生物学最新文献

The fission yeast, Schizosaccharomyces pombe, is an excellent eukaryote model organism for studying essential biological processes. Its genome contains ∼1,200 genes essential for cell viability, most of which are evolutionarily conserved. To study these essential genes, resources enabling conditional perturbation of target genes are required. Here, we constructed comprehensive arrayed libraries of plasmids and strains to knock down essential genes in S. pombe using dCas9-mediated CRISPRi. These libraries cover ∼98% of all essential genes in fission yeast. We estimate that in ∼60% of these strains, transcription of a target gene was repressed so efficiently that cell proliferation was significantly inhibited. To demonstrate the usefulness of these libraries, we performed metabolic analyses with knockdown strains and revealed flexible interaction among metabolic pathways. Libraries established in this study enable comprehensive functional analyses of essential genes in S. pombe and will facilitate the understanding of essential biological processes in eukaryotes.

When you perceive or remember something, other related things come to mind, affecting how these competing items are subsequently perceived and remembered. Such behavioural consequences are believed to result from changes in the overlap of neural representations of these items, especially in the hippocampus. According to multiple theories, hippocampal overlap should increase (integration) when there is high coactivation between cortical representations. However, prior studies used indirect proxies for coactivation by manipulating stimulus similarity or task demands. Here, we induce coactivation in visual cortex more directly using closed-loop neurofeedback from real-time functional magnetic resonance imaging (fMRI). While viewing one object, participants were rewarded for activating the representation of another object as strongly as possible. Across multiple real-time fMRI sessions, participants succeeded in using this neurofeedback to increase coactivation. Compared with a baseline of untrained objects, this protocol led to memory integration in behaviour and the brain: the trained objects became harder for participants to discriminate behaviourally in a categorical perception task and harder to discriminate neurally from patterns of fMRI activity in their hippocampus as a result of losing unique features. These findings demonstrate that neurofeedback can be used to alter and combine memories.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

This study explores the subjective evaluation of supplementary motor area (SMA) regulation performance in a real-time functional magnetic resonance imaging neurofeedback (fMRI-NF) task. In fMRI-NF, people learn how to self-regulate their brain activity by performing mental actions to achieve a certain target level (TL) of blood-oxygen-level-dependent (BOLD) activation. Here, we studied two types of self-evaluation: performance predictions and perceived confidence in the prediction judgement. Participants completed three sessions of SMA regulation in a 7 T fMRI scanner, performing a mental drawing task. During each trial, they modulated their imagery strategy to achieve one of two different levels of SMA activation and reported a performance prediction and their confidence in the prediction before receiving delayed BOLD-activation feedback. Results show that participants' performance predictions improved with learning throughout the three sessions, and that these improvements were not driven exclusively by their knowledge of previous performance. Confidence reports on the other hand showed no change throughout training and did not correlate with better and worse predictions. In addition to shedding light on mechanisms of internal self-evaluation during neurofeedback training, these results also point to a dissociation between predictions of performance and confidence reports in the presence of feedback. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Neurofeedback allows individuals to monitor and self-regulate their brain activity, potentially improving human brain function. Beyond the traditional electrophysiological approach using primarily electroencephalography, brain haemodynamics measured with functional magnetic resonance imaging (fMRI) and more recently, functional near-infrared spectroscopy (fNIRS) have been used (haemodynamic-based neurofeedback), particularly to improve the spatial specificity of neurofeedback. Over recent years, especially fNIRS has attracted great attention because it offers several advantages over fMRI such as increased user accessibility, cost-effectiveness and mobility-the latter being the most distinct feature of fNIRS. The next logical step would be to transfer haemodynamic-based neurofeedback protocols that have already been proven and validated by fMRI to mobile fNIRS. However, this undertaking is not always easy, especially since fNIRS novices may miss important fNIRS-specific methodological challenges. This review is aimed at researchers from different fields who seek to exploit the unique capabilities of fNIRS for neurofeedback. It carefully addresses fNIRS-specific challenges and offers suggestions for possible solutions. If the challenges raised are addressed and further developed, fNIRS could emerge as a useful neurofeedback technique with its own unique application potential-the targeted training of brain activity in real-world environments, thereby significantly expanding the scope and scalability of haemodynamic-based neurofeedback applications.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Neurofeedback (NF) is endogenous neuromodulation of circumscribed brain circuitry. While its use of real-time brain activity in a closed-loop system is similar to brain-computer interfaces, instead of controlling an external device like the latter, the goal of NF is to change a targeted brain function. In this special issue on NF, we present current and future methods for extracting and manipulating neural function, how these methods may reveal new insights about brain function, applications, and rarely discussed ethical considerations of guiding and interpreting the brain activity of others. Together, the articles in this issue outline the possibilities of NF use and impact in the real world, poising to influence the development of more effective and personalized NF protocols, improving the understanding of underlying psychological and neurological mechanisms and enhancing treatment precision for various neurological and psychiatric conditions.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Neurofeedback is a brain-training technique that continues to develop via ongoing innovations, and that has broadening potential impact. Once confined primarily to clinical and research settings, it is increasingly being used in the general population. Such development raises concerns about the current regulatory mechanisms and their adequacy in protecting patterns of economic and political decision-making from the novel technology. As studies have found neurofeedback to change subjects' preferences and mental associations covertly, there is a possibility it will be abused for political and commercial gains. Current regulatory practices (including disclaimer requirements, unfair and deceptive trade practice statutes and undue influence law) may be avenues from which to regulate neurofeedback influence. They are, however, limited. Regulating neurofeedback will face the line-drawing problem of determining when it induces an unacceptable level of influence. We suggest experiments that will clarify how the parameters of neurofeedback training affect its level of influence. In addition, we assert that the reactive nature of the traditional models of regulation will be inadequate against this and other rapidly transforming technologies. An integrated and proactive regulatory system designed for flexibility must be adopted to protect society in this era of modern technological advancement. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Two protocadherins, Dachsous and Fat, regulate organ growth in Drosophila via the Hippo pathway. Dachsous and Fat bind heterotypically to regulate the abundance and subcellular localization of a "core complex" consisting of Dachs, Dlish, and Approximated. This complex localizes to the junctional cortex where it represses Warts. Dachsous is believed to promote growth by recruiting and stabilizing this complex, while Fat represses growth by promoting its degradation. Here, we examine the functional relationships between the intracellular domains of Dachsous and Fat and the core complex. While Dachsous promotes the accumulation of core complex proteins in puncta, it is not required for their assembly. Indeed, the core complex accumulates maximally in the absence of both Dachsous and Fat. Furthermore, Dachsous represses growth in the absence of Fat by removing the core complex from the junctional cortex. Fat similarly recruits core complex components but promotes their degradation. Our findings reveal that Dachsous and Fat coordinately constrain tissue growth by repressing the core complex.

