27 research outputs found
Autonomous, bidding, credible, decentralized, ethical, and funded (ABCDEF) publishing [version 2; peer review: 1 approved, 2 approved with reservations]
Scientists write research articles, process ethics reviews, evaluate proposals and research, and seek funding. Several strategies have been proposed to optimize these operations and to decentralize access to research resources and opportunities. For instance, we previously proposed the trinity review method, combining registered reports with financing and research ethics assessments. However, previously proposed systems have a number of shortcomings, including how to implement them, e.g., who manages them, how incentives for reviewers are paid, etc. Various solutions have been proposed to address these issues, employing methods based on blockchain technologies, called “decentralized science (DeSci)”. Decentralized approaches that exploit these developments offer potentially profound improvements to the troubled scientific ecosystem. Here, we propose a system that integrates ethics reviews, peer reviews, and funding in a decentralized manner, based on Web3 technology. This new method, named ABCDEF publishing, would enhance the speed, fairness, and transparency of scientific research and publishing
Diffusion functional MRI reveals global brain network functional abnormalities driven by targeted local activity in a neuropsychiatric disease mouse model
Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as an alternative functional imaging method to detect brain activity without confounding hemodynamic effects. Here, taking advantage of this DfMRI feature, we investigated abnormalities of dynamic brain function in a neuropsychiatric disease mouse model (glial glutamate transporter-knockdown mice with obsessive-compulsive disorder [OCD]-related behavior). Our DfMRI approaches consisted of three analyses: resting state brain activity, functional connectivity, and propagation of neural information. We detected hyperactivation and biased connectivity across the cortico-striatal-thalamic circuitry, which is consistent with known blood oxygen-level dependent (BOLD)-fMRI patterns in OCD patients. In addition, we performed ignition-driven mean integration (IDMI) analysis, which combined activity and connectivity analyses, to evaluate neural propagation initiated from brain activation. This analysis revealed an unbalanced distribution of neural propagation initiated from intrinsic local activation to the global network, while these were not detected by the conventional method with BOLD-fMRI. This abnormal function detected by DfMRI was associated with OCD-related behavior. Together, our comprehensive DfMRI approaches can successfully provide information on dynamic brain function in normal and diseased brains
TOB is an effector of the hippocampus-mediated acute stress response
Stress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood. Transducer of ErbB2.1, known as TOB, is involved in different physiological functions, including cellular stress and immediate response to stimulation. In this study, we investigated the role of TOB in psychological stress machinery at molecular, neural circuit, and behavioral levels. Interestingly, TOB protein levels increased after mice were exposed to acute stress. At the neural circuit level, functional magnetic resonance imaging (fMRI) suggested that intra-hippocampal and hippocampal-prefrontal connectivity were dysregulated in Tob knockout (Tob-KO) mice. Electrophysiological recordings in hippocampal slices showed increased postsynaptic AMPAR-mediated neurotransmission, accompanied by decreased GABA neurotransmission and subsequently altered Excitatory/Inhibitory balance after Tob deletion. At the behavioral level, Tob-KO mice show abnormal, hippocampus-dependent, contextual fear conditioning and extinction, and depression-like behaviors. On the other hand, increased anxiety observed in Tob-KO mice is hippocampus-independent. At the molecular level, we observed changes in factors involved in stress response like decreased stress-induced LCN2 expression and ERK phosphorylation, as well as increased MKP-1 expression. This study introduces TOB as an important modulator in the hippocampal stress signaling machinery. In summary, we reveal a molecular pathway and neural circuit mechanism by which Tob deletion contributes to expression of pathological stress-related behavior
Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats
