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Scientific Reports Jan 2024Ectodermal neural cortex 1 (ENC1) is a protein that plays a crucial role in the regulation of various cellular processes such as cell proliferation, differentiation, and... (Review)
Review
Ectodermal neural cortex 1 (ENC1) is a protein that plays a crucial role in the regulation of various cellular processes such as cell proliferation, differentiation, and apoptosis. Numerous studies have shown that ENC1 is overexpressed in various types of cancers, including breast, lung, pancreatic, and colorectal cancer, and its upregulation is correlated with a poorer prognosis. In addition to its role in cancer growth and spreading, ENC1 has also been linked to neuronal process development and neural crest cell differentiation. In this review, we provide an overview of the current knowledge on the relationship between ENC1 and cancer. We discuss the molecular mechanisms by which ENC1 contributes to tumorigenesis, including its involvement in multiple oncogenic signaling pathways. We also summarize the potential of targeting ENC1 for cancer therapy, as its inhibition has been shown to significantly reduce cancer cell invasion, growth, and metastasis. Finally, we highlight the remaining gaps in our understanding of ENC1's role in cancer and propose potential directions for future research.
Topics: Microfilament Proteins; Neoplasms; Neurites; Nuclear Proteins; Humans
PubMed: 38177640
DOI: 10.1038/s41598-023-50914-7 -
Molecules (Basel, Switzerland) Oct 2023The application of lithium metal batteries is limited by the drawbacks of safety problems and Li dendrite formation. Quasi-solid-state electrolytes (QSSEs) are the most...
The application of lithium metal batteries is limited by the drawbacks of safety problems and Li dendrite formation. Quasi-solid-state electrolytes (QSSEs) are the most promising alternatives to commercial liquid electrolytes due to their high safety and great compatibility with electrodes. However, Li dendrite formation and the slow Li diffusion in QSSEs severely hinder uniform Li deposition, thus leading to Li dendrite growth and short circuits. Herein, an eco-friendly and low-cost sodium lignosulfonate (LSS)-assisted PVDF-based QSSE is proposed to induce uniform Li deposition and inhibit Li dendrite growth. Li symmetric cells with 5%-LSS QSSE possess a high Li transfer number of 0.79, and they exhibit a long cycle life of 1000 h at a current density/areal capacity of 1 mA cm/5 mAh cm. Moreover, due to the fast electrochemical dynamics endowed by the improved compatibility of the electrodes and fast Li diffusion, the LFP/5%-LSS/Li full cells still maintain a high capacity of 110 mAh g after 250 cycles at 6C. This work provides a novel and promising choice that uses eco-friendly LSS as an additive to PVDF-based QSSE in Li metal batteries.
PubMed: 37836748
DOI: 10.3390/molecules28196905 -
Cell Reports May 2024Neuronal morphology influences synaptic connectivity and neuronal signal processing. However, it remains unclear how neuronal shape affects steady-state distributions of...
Neuronal morphology influences synaptic connectivity and neuronal signal processing. However, it remains unclear how neuronal shape affects steady-state distributions of organelles like mitochondria. In this work, we investigated the link between mitochondrial transport and dendrite branching patterns by combining mathematical modeling with in vivo measurements of dendrite architecture, mitochondrial motility, and mitochondrial localization patterns in Drosophila HS (horizontal system) neurons. In our model, different forms of morphological and transport scaling rules-which set the relative thicknesses of parent and daughter branches at each junction in the dendritic arbor and link mitochondrial motility to branch thickness-predict dramatically different global mitochondrial localization patterns. We show that HS dendrites obey the specific subset of scaling rules that, in our model, lead to realistic mitochondrial distributions. Moreover, we demonstrate that neuronal activity does not affect mitochondrial transport or localization, indicating that steady-state mitochondrial distributions are hard-wired by the architecture of the neuron.
Topics: Animals; Dendrites; Mitochondria; Drosophila melanogaster; Drosophila; Neurons
PubMed: 38717903
DOI: 10.1016/j.celrep.2024.114190 -
Cell Reports Mar 2024Stroke, trauma, and neurodegenerative disorders cause loss of neurites (axons and dendrites) in addition to neuronal death. Neurite loss may result directly from a...
Stroke, trauma, and neurodegenerative disorders cause loss of neurites (axons and dendrites) in addition to neuronal death. Neurite loss may result directly from a primary insult, secondary to parental neuron death, or secondary to a post-injury inflammatory response. Here, we use lipopolysaccharide and the alarmin S100β to selectively evaluate neurite loss caused by the inflammatory response. Activation of microglia and infiltrating macrophages by these stimuli causes neurite loss that far exceeds neuronal death, both in vitro and in vivo. Neurite loss is accompanied by the formation of cofilactin rods and aggregates (CARs), which are polymers of cofilin-1 and actin induced by oxidative stress and other factors. Mice deficient in either cofilin-1 or the superoxide-generating enzyme NADPH oxidase-2 show reduced CAR formation, neurite loss, and motor impairment. The findings identify a mechanism by which inflammation leads to neurite loss via CAR formation and highlight the relevance of neurite loss to functional impairment.
