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Transcriptional landscapes at the intersection of neuronal apoptosis and substance P-induced survival: exploring pathways and drug targets.

ABSTRACT: A change in the delicate equilibrium between apoptosis and survival regulates the neurons fate during the development of nervous system and its homeostasis in adulthood. Signaling pathways promoting or protecting from apoptosis are activated by multiple signals, including those elicited by neurotrophic factors, and depend upon specific transcriptional programs. To decipher the rescue program induced by substance P (SP) in cerebellar granule neurons, we analyzed their whole-genome expression profiles after induction of apoptosis and treatment with SP. Transcriptional pathways associated with the survival effect of SP included genes encoding for proteins that may act as pharmacological targets. Inhibition of one of these, the Myc pro-oncogene by treatment with 10058-F4, reverted in a dose-dependent manner the rescue effect of SP. In addition to elucidate the transcriptional mechanisms at the intersection of neuronal apoptosis and survival, our systems biology-based perspective paves the way towards an innovative pharmacology based on targets downstream of neurotrophic factor receptors.

SUBMITTER: Paparone S

PROVIDER: S-EPMC4979452 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Transcriptional landscapes at the intersection of neuronal apoptosis and substance P-induced survival: exploring pathways and drug targets.

Paparone S S Severini C C Ciotti M T MT D'Agata V V Calissano P P Cavallaro S S

Cell death discovery 20160801

A change in the delicate equilibrium between apoptosis and survival regulates the neurons fate during the development of nervous system and its homeostasis in adulthood. Signaling pathways promoting or protecting from apoptosis are activated by multiple signals, including those elicited by neurotrophic factors, and depend upon specific transcriptional programs. To decipher the rescue program induced by substance P (SP) in cerebellar granule neurons, we analyzed their whole-genome expression prof ...[more]

PMID: 27551538

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Project description:BackgroundAn enduring challenge remains about how to effectively implement programs, services, or practices. Too often, implementation does not achieve its intended effectiveness, fidelity, and sustainability, even when frameworks or theories determine implementation strategies and actions. A different approach is needed. This scoping review joined two markedly different bodies of literature: implementation and hermeneutics. Implementation is usually depicted as focused, direct, and somewhat linear, while hermeneutics attends to the messiness of everyday experience and human interaction. Both, however, are concerned with practical solutions to real-life problems. The purpose of the scoping review was to summarize existing knowledge on how a hermeneutic approach has informed the process of implementing health programs, services, or practices.MethodsWe completed a scoping review by taking a Gadamerian hermeneutic approach to the JBI scoping review method. Following a pilot search, we searched eight health-related electronic databases using broadly stated terms such as implementation and hermeneutics. A diverse research team that included a patient and healthcare leader, working in pairs, independently screened titles/abstracts and full-text articles. Through the use of inclusion criteria and full-team dialogue, we selected the final articles and identified their characteristics, hermeneutic features, and implementation components.ResultsElectronic searches resulted in 2871 unique studies. After full-text screening, we retained six articles that addressed both hermeneutics and implementing a program, service, or practice. The studies varied widely in location, topic, implementation strategies, and hermeneutic approach. All addressed assumptions underpinning implementation, the human dimensions of implementing, power differentials, and knowledge creation during implementation. All studies addressed issues foundational to implementing such as cross-cultural communication and surfacing and addressing tensions during processes of change. The studies showed how creating conceptual knowledge was a precursor to concrete, instrumental knowledge for action and behavioral change. Finally, each study demonstrated how the hermeneutic process of the fusion of horizons created new understandings needed for implementation.ConclusionsHermeneutics and implementation have rarely been combined. The studies reveal important features that can contribute to implementation success. Implementers and implementation research may benefit from understanding, articulating, and communicating hermeneutic approaches that foster the relational and contextual foundations necessary for successful implementation.Trial registrationThe protocol was registered at the Centre for Open Science on September 10, 2019. MacLeod M, Snadden D, McCaffrey G, Zimmer L, Wilson E, Graham I, et al. A hermeneutic approach to advancing implementation science: a scoping review protocol 2019. Accessed at osf.io/eac37.

Dataset Information

Transcriptional landscapes at the intersection of neuronal apoptosis and substance P-induced survival: exploring pathways and drug targets.

Publications

Transcriptional landscapes at the intersection of neuronal apoptosis and substance P-induced survival: exploring pathways and drug targets.

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