bluuebunny/crossref_metadata_2025 huggingface dataset:
CHD8 haploinsufficiency alters the developmental trajectories of human excitatory and inhibitory neurons linking autism phenotypes with transient cellular defects
Authors: Villa Carlo Emanuele , Cheroni Cristina , López-Tóbon Alejandro , Dotter Christoph P. , Oliveira Bárbara , Sacco Roberto , Yahya Aysan Cerag , Morandell Jasmin , Gabriele Michele , Sommer Christoph , Gabitto Mariano , Testa Giuseppe , Novarino Gaia
Published: November 2020

Chromodomain helicase DNA-binding 8 (CHD8) is one of the most frequently mutated genes causative of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly and hence implicates cortical abnormalities in this form of ASD, the neurodevelopmental impact of human CHD8 haploinsufficiency remains unexplored. Here we combined human cerebral organoids and single cell transcriptomics to define the effect of ASD-linked CHD8 mutations on human cortical development. We found that CHD8 haploinsufficiency causes a major disruption of neurodevelopmental trajectories with an accelerated generation of inhibitory neurons and a delayed production of excitatory neurons alongside the ensuing protraction of the proliferation phase. This imbalance leads to a significant enlargement of cerebral organoids aligned to the macrocephaly observed in patients with CHD8 mutations. By adopting an isogenic design of patient-specific mutations and mosaic cerebral organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Finally, our results assign different CHD8-dependent molecular defects to particular cell types, pointing to an abnormal and extended program of proliferation and alternative splicing specifically affected in, respectively, the radial glial and immature neuronal compartments. By identifying temporally restricted cell-type specific effects of human CHD8 mutations, our study uncovers developmental alterations as reproducible endophenotypes for neurodevelopmental disease modelling.
Ethanolamine-phosphate on the second mannose is the preferential bridge for some of the brain GPI-anchored proteins
Authors: Ishida Mizuki , Maki Yuta , Ninomiya Akinori , Takada Yoko , Campeau Philippe , Kinoshita Taroh , Murakami Yoshiko
Published: November 2020

Glycosylphosphatidylinositols (GPIs) are glycolipids that anchor many proteins (GPI-APs) on the cell surface. The core glycan of GPI precursor has three mannoses, which in mammals, are all modified by ethanolamine-phosphate (EthN-P). It is postulated that EthN-P on the third mannose (EthN-P-Man3) is the bridge between GPI to the protein and the second (EthN-P-Man2) is removed after GPI-protein attachment. However, EthN-P-Man2 may not be always transient, as mutations of PIGG, the enzyme that transfers EthN-P to Man2, result in inherited GPI deficiencies (IGDs), characterized by neuronal dysfunctions. Here, we show EthN-P on Man2 is the preferential bridge in some GPI-APs, among them, the ect-5’-nucleotidase and netrin G2. We found that CD59, a GPI-AP, is attached via EthN-P-Man2 both in PIGB-knockout cells, in which GPI lacks Man3 and with a small fraction, in wild type cells. Our findings modify the current view of GPI anchoring and provide mechanistic bases of IGDs caused by PIGG mutations.
Retinal glial cells under hypoxia possibly function in mammalian myopia by responding to mechanical stimuli, affecting hormone metabolism and peptide secretion
Authors: Zhang Xuhong , Wen Yingying , Jin Le , Zhang Dongyan , Zhang Liyue , Xie Chen , Guo Dongyu , Tong Jianping , Shen Ye
Published: November 2020

Purpose

Changes in the retina and the choroid blood vessels are regularly observed in myopia. The aim of this study is to test if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia.

Method

We adapted the common form-deprivation myopia mouse model and used the retina slice and whole-mount immunofluorescence technique to evaluate changes in the morphology, and distribution of retinal glial cells. We then searched the Gene Expression Omnibus database for series on myopia and retinal glial cells (astrocytes and Müller cells). Using review articles and the National Center for Biotechnology Information gene database, we obtained clusters of myopia-related gene lists. By searching SwissTargetPrediction, we collected information on atropine target proteins. We then used online tools to find the Gene Ontology analysis enriched clusters, pathways, and proteins that provide correlative evidence.

