生物学最新文献

The malaria-causing parasite, P. falciparum, replicates through schizogony, a tightly orchestrated process where numerous daughter parasites are formed simultaneously. Proper division and segregation of one-per-cell organelles, like the mitochondrion and apicoplast, are essential, yet remain poorly understood. We developed a new reporter parasite line that allows visualization of the mitochondrion in blood and mosquito stages. Using high-resolution 3D imaging, we found that the mitochondrion orients in a cartwheel structure, prior to stepwise, non-geometric division during last-stage schizogony. Analysis of focused ion beam scanning electron microscopy data confirmed these mitochondrial division stages. Furthermore, these data allowed us to elucidate apicoplast division steps, highlighted its close association with the mitochondrion, and showed putative roles of the centriolar plaques in apicoplast segregation. These observations form the foundation for a new detailed mechanistic model of mitochondrial and apicoplast division and segregation during P. falciparum schizogony and pave the way for future studies into the proteins and protein complexes involved in organelle division and segregation.

Excess dietary intake of saturated fatty acids (SFAs) induces glucose intolerance and metabolic disorders. In contrast, unsaturated fatty acids (UFAs) elicit beneficial effects on insulin sensitivity. However, it remains elusive how SFAs and UFAs signal differentially toward insulin signaling to influence glucose homeostasis. Here, using a croaker model, we report that dietary palmitic acid (PA), but not oleic acid or linoleic acid, leads to dysregulation of mTORC1, which provokes systemic insulin resistance. Mechanistically, we show that PA profoundly elevates acetyl-CoA derived from mitochondrial fatty acid β oxidation to intensify Tip60-mediated Rheb acetylation, which triggers mTORC1 activation by promoting the interaction between Rheb and FKBPs. Subsequently, hyperactivation of mTORC1 enhances IRS1 serine phosphorylation and inhibits TFEB-mediated IRS1 transcription, inducing impairment of insulin signaling. Collectively, our results reveal a conserved molecular insight into the mechanism by which Tip60-mediated Rheb acetylation induces mTORC1 activation and insulin resistance under the PA condition, which may provide therapeutic avenues to intervene in the development of T2D.

Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). Thirty-seven eligible participants were randomized into an experimental group (n = 18) and a passive control group (n = 19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach's feasibility. NF learning showed a statistical trend for increases in frontal-midline theta from session to session with a large effect size and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EF improvements, but significant self-reported gains in daily EFs-working memory, shifting, monitoring and inhibition-showing medium and high effect sizes. The experimental group's significant gains in their key training goals underscored the approach's external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

During fMRI neurofeedback participants learn to self-regulate activity in relevant brain areas and networks based on ongoing feedback extracted from measured responses in those regions. This closed-loop approach has been successfully applied to reduce symptoms in mood disorders such as depression by showing participants a thermometer-like display indicating the strength of activity in emotion-related brain areas. The hitherto employed conventional neurofeedback is, however, 'blind' with respect to emotional content, i.e. patients instructed to engage in a specific positive emotion could drive the neurofeedback signal by engaging in a different (positive or negative) emotion. In this future perspective, we present a new form of neurofeedback that displays semantic information of emotions to the participant. Semantic information is extracted online using real-time representational similarity analysis of emotion-specific activity patterns. The extracted semantic information can be provided to participants in a two-dimensional semantic map depicting the current mental state as a point reflecting its distance to pre-measured emotional mental states (e.g. 'happy', 'content', 'sad', 'angry'). This new approach provides transparent feedback during self-regulation training, and it has the potential to enable more specific training effects for future therapeutic applications such as clinical interventions in mood disorders.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

With the spread of smartphones and computer games, concerns have escalated regarding the rising prevalence of gaming disorder. Patients often display attentional biases, unconsciously turning their attention towards gaming-related stimuli. However, attempts to discover and ameliorate these attentional deficits have yielded inconsistent outcomes, potentially due to the dynamic nature of attentional bias. This study investigated neural mechanisms underlying attentional bias state by combining neuroimaging (functional magnetic resonance imaging -fMRI) with an approach-avoidance task tailored to an individual's gaming preference. We conducted a multivariate pattern analysis of endogenous brain activity in 21 participants with probable gaming disorder. Our analyses revealed that activity patterns in the insula tracked temporal attentional bias states specific to gaming stimuli. A broad network of frontal and parietal regions instead appeared to predict a general temporal attentional bias state. Finally, we conducted a proof-of-concept study for 'just-in-time' attentional bias training through fMRI-decoded neurofeedback of insula activity patterns, named decoded attentional bias training (DecABT). Our preliminary results suggest that DecABT may help to decrease the attractiveness of gaming stimuli via a insula- and precuneus-based neural mechanism. This work provides new evidence for the insula as an endogenous regulator of attentional bias states in gaming disorder and a starting point to develop novel, individualized therapeutic approaches to treat addiction.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

