Membrane Computing as a Modelling Tool: Looking Back and Forward from Sevilla

This paper is a tribute to Prof. Mario de Jesús Pérez- Jiménez. An overview of modelling applications in membrane computing has been compiled, trying to narrate it from a historical perspective and including numerous bibliographical references. Since being exhaustive was obviously out of scope, this quick tour on almost two decades of applications is biased, paying special attention to the contributions in which Prof. Pérez-Jiménez and members of his research group were involved.Ministerio de Economía y Competitividad TIN2017-89842-

The Actin-Binding Protein Capulet Genetically Interacts with the Microtubule Motor Kinesin to Maintain Neuronal Dendrite Homeostasis

BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease

New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis

A new human hepatocellular carcinoma (HCC) cell line with a highly metastatic potential was established from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and growth in nude mice. The line, designated MHCC97, has been cultivated for 18 months and subcultured for more than 90 passages. The line was showed to be of human origin by karyotype analysis. The cells were either grown as compact colonies (in clusters) or as a monolayered sheet with about 31 h of population-doubling time, exhibited typical malignant epithelial in morphology and were positive for α-fetoprotein (AFP). Flow cytometric analysis of the cell DNA content showed an aneuploid pattern, and its index was 1.5 as compared to that of normal human peripheral blood lymphocytes. Karyotypic analyses of G- and C-banding techniques revealed that all cells presented chromosome abnormalities in number and structure. The number of cell line MHCC97 chromosome ranged from 59 to 65 with a modal number of 60 and 61. At least two common chromosome markers, i(1q) and der(4)t(4;?)(4pter→q35::?), were present in all cells, and deletion of Y chromosome also occurred in all cells. The subcutaneous and intrahepatic xenografts were formed and metastatic lesions in lungs were found after the cells were inoculated into nude mice. The rate of metastasis to lungs was 100% using orthotopic inoculation. Reverse transcription polymerase chain reaction products revealed positive expressions of integrin α5 and β1, urokinase type plasminogen activator receptor (uPAR), vascular endothelial growth factor and nm23-H1 mRNAs of cell line MHCC97. Immunostaining of c-Met, uPAR showed strongly positive in both subcutaneous xenografts and lung metastatic lesions; while positive in xenografts and negative in metastatic lesions for integrin α5, β1. E-cadherin and P53 was not expressed either in xenograft or in the metastatic lesions. PCR products of HBsAg and HBxAg were both positive. The cell line MHCC97 still retained some characteristic features of original tumour. Establishment of cell line MHCC97 should be beneficial to the studies of HCC metastatic mechanisms. © 1999 Cancer Research Campaig

Ovarian small cell carcinoma complicated by carcinomatous meningitis

Meningeal metastasis is rare in the clinical course of ovarian carcinoma and its prognosis is extremely poor. We experienced a case of carcinomatous meningitis from metastatic ovarian small cell carcinoma. A 33-year-old woman with atypical genital bleeding, was diagnosed with a right ovarian tumor and referred to our department. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy. It was an optimal debulking surgery. She was diagnosed with ovarian carcinoma classified as Stage IIIc according to the Féderation Internationale de Gynécologie et d’Obstétrique classification system. Histological findings showed small cell carcinoma of the pulmonary type. The tumor was bilateral with paraaortic lymph node involvement. The patient was treated with irinotecan and cisplatin (CPT-P therapy). After 4 courses of CPTP therapy, multiple liver metastases and Virchow’s lymph node metastases were found. She was treated with amrubicin as a secondline chemotherapy, but the treatment was ineffective. Five months after surgery, the patient complained of severe headache and nausea. Lumbar puncture was performed and cytology was positive. Magnetic resonance brain imaging indicated meningeal thickening. The patient was diagnosed with meningeal metastasis and received 19-Gy whole cranial irradiation. In spite of these treatments, her disease progressed rapidly and she was often drowsy. She died of aspiration pneumonia 6 months after surgery