bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attentional selection and communication through coherence: Scope and limitations
Authors: Greenwood Priscilla E. , Ward Lawrence M. 
Published: August 2023

AbstractSynchronous neural oscillations are strongly associated with a variety of perceptual, cognitive, and behavioural processes. It has been proposed that the role of the synchronous oscillations in these processes is to facilitate information transmission between brain areas, the ‘communication through coherence,’ or CTC hypothesis.The details of how this mechanism would work, however, and its causal status, are still unclear. Here we investigate computationally a proposed mechanism for selective attention that directly implicates the CTC as causal. The mechanism involves alpha band (about 10 Hz) oscillations, originating in the pulvinar nucleus of the thalamus, being sent to communicating cortical areas, organizing gamma (about 40 Hz) oscillations there, and thus facilitating phase coherence and communication between them. This is proposed to happen contingent on control signals sent from higher-level cortical areas to the thalamic reticular nucleus, which controls the alpha oscillations sent to cortex by the pulvinar. We studied the scope of this mechanism in parameter space, and limitations implied by this scope, using a computational implementation of our conceptual model. Our results indicate that, although the CTC-based mechanism can account for some effects of top-down and bottom-up attentional selection, its limitations indicate that an alternative mechanism, in which oscillatory coherence is caused by communication between brain areas rather than being a causal factor for it, might operate in addition to, or even instead of, the CTC mechanism.Author summaryThe ability to select some stimulus or stimulus location from all of those available to our senses is critical to our ability to navigate our complex biological and social niche, and to organize appropriate actions to accomplish our goals, namely to survive and to reproduce. We study here a possible mechanism by which the brain could accomplish attentional selection. We show that the interaction between 10 Hz and 40 Hz neural oscillations can provide increases in coherence and information transmission between computationally modelled cortical areas. Our results support the idea that synchronization between oscillations facilitates communication between cortical areas. Limitations and sensitivities to the model, however, also point to the idea that the relation between coherence and communication could go in the opposite direction in some cases, particularly when attention is not involved.
Identification of resistance mechanisms to small-molecule inhibition of TEAD-regulated transcription
Authors: Kulkarni Aishwarya , Mohan Varshini , Tang Tracy T. , Post Leonard , Manning Murray , Thio Niko , Parker Benjamin L. , Rosenbluh Joseph , Vissers Joseph H.A. , Harvey Kieran F. 
Published: August 2023

ABSTRACTThe Hippo tumour suppressor pathway controls transcription by regulating nuclear abundance of YAP and TAZ, which activate transcription with the TEAD1-TEAD4 DNA-binding proteins. Recently, several small-molecule inhibitors of YAP and TEADs have been reported, with some now entering clinical trials for different cancers. Here, we investigated the cellular response to TEAD palmitoylation inhibitors, using a combination of genomic and genetic strategies. Genome-wide CRISPR/Cas9 screens identified genes that modulate the cellular response to TEAD inhibition, including members of the Hippo, MAPK and JAK-STAT signaling pathways. By exploring gene expression programs of mutant cells, we found that MAPK pathway hyperactivation confers resistance to TEAD inhibition by reinstating expression of a subset of YAP/TEAD target genes. Consistent with this, combined inhibition of TEAD and the MAPK protein MEK, synergistically blocked proliferation of several mesothelioma and lung cancer cell lines and more potently reduced the growth of patient-derived lung cancers in vivo. Collectively, we reveal mechanisms by which cells can overcome small-molecule inhibition of TEADs and potential strategies to enhance the anti-tumor activity of emerging Hippo pathway targeted therapies.
Distinct mechanisms by which antioxidant transcription factors Nrf1 and Nrf2 as drug targets contribute to the anticancer efficacy of Cisplatin on hepatoma cells
Authors: Wufuer Reziyamu , Liu Keli , Jingfeng  , Wang Meng , Hu Shaofan , Chen Feilong , Lin Shanshan , Zhang Yiguo 
Published: August 2023