Topics: Mice; Animals; Neurites; Neurons; Axons; Neurodegenerative Diseases; Inflammation
PubMed: 38451813
DOI: 10.1016/j.celrep.2024.113914 -
Cells Sep 2023While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain...
While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. To understand the function of miRNAs during the AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activated essential neuronal genes to initiate the reprogramming process but also induced miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and were also upregulated by NeuroD1. We further showed that manipulating the miR-375 level regulated nELAVLs' expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs were also induced by the reprogramming factors Neurog2 and ASCL1 in HA, suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improved NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA and did not appear to compromise the maturation of the reprogrammed neurons. Lastly, overexpression of miR-375-refractory ELAVL4 induced apoptosis and reversed the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrated a neuroprotective role of miR-375 during NeuroD1-mediated AtN reprogramming.
Topics: Humans; Animals; Mice; Astrocytes; Neurons; Neurites; Apoptosis; MicroRNAs; Nerve Tissue Proteins; Basic Helix-Loop-Helix Transcription Factors
PubMed: 37681934
DOI: 10.3390/cells12172202 -
Nature Communications Jul 2023Metallic zinc anodes of aqueous zinc ion batteries suffer from severe dendrite and side reaction issues, resulting in poor cycling stability, especially at high rates...
Metallic zinc anodes of aqueous zinc ion batteries suffer from severe dendrite and side reaction issues, resulting in poor cycling stability, especially at high rates and capacities. Herein, we develop two three-dimensional hierarchical graphene matrices consisting of nitrogen-doped graphene nanofibers clusters anchored on vertical graphene arrays of modified multichannel carbon. The graphene matrix with radial direction carbon channels possesses high surface area and porosity, which effectively minimizes the surface local current density, manipulates the Zn ions concentration gradient, and homogenizes the electric field distribution to regulate Zn deposition. As a result, the engineered matrices achieve a superior coulombic efficiency of 99.67% over 3000 cycles at 120 mA cm, the symmetric cells with the composite zinc anode demonstrates 2600 h dendrite-free cycles at 80 mA cm and 80 mAh cm. The as-designed full cell exhibits an inspiring capacity of 16.91 mAh cm. The Zn capacitor matched with activated carbon shows a superior long-term cycle performance of 20000 cycles at 40 mA cm. This strategy of constructing a 3D hierarchical structure for Zn anodes may open up a new avenue for metal anodes operating under high rates and capacities.
Topics: Graphite; Charcoal; Electric Power Supplies; Electrodes; Zinc
PubMed: 37452017
DOI: 10.1038/s41467-023-39947-8 -
BMC Medicine Jul 2023Schizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported...
BACKGROUND
Schizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported that single nucleotide polymorphisms spanning chromosome 3p21.1 showed significant associations with both schizophrenia and BD, and a risk SNP rs2251219 was in linkage disequilibrium with a human specific Alu polymorphism rs71052682, which showed enhancer effects on transcriptional activities using luciferase reporter assays in U251 and U87MG cells.
METHODS
CRISPR/Cas9-directed genome editing, real-time quantitative PCR, and public Hi-C data were utilized to investigate the correlation between the Alu polymorphism rs71052682 and NISCH. Primary neuronal culture, immunofluorescence staining, co-immunoprecipitation, lentiviral vector production, intracranial stereotaxic injection, behavioral assessment, and drug treatment were used to examine the physiological impacts of Nischarin (encoded by NISCH).
RESULTS
Deleting the Alu sequence in U251 and U87MG cells reduced mRNA expression of NISCH, the gene locates 180 kb from rs71052682, and Hi-C data in brain tissues confirmed the extensive chromatin contacts. These data suggested that the genetic risk of schizophrenia and BD predicted elevated NISCH expression, which was also consistent with the observed higher NISCH mRNA levels in the brain tissues from psychiatric patients compared with controls. We then found that overexpression of NISCH resulted in a significantly decreased density of mushroom dendritic spines with a simultaneously increased density of thin dendritic spines in primary cultured neurons. Intriguingly, elevated expression of this gene in mice also led to impaired spatial working memory in the Y-maze. Given that Nischarin is the target of anti-hypertensive agents clonidine and tizanidine, which have shown therapeutic effects in patients with schizophrenia and patients with BD in preliminary clinical trials, we demonstrated that treatment with those antihypertensive drugs could reduce NISCH mRNA expression and rescue the impaired working memory in mice.
CONCLUSIONS
We identify a psychiatric risk gene NISCH at 3p21.1 GWAS locus influencing dendritic spine morphogenesis and cognitive function, and Nischarin may have potentials for future therapeutic development.
Topics: Humans; Mice; Animals; Dendritic Spines; Genome-Wide Association Study; Cognition; Polymorphism, Single Nucleotide; Morphogenesis; RNA, Messenger
PubMed: 37443018
DOI: 10.1186/s12916-023-02931-6 -
PloS One 2023The retina is an intricately organized neural tissue built on cone and rod pathways for color and night vision. Genetic mutations that disrupt the proper function of the...
