Multifactorial approach is needed to unravel the maturation phases of human neurons derived from induced pluripotent stem cells.

Neurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of human neuronal development under healthy and pathological conditions. However, multiple studies have demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of human neurons derived from iPSCs.

Development of a Genetically Encoded Sensor for Arginine.

The amino acid l-arginine (Arg) plays important roles in multiple metabolic and physiological processes, and changes in its concentration have been implicated in pathological processes. While it is important to measure Arg levels in biological systems directly and in real-time, existing Arg sensors respond to l-ornithine or l-lysine. Here we report ArgS1, a new Arg sensor.

Specialized pro-resolving lipid mediators: a key player in resolving inflammation in autoimmune diseases.

Uncontrolled hyperactivation of the immune system is the central mechanism underlying the pathogenesis of autoimmune diseases. Timely control of the inflammatory response is essential to prevent inflammation progression and organ damage. Specialized pro-resolving lipid mediators (SPMs) are autacoid molecules derived from essential polyunsaturated fatty acids during acute inflammatory responses.

A constellation of anatomical variation: middle scalene, wrist extensor, and aortic arch variants share embryological origins in cervical somites.

During dissection of a 70-year-old male donor, several anatomical variations were observed, highlighted by a bilateral variant middle scalene muscle in the superolateral thoracic wall. The variant scalene muscle was traced from the transverse processes of cervical vertebrae to the fourth rib with a pronounced fascial slip. The elongated middle scalene muscle was thick in girth and abnormally wide at its insertion (56.

Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease.

In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether the parental origin of the 5xFAD transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance of the transgene led to a 2-fold higher plaque burden compared with maternal inheritance, a finding consistent across multiple 5xFAD colonies.

Closed-loop modulation of remote hippocampal representations with neurofeedback.

Humans can remember specific remote events without acting on them and influence which memories are retrieved based on internal goals. However, animal models typically present sensory cues to trigger memory retrieval and then assess retrieval based on action. Thus, it is difficult to determine whether measured neural activity patterns relate to the cue(s), the memory, or the behavior.

The impact of linguistic complexity on feasibility and reliability of language mapping in aphasic glioma patients.

Background: Reliable language mappings require sufficient language skills. This study evaluated whether linguistic task properties impact feasibility and reliability of navigated transcranial magnetic stimulation (nTMS)-based language mappings in aphasic glioma patients.

Methods: The effect of linguistic complexity on naming accuracy during baseline testing without stimulation and on the number of errors during nTMS was evaluated for 16 moderately and 4 severely expressive aphasic patients.

Multi-modal investigation reveals pathogenic features of diverse DDX3X missense mutations.

De novo mutations in the RNA binding protein DDX3X cause neurodevelopmental disorders including DDX3X syndrome and autism spectrum disorder. Amongst ~200 mutations identified to date, half are missense. While DDX3X loss of function is known to impair neural cell fate, how the landscape of missense mutations impacts neurodevelopment is almost entirely unknown.

Dedicator of Cytokinesis 2 regulates cytoskeletal actin dynamics and is essential for platelet biogenesis and functions.

Aims: Dedicator of Cytokinesis 2 (DOCK2), a member of the DOCK family of Guanine nucleotide exchange factors that specifically act on the Rho GTPases including Rac and Cdc42, plays pivotal roles in the regulation of leukocyte homeostasis. However, its functions in platelets remain unknown.

Methods And Results: Using mice with genetic deficiency of DOCK2 (Dock2-/-), we showed that Dock2-/-mice exhibited a macrothrombocytopenic phenotype characterized as decreased platelet count and enlarged platelet size by transmission electron microscopy.

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

Purpose: This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose.

Saponins enhance the stability and cost-efficiency of human embryonic stem cell culture.

