Borregaardcoyne0747
Six mutations in the salt-inducible kinase 1 (SIK1)-coding gene have been identified in patients with early infantile epileptic encephalopathy (EIEE-30) accompanied by autistic symptoms. Two of the mutations are non-sense mutations that truncate the C-terminal region of SIK1. It has been shown that the C-terminal-truncated form of SIK1 protein affects the subcellular distribution of SIK1 protein, tempting to speculate the relevance to the pathophysiology of the disorders. We generated SIK1-mutant (SIK1-MT) mice recapitulating the C-terminal-truncated mutations using CRISPR/Cas9-mediated genome editing. SIK1-MT protein was distributed in the nucleus and cytoplasm, whereas the distribution of wild-type SIK1 was restricted to the nucleus. We found the disruption of excitatory and inhibitory (E/I) synaptic balance due to an increase in excitatory synaptic transmission and enhancement of neural excitability in the pyramidal neurons in layer 5 of the medial prefrontal cortex in SIK1-MT mice. We also found the increased repetitive behavior and social behavioral deficits in SIK1-MT mice. The risperidone administration attenuated the neural excitability and excitatory synaptic transmission, but the disrupted E/I synaptic balance was unchanged, because it also reduced the inhibitory synaptic transmission. Risperidone also eliminated the repetitive behavior but not social behavioral deficits. These results indicate that risperidone has a role in decreasing neuronal excitability and excitatory synapses, ameliorating repetitive behavior in the SIK1-truncated mice.Trigeminal nerve injury is known to cause severe persistent pain in the orofacial region. This pain is difficult to diagnose and treat. Recently, many animal studies have reported that rewiring of the peripheral and central nervous systems, non-neuronal cell activation, and up- and down-regulation of various molecules in non-neuronal cells are involved in the development of this pain following trigeminal nerve injury. However, there are many unknown mechanisms underlying the persistent orofacial pain associated with trigeminal nerve injury. In this review, we address recent animal data regarding the involvement of various molecules in the communication of neuronal and non-neuronal cells and examine the possible involvement of ascending pathways in processing pathological orofacial pain. We also address the clinical observations of persistent orofacial pain associated with trigeminal nerve injury and clinical approaches to their diagnosis and treatment.Chromatin remodeling proteins utilize the energy from ATP hydrolysis to mobilize nucleosomes often creating accessibility for transcription factors within gene regulatory elements. Aberrant chromatin remodeling has diverse effects on neuroprogenitor homeostasis altering progenitor competence, proliferation, survival, or cell fate. Previous work has shown that inactivation of the ISWI genes, Smarca5 (encoding Snf2h) and Smarca1 (encoding Snf2l) have dramatic effects on brain development. Smarca5 conditional knockout mice have reduced progenitor expansion and severe forebrain hypoplasia, with a similar effect on the postnatal growth of the cerebellum. In contrast, Smarca1 mutants exhibited enlarged forebrains with delayed progenitor differentiation and increased neuronal output. Here, we utilized cerebellar granule neuron precursor (GNP) cultures from Smarca1 mutant mice (Ex6DEL) to explore the requirement for Snf2l on progenitor homeostasis. The Ex6DEL GNPs showed delayed differentiation upon plating that was not attributed to changes in the Sonic Hedgehog pathway but was associated with overexpression of numerous positive effectors of proliferation, including targets of Wnt activation. Transcriptome analysis identified increased expression of Fosb and Fosl2 while ATACseq experiments identified a large increase in chromatin accessibility at promoters many enriched for Fos/Jun binding sites. Nonetheless, the elevated proliferation index was transient and the Ex6DEL cultures initiated differentiation with a high concordance in gene expression changes to the wild type cultures. Genes specific to Ex6DEL differentiation were associated with an increased activation of the ERK signaling pathway. Taken together, this data provides the first indication of how Smarca1 mutations alter progenitor cell homeostasis and contribute to changes in brain size.In immersive virtual reality, the own body is often visually represented by an avatar. This may induce a feeling of body ownership over the virtual limbs. Importantly, body ownership and the motor system share neural correlates. Yet, evidence on the functionality of this neuroanatomical coupling is still inconclusive. Findings from previous studies may be confounded by the congruent vs. incongruent multisensory stimulation used to modulate body ownership. This study aimed to investigate the effect of body ownership and congruency of information on motor performance in immersive virtual reality. We aimed to modulate body ownership by providing congruent vs. incongruent visuo-tactile stimulation (i.e., participants felt a brush stroking their real fingers while seeing a virtual brush stroking the same vs. different virtual fingers). To control for congruency effects, unimodal stimulation conditions (i.e., only visual or tactile) with hypothesized low body ownership were included. Fifty healthy participants performed a decision-making (pressing a button as fast as possible) and a motor task (following a defined path). Body ownership was assessed subjectively with established questionnaires and objectively with