extrinsic cues
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2022 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Eva Parga-Dans ◽  
Pablo Alonso González ◽  
Raimundo Otero-Enríquez

Purpose The complexity in determining the quality of a credence good like wine increases due to the lack of mandatory ingredient labeling. This has generated a significant information asymmetry in the wine market, leading consumers to delegate their purchase decisions to expert rankings and wine guides. This paper explores whether expert assessments reduce the information asymmetry caused by the absence of ingredient labeling in the wine market.Design/methodology/approach By employing analysis of variance (ANOVA) in a sample of 304 wines included in the Wine Guide of the Spanish Consumers Organization (OCU), this paper assesses the extent to which expert assessments based on sensory evaluations converge with the objective cues provided by laboratory analysis in wine quality evaluations.Findings Results reveal a mismatch between expert assessments and laboratory analyses. Chemical aspects such as SO2 levels or volatile acidity, sensorial factors such as intensity and persistence, and extrinsic variables such as the region of origin or wine type play an important role in the quality ranking of wines.Originality/value These findings call for the inclusion of objective intrinsic cues in expert sensory assessments to provide consumers reliable information about wines and to resolve the apparent dissonances in wine quality assessments.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Daniel Feliciano ◽  
Carolyn M. Ott ◽  
Isabel Espinosa-Medina ◽  
Aubrey V. Weigel ◽  
Lorena Benedetti ◽  
...  

AbstractCells in many tissues, such as bone, muscle, and placenta, fuse into syncytia to acquire new functions and transcriptional programs. While it is known that fused cells are specialized, it is unclear whether cell-fusion itself contributes to programmatic-changes that generate the new cellular state. Here, we address this by employing a fusogen-mediated, cell-fusion system to create syncytia from undifferentiated cells. RNA-Seq analysis reveals VSV-G-induced cell fusion precedes transcriptional changes. To gain mechanistic insights, we measure the plasma membrane surface area after cell-fusion and observe it diminishes through increases in endocytosis. Consequently, glucose transporters internalize, and cytoplasmic glucose and ATP transiently decrease. This reduced energetic state activates AMPK, which inhibits YAP1, causing transcriptional-reprogramming and cell-cycle arrest. Impairing either endocytosis or AMPK activity prevents YAP1 inhibition and cell-cycle arrest after fusion. Together, these data demonstrate plasma membrane diminishment upon cell-fusion causes transient nutrient stress that may promote transcriptional-reprogramming independent from extrinsic cues.


2021 ◽  
Author(s):  
Paul J Cullen ◽  
Beatriz Gonzalez

All cells maintain an axis of polarity that directs the orientation of growth. Cell polarity can be reorganized during development and in response to extrinsic cues to produce new cell types. Rho GTPases are central regulators of cell polarity and signal-dependent cell differentiation. We show here that one of the best understood Rho GTPases, the highly conserved yeast Cdc42p, is turned over by members of the Heat Shock family of Proteins (HSPs). The Hsp40p chaperone, Ydj1p, was required for turnover of Cdc42p by the NEDD4 E3 ubiquitin ligase, Rsp5p, in the proteosome. Cdc42p turnover was regulated by HSPs at high temperatures, and in aging cells where the protein formed aggregates, implicating HSPs in Rho GTPase quality control. We also show that Cdc42pQ61L, which mimics the active (GTP-bound) conformation of the protein, was turned over at elevated levels by Ydj1p and Rsp5p. A turnover-defective version of Cdc42pQ61L led to multibudding phenotypes, implicating Cdc42 turnover in singularity in cell polarization. Cdc42p turnover also impacted MAP kinase pathway specificity. A pathway-specific scaffold, Bem4p, stabilized Cdc42p levels, which biased Cdc42p function in one MAPK pathway over another. Turnover regulation of Rho GTPases by HSPs and scaffolds provides new dimensions to the regulation of cell polarity and signal-dependent morphogenesis.


2021 ◽  
Vol 22 (14) ◽  
pp. 7339
Author(s):  
Julia Leschik ◽  
Beat Lutz ◽  
Antonietta Gentile

Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.


Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1413
Author(s):  
Marco Francesco Mazzù ◽  
Veronica Marozzo ◽  
Angelo Baccelloni ◽  
Flaminia de’ Pompeis

Many studies in the related literature have proven that the perception of flavor and healthiness can be affected by both the product’s intrinsic and extrinsic cues. Package designs, brands, colors, labels and other visual elements exert and influence consumers’ expectations and guide them toward food decisions. With the increasing initiatives promoted within Europe in support of the adoption of blockchain technology in supply chains and agri-food contexts, in the coming years, packages will be used with additional product information certified with the technology itself. Cueing packages with blockchain-certified information could affect consumers in their overall flavor and health perceptions, similarly to that previously demonstrated with other extrinsic cues. In the present study, we analyzed a sample of 310 primary grocery shoppers from Germany, Italy and the UK, demonstrating the effectiveness of technology-certified information on the package of animal milk in influencing consumers’ flavor and health perceptions and exploring the differences and similarities across the three countries and milk categories.


