The phenomenon of unstable expression of gap junction\'s proteins connexins remains a \"visiting card\" of astrocytic tumors with various degrees of malignancy. At the same time, it stays unclear what is detected by the positive expression of connexins in astrocytic tumors: gap junctions, hemi-channels, or connexin proteins in cytosol. In the present work, for the first time, we demonstrate an ultrastructural evidence of gap junctions in pleomorphic xanthoastrocytoma, a rare primary brain tumor, the intercellular characteristics of which are poorly studied and remain very discursive and controversial. The primary tumor mass was resected during craniotomy from a 57-old patient diagnosed with pleomorphic xanthoastrocytoma Grade II based on the histopathological analysis. The immunohistochemical study was conducted with primary antibodies: Neurofilament, Myelin basic protein, Glial fibrillary acidic protein, and Synaptophysin. For electron microscopic examination fragments of tumor tissue were fixed in a glutaraldehyde, postfixed in a 1% OsO4, dehydrated and embedded into resin. After the detailed clinical, histological, and immunohistochemical study we revealed some ultrastructural characteristics of the tumor, as well as the first evidence of direct intercellular connection between the tumor cells via gap junctions. Regularly arranged gap junctions connected the somas of xanthastrocytes with dark cytoplasm containing lipid drops. Besides the localization between the cell bodies, from one to several gap junctions were found between the branches of xanthoastrocytoma in tumor intercellular space in close proximity to tumor cell. Our results may indicate gap junctions as a possible structure for intercellular communication between pleomorphic xanthoastrocytoma cells.

Astrocytes play an important role in the physiological functions of the central nervous system. In this study, contact potential differences (CPD) and capacitance gradients of the cell bodies and glial filaments of astrocytes were measured. Charge propagation properties in the astrocyte gap junctions were also studied using multimode Atomic Force Microscopy (AFM) at nanometre resolution. The CPD of the cell bodies and glial filaments were 324.2 ± 138.4 and 119.1 ± 31.7 mV, respectively. The measured capacitance gradients were 1.51 ± 0.31 and 1.98 ± 0.32 zF nm-1 , respectively. The gap junctions in the astrocytes showed no charge propagation and were not electrically sensitive. This furthers our understanding of astrocytes and other types of neuroglia. LAY DESCRIPTION: Neuroglia cells play important structural and functional roles in central nervous system (CNS). Neuroglia cells exceed the number of neurons by 10∼50 and can be divided into macroglia and microglia. Astrocytes are macroglia and are the largest and most abundant cells in the CNS. Astrocytes lack axons and dendrites and do not propagate action potentials. They have few cytoplasmic organelles, but possess abundant glial filaments, the main components of the cytoskeleton. Glial filaments are composed of the glial fibrillary acidic protein (GFAP). Astrocytes produce intercellular calcium waves in their gap junctions mediated through receptor activator (such as glutamate) to permit signal transduction._ENREF_5 In addition to their role in the support and nutrition of neurons, astrocytes are involved in various types of CNS activity including: (1) cytokine secretion for neuronal survival, growth and differentiation; (2) protection from brain injury; (3) modulation of the blood brain barrier; and (4) neuronal immunity. Bidirectional crosstalk between the astrocytes and neurons exists. Astrocytes can be activated by neurotransmitters released and can themselves release gliotransmitters to act upon neurons. Astrocytes are closely related to various disease states, including epilepsy and Alzheimer\'s disease. In this study, the electrical properties of astrocytes, including the contact potential difference (CPD) and capacitance gradients of the cell bodies and glial filaments, and charge propagation in the gap junctions were investigated at the nanometer level using quantitative Kelvin Probe Force Microscopy (KPFM) and Electrostatic Force Microscopy (EFM). The CPD of the cell bodies and glial filaments of the astrocytes were 324.2 mV and 119.1 mV, respectively. Capacitance gradients of the cell bodies and glial filaments of the astrocytes were 1.51 zF/nm and 1.98 zF/nm, respectively. Gap junctions in the astrocytes do not perform charge propagation functions and the astrocytes are not electrically sensitive. One should note that these results from KPFM and EFM were measured on dried cell and the situation might be different when studying in operando environment, still these findings aid our understanding of the electrical properties and functions of astrocytes, and further our knowledge of the electrical properties of the CNS.

Oculodentodigital dysplasia (ODDD; MIM #164200), a rare genetic disorder characterized by abnormal craniofacial, dental, ocular, and digital features, is caused by mutations in the gap junction alpha-1 (GJA1) gene. We report a case of a 6-year-old male who presented with dysmorphic facial features (short palpebral fissure, thin nose with hypoplastic alae nasi, and flat face), bilateral syndactyly, abnormal dentition, and proportionate short stature with growth hormone deficiency. A novel de novo heterozygous missense mutation (c.221A>C, p.H74P) in GJA1 was identified by targeted gene panel sequencing. This is the first case report of a novel ODDD-causing mutation in GJA1 confirmed by genetic analysis in Korea.

