1,721,034 research outputs found
Corticotropin-releasing factor receptors couple to multiple g-proteins to activate diverse intracellular signaling pathways in mouse hippocampus: role in neuronal excitability and associative learning
Get PDFCorticotropin-releasing factor (CRF) exerts a key neuroregulatory control on stress responses in various regions of the mammalian brain, including the hippocampus. Using hippocampal slices, extracts, and whole animals, we investigated the effects of human/rat CRF (h/rCRF) on hippocampal neuronal excitability and hippocampus-dependent learning in two mouse inbred strains, BALB/c and C57BL/6N. Intracellular recordings from slices revealed that application of h/rCRF increased the neuronal activity in both mouse inbred strains. Inhibition of protein kinase C (PKC) by bisindolylmaleimide I (BIS-I) prevented the h/rCRF effect only in hippocampal slices from BALB/c mice but not in slices from C57BL/6N mice. Inhibition of cAMP-dependent protein kinase (PKA) by H-89 abolished the h/rCRF effect in slices from C57BL/6N mice, with no effect in slices from BALB/c mice. Accordingly, h/rCRF elevated PKA activity in hippocampal slices from C57BL/6N mice but increased only PKC activity in the hippocampus of BALB/c mice. These differences in h/rCRF signal transduction were also observed in hippocampal membrane suspensions from both mouse strains. In BALB/c mice, hippocampal CRF receptors coupled to Gq/11 during stimulation by h/rCRF, whereas they coupled to Gs, Gq/11, and Gi in C57BL/6N mice. As expected on the basis of the slice experiments, h/rCRF improved context-dependent fear conditioning of BALB/c mice in behavioral experiments, and BIS-I prevented this effect. However, although h/rCRF increased neuronal spiking in slices from C57BL/6N mice, it did not enhance conditioned fear. These results indicate that the CRF system activates different intracellular signaling pathways in mouse hippocampus and may have distinct effects on associative learning depending on the mouse strain investigated
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The role of CRH receptors and their agonists in myometrial contractility and quiescence during pregnancy and labour
No full textThe mechanism of human labor remains a scientific enigma. Corticotropin-releasing hormone (CRH), a hypothalamic peptide that controls the response of the body to stress and which is also produced by the placenta and intrauterine tissues during pregnancy is potentially involved in the onset of labor. CRH is part of a family of mammalian peptides that includes the urocortins (UCNs), which are also expressed by the placenta and intrauterine tissues. During human pregnancy, CRH appears to target multiple feto-maternal tissues, including the myometrium, implicating CRH in the regulation of the transition from relaxation to active uterine contractions. The myometrial actions of CRH are mediated via a wide network of specific G-protein coupled membrane-bound receptors. These receptors have various functional properties, depending on the receptor subtype, the ability of agonists to activate specific signalling cascades and the stage of pregnancy. In addition, their function is dependant upon other intracellular signals via communication between signalling cascades, suggesting potential multiple roles of CRH and other CRH-like peptides during pregnancy and labor. This review will provide the current concepts about the role of CRH and UCNs and their myometrial receptors during pregnancy, labor and delivery
CRH-R splicing in estrogen-sensitive breast cancer
Get PDFAlternative pre-mRNA splicing contributes in the acquired genomic alterations involved in the pathobiology of cancer development and progression.1 In normal biological systems, this mechanism allows protein complexity and diversity by increasing gene coding capacity and promoting expression of several related proteins with diverse and even antagonistic functions. However, in pathological settings such as cancer, mutations in splicing regulatory elements and/or alterations in the cellular splicing machinery can change splicing patterns and result in the generation of aberrantly spliced pre-mRNAs that favor development of the malignant state
Insights into mechanisms of corticotropin-releasing hormone receptor signal transduction
No full textDuring evolution, mammals have developed remarkably similar molecular mechanisms to respond to external challenges and maintain survival. Critical regulators of these mechanisms are the family of ‘stress’-peptides that consists of the corticotropin-releasing hormone (CRH) and urocortins (Ucns). These neuropeptides ‘fine-tune’ integration of an intricate series of physiological responses involving the autonomic, endocrine, immune, cardiovascular and reproductive systems, which
induce a spectrum of behavioural and homeostatic changes. CRH and Ucns exert their actions by activating two types of CRH receptors (CRH-R), CRH-R1 and CRH-R2, which belong to the class-B1 family of GPCRs. The CRH-Rs exhibit signalling promiscuity facilitated by their ability to couple to multiple G-proteins and regulate diverse intracellular networks that involve intracellular effectors such as cAMP and an array of PKs in an agonist and tissue-specific manner, a property that allows them