Background: Mast cells (MCs) are implicated in inflammation and tissue remodeling. Accumulation of lung MCs is described in pulmonary hypertension (PH); however, whether MC degranulation and c-kit, a tyrosine kinase receptor critically involved in MC biology, contribute to the pathogenesis and progression of PH has not been fully explored.Methods: Pulmonary MCs of idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-injected rats (MCT-rats) were examined by histochemistry and morphometry. Effects of the specific c-kit inhibitor PLX and MC stabilizer cromolyn sodium salt (CSS) were investigated in MCT-rats both by the preventive and therapeutic approaches. Hemodynamic and right ventricular hypertrophy measurements, pulmonary vascular morphometry and analysis of pulmonary MC localization/counts/activation were performed in animal model studies.Results: There was a prevalence of pulmonary MCs in IPAH patients and MCT-rats as compared to the donors and healthy rats, respectively. Notably, the perivascular MCs were increased and a majority of them were degranulated in lungs of IPAH patients and MCT-rats (p < 0.05 versus donor and control, respectively). In MCT-rats, the pharmacological inhibitions of MC degranulation and c-kit with CSS and PLX, respectively by a preventive approach (treatment from day 1 to 21 of MCT-injection) significantly attenuated right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH). Moreover, vascular remodeling, as evident from the significantly decreased muscularization and medial wall thickness of distal pulmonary vessels, was improved. However, treatments with CSS and PLX by a therapeutic approach (from day 21 to 35 of MCT-injection) neither improved hemodynamics and RVH nor vascular remodeling.Conclusions: The accumulation and activation of perivascular MCs in the lungs are the histopathological features present in clinical (IPAH patients) and experimental (MCT-rats) PH. Moreover, the accumulation and activation of MCs in the lungs contribute to the development of PH in MCT-rats. Our findings reveal an important pathophysiological insight into the role of MCs in the pathogenesis of PH in MCT- rats
Developing a short-term phenomenological training program: A report of methodological lessons
2020 Elsevier Ltd We discuss our attempts to develop a short-term phenomenological training program for training naïve participants in phenomenological skills. After reviewing existing methodologies for collecting phenomenological data and clarifying the benefit of the short-term training approach, we present two training programs and two experiments that tested their effectiveness. Experiment 1 tested the two-stage training program, which consists of (i) the illusion training which instructs participants to describe the experience of a visual illusion and (ii) the guidance training which offers individualized feedbacks for improving their description. This program proved effective, but also excessively skill-demanding. Experiment 2 tested the one-stage training program, consisting only of the illusion training; it was easier to use, but exhibited a smaller training effect. The paper concludes by delineating methodological lessons from the experiments focusing on three themes: (i) Individual difference in phenomenological aptitude; (ii) Bounded transferability of phenomenological skills; (iii) Active intervention in the learning process
Developing a short-term phenomenological training program: A report of methodological lessons
We discuss our attempts to develop a short-term phenomenological training program for training naïve participants in phenomenological skills. After reviewing existing methodologies for collecting phenomenological data and clarifying the benefit of the short-term training approach, we present two training programs and two experiments that tested their effectiveness. Experiment 1 tested the two-stage training program, which consists of (i) the illusion training which instructs participants to describe the experience of a visual illusion and (ii) the guidance training which offers individualized feedbacks for improving their description. This program proved effective, but also excessively skill-demanding. Experiment 2 tested the one-stage training program, consisting only of the illusion training; it was easier to use, but exhibited a smaller training effect. The paper concludes by delineating methodological lessons from the experiments focusing on three themes: (i) Individual difference in phenomenological aptitude; (ii) Bounded transferability of phenomenological skills; (iii) Active intervention in the learning process
Functions of consciousness : conceptual clarification
There are many theories of the functions of consciousness. How these theories relate to each other, how we should assess them, and whether any integration of them is possible are all issues that remain unclear. To contribute to a solution, this paper offers a conceptual framework to clarify the theories of the functions of consciousness. This framework consists of three dimensions: (i) target, (ii) explanatory order, and (iii) necessity/sufficiency. The first dimension, target, clarifies each theory in terms of the kind of consciousness it targets. The second dimension, explanatory order, clarifies each theory in terms of how it conceives of the explanatory relation between consciousness and function. The third dimension, necessity/sufficiency, clarifies each theory in terms of the necessity/sufficiency relation posited between consciousness and function. We demonstrate the usefulness of this framework by applying it to some existing scientific and philosophical theories of the functions of consciousness