Multiomics of early epileptogenesis in mice reveals phosphorylation and dephosphorylation-directed growth and synaptic weakening.

To investigate the phosphorylation-based signaling and protein changes occurring early in epileptogenesis, the hippocampi of mice treated with pilocarpine were examined by quantitative mass spectrometry at 4 and 24 h post-status epilepticus at vast depth. Hundreds of posttranscriptional regulatory proteins were the major early targets of increased phosphorylation. At 24 h, many protein level changes were detected and the phosphoproteome continued to be perturbed.

Paroxysmal dystonia results from the loss of RIM4 in Purkinje cells.

Full-length RIM1 and 2 are key components of the presynaptic active zone that ubiquitously control excitatory and inhibitory neurotransmitter release. Here, we report that the function of the small RIM isoform RIM4, consisting of a single C2 domain, is strikingly different from that of the long isoforms. RIM4 is dispensable for neurotransmitter release but plays a postsynaptic, cell type-specific role in cerebellar Purkinje cells that is essential for normal motor function.

Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma.

Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the () gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner.

Development and Testing of a Chronic-Disease Patient Experience Mapping Toolbox.

Background: Stakeholders increasingly expect research and care delivery to be guided by and to optimize patient experiences. However, standardized tools to engage patients to gather high-quality data about their experiences, priorities, and desired outcomes are not publicly available. The objective of this study was to develop and test a Toolbox with a disease-agnostic interview guide template and accompanying resources to assist researchers in engaging patients living with chronic disease in a dialogue about their experiences.

Highly dynamic inflammatory and excitability transcriptional profiles in hippocampal CA1 following status epilepticus.

Transient brain insults including status epilepticus (SE) can initiate a process termed 'epileptogenesis' that results in chronic temporal lobe epilepsy. As a consequence, the entire tri-synaptic circuit of the hippocampus is fundamentally impaired. A key role in epileptogenesis has been attributed to the CA1 region as the last relay station in the hippocampal circuit and as site of aberrant plasticity, e.

Ganglioglioma cells potentiate neuronal network synchronicity and elicit burst discharges via released factors.

Gangliogliomas (GGs) represent the most frequent glioneuronal tumor entity associated with chronic recurrent seizures; rare anaplastic GGs variants retain the glioneuronal character. So far, key mechanisms triggering chronic hyperexcitability in the peritumoral area are unresolved. Based on a recent mouse model for anaplastic GG (BRAF, mTOR activation and Trp53) we here assessed the influence of GG-secreted factors on non-neoplastic cells in-vitro.

Not simply a matter of parents-Infants' sleep-wake patterns are associated with their regularity of eating.

In adults there are indications that regular eating patterns are related to better sleep quality. During early development, sleep and eating habits experience major maturational transitions. Further, the bacterial landscape of the gut microbiota undergoes a rapid increase in complexity.

Learning during sleep in humans - A historical review.

Sleep helps to consolidate previously acquired memories. Whether new information such as languages and other useful skills can also be learned during sleep has been debated for over a century, however, the sporadic studies' different objectives and varied methodologies make it difficult to draw definitive conclusions. This review provides a comprehensive overview of the history of sleep learning research conducted in humans, from its empirical beginnings in the 1940s to the present day.

SV2B defines a subpopulation of synaptic vesicles.

Synaptic vesicles can undergo several modes of exocytosis, endocytosis, and trafficking within individual synapses, and their fates may be linked to different vesicular protein compositions. Here, we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy. SV2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone.

Phosphorylation-state dependent intraneuronal sorting of Aβ differentially impairs autophagy and the endo-lysosomal system.

AD: Alzheimer disease; APP: amyloid beta precursor protein; ATG: autophagy related; Aβ: amyloid-β; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; EEA1: early endosome antigen 1; FA: formic acid; GFP: green fluorescent protein; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP2: microtubule-associated protein 2; nmAβ: non-modified amyloid-β; npAβ: non-phosphorylated amyloid-β; pAβ: phosphorylated amyloid-β; p-Ser26Aβ: amyloid-β phosphorylated at serine residue 26; p-Ser8Aβ: amyloid-β phosphorylated at serine residue 8; RAB: RAB, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestome 1; YFP: yellow fluorescent protein.