Neurofeedback (NF) has emerged as a promising avenue for demonstrating process-related neuroplasticity, enabling self-regulation of brain function. NF targeting the amygdala has drawn attention to therapeutic potential in psychiatry, by potentially harnessing emotion-regulation processes. However, not all individuals respond equally to NF training, possibly owing to varying self-regulation abilities. This underscores the importance of understanding the mechanisms behind successful neuromodulation (i.e. capacity). This study aimed to investigate the establishment and neural correlates of neuromodulation capacity using data from repeated sessions of amygdala electrical fingerprint (Amyg-EFP)-NF and post-training functional magnetic resonance imaging (fMRI)-NF sessions. Results from 97 participants (healthy controls and post-traumatic stress disorder and fibromyalgia patients) revealed increased Amyg-EFP neuromodulation capacity over training, associated with post-training amygdala-fMRI modulation capacity and improvements in alexithymia. Individual differenaces in this capacity were associated with pre-training amygdala reactivity and initial neuromodulation success. Additionally, amygdala downregulation during fMRI-NF co-modulated with other regions such as the posterior insula and parahippocampal gyrus. This combined modulation better explained EFP-modulation capacity and improvement in alexithymia than the amygdala modulation alone, suggesting the relevance of this broader network to gained capacity. These findings support a network-based approach for NF and highlight the need to consider individual differences in brain function and modulation capacity to optimize NF interventions. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Successful axonal regeneration following injury requires the effective allocation of energy. How axons withstand the initial disruption in mitochondrial energy production caused by the injury and subsequently initiate regrowth is poorly understood. Transcriptomic data showed increased expression of glycolytic genes after optic nerve crush in retinal ganglion cells with the co-deletion of Pten and Socs3. Using retinal cultures in a multicompartment microfluidic device, we observed increased regrowth and enhanced mitochondrial trafficking in the axons of Pten and Socs3 co-deleted neurons. While wild-type axons relied on mitochondrial metabolism, after injury, in the absence of Pten and Socs3, energy production was supported by local glycolysis. Specific inhibition of lactate production hindered injury survival and the initiation of regrowth while slowing down glycolysis upstream impaired regrowth initiation, axonal elongation, and energy production. Together, these observations reveal that glycolytic ATP, combined with sustained mitochondrial transport, is essential for injury-induced axonal regrowth, providing new insights into the metabolic underpinnings of axonal regeneration.