure.FindingsResearch findings confirmed the viability of the ICT-supported iIMO framework, its positive effects on SMEs' organisational performance, and exhibited ample empirical evidence for the proficiency of the iIMO concept and its suitability for operationalisation by SMEs.Originality/valueThis study introduces ICTs as a novel IMO dimension which considers the undergoing holistic digitalisation of businesses. In addition, the present research posits the plausibility and confirms the benefits that arise following iIMO implementation in SMEs.