Result

Glial fibrillary acidic protein fluorescence was observed in mice eyes that were covered and deprived of light for five days compared to uncovered eyes, and the cell morphology became more star-like. From in silico experiments, we identified several pathways and proteins that were common to both myopia and retinal glial cells in hypoxic conditions. The common pathways in human astrocytes represented response to mechanical stimuli, peptide secretion, skeletal system development, and monosaccharide binding. In mouse Müller cells, the pathways represented membrane raft and extracellular structure organisation. The proteins common to myopia and hypoxic glial cells were highly relevant to atropine target proteins.

Conclusion

Retinal astrocytes and Müller cells under hypoxic conditions contribute to the development of myopia, and may be a valid target for atropine.
The FABRIC Cancer Portal: A Ranked Catalogue of Gene Selection in Tumors over the Human Coding Genome
Authors: Kelman Guy , Brandes Nadav , Linial Michal
Published: November 2020

We present The FABRIC Cancer Portal, a comprehensive catalogue of gene selection in cancer covering the entire human coding genome (~18,000 protein-coding genes) across 33 cancer types and pan-cancer. Genes in the portal are ranked according to the strength of evidence for selection in tumor, based on rigorous and robust statistics. Gene selection is quantified by combining genomic data with rich proteomic annotations. The portal includes a selected set of cross-references to the most relevant resources providing genomic, proteomic and cancer-related information. We showcase the portal with known and overlooked cancer genes, demonstrating the usefulness of the portal via its simple visual interface that allows to pivot between gene-centric and cancer-type views. The portal is available at fabric-cancer.huji.ac.il.
Bias invariant RNA-seq metadata annotation
Authors: Wartmann Hannes , Heins Sven , Kloiber Karin , Bonn Stefan
Published: November 2020

Recent technological advances have resulted in an unprecedented increase in publicly available biomedical data, yet the reuse of the data is often precluded by experimental bias and a lack of annotation depth and consistency. Here we investigate RNA-seq metadata prediction based on gene expression values. We present a deep-learning based domain adaptation algorithm for the automatic annotation of RNA-seq metadata. We show how our algorithm outperforms existing approaches as well as traditional deep learning methods for the prediction of tissue, sample source, and patient sex information across several large data repositories. By using a model architecture similar to siamese networks the algorithm is able to learn biases from datasets with few samples. Our domain adaptation approach achieves metadata annotation accuracies up to 12.3% better than a previously published method. Lastly, we provide a list of more than 10,000 novel tissue and sex label annotations for 8,495 unique SRA samples.
Constraint-based metabolic control analysis for rational strain engineering
Authors: Tsouka Sophia , Ataman Meric , Hameri Tuure , Miskovic Ljubisa , Hatzimanikatis Vassily
Published: November 2020

The advancements in genome editing techniques over the past years have rekindled interest in rational metabolic engineering strategies. While Metabolic Control Analysis (MCA) is a well-established method for quantifying the effects of metabolic engineering interventions on flows in metabolic networks and metabolic concentrations, it fails to account for the physiological limitations of the cellular environment and metabolic engineering design constraints. We report here a constraint-based framework based on MCA, Network Response Analysis (NRA), for the rational genetic strain design that incorporates biologically relevant constraints, as well as genome editing restrictions. The NRA core constraints being similar to the ones of Flux Balance Analysis, allow it to be used for a wide range of optimization criteria and with various physiological constraints. We show how the parametrization and introduction of biological constraints enhance the NRA formulation compared to the classical MCA approach, and we demonstrate its features and its ability to generate multiple alternative optimal strategies given several user-defined boundaries and objectives. In summary, NRA is a sophisticated alternative to classical MCA for rational metabolic engineering that accommodates the incorporation of physiological data at metabolic flux, metabolite concentration, and enzyme expression levels.
Multimodal neuroimaging markers of variation in cognitive ability in older HIV+ men
Authors: Cruz Ana Lucia Fernandez , Chen Chien-Ming , Sanford Ryan , Collins D. Louis , Brouillette Marie-Josée , Mayo Nancy E. , Fellows Lesley K.
Published: November 2020

Objective

This study used converging methods to define the structural and functional characteristics of the neural substrates underlying variation in cognitive ability in older men with well-controlled HIV infection.

