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The mutational burden in os odontoideum patients.

BACKGROUND: Os odontoideum(OO) is a rare bone malformation at the craniovertebral junction, the presence of which can lead to potential instability of atlantoaxial joints. The cause, prevalence and treatment of OO are still controversial. There are two main theories regarding the pathogenesis of OO: congenital factors and traumatic factors. The congenital hypothesis suggests that the lesion results from segmental defects caused by incomplete fusion of the dens and the axis vertebral body during embryonic development. Our research team previously reported a case series involving three generatio

Perturbed cell cycle phase-dependent positioning and nuclear migration of retinal progenitors along the apico-basal axis underlie global retinal disorganization in the LCA8-like mouse model.

Combined removal of Crb1 and Crb2 from the developing optic vesicle evokes cellular and laminar disorganization by disrupting the apical cel … s. Upon removal of CRB1 and CRB2, apical structures of the RPCs, determined by markers of cilia and centrosomes, are basally shifted. In addition, the positioning of the somata of the M-phase cells, normally localized at the apical surface of the retinal epithelium, is basally shifted in a nearly randomized pattern along the apico-basal axis. Consequently, w …

Cep55 overexpression causes male-specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling.

Spermatogenesis is a dynamic process involving self-renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. Centrosomal protein 55 kDa (CEP55) is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. In germ cells, CEP55, in partnership with testes expressed-14 (TEX14) protein, has also been shown to be an integral component of intercel

Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins: Clinical and Molecular Implications in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC h

Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size.

The human cerebral cortex is distinguished by its large size and abundant gyrification, or folding. However, the evolutionary mechanisms that drive cortical size and structure are unknown. Although genes that are essential for cortical developmental expansion have been identified from the genetics of human primary microcephaly (a disorder associated with reduced brain size and intellectual disability) 1 , studies of these genes in mice, which have a smooth cortex that is one thousand times smaller than the cortex of humans, have provided limited insight. Mutations in abnormal spindle-like micr

Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.

BACKGROUND: Chronic kidney disease (CKD) is a progressive disease for which there is no effective cure. We aimed to identify potential drug targets for CKD and kidney function by integrating plasma proteome and transcriptome. METHODS: We designed a comprehensive analysis pipeline involving two-sample Mendelian randomization (MR) (for proteins), summary-based MR (SMR) (for mRNA), and colocalization (for coding genes) to identify potential multi-omics biomarkers for CKD and combined the protein-protein interaction, Gene Ontology (GO), and single-cell annotation to explore the potential biologic

Influence of genetic markers on survival in non-small cell lung cancer.

Cisplatin or carboplatin is commonly used with gemcitabine, docetaxel, paclitaxel or vinorelbine as chemotherapy doublets in the treatment o … Lys751Lys and can benefit from docetaxel/ cisplatin treatment. Genes involved in spindle formation, centrosome functions and mRNA transport along the microtubule tracks should provide further information on potential markers of docetaxel resistance.

CHILOMASTIX MESNILI AND A METHOD FOR ITS CULTURE.

1. Cases of flagellate infection of man by Chilomastix mesnili have been reported from nearly every locality in the world. They are fairly abundant in the United States and are often confused with cases of infection by Trichomonas intestinalis. 2. The shape of Chilomastix is pyriform. The body contains the following structures: nucleus, centrosome, primary, secondary, and tertiary blepharoplasts, parabasal, parastyle, peristomal fiber, ventral cytostome, cytostomal flagellum, three anterior flagella, food vacuoles with bacterial inclusions, and a posterior spine-like process, the hold-fast org…

Novel interaction partners of Bardet-Biedl syndrome proteins.

Bardet-Biedl syndrome (BBS) is a rare, developmental disorder characterized by six major symptoms: rod-cone dystrophy, obesity, polydactyly, renal abnormalities, learning difficulties, and hypogonadism. Secondary features include cardiac and hepatic anomalies, metabolic disturbancies, and hearing loss. BBS is genetically heterogeneous with 12 disease genes (BBS1-BBS12) described thus far. Current data suggest a functional disturbance in ciliary function and intraflagellar transport being associated with the phenotype. However, the precise functions of the BBS proteins have yet to be elucidated

An evolutionarily conserved gene required for proper microtubule architecture in Caenorhabditis elegans.

UNLABELLED: Rhinacanthus nasutus (L.) Kurz is an herbal plant with distinctive medicinal properties which have been used in Ayurvedic treatments for several diseases. This study explored the preliminary antioxidant, antidiabetic, and antibacterial activities of R. nasutus rhizomes using both in vitro and computational docking methods. R. nasutus rhizomes were sequentially extracted using n-hexane (HRN), chloroform (CRN), and methanol (MRN). These fractions were analysed for total phenolic and flavonoid content. Antioxidant capacity was measured via phosphomolybdate and DPPH scavenging assays,

Pitchfork regulates primary cilia disassembly and left-right asymmetry.

A variety of developmental disorders have been associated with ciliary defects, yet the controls that govern cilia disassembly are largely unknown. Here we report a mouse embryonic node gene, which we named Pitchfork (Pifo). Pifo associates with ciliary targeting complexes and accumulates at the basal body during cilia disassembly. Haploinsufficiency causes a unique node cilia duplication phenotype, left-right asymmetry defects, and heart failure. This phenotype is likely relevant in humans, because we identified a heterozygous R80K PIFO mutation in a fetus with situs inversus and cystic liver

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

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… Furthermore, the NEK2 protein is essential for centrosome integrity and plays a role in the regulation of centrosome separation [ 20 ]. By employing immunofluorescence microscopy and biochemical fractionation, NEK2 was found in the centrosome. … In addition, NEK2 localizes to the centrosome throughout the cell cycle, and its kinase activity and overexpression promote the centrosome split into fragments diffuse [ 20 ]. …

[Clinical significance of fluoroscopic patterns specific for the mitotic spindle in patients with rheumatic diseases].