AbstractCisplatin (cis-Dichlorodiamineplatinum[II], CDDP) is generally accepted as a platinum-based alkylating agent type of the DNA-damaging anticancer drug, which is widely administrated in clinical treatment of many solid tumors. The pharmacological effect of CDDP is mainly achieved by replacing the chloride ion (Cl−) in its structure with H2O to form active substances with the strong electrophilic properties and then react with any nucleophilic molecules, primarily leading to genomic DNA damage and subsequent cell death. In this process, those target genes driven by the consensus electrophilic and/or antioxidant response elements (EpREs/AREs) in their promoter regions are also activated or repressed by CDDP. Thereby, we here examined the expression profiling of such genes regulated by two principal antioxidant transcription factors Nrf1 and Nrf2 (both encoded byNfe2l1andNfe2l2,respectively) in diverse cellular signaling responses to this intervention. The results demonstrated distinct cellular metabolisms, molecular pathways and signaling response mechanisms by which Nrf1 and Nrf2 as the drug targets differentially contribute to the anticancer efficacy of CDDP on hepatoma cells and xenograft tumor mice. Interestingly, the role of Nrf1, rather than Nrf2, is required for the anticancer effect of CDDP, to suppress malignant behavior of HepG2 cells by differentially monitoring multi-hierarchical signaling to gene regulatory networks. To our surprise, it was found there exists a closer relationship of Nrf1α than Nrf2 with DNA repair, but the hyperactive Nrf2 inNrf1α−/−cells manifests a strong correlation with its resistance to CDDP, albeit their mechanistic details remain elusive.
Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains
Authors: Mancinelli Chiara , Marx Dagan C. , Gonzalez-Hernandez Alberto J. , Huynh Kevin , Mancinelli Lucia , Arefin Anisul , Khelashvilli George , Levitz Joshua , Eliezer David 
Published: August 2023

AbstractG protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical interactions with the transmembrane core of active GPCRs, all three classes of transducers have also been reported to interact with receptor C-terminal domains (CTDs). An underexplored aspect of GPCR CTDs is their possible role as lipid sensors given their proximity to the membrane. CTD-membrane interactions have the potential to control the accessibility of key regulatory CTD residues to downstream effectors and transducers. Here we report that the CTDs of two closely related family C GPCRs, metabotropic glutamate receptor 2 (mGluR2) and mGluR3, bind to membranes and that this interaction can regulate receptor function. We first characterize CTD structure with NMR spectroscopy, revealing lipid composition-dependent modes of membrane binding. Using molecular dynamics simulations and structure-guided mutagenesis, we then identify key conserved residues and cancer-associated mutations that modulate CTD-membrane binding. Finally, we provide evidence that mGluR3 transducer coupling is controlled by CTD-membrane interactions in live cells, which may be subject to regulation by CTD phosphorylation and changes in membrane composition. This work reveals a novel mechanism of GPCR modulation, suggesting that CTD-membrane binding may be a general regulatory mode throughout the broad GPCR superfamily.Significance StatementG protein-coupled receptors (GPCRs) allow cells to sense and respond to their environment and constitute the largest class of targets for approved therapeutic drugs. Temporally precise GPCR signaling is achieved by coupling the binding of extracellular ligands to the binding of intracellular signal transducers (e.g. heterotrimeric G proteins) and regulators (e.g. β-arrestins). The C-terminal domains (CTDs) of GPCRs are targets of various post-translational modifications and play a critical role in transducer and regulator recruitment. Here we report novel interactions of the CTDs of two GPCRs of the metabotropic glutamate receptor family with cellular membranes. These interactions serve to regulate CTD accessibility and thus, mGluR coupling to transducers and regulators. We propose that dynamic CTD-membrane interaction constitutes a general mechanism for regulating GPCR function.
Structure ofC. elegansTMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction
Authors: Clark Sarah , Jeong Hanbin , Posert Rich , Goehring April , Gouaux Eric 
Published: August 2023

AbstractMechanotransduction is the process by which a mechanical force, such as touch, is converted into an electrical signal. Transmembrane channel-like (TMC) proteins are an evolutionarily-conserved family of ion channels whose function has been linked to a variety of mechanosensory processes, including hearing and balance sensation in vertebrates and locomotion inDrosophila. The molecular features that tune homologous TMC ion channel complexes to diverse mechanical stimuli are unknown.Caenorhabditis elegansexpress two TMC homologs, TMC-1 and TMC-2, both of which are the likely pore-forming subunits of mechanosensitive ion channels but differ in their expression pattern and functional role in the worm. Here we present the single particle cryo-electron microscopy structure of the native TMC-2 complex isolated fromC. elegans. The complex is composed of two copies each of the pore-forming TMC-2 subunit, the calcium and integrin binding protein CALM-1 and the transmembrane inner ear protein TMIE. Comparison of the TMC-2 complex to the recently published cryo-EM structure of theC. elegansTMC-1 complex reveals differences in subunit composition and highlights conserved protein-lipid interactions, as well as other structural features, that together suggest a mechanism for TMC-mediated mechanosensory transduction.Significance StatementOne mechanism by which organisms sense their environment is through the perception of mechanical stimuli such as sound, touch, and vibration. Transmembrane channel-like (TMC) proteins are ion channels whose function has been linked to a variety of mechanosensitive processes, including hearing and balance in vertebrates and touch sensation in worms. The molecular mechanisms by which TMCs respond to mechanical stimuli are unknown. Here we present the structure of the TMC-2 complex isolated from worms. Comparison of the TMC-2 complex to the recently solved structure of the worm TMC-1 complex highlights common structural features that are likely important for sensing mechanical stimuli yet also illuminates key differences that may explain the distinct functional roles of TMC-1 and TMC-2 in the worm.
A novel patient-derived cellular platform for validating microglia-targeted therapeutics for Alzheimer’s disease
Authors: Cuní-López Carla , Stewart Romal , Okano Satomi , Redlich Garry L. , Appleby Mark W. , White Anthony R. , Quek Hazel 
Published: August 2023

