Coordinated Spatial Pattern Formation in Biomolecular Communication Networks

This paper proposes a control theoretic framework to model and analyze the self-organized pattern formation of molecular concentrations in biomolecular communication networks, emerging applications in synthetic biology. In biomolecular communication networks, bio-nanomachines, or biological cells, communicate with each other using a cell-to-cell communication mechanism mediated by a diffusible signaling molecule, thereby the dynamics of molecular concentrations are approximately modeled as a reaction-diffusion system with a single diffuser. We first introduce a feedback model representation of the reaction-diffusion system and provide a systematic local stability/instability analysis tool using the root locus of the feedback system. The instability analysis then allows us to analytically derive the conditions for the self-organized spatial pattern formation, or Turing pattern formation, of the bionanomachines. We propose a novel synthetic biocircuit motif called activator-repressor-diffuser system and show that it is one of the minimum biomolecular circuits that admit self-organized patterns over cell population

ErbB2 and NFκB Overexpression as Predictors of Chemoradiation Resistance and Putative Targets to Overcome Resistance in Muscle-Invasive Bladder Cancer

Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC

Sex-inducing effects toward planarians widely present among parasitic flatworms

Summary Various parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms.journal articl

Effects of eicosapentaenoic acid on peri-procedural (type IVa) myocardial infarction following elective coronary stenting

AbstractObjectivesThe aim of this study was to assess the effect of eicosapentaenoic acid (EPA) on peri-procedural (type IVa) myocardial infarction (MI) following elective percutaneous coronary intervention (PCI).Methods and resultsWe analyzed data from 165 of 178 consecutive patients with stable angina pectoris who underwent de novo successful stent implantation in the native coronary artery. Patients were assigned to receive statin therapy in combination with 1800mg/day of EPA or statin alone. Post-procedural index of microcirculatory resistance (IMR) values were calculated for 30 patients in the EPA group and 32 controls. In the multivariate logistic model, EPA administration, low kidney function, and the presence of slow flow/no reflow were significantly and independently associated with type IVa MI. Post-procedural IMR values were significantly lower in the EPA group [19.8 (6.4, 51.1) vs. 27.8 (8.2, 89.3), p=0.003] compared to the control group.ConclusionsPre-treatment with EPA in addition to statins significantly reduced the incidence of type IVa MI compared to statin therapy only, which may be attributed to the ability of EPA to reduce microvascular dysfunction induced by PCI

Long-Term Diet Supplementation with Lactobacillus paracasei K71 Prevents Age-Related Cognitive Decline in Senescence-Accelerated Mouse Prone 8

This study aimed to assess the suppressive effect of long-term diet supplementation with Lactobacillus strains on cognitive decline in the senescence-accelerated mouse prone 8 (SAMP8) model. For 43 weeks, fourteen-week-old female SAMP8 mice were fed a standard diet containing 0.05% (w/w) Lactobacillus casei subsp. casei 327 (L. 327) or Lactobacillusparacasei K71 (L. K71) derived from rice grains and sake lees, respectively. SAMP8 mice that were fed a L. K71-supplemented diet had better cognitive performance compared with the control and L. 327 groups in the Barnes maze and passive avoidance tests. An ELISA analysis revealed that the levels of serotonin were elevated in the serum and brain tissue of L. K71-fed mice. The protein expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), and phosphorylated CREB were evaluated using western blot. Long-term administration of L. K71 resulted in increased protein expression of BDNF and CREB phosphorylation in the hippocampus. These results suggest that prolonged intake of a diet supplemented with a Lactobacillus strain derived from sake lees may prevent age-dependent cognitive decline by upregulating BDNF expression in the hippocampus