BRCA1 Mutation Leads to Deregulated Ubc9 Levels which Triggers Proliferation and Migration of Patient-Derived High Grade Serous Ovarian Cancer and Triple Negative Breast Cancer Cells

Women who carry a germline mutation in BRCA1 gene typically develop triple negative breast cancers (TNBC) and high grade serous ovarian cancers (HGSOC). Previously, we reported that wild type BRCA1 proteins, unlike the disease-associated mutant BRCA1 proteins to bind the sole sumo E2-conjugating enzyme Ubc9. In this study, we have used clinically relevant cell lines with known BRCA1 mutations and report the in-vivo association of BRCA1 and Ubc9 in normal mammary epithelial cells but not in BRCA1 mutant HGSOC and TNBC cells by immunofluorescence analysis. BRCA1-mutant HGSOC / TNBC cells and ovarian tumor tissues showed increased expression of Ubc9 compared to BRCA1 reconstituted HGSOC, normal mammary epithelial cells and matched normal ovarian tissues. Knockdown of Ubc9 expression resulted in decreased proliferation and migration of BRCA1 mutant TNBC and HGSOC cells. This is the first study demonstrating the functional link between BRCA1 mutation, high Ubc9 expression and increased migration of HGSOC and TNBC cells. High Ubc9 expression due to BRCA1 mutation may trigger an early growth and transformation advantage to normal breast and ovarian epithelial cells resulting in aggressive cancers. Future work will focus on studying whether Ubc9 expression could show a positive correlation with BRCA1 linked HGSOC and basal like TNBC phenotype

Quantum Spectra of Hydrogen Atoms in Various Magnetic Fields with the Closed Orbit Theory

The quantum spectra of hydrogen atoms in various magnetic fields have been calculated with the closed orbit theory. The magnitude of the magnetic field decreases from 5.96 T to 0.56T with a step of 0.6T. We demonstrate schematically that the closed orbits disappear with the decrease of the magnitude of the magnetic field when the corresponding finite resolution of experiment is fixed. This may give us a good way to control the shape and the number of the closed orbits in the system, and thus to control where a peak should exist in the Fourier transformation of the quantum spectra.Comment: 4 page

Single Nucleotide Polymorphisms of 8 Inflammation-related Genes and their Associations with Smoking-related Cancers

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers. © 2010 UICC

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility

Noise Reduction by Diffusional Dissipation in a Minimal Quorum Sensing Motif

Cellular interactions are subject to random fluctuations (noise) in quantities of interacting molecules. Noise presents a major challenge for the robust function of natural and engineered cellular networks. Past studies have analyzed how noise is regulated at the intracellular level. Cell–cell communication, however, may provide a complementary strategy to achieve robust gene expression by enabling the coupling of a cell with its environment and other cells. To gain insight into this issue, we have examined noise regulation by quorum sensing (QS), a mechanism by which many bacteria communicate through production and sensing of small diffusible signals. Using a stochastic model, we analyze a minimal QS motif in Gram-negative bacteria. Our analysis shows that diffusion of the QS signal, together with fast turnover of its transcriptional regulator, attenuates low-frequency components of extrinsic noise. We term this unique mechanism “diffusional dissipation” to emphasize the importance of fast signal turnover (or dissipation) by diffusion. We further show that this noise attenuation is a property of a more generic regulatory motif, of which QS is an implementation. Our results suggest that, in a QS system, an unstable transcriptional regulator may be favored for regulating expression of costly proteins that generate public goods

Computation of Steady-State Probability Distributions in Stochastic Models of Cellular Networks

Cellular processes are “noisy”. In each cell, concentrations of molecules are subject to random fluctuations due to the small numbers of these molecules and to environmental perturbations. While noise varies with time, it is often measured at steady state, for example by flow cytometry. When interrogating aspects of a cellular network by such steady-state measurements of network components, a key need is to develop efficient methods to simulate and compute these distributions. We describe innovations in stochastic modeling coupled with approaches to this computational challenge: first, an approach to modeling intrinsic noise via solution of the chemical master equation, and second, a convolution technique to account for contributions of extrinsic noise. We show how these techniques can be combined in a streamlined procedure for evaluation of different sources of variability in a biochemical network. Evaluation and illustrations are given in analysis of two well-characterized synthetic gene circuits, as well as a signaling network underlying the mammalian cell cycle entry

A review on boiling heat transfer enhancement with nanofluids

There has been increasing interest of late in nanofluid boiling and its use in heat transfer enhancement. This article covers recent advances in the last decade by researchers in both pool boiling and convective boiling applications, with nanofluids as the working fluid. The available data in the literature is reviewed in terms of enhancements, and degradations in the nucleate boiling heat transfer and critical heat flux. Conflicting data have been presented in the literature on the effect that nanofluids have on the boiling heat-transfer coefficient; however, almost all researchers have noted an enhancement in the critical heat flux during nanofluid boiling. Several researchers have observed nanoparticle deposition at the heater surface, which they have related back to the critical heat flux enhancement