Methods

Seventy-six HIV+ men treated with combination antiretrovirals completed attention and inhibitory control tasks tapping different cortico-subcortical circuits while time-locked high-density EEG was acquired. Fifty-four also underwent structural MRI. We investigated relationships between task-evoked EEG responses, cognitive ability and immunocompromise. MRI suggested a subcortical basis for the observed EEG effects.

Results

EEG activity was associated with cognitive ability at later (P300) but not earlier processing stages of both tasks. However, only the P300 evoked by the attention task was associated with past HIV infection severity. Source localization confirmed that the tasks engaged different brain circuits. Thalamus volumes correlated with P300 amplitudes evoked by the attention task, while globus pallidus volumes were related to the P300 in both tasks.

Interpretation

This is the first study to combine structural and functional imaging in an overlapping sample to address the neural circuits related to cognitive dysfunction in HIV. Neural substrates of attention were more affected than those supporting inhibitory control. Preliminary evidence suggests these differences may relate to vulnerability of the thalamus to the effects of HIV. Our results suggest high-yield tasks and circuit targets for future work.
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

Experimental 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

Here 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

Eukaryotic 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

Objectives

To 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.

Design

The 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.

Setting

Swiss National Science Foundation (SNSF).

Participants

Postdoc.Mobility panel reviewers and additional expert reviewers.

Primary outcome measure

Per cent agreement between the simplified and official evaluation method with 95% confidence intervals (95% CI).

Results

The 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.

Conclusion

Agreement 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

The 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

Background

IDH1/2-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.

Methods

We 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.

Results

We 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.

Conclusions

These 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 study

IDH1/2 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

Rationale

There 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.

Objective

We investigated whether sequential delivery of FRT followed by VTP 7 days later improves PCa tumor control compared to monotherapy with FRT or VTP alone.

Findings

FRT 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.

Conclusion

Taken 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

The 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

The 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

Selfish 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.
The hydrochloride salt of 4-hydroxy-N,N-di-n-propyltryptamine (4-HO-DPT)
Authors: Sammeta Vamshikrishna Reddy , Rasapalli Sivappa , Chadeayne Andrew R. , Golen James A. , Manke David R.
Published: November 2020

The title compound, 4-hydroxy-N,N-di-n-propyltryptammonium (4-HO-DPT) chloride {systematic name: N-[2-(4-hydroxy-1H-indol-3-yl)ethyl]-N-propylpropan-1-aminium chloride}, C16H25N2O+·Cl−, has a singly protonated tryptammonium cation and one chloride anion in the asymmetric unit. A series of N—H...Cl and O—H...Cl hydrogen bonds connect the ions together in ladder chains along [010].
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

Purpose

The 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/approach

The proposed concept was empirically investigated by means of surveying 316 SME employees with the application of a multi-stage sampling procedure.

Findings

Research 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/value

This 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.
Corporate social responsibility and independent employee representation: an ethical contradiction?
Authors: Ryan Lorraine , Turner Thomas
Published: November 2020

Purpose

Many familiar global corporations have well-developed corporate social responsibility (CSR) policies that enunciate socially caring values that include the dignity and well-being of their employees. Yet opposition to independent employee voice from companies with trumpeted CSR credentials indicates an uncomfortable contradiction between rhetoric and reality in the treatment of employees as valued stakeholders. The purpose of this paper is to explore these contradictions using the lens of a libertarian tradition.

Design/methodology/approach

The CSR statements of three companies are examined to provide the context for their espoused values towards employees. Media, trade union and academic publications on each of the companies are then considered to identify systematic evidence of anti-union practices.

Findings

The paper illustrates the paradox of companies with espoused CSR policies advocating the dignity and well-being of their employees with often explicit coercive anti-union practices. These practices are a constraint on the negative freedom/liberty of employees in the libertarian tradition and amount to unethical behaviour on the part of the firm.