Lack of association between behavioral development and simplified topographical markers of the sleep EEG in infancy.

The sleep EEG mirrors neuronal connectivity, especially during development when the brain undergoes substantial rewiring. As children grow, the slow-wave activity (SWA; 0.75-4.

Munc13- and SNAP25-dependent molecular bridges play a key role in synaptic vesicle priming.

Synaptic vesicle tethering, priming, and neurotransmitter release require a coordinated action of multiple protein complexes. While physiological experiments, interaction data, and structural studies of purified systems were essential for our understanding of the function of the individual complexes involved, they cannot resolve how the actions of individual complexes integrate. We used cryo-electron tomography to simultaneously image multiple presynaptic protein complexes and lipids at molecular resolution in their native composition, conformation, and environment.

Early cortical oligodendrocyte precursor cells are transcriptionally distinct and lack synaptic connections.

Oligodendrocyte precursor cells (OPCs) generate oligodendrocytes, a process that may be tuned by neuronal activity, possibly via synaptic connections to OPCs. However, a developmental role of synaptic signaling to OPCs has so far not been shown unequivocally. To address this question, we comparatively analyzed functional and molecular characteristics of highly proliferative and migratory OPCs in the embryonic brain.

Bedtime to the brain: how infants' sleep behaviours intertwine with non-rapid eye movement sleep electroencephalography features.

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioural function. Observational research has associated early life sleep problems with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep behaviours (e.

A Foundation for Patient-Centered Core Impact Sets: Key Learnings from Past and Existing Approaches.

Despite growing commitment to patient centricity, challenges persist in consistently identifying the impacts of disease and/or treatment that patients report as most important to them, especially across myriad potential downstream uses. Patient-centered core impact sets (PC-CIS), disease-specific lists of impacts that patients report as most important, are proposed as a solution. But, PC-CIS is a new concept, currently in the pilot stage with patient advocacy groups.

Neural correlates of sleep-induced benefits on traumatic memory processing.

Recent findings indicate that sleep after trauma compared to sleep loss inhibits intrusive memory development, possibly by promoting adequate memory consolidation and integration. However, the underlying neural mechanisms are still unknown. Here, we examined the neural correlates underlying the effects of sleep on traumatic memory development in 110 healthy participants using a trauma film paradigm and an implicit memory task with fMRI recordings in a between-subjects design.

Memory reactivations during sleep: a neural basis of dream experiences?

Newly encoded memory traces are spontaneously reactivated during sleep. Since their discovery in the 1990s, these memory reactivations have been discussed as a potential neural basis for dream experiences. New results from animal and human research, as well as from the rapidly growing field of sleep and dream engineering, provide essential insights into this question, and reveal both strong parallels and disparities between the two phenomena.

Identification and validation of NFIA as a novel prognostic marker in renal cell carcinoma.

Prognostic tools are an essential component of the clinical management of patients with renal cell carcinoma (RCC). Although tumour stage and grade can provide important information, they fail to consider patient- and tumour-specific biology. In this study, we set out to find a novel molecular marker of RCC by using hepatocyte nuclear factor 4A (HNF4A), a transcription factor implicated in RCC progression and malignancy, as a blueprint.

Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF.

Extracellular vesicles (EVs) have emerged as mediators of cellular communication, in part via the delivery of associated microRNAs (miRNAs), small non-coding RNAs that regulate gene expression. We show that brain-derived neurotrophic factor (BDNF) mediates the sorting of miR-132-5p, miR-218-5p, and miR-690 in neuron-derived EVs. BDNF-induced EVs in turn increase excitatory synapse formation in recipient hippocampal neurons, which is dependent on the inter-neuronal delivery of these miRNAs.

The sleeping brain's connectivity and family environment: characterizing sleep EEG coherence in an infant cohort.

Brain connectivity closely reflects brain function and behavior. Sleep EEG coherence, a measure of brain's connectivity during sleep, undergoes pronounced changes across development under the influence of environmental factors. Yet, the determinants of the developing brain's sleep EEG coherence from the child's family environment remain unknown.