AbstractThe scarcity of effective biomarkers and therapeutic strategies for predicting disease onset and progression in Alzheimer’s disease (AD) is a major challenge to improve much-needed therapeutic outcomes. Conventional drug discovery approaches have been unsuccessful in providing efficient interventions due to their ‘one-size-fits-all’ nature. As an alternative, personalised drug development holds promise to pre-select responders and identify suitable drug efficacy indicators. In this study, we established a preclinical drug testing strategy by assessing the efficacy of anti-inflammatory drugs in 2D and 3Din vitromodels of monocyte-derived microglia-like cells (MDMi) derived from AD and mild cognitive impairment (MCI) patients, and matched healthy individuals. We observed that the cytokine inflammatory profiles of MDMi in response to drugs clustered separately between cohorts, with the 3D model showing a more defined separation between healthy and patient donors than 2D. By ranking donor and cytokine responses to drugs, we identified that drug efficacy was limited in AD patients and involved cohort-specific responsive cytokines. Our findings suggest that MDMi models have the potential to predict disease progression, stratify responders and identify biomarkers for estimating the efficacy of microglia-targeted drugs. Together, our pipeline could serve as a valuable tool to enhance the clinical translational value of preclinical drug screens and ultimately improve drug outcomes for AD.
Haplotype differences in common bean accessions confer the capacity to flower under Scandinavian summer conditions
Authors: Rendón-Anaya M , Buinovskaja G , Yu L , Ingvarsson PK 
Published: August 2023

AbstractThe capacity to flower under long days has been a major pre-requisite for the adaptation of the common bean to European climates. The complexity of such adaptation has been studied, mostly under the optics of QTL mapping, but still the genetic basis of the trait remains elusive. In the current study we sequenced a collection of >200 accessions ofP. vulgarisof Mesoamerican, Andean and European origin, for which the flowering capacity under long days during the summer season in Sweden was evaluated. Our variant calling strategy allowed us to identify 16.9e6SNPs and 38.6e3long structural variants. Furthermore, we observed gene-pool specific selective sweeps that correspond to the independent domestication events in the Americas. GWAS and haplotype structure tests identified single nucleotide and structural variants strongly associated to the capacity to flower under long days, particularly in chromosome 1.
Acetylcholine Modulates the Precision of Prediction Error in the Auditory Cortex
Authors: Pérez-González David , Lao-Rodríguez Ana B. , Aedo-Sánchez Cristian , Malmierca Manuel S. 
Published: August 2023

ABSTRACTA fundamental property of sensory systems is their ability to detect novel stimuli in the ambient environment. The auditory brain contains neurons that decrease their response to repetitive sounds but increase their firing rate to novel or deviant stimuli; the difference between both responses is known as stimulus-specific adaptation or neuronal mismatch (nMM). Here, we tested the effect of microiontophoretic applications of ACh on the neuronal responses in the auditory cortex (AC) of anesthetized rats during an auditory oddball paradigm, including cascade controls. Results indicate that ACh modulates the nMM, affecting prediction error responses but not repetition suppression, and this effect is manifested predominantly in infragranular cortical layers. The differential effect of ACh on responses to standards, relative to deviants (in terms of averages and variances), were consistent with the representational sharpening that accompanies an increase in the precision of prediction errors. These findings suggest that ACh plays an important role in modulating prediction error signaling in the AC and gating the access of these signals to higher cognitive levels.
Supply chain management practices (SCMPs) and performance nexus in developing and emerging economies (DEEs): a systematic review
Authors: Baisa Goitom Abera , Schäfer Joachim G. , Alemu Abebe Ejigu 
Published: August 2023

PurposeThis study aims to synthesize and analyze research on the Supply Chain Management Practices (SCMPs)-performance nexus, examine current knowledge, identify emerging trends, and provide plausible suggestions for future research engagements in the manufacturing sector in the context of Developing and Emerging Economies (DEEs).Design/methodology/approachFollowing a systematic review approach, this study analyzed 20 peer-reviewed scientific journal articles published between 2007 and 2021. The study sample was systematically selected from the Web of Science (WoS) and Google Scholar databases, following strict evaluation and selection criteria.FindingsNumerous dimensions of SCMPs have been considered in the extant literature; however, six have stood out as the most common. In addition, operational performance stood out as the most widely investigated measure in the SCM literature. Moreover, SCMPs have predominantly shown positive effects on performance outcomes. Methodological issues that future studies should consider are suggested.Research limitations/implicationsThe sample size was not sufficiently large relative to the rule of thumb set in the literature because of the scarcity of studies in the manufacturing sector in the DEEs context. Despite these limitations, the results of this study provide crucial insights into knowledge and practice.Originality/valueThis review is the first of its kind to examine the SCMPs-performance nexus in the context of DEEs. Based on the findings of this study, future research directions are proposed.
How is entrepreneurial marketing shaped by E-commerce technology: a case study of Chinese pure-play e-retailers
Authors: Hong Yiwen , Sawang Sukanlaya , Yang Hsiao-Pei (Sophie) 
Published: August 2023