Originality/value

The paper offers important insights into the disconnection common in many firms between normative ethical claims in CSR statements to treat employees as valued legitimate stakeholders and the reality in the workplace.
Assessing entrepreneurial competences: insights from a business model challenge
Authors: Bolzani Daniela , Luppi Elena
Published: November 2020

Purpose

While the number of entrepreneurship education programmes offered around the world is on the rise, research into the assessment of entrepreneurship education programmes is still lacking. The purpose of this paper is to take the stance that entrepreneurship education has to focus on a set of transversal competences aimed at teaching individuals to become more enterprising, and develop a framework and practical proposal for the teaching and assessment of entrepreneurial competences.

Design/methodology/approach

The authors followed a three-pronged research design. First, the authors reviewed the literature and practices on the definition of entrepreneurial competences and measures for their assessment and identified a rubric of competences and a set of assessment tools. Second, the authors tested the identified tools to assess entrepreneurial competences through the development of an intensive extra-curricular initiative on entrepreneurship based on a business model challenge. Third, the authors evaluated the outcomes of this experience based on 72 student pre-test and post-test survey responses.

Findings

The authors assessed the impact of participation in a business model challenge with regard to five competence areas: positive attitude and initiative; communication and interaction; team-work and collaboration; critical and analytical thinking or problem solving, including risk assessment; creativity and innovation. The authors found no relevant changes across these dimensions, concluding that the mere exposure to the business challenge was not a sufficient condition for stimulating the development of entrepreneurial competences in our sample.

Originality/value

This work provides a relevant contribution to researchers, educators and policymakers by taking an interdisciplinary approach to reviewing previous literature and proposing ways of assessing transversal competences in the context of entrepreneurship education.
Pedagogical innovation in higher education and active learning methodologies – a case study
Authors: Carvalho Andreia , Teixeira Sergio Jesus , Olim Leonilde , Campanella Sancha de , Costa Teresa
Published: November 2020

Purpose

The aim of this study is to obtain a broader knowledge of innovative pedagogical practices in higher education, by analysing the particular case of the Higher Institute of Administration and Languages (ISAL). The literature review reveals a gap in this scientific field, and filling this gap is as imperative as the need to articulate higher education with the Students' Profile by the End of Compulsory Schooling.

Design/methodology/approach

This research adopts a qualitative methodological approach, in order to analyse the students and teachers' perceptions of the active learning methodologies implemented at ISAL. Data were collected from a closed-ended questionnaire, aimed at a population composed of students and teachers.

Findings

The literature review reveals a gap in this scientific field, particularly in Portugal. Filling this gap is as imperative as the need to articulate higher education with the Students' Profile by the End of Compulsory Schooling.

Practical implications

With the adoption of this methodological approach, this research intends to verify not only whether the innovative pedagogical practices addressed in the literature review are implemented in this institution, but also to identify obstacles to their implementation. With regard to the results, several pedagogical innovation practices are already implemented, even though some limitations to their implementation are identified.

Originality/value

This research allows identifying indicators that are essential to outline an intervention plan in the pedagogical practices implemented at ISAL or other higher education institutions and contributes to assessing the current state of pedagogical practices in higher education.
Analysis of the channeling of water injection in low permeability reservoirs with interlayer considering the seepage–stress coupling
Authors: Youjun Ji , Vafai K. , Xu Huijin , Jianjun Liu
Published: November 2020

Purpose

This paper aims to establish a mathematical model for water-flooding considering the impact of fluid–solid coupling to describe the process of development for a low-permeability reservoir. The numerical simulation method was used to analyze the process of injected water channeling into the interlayer.

Design/methodology/approach

Some typical cores including the sandstone and the mudstone were selected to test the permeability and the stress sensitivity, and some curves of the permeability varying with the stress for the cores were obtained to demonstrate the sensitivity of the formation. Based on the experimental results and the software Eclipse and Abaqus, the main injection parameters to reduce the amount of the injected water in flowing into the interlayer were simulated.

Findings

The results indicate that the permeability of the mudstone is more sensitive to the stress than sandstone. The injection rate can be as high as possible on the condition that no crack is activated or a new fracture is created in the development. For the B82 block of Daqing oilfield, the suggested pressure of the production pressure should be around 1–3MPa, this pressure must be gradually reached to get a higher efficiency of water injection and avoid damaging the casing.