2021 ◽  
Author(s):  
Yasushi Nakagawa ◽  
Timothy Monko ◽  
Jaclyn Rebertus ◽  
Jeff Stolley ◽  
Stephen R Salton

Area-specific axonal projections from the mammalian thalamus shape unique cellular organization in target areas in the adult neocortex. How these axons control neurogenesis and early neuronal fate specification is poorly understood. By using mutant mice lacking the majority of thalamocortical axons, we show that these axons increase the number of layer 4 neurons in primary sensory areas by enhancing neurogenesis and shifting the fate of superficial layer neurons to that of layer 4 by the neonatal stage. Part of these area-specific roles are played by the thalamus-derived molecule, VGF. Our work reveals that extrinsic cues from sensory thalamic projections have an early role in the formation of cortical cytoarchitecture by enhancing the production and specification of layer 4 neurons.


2021 ◽  
Vol 218 (8) ◽  
Author(s):  
Xinying Zong ◽  
Xiaolei Hao ◽  
Beisi Xu ◽  
Jeremy Chase Crawford ◽  
Shaela Wright ◽  
...  

T reg cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How their robust function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of T reg lineage–specifying factor Foxp3. Foxp3 enhancers are known as distinct readers of environmental cues controlling T reg cell induction or lineage stability. However, their single deficiencies cause mild, if any, immune dysregulation, leaving the key transcriptional mechanisms determining Foxp3 expression and thereby T reg cell suppressive capacity uncertain. We examined the collective activities of Foxp3 enhancers and found that they coordinate to maximize T reg cell induction, Foxp3 expression level, or lineage stability through distinct modes and that ablation of synergistic enhancers leads to lethal autoimmunity in young mice. Thus, the induction and maintenance of a diverse, stable T reg cell repertoire rely on combinatorial Foxp3 enhancers, suggesting broad, stage-specific, synergistic activities of cell-intrinsic factors and cell-extrinsic cues in determining T reg cell suppressive capacity.


2021 ◽  
Author(s):  
Laurel A Rohde ◽  
Arianne Bercowsky-Rama ◽  
Jose Negrete ◽  
Guillaume Valentin ◽  
Sundar Ram Naganathan ◽  
...  

Sequential segmentation of the body axis is fundamental to vertebrate embryonic patterning. This relies on the segmentation clock, a multi-cellular oscillating genetic-network, which mainifests as tissue-level kinematic waves of gene expression that arrest at the position of each new segment. How this hallmark wave pattern is generated is an open question. We compare cellular-resolution oscillatory patterns in the embryo to those generated cell-autonomously in culture without extrinsic signals. We find striking similarity, albeit with greater variability in the timing of clock arrest in culture. Our simple physical description of a clock controlled by a noisy cell-intrinsic timer captures these dynamics. We propose the segmentation clock integrates an intrinsic, timer-driven oscillatory program, which underlies the waves and arrest, with extrinsic cues regulating the intrinsic timer's duration and precision.


Development ◽  
2021 ◽  
Vol 148 (6) ◽  
pp. dev194514
Author(s):  
Vincent Mouilleau ◽  
Célia Vaslin ◽  
Rémi Robert ◽  
Simona Gribaudo ◽  
Nour Nicolas ◽  
...  

ABSTRACTRostro-caudal patterning of vertebrates depends on the temporally progressive activation of HOX genes within axial stem cells that fuel axial embryo elongation. Whether the pace of sequential activation of HOX genes, the 'HOX clock', is controlled by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studied HOX clock pacing in human pluripotent stem cell-derived axial progenitors differentiating into diverse spinal cord motor neuron subtypes. We show that the progressive activation of caudal HOX genes is controlled by a dynamic increase in FGF signaling. Blocking the FGF pathway stalled induction of HOX genes, while a precocious increase of FGF, alone or with GDF11 ligand, accelerated the HOX clock. Cells differentiated under accelerated HOX induction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. The pacing of the HOX clock is thus dynamically regulated by exposure to secreted cues. Its manipulation by extrinsic factors provides synchronized access to multiple human neuronal subtypes of distinct rostro-caudal identities for basic and translational applications.This article has an associated ‘The people behind the papers’ interview.


Author(s):  
Eda R. Machado ◽  
Ida Annunziata ◽  
Diantha van de Vlekkert ◽  
Gerard C. Grosveld ◽  
Alessandra d’Azzo

During primary tumorigenesis isolated cancer cells may undergo genetic or epigenetic changes that render them responsive to additional intrinsic or extrinsic cues, so that they enter a transitional state and eventually acquire an aggressive, metastatic phenotype. Among these changes is the alteration of the cell metabolic/catabolic machinery that creates the most permissive conditions for invasion, dissemination, and survival. The lysosomal system has emerged as a crucial player in this malignant transformation, making this system a potential therapeutic target in cancer. By virtue of their ubiquitous distribution in mammalian cells, their multifaced activities that control catabolic and anabolic processes, and their interplay with other organelles and the plasma membrane (PM), lysosomes function as platforms for inter- and intracellular communication. This is due to their capacity to adapt and sense nutrient availability, to spatially segregate specific functions depending on their position, to fuse with other compartments and with the PM, and to engage in membrane contact sites (MCS) with other organelles. Here we review the latest advances in our understanding of the role of the lysosomal system in cancer progression. We focus on how changes in lysosomal nutrient sensing, as well as lysosomal positioning, exocytosis, and fusion perturb the communication between tumor cells themselves and between tumor cells and their microenvironment. Finally, we describe the potential impact of MCS between lysosomes and other organelles in propelling cancer growth and spread.


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