RESUMO
Peer review is an important part of the scientific process, but traditional peer review at journals is coming under increased scrutiny for its inefficiency and lack of transparency. As preprints become more widely used and accepted, they raise the possibility of rethinking the peer-review process. Preprints are enabling new forms of peer review that have the potential to be more thorough, inclusive, and collegial than traditional journal peer review, and to thus fundamentally shift the culture of peer review toward constructive collaboration. In this Consensus View, we make a call to action to stakeholders in the community to accelerate the growing momentum of preprint sharing and provide recommendations to empower researchers to provide open and constructive peer review for preprints.
Assuntos
Revisão por Pares , Pesquisadores , Humanos , Movimento (Física)RESUMO
The EMBO Journal has extended its Transparent Process beyond journal confines to post referee comments alongside preprint versions of papers and to partner with Review Commons, a pre-journal peer-review platform for Refereed Preprints in the life sciences.
Assuntos
Revisão da Pesquisa por Pares/normas , Publicações Periódicas como Assunto , Pré-Publicações como Assunto , Editoração/normas , HumanosRESUMO
EMBO Press and ASAPbio launch Review Commons, a platform to provide authors with journal-independent peer review of their manuscripts and preprints.
Assuntos
Revisão da Pesquisa por Pares/métodos , Pesquisa Biomédica , Políticas Editoriais , Humanos , EditoraçãoRESUMO
Molecular Systems Biology warmly welcomes its new academic Chief Editor, M. Madan Babu. Madan shared his thoughts on the evolution of the field and the importance of bridging disciplines to enable next generation systems biology.
Assuntos
Publicações Periódicas como Assunto , Biologia de Sistemas , Humanos , Revisão por Pares , Pesquisa Translacional BiomédicaAssuntos
Biologia Computacional/métodos , Processamento de Imagem Assistida por Computador/métodos , Metadados , Algoritmos , Animais , Congressos como Assunto , Microscopia Crioeletrônica/métodos , Mineração de Dados/métodos , Bases de Dados Factuais , Diagnóstico por Imagem/métodos , Humanos , Microscopia , SoftwareRESUMO
We report on a study of epitaxially grown ultrathin Pb films that are only a few atoms thick and have parallel critical magnetic fields much higher than the expected limit set by the interaction of electron spins with a magnetic field, that is, the Clogston-Chandrasekhar limit. The epitaxial thin films are classified as dirty-limit superconductors because their mean-free paths, which are limited by surface scattering, are smaller than their superconducting coherence lengths. The uniformity of superconductivity in these thin films is established by comparing scanning tunneling spectroscopy, scanning superconducting quantum interference device (SQUID) magnetometry, double-coil mutual inductance, and magneto-transport, data that provide average superfluid rigidity on length scales covering the range from microscopic to macroscopic. We argue that the survival of superconductivity at Zeeman energies much larger than the superconducting gap can be understood only as the consequence of strong spin-orbit coupling that, together with substrate-induced inversion-symmetry breaking, produces spin splitting in the normal-state energy bands that is much larger than the superconductor's energy gap.
Assuntos
Gráficos por Computador , Internet , Semântica , Humanos , Aprendizado de Máquina , Fluxo de TrabalhoRESUMO
Control of cellular survival and proliferation is dependent on extracellular signals and is a prerequisite for ordered tissue development and maintenance. Activation of the cAMP responsive element binding protein (CREB) by phosphorylation has been implicated in the survival of mammalian cells. To define its roles in the mouse central nervous system, we disrupted Creb1 in brain of developing and adult mice using the Cre/loxP system. Mice with a Crem(-/-) background and lacking Creb in the central nervous system during development show extensive apoptosis of postmitotic neurons. By contrast, mice in which both Creb1 and Crem are disrupted in the postnatal forebrain show progressive neurodegeneration in the hippocampus and in the dorsolateral striatum. The striatal phenotype is reminiscent of Huntington disease and is consistent with the postulated role of CREB-mediated signaling in polyglutamine-triggered diseases.
Assuntos
Encéfalo/fisiologia , Degeneração Neural/etiologia , Proteínas Repressoras , Fatores de Transcrição/fisiologia , Animais , Apoptose , Corpo Estriado/patologia , Modulador de Elemento de Resposta do AMP Cíclico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Feminino , Humanos , Doença de Huntington/etiologia , Doença de Huntington/genética , Doença de Huntington/patologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Degeneração Neural/genética , Degeneração Neural/patologia , Peptídeos/genética , Fenótipo , Transdução de Sinais , Fatores de Transcrição/deficiência , Fatores de Transcrição/genéticaRESUMO
Marijuana and its main psychotropic ingredient Delta(9)-tetrahydrocannabinol (THC) exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1), which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release gamma aminobutyric acid), cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug. These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.
Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Dronabinol/farmacologia , Psicotrópicos/farmacologia , Receptor CB1 de Canabinoide/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Ácido Glutâmico/metabolismo , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Interneurônios/patologia , Masculino , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Neocórtex/efeitos dos fármacos , Neocórtex/patologia , Neocórtex/fisiopatologia , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Limiar da Dor/efeitos dos fármacos , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Induction of specific gene expression patterns in response to activity confers functional plasticity to neurons. A principal role in the regulation of these processes has been ascribed to the cAMP responsive element binding protein (CREB). Using genome-wide expression profiling in mice lacking CREB in the forebrain, accompanied by deletion of the cAMP responsive element modulator gene (CREM), we here show that the role of these proteins in activity-induced gene expression is surprisingly selective and highly context dependent. Thus, only a very restricted subset of activity-induced genes (i.e., Gadd45b or Nr4a2) requires these proteins for their induction in the hippocampus after kainic acid administration, while they are required for most of the cocaine-induced expression changes in the striatum. Interestingly, in the absence of CREB, CREM is able to rescue activity-regulated transcription, which strengthens the notion of overlapping functions of the two proteins. In addition, we show that cholesterol metabolism is dysregulated in the brains of mutant mice, as reflected coordinated expression changes in genes involved in cholesterol synthesis and neuronal accumulation of cholesterol. These findings provide novel insights into the role of CREB and CREM in stimulus-dependent transcription and neuronal homeostasis.
Assuntos
Colesterol/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Neurônios/metabolismo , Animais , Sequência de Bases , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Modulador de Elemento de Resposta do AMP Cíclico/deficiência , Modulador de Elemento de Resposta do AMP Cíclico/genética , Modulador de Elemento de Resposta do AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/deficiência , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Feminino , Perfilação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Homeostase , Ácido Caínico/toxicidade , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Degeneração Neural/genética , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Plasticidade Neuronal , Neurônios/efeitos dos fármacos , Neurônios/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais , Transcrição GênicaRESUMO
Synaptic activity-dependent gene expression is critical for certain forms of neuronal plasticity and survival in the mammalian nervous system, yet the mechanisms by which coordinated regulation of activity-induced genes supports neuronal function is unclear. Here, we show that deletion of serum response factor (SRF) in specific neuronal populations in adult mice results in profound deficits in activity-dependent immediate early gene expression, but components of upstream signaling pathways and cyclic AMP-response element binding protein (CREB)-dependent transactivation remain intact. Moreover, SRF-deficient CA1 pyramidal neurons show attenuation of long-term synaptic potentiation, a model for neuronal information storage. Furthermore, in contrast to the massive neurodegeneration seen in adult mice lacking CREB family members, SRF-deficient adult neurons show normal morphologies and basal excitatory synaptic transmission. These findings indicate that the transcriptional events underlying neuronal survival and plasticity are dissociable and that SRF plays a prominent role in use-dependent modification of synaptic strength in the adult brain.
Assuntos
Regulação da Expressão Gênica/genética , Hipocampo/metabolismo , Plasticidade Neuronal/genética , Terminações Pré-Sinápticas/metabolismo , Fator de Resposta Sérica/fisiologia , Transmissão Sináptica/genética , Animais , Sobrevivência Celular/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Genes Precoces/fisiologia , Hipocampo/citologia , Potenciação de Longa Duração/genética , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Camundongos Knockout , Camundongos Mutantes , Técnicas de Cultura de Órgãos , Terminações Pré-Sinápticas/ultraestrutura , Células Piramidais/citologia , Células Piramidais/metabolismo , Fator de Resposta Sérica/genética , Fator de Resposta Sérica/metabolismo , Transdução de Sinais/genética , Ativação Transcricional/fisiologiaRESUMO
Biological rhythms are driven in mammals by a central circadian clock located in the suprachiasmatic nucleus (SCN). Light-induced phase shifting of this clock is correlated with phosphorylation of CREB at Ser133 in the SCN. Here, we characterize phosphorylation of CREB at Ser142 and describe its contribution to the entrainment of the clock. In the SCN, light and glutamate strongly induce CREB Ser142 phosphorylation. To determine the physiological relevance of phosphorylation at Ser142, we generated a mouse mutant, CREB(S142A), lacking this phosphorylation site. Light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN are significantly attenuated in CREB(S142A) mutants. Our findings provide genetic evidence that CREB Ser142 phosphorylation is involved in the entrainment of the mammalian clock and reveal a novel phosphorylation-dependent regulation of CREB activity.