Originality/value

This work is beneficial to ensure stable production and provide technical support to the production of low permeability reservoirs containing an interlayer.
Water efficiency in Malaysian commercial buildings: a green initiative and cost–benefit approach
Authors: Mohd Zaini Farhana , Kwong Qi Jie , Jack Lynne Barbara
Published: November 2020

Purpose

The demand for potable water increases with population growth, given its role in sustaining life. As part of a wider approach to ensuring sustainable provision, this has prompted a number of carefully formulated water efficiency improvement plans for buildings, one of the highest water-consuming sectors. This paper presents a detailed analysis of water efficiency potential for a multi-storey commercial complex and an office building in central Malaysia.

Design/methodology/approach

In this study, a detailed analysis of the water use and efficiency of the water fittings was carried out. Important data such as historical water use and details of water fittings were acquired during a field survey. A series of water flow rate tests were conducted at the selected buildings and each of the water systems was analysed separately, using the criteria of water efficiency stipulated by a locally applied green building tool. A comparison of water consumption before and after the improvement plan was then made.

Findings

Findings from the field surveys indicate that only some of the water fittings were certified with recognised efficiency ratings, which suggests a good opportunity for improvement. The proposed replacement of more-efficient fittings could potentially improve the obtainable green credit points by at least 10 from a maximum of 15. A cost–benefit analysis for a water fitting replacement scheme shows that the estimated payback period is less lengthy for the larger commercial building due to the higher potential savings.

Practical implications

Strategies for improvements in water efficiency for existing non-residential buildings are provided in this paper. The same water consumption analysis procedure can be used by maintenance engineers and other practitioners in building assessments where water efficiency and sustainability in building operation are of concern.

Originality/value

This case study responds to the need for efficient use of freshwater and provides insight into the water efficiency opportunities for commercial buildings. The potential cost savings for replacements of inefficient water fittings have been analysed using a green building tool as a guide. This has not been extensively analysed in previous studies.
A critical review and reconstruction of perceptual brand equity
Authors: Tasci Asli D.A.
Published: November 2020

Purpose

The purpose of this paper is to: distinguish between financial brand equity and perceptual brand equity; distinguish among different stakeholder perspectives on customer-based brand equity, consumer-based brand equity (CBBE) (consumer, customer, employee and resident); contrast the original definitions and measures of CBBE by Aaker and Keller; identify the deviations from the original conceptualizations and measures of CBBE by Aaker and Keller; discuss the evolution of the most commonly used CBBE components; analyze the structural relations of the most common CBBE components and generate conceptual, structural, relational and methodological suggestions for future research.

Design/methodology/approach

This critical review conducted a narrative analysis of the perceptual brand equity literature (CBBE) by inventorying about 200 empirical and conceptual CBBE studies in several different contexts. Studies that included CBBE, brand equity, customer-based brand equity and consumer-based brand equity were included in this review. Only 87 representative studies that either conceptually defined or empirically measured CBBE and its components were included in the deep analysis.

Findings

The review revealed that the literature is divergent in terms of CBBE components or structural relations among components in any context including tourism and hospitality. Even though about 40 different CBBE components exist in different contexts, the totality of the CBBE literature reflects a consensus on five components of CBBE, brand familiarity/brand awareness, brand image/brand associations, perceived quality, consumer value and brand loyalty, all of which collectively define the total meanings of a brand from consumer/customer perspective.

Research limitations/implications

Keeping these five components intact, this study suggests a concise CBBE definition, conceptual clarifications for these components, a model reflecting their structural relations and a framework of parsimonious measures. The study makes future research recommendations in terms of using uniform CBBE components, measures and relational structure among components, identifying the relationship between CBBE and financial-based brand equity and comparing different stakeholder perspectives on CBBE in future research.

Originality/value

With these observations and suggestions, this critical review provides a guideline for more robust theory development of the CBBE construct. Additionally, it offers a parsimonious and practical CBBE blueprint for the practitioners who include CBBE as a strategic market metric in their marketing and research plans. Furthermore, it suggests standardization in CBBE research to enable systematic reviews with meta-analysis of the CBBE literature in the future. Using standard components, measures and relational models in CBBE research, as was suggested in this study, would allow meta-analysis for a meaningful comparison of results between different brands, products and even industries.