The cardiac Monodomain model is a mathematical model extensively used in studies of propagation of bioelectric wavefronts in the heart. To be able to use the model for complex and large cardiac simulations, such as the case of whole heart and 3D simulations, some parameters of the model that are known to physiologically vary in space, such as the intracellular conductivity, are traditionally kept constant at effective values. These effective values can be obtained via a mathematical procedure called homogenization. In this work we revisit the classical homogenized monodomain formulation to evaluate its ability to reproduce the situation of low gap junctional coupling. This situation arises in many pathological conditions such as during ischemia. Our numerical results suggest some limitations of the homogenized cardiac Monodomain model under these conditions in terms of computed conduction velocity and Action Potential waverforms.

暂无摘要。

We report a patient of Charcot-Marie-Tooth disease (CMT) accompanied by transient splenium abnormality in brain MRI. A 34-year-old man suffered from chronic progressive unsteadiness and sensory disturbance of all limbs. Neurological examination showed muscle weakness and atrophy in the distal extremities with pes cavus, mild sensory disturbance of four extremities and generalized decreased reflexes. The nerve conduction study described the presence of sensory-motor polyneuropathy. We could not investigate his GJB1 gene. However, we suspected that he was X-linked CMT (CMTX), because his electrophysiological findings showed intermediate slowing of MCV, and auditory brain-stem response (ABR) demonstrated central conduction slowing. Brain MRI revealed the abnormal high signal intensity in the splenium of the corpus callosum on T2-weighted image. This lesion diminished two months later without any treatment. Recently, there had been reported transient splenium abnormality in CMTX cases, and there were clinical similarities between the cases of these reports and our case. We considered that the pathophysiology of this case was the disruption of gap junction communications expressed between oligodendrocyte and astrocytes induced by connexin 32 (Cx32) mutations. Furthermore, the transient functional disturbance of astrocytes would be another pathophysiologic mechanism of splenium abnormality.

A 15-year-old Japanese female without contributory personal or family medical history had demonstrated irregular, keratotic plaques in the lower extremities since infancy that had been gradually enlarging. The keratotic plaques showed partial erythematous change, which altered shape over a relatively short period, leaving pigmentation. The biopsy specimen taken from the erythematous, keratotic plaque showed typical church-spire-like papillomatosis with acanthosis, and thickening of granular and horny layers. Gene analysis targeting connexin 30.3 and 31, based on the diagnosis of erythrokeratoderma variabilis, did not demonstrate any abnormality of these genes. However, ultrastructural observation disclosed an increased amount of gap junctions, some of which showed four layers on high-powered electron microscopy, suggesting loosened connection of the plasma membrane of the keratinocytes through the gap junctions. This loosened gap junction structure was also observed in a case of lamellar ichthyosis, examined as a reference. The disturbed cell-to-cell interaction through latent damage to the gap junctions may be related to the keratotic changes of the epidermis in these skin diseases.

Synchronised signal transduction between cells is crucial, since it assures fast and immutable information processing, which is vital for flawless functioning of living organisms. The question arises how to recognise the ability of a cell to be easily coupled with other cells. In the present paper, we investigate the system properties that determine best coupling abilities and assure the most efficient signal transduction between cells. A case study is done for intercellular calcium oscillations. For a particular diffusion-like coupled system of cellular oscillators, we determined the minimal gap-junctional permeability that is necessary for synchronisation of initially asynchronous oscillators. Our results show that dissipation is a crucial system property that determines the coupling ability of cellular oscillators. We found that low dissipation assures synchronisation of coupled cells already at very low gap-junctional permeability, whereas highly dissipative oscillators require much higher gap-junctional permeability in order to synchronise. The results are discussed in the sense of their biological importance for systems where the synchronous responses of cells were recognised to be indispensable for appropriate physiological functioning of the tissue.

暂无摘要。

A case of cystic embryonal sarcoma of the kidney (CESK) with a rapidly fatal outcome was recently reported.1 Here, we report another case of a 12-year-old boy with a localized but ill-defined submucosal lesion of CESK in the right renal pelvis. The tumor consisted principally of small mesenchymal cells with oval to spindle nuclei and scanty cytoplasm, infiltrating in dense arrangements. Two growth patterns were distinguished in the tumor cells: (i) a diffuse infiltrating pattern without an epithelial component; and (ii) a foliated pattern with an epithelial lining over the surface. Foci of the diffuse pattern predominated over those that were lobular, infiltrating superficial layers of renal sinuses and along pyramids, in both of which remarkable intravenous invasion was evident. Foci of the foliated pattern invaded deeper portions of a few sinuses and frequently penetrated into their veins, producing together with their epithelial lining a characteristic foliated structure. Lining epithelial cells around lobular foci often appeared hob-nailed or eosinophilic in the cytoplasm. Despite the remarkable intravenous encroachment, the patient has remained well without a recurrence for more than 26 years after a simple nephrectomy. The present case report expands our understanding of the biological nature of CESK.