Is the myonuclear domain ceiling hypothesis dead?

Muscle fibres are multinuclear cells, and the cytoplasmic territory where a single myonucleus controls transcriptional activity is called the myonuclear domain (MND). MND size shows flexibility during muscle hypertrophy. The MND ceiling hypothesis states that hypertrophy results in the expansion of MND size to an upper limit or MND ceiling, beyond which additional myonuclei via activation of satellite cells are required to support further growth. However, the debate about the MND ceiling hypothesis is far from settled, and various studies show conflicting results about the existence or otherwise of MND ceiling in hypertrophy. The aim of this review is to summarise the literature about the MND ceiling in various settings of hypertrophy and discuss the possible factors contributing to a discrepancy in the literature. We conclude by describing the physiological and clinical significance of the MND ceiling limit in the muscle adaptation process in various physiological and pathological conditions.

The use of polypropylene mesh in thoracoplasty: an experimental and clinical study

Relevance. Thoracoplasty is an effective way to close the cavity of destruction of the lung tissue and achieve clinical recovery in case of fibro-cavernous pulmonary tuberculosis. A promising direction of creating selective collapse in thoracoplasty is the use of synthetic mesh implants. The purpose of the study was to assess the effect of synthetic implants from the “Surgipro" polypropylene mesh on the inflammatory and reparative reaction in thoracoplasty. Materials and methods. The work was performed on male Wistar rats weighing 250±50 grams (n=12). The “Surgipro” polypropylene mesh was implanted on the right posterolateral surface of the chest (n=9). As control, the material was taken from intact rats (n=3), which were kept in the same conditions as experimental animals. The study material was biopsy specimens of the muscular aponeurotic scar of the posterolateral surface of the chest of rats. The cellular composition and total number of mast cells were determined. A clinical study was conducted on 26 cases of thoracoplastic with the use of polypropylene mesh in the pulmonary-surgical department of the Seaside regional antituberculous dispensary in Vladivostok. Results. During the experimental study, it was recorded that the implant used in the reconstruction of the chest has a pronounced reactogenicity from the first day, which manifests itself as a local inflammatory reaction with the concentration of mast cells. The population of mast cells progressively declined by the 30th day, while an increase in the number of macrophages and fibroblasts was observed with the advent of giant multinuclear cells of foreign bodies. On the 30th day after the operation, a widespread post-inflammatory reactive fibrosis and angiomatosis with chronic productive inflammation was observed in the experiment. In clinical observation, the resulting inflammatory reaction around the endoprosthesis spreads to the surrounding tissues and lung, which contributes to the formation of pronounced pulmonary fibrosis and restriction of a specific process.

Effect of Chemical Mutagens on Chromosomal behavior of Allium cepa L

Effect of chemical mutagens was studied in mitotic cells of Allium cepa L. For this purpose root tips were treated with saturated solution of peradichloro benzene, 0.2% EMS and 0.2 % freshly prepared colchicines for 4hours to 9hours.The studies revealed a wide range of chromosomal abnormalities such as stickiness, laggards, chromosomal bridge, unequal separation, nuclear budding, multinuclear cells etc.The parentage of chromosomal abnormalities in different mitotic stages were calculated on mitotic index, frequency of phases and percentage of abnormalities in mitosis. The chromosomal abnormalities increase with increase duration of treatment. The results showed that in colchicines and EMS more than 50% abnormalities ware observed after 8 hrs of treatment, while in PDB it takes 6 hours treatment. Minimum MI was recorded as 65% in controlled cells. In colchicines and EMS treated cells 0.9.5%, 20% MI ware observed after 8hrs of treatment. Whereas in PDB maximum 23% MI was recorded in cells treated for 6hrs.

The Glycoprotein B Cytoplasmic Domain Lysine Cluster Is Critical for Varicella-Zoster Virus Cell-Cell Fusion Regulation and Infection

ABSTRACT The conserved glycoproteins gB and gH-gL are essential for herpesvirus entry and cell-cell fusion induced syncytium formation, a characteristic of varicella-zoster virus (VZV) pathology in skin and sensory ganglia. VZV syncytium formation, which has been implicated in the painful condition of postherpetic neuralgia, is regulated by the cytoplasmic domains of gB (gBcyt) via an immunoreceptor tyrosine-based inhibition motif (ITIM) and gH (gHcyt). A lysine cluster (K894, K897, K898, and K900) in the VZV gBcyt was identified by sequence alignment to be conserved among alphaherpesviruses, suggesting a functional role. Alanine and arginine substitutions were used to determine if the positive charge and susceptibility to posttranslational modifications of these lysines contributed to gB/gH-gL cell-cell fusion. Critically, the positive charge of the lysine residues was necessary for fusion regulation, as alanine substitutions induced a 440% increase in fusion compared to that of the wild-type gBcyt while arginine substitutions had wild-type-like fusion levels in an in vitro gB/gH-gL cell fusion assay. Consistent with these results, the alanine substitutions in the viral genome caused exaggerated syncytium formation, reduced VZV titers (−1.5 log10), and smaller plaques than with the parental Oka (pOka) strain. In contrast, arginine substitutions resulted in syncytia with only 2-fold more nuclei, a −0.5-log10 reduction in titers, and pOka-like plaques. VZV mutants with both an ITIM mutation and either alanine or arginine substitutions had reduced titers and small plaques but differed in syncytium morphology. Thus, effective VZV propagation is dependent on cell-cell fusion regulation by the conserved gBcyt lysine cluster, in addition to the gBcyt ITIM and the gHcyt. IMPORTANCE Varicella-zoster virus (VZV) is a ubiquitous pathogen that causes chickenpox and shingles. Individuals afflicted with shingles risk developing the painful condition of postherpetic neuralgia (PHN), which has been difficult to treat because the underlying cause is not well understood. Additional therapies are needed, as the current vaccine is not recommended for immunocompromised individuals and its efficacy decreases with the age of the recipient. VZV is known to induce the formation of multinuclear cells in neuronal tissue, which has been proposed to be a factor contributing to PHN. This study examines the role of a lysine cluster in the cytoplasmic domain of the VZV fusion protein, gB, in the formation of VZV induced multinuclear cells and in virus replication kinetics and spread. The findings further elucidate how VZV self-regulates multinuclear cell formation and may provide insight into the development of new PHN therapies.

Complete Surgical Resection of a Leiomyosarcoma Arising from the Inferior Vena Cava

A 76-year-old Japanese man was referred to our hospital with chief complaint of right hypochondoralgia. Abdominal ultrasound showed a retroperitoneal tumor in the suprarenal region of the right kidney. Computed tomography revealed an enhanced lobular tumor with irregular, circumscribed, and indistinct border. Ultrasound-guided biopsy was performed. The tumor consisted of spindle-shaped cells with a giant nucleus and multinuclear cells. The diagnosis was leiomyosarcoma by immunohistochemical staining. The patient underwent surgery accessed by a right eighth intercostal thoracoabdominal incision. The tumor was completely resected, accompanied by removal of the posterosuperior segment of the right hepatic lobe, right adrenal gland, and a portion of the inferior vena cava (IVC). The histopathologic diagnosis was leiomyosarcoma arising from the IVC. We present a rare case of a successfully managed leiomyosarcoma of the IVC. This case suggests the importance of curative surgical resection of the tumor due to low efficacy of adjuvant chemotherapy for leiomyosarcoma.