OBJECTIVE: To determine the clinical significance of anti-NuMA and anti-HsEg5 antibodies in a group of patients affected with rheumatic diseases. MATERIALS AND METHODS: Indirect immunofluorescence on HEp-2000 cells at serum dilution of 1:40 was used to examine 26 sera which had previously showed a "mitotic spindle" fluoroscopic pattern type during laboratory routine. RESULTS: 21 sera (80,7%) were identified with NuMA and 5 (19,3%) with HsEg5 patterns alone or associated with other ANA patterns. However only patients with isolated positivity and that is 15 with NuMA and 4 with HsEg5 stainings

Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease.

BACKGROUND: Myelofibrosis occurs as primary myelofibrosis or as a late occurrence in the evolution of essential thrombocythaemia and polycythaemia vera. It is the rarest of the three classic myeloproliferative neoplasms (MPN). Polyploidy has only rarely been reported in MPN despite the prominent involvement of abnormal megakaryocytes. The use of peripheral blood samples containing increased numbers of haematopoietic progenitors has improved the output from cytogenetic studies in myelofibrosis and together with the use of single nucleotide polymorphism arrays (SNPa) has contributed to an improv

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… Centrosome studies Centrosome studies on CD34 cells of five cases with MF showed no structural centrosome abnormalities (data not shown). Micronucleus studies Viable mononuclear cells were available from Case no. 1 for additional studies using the micronucleus assay. … Centrosome studies The technique for centrosome analysis was based on a modification of the method of Gisselsson et al. [ 14 ]. …

A novel phthalimide derivative, TC11, has preclinical effects on high-risk myeloma cells and osteoclasts.

Despite the recent advances in the treatment of multiple myeloma (MM), MM patients with high-risk cytogenetic changes such as t(4;14) translocation or deletion of chromosome 17 still have extremely poor prognoses. With the goal of helping these high-risk MM patients, we previously developed a novel phthalimide derivative, TC11. Here we report the further characterization of TC11 including anti-myeloma effects in vitro and in vivo, a pharmacokinetic study in mice, and anti-osteoclastogenic activity. Intraperitoneal injections of TC11 significantly delayed the growth of subcutaneous tumors in hu

The 8p11 myeloproliferative syndrome: Genotypic and phenotypic classification and targeted therapy.

EMS(8p11 myeloproliferative syndrome, EMS) is an aggressive hematological neoplasm with/without eosinophilia caused by a rearrangement of the FGFR1 gene at 8p11-12. It was found that all cases carry chromosome abnormalities at the molecular level, not only the previously reported chromosome translocation and insertion but also a chromosome inversion. These abnormalities produced 17 FGFR1 fusion genes, of which the most common partner genes are ZNF198 on 13q11-12 and BCR of 22q11.2. The clinical manifestations can develop into AML (acute myeloid leukemia), T-LBL (T-cell lymphoblastic lymphoma),

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… FOP is also in the centrosome and participates in forming an MT-anchored centrosome complex ( 19 ). … CEP110 and ninein are located in a specific domain of the centrosome associated with centrosome maturation. J Cell Sci (2002) 115:1825–1835. doi: 10.1242/jcs.115.9.1825 22. Mugneret F, Chaffanet M, Maynadié M, Guasch G, Favre B, Casasnovas O, et al. …

Stromal elements for tumor diagnosis: a brief review of diagnostic electron microscopic features.

Tumor diagnosis mainly depends on the appearance of the tumor cells in recapitulating the appearance of primordial cells from which they ari … es such as neurofibromatosis and Carney's triad. They simulate the appearance of railroad tracks or centrosomes. The reason for this is not known. The authors speculate that such collagen crystallization may be caused by genetic alterations involving collagenosis. Further studies will be necessary to clarify their pathogenesis. Another peculiar stromal chang …

The Potential of Nuclear Pore Complexes in Cancer Therapy.

Nuclear pore complexes (NPCs) play a critical role in regulating transport-dependent gene expression, influencing various stages of cancer development and progression. Dysregulation of nucleocytoplasmic transport has profound implications, particularly in the context of cancer-associated protein mislocalization. This review provides specific information about the relationship between nuclear pore complexes, key regulatory proteins, and their impact on cancer biology. Highlighting the influence of tumor-suppressor proteins as well as the potential of gold nanoparticles and intelligent nanosyste

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… Interaction of CRM1 with the BRCA1 gene (breast and ovarian cancer) is essential for a centrosome DNA damage checkpoint. … This, in turn, catalyzes the ubiquitination of downstream substrates essential for regulating centrosome amplification during the DNA damage response [ 69 ]. …

Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients.

Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occas

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention.

The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstre

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… Genotoxic stress was induced in the MCF-7 cells harboring the DN p53 by treatment with hydroxyurea (HU) which induced centrosome amplification. Aurora-A kinase activity was linked with centrosome amplication. … The Aurora-A kinase-induced centrosome amplification was determined to be mediated by Cdk2 kinase. Molecular inhibition of Cdk2 activity by SU9516 suppressed Aurora-A centrosomal localization and consequent centrosome amplification. …