The cultivation and differentiation of human embryonic stem cells (hESCs) into organoids are crucial for advancing of new drug development and personalized cell therapies. Despite establishing of chemically defined hESC culture media over the past decade, these media's reliance on growth factors, which are costly and prone to degradation, poses a challenge for sustained and stable cell culture. Here, we introduce an hESC culture system(E6Bs) that facilitates the long-term, genetically stable expansion of hESCs, enabling cells to consistently sustain high levels of pluripotency markers, including NANOG, SOX2, TRA-1-60, and SSEA4, across extended periods.

Cortical reorganization following dorsal spinal injuries in newborn monkeys reveals a critical period in the development of the somatosensory cortex.

Lesions of the dorsal columns of the spinal cord in adult macaque monkeys lead to the loss of hand inputs and large-scale expansion of the face inputs in the hand region of the somatosensory cortex. Inputs from alternate spinal pathways do not reactivate the deafferented regions of area 3b. Here, we determined how transections of the dorsal columns done within a few days after birth affect the developing somatosensory cortex.

Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus.

The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EP) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior.

Time-Varying Spatial Propagation of Brain Networks in fMRI Data.

Spontaneous neural activity coherently relays information across the brain. Several efforts have been made to understand how spontaneous neural activity evolves at the macro-scale level as measured by resting-state functional magnetic resonance imaging (rsfMRI). Previous studies observe the global patterns and flow of information in rsfMRI using methods such as sliding window or temporal lags.

The Blood-Cerebrospinal Fluid Barrier as a Potential Entry Site for the SARS-CoV-2 Virus.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19). While SARS-CoV-2 primarily targets the lungs and airways, it can also infect other organs, including the central nervous system (CNS). The aim of this study was to investigate whether the choroid plexus could serve as a potential entry site for SARS-CoV-2 into the brain.

Stimulation of IRES-Dependent Translation by Rocaglamide A Increases the Replication and Virulence of Cricket Paralysis Virus in Lepidopteran Insect Cells.

The discovery that infections of viruses are pervasive among insects has considerable potential for future applications, such as new strategies for pest control through the manipulation of virus-host interactions. However, few studies can be found that aim to minimize (for beneficial insects) or maximize (for pests) virus impact or virulence. Viruses generally employ molecular mechanisms that deviate from the cells' to increase their replication efficiency and to avoid the immune response.

DNA methylation, histone acetylation in the regulation of memory and its modulation during aging.

Memory formation is associated with constant modifications of neuronal networks and synaptic plasticity gene expression in response to different environmental stimuli and experiences. Dysregulation of synaptic plasticity gene expression affects memory during aging and neurodegenerative diseases. Covalent modifications such as methylation on DNA and acetylation on histones regulate the transcription of synaptic plasticity genes.

Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines.

Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures to optimize the effectiveness of disease prevention and treatment. This approach is favorable in the context of brain disorders, which are often heterogeneous in their pathophysiological features, patterns of disease progression and treatment response, resulting in limited therapeutic standard-of-care. Here we highlight the transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models are poised to play in advancing precision medicine for brain disorders, particularly emerging innovations that improve the relevance of hiPSC models to human physiology.

"PyTDL": A versatile temporal difference learning algorithm to simulate behavior process of decision making and cognitive learning.

Humans and animals excel at learning complex tasks through reward-based feedback, dynamically adjusting value expectations and choices based on past experiences to optimize outcomes. However, understanding the hidden cognitive components driving these behaviors remains challenging. Neuroscientists use the Temporal Difference (TD) learning model to estimate cognitive elements like value representation and prediction error during learning and decision-making processes.

Long-term mindfulness meditation increases occurrence of sensory and attention brain states.

Interest has been growing in the use of mindfulness meditation (MM) as a therapeutic practice, as accumulating evidence highlights its potential to effectively address a range of mental conditions. While many fMRI studies focused on neural activation and functional connectivity during meditation, the impact of long-term MM practice on spontaneous brain activity, and on the expression of resting state networks over time, remains unclear. Here, intrinsic functional network dynamics were compared between experienced meditators and meditation-naïve participants during rest.