to exert unique roles in the integration of homeostatic mechanisms. We only now begin to unravel the plethora of CRH-R biological actions and the transcriptional and post-translational mechanisms such as alternative mRNA splicing or phosphorylation-mediated desensitization developed to tightly control CRH-Rs biological activity and regulate their physiological actions. This review summarizes the current understanding of CRH-R signalling complexity and regulatory mechanisms that underpin cellular responses to CRH and Uc
Landscape of Future blood testing in healthcare practice - Professor Dimitris Grammatopoulos (University of Warwick)
No full text<p>This video is the third talk from our Future of Healthcare: Remote Blood Testing, Monitoring & AI Meeting that took place on 07-08/11/2023. </p>
<p>Landscape of Future blood testing in healthcare practice – Professor Dimitris Grammatopoulos (University of Warwick). </p>
<p>Bio: Dimitris Grammatopoulos, PhD, FRCPath, is Professor of Molecular Medicine at Warwick Medical School and Consultant in Clinical Biochemistry and Molecular Diagnostics at the University Hospitals of Coventry and Warwickshire, NHS Trust, United Kingdom. He also leads the Novel Biomarkers theme of the Institute of Precision Diagnostics and Translational Medicine, Pathology-UHCW NHS Trust, where he combines clinical expertise in diagnostic laboratory medicine with a research track-record in application of cutting edge multidiscipline methodologies in routine clinical diagnostics. He received academic and clinical training in Newcastle, Bristol, Johns Hopkins-Baltimore and Warwick. He has expertise in biochemical/molecular diagnosis of many endocrine and metabolic disorders. His translational research interest is focused on stress hormones and homeostatic adaptations of fetal development to maternal disease as well as development of novel -omics based biomarker approaches suitable for precision medicine and better characterisation of patient phenotype. He has experience around use of AI and ML for development and refinement of clinical and diagnostic pathways for complex chronic conditions that are considered as national priorities. Dimitris is the Lead in Diagnostics, Global Health Priorities in Health, University of Warwick.</p>
<p>Further details on this event can be found at:<a href="https://futurebloodtesting.org/event/the-future-of-healthcare-remote-blood-testing-monitoring-ai/"> https://futurebloodtesting.org/event/the-future-of-healthcare-remote-blood-testing-monitoring-ai/</a></p>
<p>This video is an output from the Future Blood Testing Network which is funded by EPSRC under Grant Number EP/W000652/1</p>
<p>YouTube Link: <a href="https://www.youtube.com/watch?v=8tL9FEqIv6o&list=PL_5Zbof1GNkCZLgQwZnxsMTQUELUCQHlp&index=3">https://www.youtube.com/watch?v=8tL9FEqIv6o&list=PL_5Zbof1GNkCZLgQwZnxsMTQUELUCQHlp&index=3</a></p>
Transforming the UK's diagnostics agenda after COVID-19 and grand challenges – Future Blood Testing Landscape report - Prof Dimitris Grammatopoulos (University Hospitals Coventry & Warwickshire, University of Warwick)
No full textThis video is the second talk from our two day Future Blood Testing: Challenges & Opportunities Event that took place on the 13/09/2022.
Transforming the UK’s diagnostics agenda after COVID-19 and grand challenges – Future Blood Testing Landscape report - Prof Dimitris Grammatopoulos (University Hospitals Coventry & Warwickshire, University of Warwick)
Bio: Dimitris Grammatopoulos, PhD, FRCPath, is Professor of Molecular Medicine at Warwick Medical School and Consultant in Clinical Biochemistry and Molecular Diagnostics at the University Hospitals of Coventry and Warwickshire, NHS Trust, United Kingdom. He also leads the Novel Biomarkers theme of the Institute of Precision Diagnostics and Translational Medicine, Pathology-UHCW NHS Trust. where he combines clinical expertise in diagnostic laboratory medicine with a research track-record in application of cutting edge multidiscipline methodologies in routine clinical diagnostics. He received academic and clinical training in Newcastle, Bristol, Johns Hopkins-Baltimore and Warwick. He has expertise in biochemical/molecular diagnosis of many endocrine and metabolic disorders. His translational research interest is focused on stress hormones and homeostatic adaptations of fetal development to maternal disease as well as development of novel -omics based biomarker approaches suitable for precision medicine and better characterisation of patient phenotype. He has experience around use of AI and ML for development and refinement of clinical and diagnostic pathways for complex chronic conditions that are considered as national priorities. Dimitris is the Lead in Diagnostics, Global Health Priorities in Health, University of Warwick.
Further details on this event can be found at: https://futurebloodtesting.org/event/13-14-09-2022/
This video is an output from the Future Blood Testing Network which is funded by EPSRC under Grant Number EP/W000652/1
YouTube Link: https://youtu.be/HiOlRzJPR7
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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