galvanic skin response (GSR) when exposed to a virtual threat. Our results suggest that congruency of information may decrease reaction times and completion time of motor tasks in immersive virtual reality. Moreover, subjective body ownership is associated with faster reaction times, whereas its benefit on motor task performance needs further investigation. Therefore, it might be beneficial to provide congruent information in immersive virtual environments, especially during the training of motor tasks, e.g., in neurorehabilitation interventions.The altered functional connectivity (FC) in amblyopia has been investigated by many studies, but the specific causality of brain connectivity needs to be explored further to understand the brain activity of amblyopia. We investigated whether the effective connectivity (EC) of children and young adults with amblyopia was altered. The subjects included 16 children and young adults with left eye amblyopia and 17 healthy controls (HCs). The abnormalities between the left/right primary visual cortex (PVC) and the other brain regions were investigated in a voxel-wise manner using the Granger causality analysis (GCA). According to the EC results in the HCs and the distribution of visual pathways, 12 regions of interest (ROIs) were selected to construct an EC network. The alteration of the EC network of the children and young adults with amblyopia was analyzed. In the voxel-wise manner analysis, amblyopia showed significantly decreased EC between the left/right of the PVC and the left middle frontal gyrus/left inferior frontal gyrus compared with the HCs. In the EC network analysis, compared with the HCs, amblyopia showed significantly decreased EC from the left calcarine fissure, posterior cingulate gyrus, left lingual gyrus, right lingual gyrus, and right fusiform gyrus to the right calcarine fissure. Amblyopia also showed significantly decreased EC from the right inferior frontal gyrus and right lingual gyrus to the left superior temporal gyrus compared with the HCs in the EC network analysis. The results may indicate that amblyopia altered the visual feedforward and feedback pathway, and amblyopia may have a greater relevance with the feedback pathway than the feedforward pathway. Amblyopia may also correlate with the feedforward of the third visual pathway.Compared with the traditional neurofeedback paradigm, the cognition-guided neurofeedback brain-computer interface (BCI) is a novel paradigm with significant effect on nicotine addiction. However, the cognition-guided neurofeedback BCI dataset is extremely lacking at present. This paper provides a BCI dataset based on a novel cognition-guided neurofeedback on nicotine addiction. Twenty-eight participants are recruited and involved in two visits of neurofeedback training. This cognition-guided neurofeedback includes two phases an offline classifier construction and a real-time neurofeedback training. The original electroencephalogram (EEG) raw data of two phases are provided and evaluated in this paper. The event-related potential (ERP) amplitude and channel waveform suggest that our BCI dataset is of good quality and consistency. During neurofeedback training, the participants' smoking cue reactivity patterns have a significant reduction. The mean accuracy of the multivariate pattern analysis (MVPA) classifier can reach approximately 70%. This novel cognition-guided neurofeedback BCI dataset can be used to develop comparisons with other neurofeedback systems and provide a reference for the development of other BCI algorithms and neurofeedback paradigms on addiction.
Historical change in the availability of kin beyond the household has long interested scholars, but there has been little comparable evidence on long-run change. While generally accepted that individuals lived near kin historically, no systematic measures have been available to assess historical kin propinquity at the national level.
With the release of historical complete count United States census data from the Integrated Public Use Microdata Series (IPUMS), a robust estimate of patrilineal kin propinquity for the United States nationally from 1790 to 1940 is calculated. Defined as the probability of non-random isonymy within an enumeration district, the estimate of patrilineal kin propinquity relies on the sequential ordering of households in the census.
The United States experienced a long-run decline in patrilineal kin propinquity from nearly 50% of households in 1790 to 17% of households in 1940. The age patterns of kin propinquity show substantial variation across the life course, and regional differences demonstrate the impact of economic and demographic conditions. The decline in kin propinquity reflected urbanization and the decline of agriculture, declining kin availability, growing distance between potential kin links, and a change in preferences of living near kin.
This is the first study to produce a systematic estimate of patrilineal kin propinquity at the national level for the United States between 1790 and 1940. Researchers can use this meaningful measure of patrilineal kin propinquity to better explain its relationships with other demographic behaviors and outcomes such as fertility, mortality, and migration choices.
This is the first study to produce a systematic estimate of patrilineal kin propinquity at the national level for the United States between 1790 and 1940. check details Researchers can use this meaningful measure of patrilineal kin propinquity to better explain its relationships with other demographic behaviors and outcomes such as fertility, mortality, and migration choices.