PurposeThe focus of this study is on how online-only retailers, known as pure-play e-retailers, leverage e-commerce platforms to identify and pursue market opportunities. Through the perspective of entrepreneurial marketing, this study aims to explore the influence of e-commerce technologies on the decision-making process of entrepreneurial marketing. This exploration is conducted via a case study of pure-play e-retailers based in China.Design/methodology/approachThis study utilised a qualitative case study methodology to examine the complex processes of entrepreneurial marketing in an online environment. The study gathered detailed insights from both owner-managers and staff members of eight pure-play e-retail businesses. Additionally, the research involved a careful review of the firms' webpages and social media pages. This holistic approach facilitated a comprehensive understanding of their marketing strategies and practices.FindingsThe case study findings indicate that while many core aspects of entrepreneurial marketing remain important, there are distinct factors influencing the entrepreneurial marketing decision-making in the online marketplace. The online EM framework can be visualised as follows: (1) trend-orientated as well as innovative-orientated (2) data-orientated and entrepreneur-orientated (3) innovative-driven customer stimulation (4) orientated towards both platforms and proactiveness.Originality/valueThe paper provides an initial understanding of how digitalisation is enabling and transforming entrepreneurship in companies with high level digitalisation but low level digital development. Building on current entrepreneurial marketing literature, this paper develops an online entrepreneurial marketing framework to enhance understanding of the interaction between e-commerce technology and entrepreneurial marketing decision making.
Investigating the asymmetric effect of income inequality on financial fragility in South Africa and selected emerging markets: a Bayesian approach with hierarchical priors
Authors: Zungu Lindokuhle Talent , Greyling Lorraine 
Published: August 2023

PurposeThis study aims to test the validity of the Rajan theory in South Africa and other selected emerging markets (Chile, Peru and Brazil) during the period 1975–2019.Design/methodology/approachIn this study, the researchers used time-series data to estimate a Bayesian Vector Autoregression (BVAR) model with hierarchical priors. The BVAR technique has the advantage of being able to accommodate a wide cross-section of variables without running out of degrees of freedom. It is also able to deal with dense parameterization by imposing structure on model coefficients via prior information and optimal choice of the degree of formativeness.FindingsThe results for all countries except Peru confirmed the Rajan hypotheses, indicating that inequality contributes to high indebtedness, resulting in financial fragility. However, for Peru, this study finds it contradicts the theory. This study controlled for monetary policy shock and found the results differing country-specific.Originality/valueThe findings suggest that an escalating level of inequality leads to financial fragility, which implies that policymakers ought to be cautious of excessive inequality when endeavouring to contain the risk of financial fragility, by implementing sound structural reform policies that aim to attract investments consistent with job creation, development and growth in these countries. Policymakers should also be cautious when implementing policy tools (redistributive policies, a sound monetary policy), as they seem to increase the risk of excessive credit growth and financial fragility, and they need to treat income inequality as an important factor relevant to macroeconomic aggregates and financial fragility.
IT-related resources, digital marketing capabilities and business performance: moderating effects of digital orientation and technological turbulence
Authors: Ranjan Piyush 
Published: August 2023

PurposeThis research intends to develop a conceptual framework investigating how IT-related resources, namely IT advancement (ITAD) and IT alignment (ITAG), utilization relates to digital marketing capabilities (DMCs) development, which in turn improves business performance (BP), as well as how digital orientation (DO) and technological turbulence (TT) moderate these effects.Design/methodology/approachThis study employs an online email-based survey technique to collect primary cross-sectional data from 388 small and medium-sized enterprises operating in India. Moderated hierarchical regression was used to validate the hypothesized relationships.FindingsITAD and ITAG are significant drivers of DMCs, and these capabilities positively influence BP. Moreover, DO strengthens the positive effect of ITAD and ITAG on DMCs, with ITAD having a higher impact than ITAG. Similarly, DMCs have a greater positive effect on BP in an environment with high TT.Originality/valueDespite increased interest in the information technology resources required for the development of DMCs, less attention has been paid to the relationship between ITAD and ITAG resources and DMCs. In addition, few researchers investigate the moderating influence of DO on the relationship between IT-related resources and DMCs, as well as TT on the association between DMCs and BP.