The retina is an intricately organized neural tissue built on cone and rod pathways for color and night vision. Genetic mutations that disrupt the proper function of the rod circuit contribute to blinding diseases including retinitis pigmentosa and congenital stationary night blindness (CSNB). Down Syndrome cell adhesion molecule like 1 (Dscaml1) is expressed by rods, rod bipolar cells (RBCs), and sub-populations of amacrine cells, and has been linked to a middle age onset of CSNB in humans. However, how Dscaml1 contributes to this visual deficit remains unexplored. Here, we probed Dscaml1's role in the maintenance of the rod-to-RBC synapse using a loss of function mouse model. We used immunohistochemistry to investigate the anatomical formation and maintenance of the rod-to-RBC synapse in the young, adult, and aging retina. We generated 3D reconstructions, using serial electron micrographs, of rod spherules and RBCs to measure the number of invaginating neurites, RBC dendritic tip number, and RBC mitochondrial morphology. We find that while rod-to-RBC synapses form and are maintained, similar to wildtype, that there is an increase in the number of invaginating neurites in rod spherules, a reduction in RBC dendritic tips, and reduced mitochondrial volume and complexity in the Dscaml1 mutant retina compared to controls. We also observed precocious sprouting of RBC dendrites into the outer nuclear layer (ONL) of the Dscaml1 mutant retina compared to controls. These results contribute to our knowledge of Dscaml1's role in rod circuit development and maintenance and give additional insight into possible genetic therapy targets for blinding diseases and disorders like CSNB.
Topics: Humans; Mice; Animals; Retina; Synapses; Retinal Cone Photoreceptor Cells; Retinal Bipolar Cells; Aging
PubMed: 37910517
DOI: 10.1371/journal.pone.0290257 -
Scientific Reports Aug 2023The lateral lemniscus encompasses processing stages for binaural hearing, suppressing spurious frequencies and frequency integration. Within the lemniscal fibres three...
The lateral lemniscus encompasses processing stages for binaural hearing, suppressing spurious frequencies and frequency integration. Within the lemniscal fibres three nuclei can be identified, termed after their location as dorsal, intermediate and ventral nucleus of the lateral lemniscus (DNLL, INLL and VNLL). While the DNLL and VNLL have been functionally and anatomically characterized, less is known about INLL neurons. Here, we quantitatively describe the morphology, the cellular orientation and distribution of synaptic contact sites along dendrites in mature Mongolian gerbils. INLL neurons are largely non-inhibitory and morphologically heterogeneous with an overall perpendicular orientation regarding the lemniscal fibers. Dendritic ranges are heterogeneous and can extend beyond the nucleus border. INLL neurons receive VGluT1/2 containing glutamatergic and a mix of GABA- and glycinergic inputs distributed over the entire dendrite. Input counts suggest that numbers of excitatory exceed the inhibitory contact sites. Axonal projections indicate connectivity to ascending and descending auditory structures. Our data show that INLL neurons form a morphologically heterogeneous continuum and incoming auditory information is processed on thin dendrites of various length and biased to perpendicular orientation. Together with the different axonal projection patterns, this indicates that the INLL is a highly complex structure that might hold many unexplored auditory functions.
Topics: Animals; Gerbillinae; Neurons; Cell Nucleus; Auditory Pathways; Axons
PubMed: 37648787
DOI: 10.1038/s41598-023-41180-8 -
Neurobiology of Aging Feb 2024We assessed white matter (WM) integrity in MAPT mutation carriers (16 asymptomatic, 5 symptomatic) compared to 31 non-carrier family controls using diffusion tensor...
We assessed white matter (WM) integrity in MAPT mutation carriers (16 asymptomatic, 5 symptomatic) compared to 31 non-carrier family controls using diffusion tensor imaging (DTI) (fractional anisotropy; FA, mean diffusivity; MD) and neurite orientation dispersion and density imaging (NODDI) (neurite density index; NDI, orientation and dispersion index; ODI). Linear mixed-effects models accounting for age and family relatedness revealed alterations across DTI and NODDI metrics in all mutation carriers and in symptomatic carriers, with the most significant differences involving fronto-temporal WM tracts. Asymptomatic carriers showed higher entorhinal MD and lower cingulum FA and patterns of higher ODI mostly involving temporal areas and long association and projections fibers. Regression models between estimated time to or time from disease and DTI and NODDI metrics in key regions (amygdala, cingulum, entorhinal, inferior temporal, uncinate fasciculus) in all carriers showed increasing abnormalities with estimated time to or time from disease onset, with FA and NDI showing the strongest relationships. Neurite-based metrics, particularly ODI, appear to be particularly sensitive to early WM involvement in asymptomatic carriers.
Topics: Brain; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Mutation; Neurites; White Matter; Humans; Heterozygote; tau Proteins
PubMed: 38091751
DOI: 10.1016/j.neurobiolaging.2023.12.001