We aimed to replicate previous effects of functional magnetic resonance imaging neurofeedback (fMRI-NF) in right inferior frontal cortex (rIFC) on IFC activation during a Stop Task in a larger group of boys with attention-deficit/hyperactivity disorder (ADHD). The present double-blind, randomized controlled trial tested the effects of 15 runs of active versus sham fMRI-NF of rIFC on performance and activation associated with successful and failed inhibition versus Go trials during a tracking Stop task in 88 boys with ADHD (44 active; 44 sham), controlling for age and medication status. No significant group-by-time interaction effects were observed for performance or brain activation during the successful stop trials, and post hoc analysis showed very low numbers of active fMRI-NF learners. Nevertheless, during error monitoring, there was a significant group-by-time interaction effect on post-error reaction time slowing and in left IFC activation, which were both increased after active compared to sham fMRI-NF. The findings are in line with our previous observation of left IFC upregulation after fMRI-NF of rIFC relative to active fMRI-NF of parahippocampal gyrus. This highlights the potentially wider regional effects that fMRI-NF of a particular self-control target region has on other self-regulatory regions in ADHD. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Tuft cells are a rare epithelial cell type that play important roles in sensing and responding to luminal antigens. A defining morphological feature of this lineage is the actin-rich apical "tuft," which contains large fingerlike protrusions. However, details of the cytoskeletal ultrastructure underpinning the tuft, the molecules involved in building this structure, or how it supports tuft cell biology remain unclear. In the context of the small intestine, we found that tuft cell protrusions are supported by long-core bundles that consist of F-actin crosslinked in a parallel and polarized configuration; they also contain a tuft cell-specific complement of actin-binding proteins that exhibit regionalized localization along the bundle axis. Remarkably, in the sub-apical cytoplasm, the array of core actin bundles interdigitates and co-aligns with a highly ordered network of microtubules. The resulting cytoskeletal superstructure is well positioned to support subcellular transport and, in turn, the dynamic sensing functions of the tuft cell that are critical for intestinal homeostasis.

Neuroimaging technologies such as brain-computer interfaces and neurofeedback have evolved rapidly as new tools for cognitive neuroscience and as potential clinical interventions. However, along with these developments, concern has grown based on the fear of the potential misuse of neurotechnology. In October 2021, Chile became the first country to include neurorights in its Constitution. The present article is divided into two parts. In the first section, we describe the path followed by neurorights that led to its inclusion in the Chilean Constitution, and the neurotechnologies usually involved in neurorights discussions. In the second part, we discuss two potential problems of neurorights. We begin by pointing out some epistemological concerns regarding neurorights, mainly referring to the ambiguity of the concepts used in neurolegislations, the difficult relationship between neuroscience and politics and the weak reasons for urgency in legislating. We then describe the dangers of overprotective laws in medical research, based on the detrimental effect of recent legislation in Chile and the potential risk posed by neurorights to the benefits of neuroscience development. This article aims to engage with the scientific community interested in neurotechnology and neurorights in an interdisciplinary reflection of the potential consequences of neurorights.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Mogk and den Brave discuss exciting results from a comprehensive screen of heat shock response components in yeast, published in this issue by Pincus and colleagues (https://doi.org/10.1083/jcb.202401082). Their work reveals modulatory regulatory loops that fine-tune the timing of the shutdown of this highly conserved pathway.

Lysosomes, essential for intracellular degradation and recycling, employ damage-control strategies such as lysophagy and membrane repair mechanisms to maintain functionality and cellular homeostasis. Our study unveils migratory autolysosome disposal (MAD), a response to lysosomal damage where cells expel LAMP1-LC3 positive structures via autolysosome exocytosis, requiring autophagy machinery, SNARE proteins, and cell migration. This mechanism, crucial for mitigating lysosomal damage, underscores the role of cell migration in lysosome damage control and facilitates the release of small extracellular vesicles, highlighting the intricate relationship between cell migration, organelle quality control, and extracellular vesicle release.