Analytic Behaviour of Competition among Three Species

We analyse the classical model of competition between three species studied by May and Leonard ({\it SIAM J Appl Math} \textbf{29} (1975) 243-256) with the approaches of singularity analysis and symmetry analysis to identify values of the parameters for which the system is integrable. We observe some striking relations between critical values arising from the approach of dynamical systems and the singularity and symmetry analyses.Comment: 14 pages, to appear in Journal of Nonlinear Mathematical Physic

CLU "in and out": looking for a link

Cancer cells need to interact synergistically with their surrounding microenvironment to form a neoplasm and to progress further to colonize distant organs. The microenvironment can exert profound epigenetic effects on cells through cell-derived interactions between cells, or through cell-derived factors deposited into the microenvironment. Tumor progression implies immune-escaping and triggers several processes that synergistically induce a cooperation among transformed and stromal cells, that compete for space and resources such as oxygen and nutrients. Therefore, the extra cellular milieu and tissue microenvironment heterotypic interactions cooperate to promote tumor growth, angiogenesis, and cancer cell motility, through elevated secretion of pleiotropic cytokines and soluble factors. Clusterin (CLU), widely viewed as an enigmatic protein represents one of the numerous cellular factors sharing the intracellular information with the microenvironment and it has also a systemic diffusion, tightly joining the "In and the Out" of the cell with a still debated variety of antagonistic functions. The multiplicity of names for CLU is an indication of the complexity of the problem and could reflect, on one hand its multifunctionality, or alternatively could mask a commonality of function. The posited role for CLU, further supported as a cytoprotective prosurvival chaperone-like molecule, seems compelling, in contrast its tumor suppressor function, as a guide of the guardians of the genome (DNA-repair proteins Ku70/80, Bax cell death inducer), could really reflect the balanced expression of its different forms, most certainly depending on the intra- and extracellular microenvironment cross talk. The complicated balance of cytokines network and the regulation of CLU forms production in cancer and stromal cells undoubtedly represent a potential link among adaptative responses, genomic stability, and bystander effect after oxidative stresses and damage. This review focuses on the tumor-microenvironment interactions strictly involved in controlling local cancer growth, invasion, and distant metastases that play a decisive role in the regulation of CLU different forms expression and release. In addition, we focus on the pleiotropic action of the extracellular form of this protein, sCLU, that may play a crucial role in redirecting stromal changes, altering intercellular communications binding cell surface receptors and contributing to influence the secretion of chemokines in paracrine and autocrine fashion. Further elucidation of CLU functions inside and outside ("in and out") of cancer cell are warranted for a deeper understanding of the interplay between tumor and stroma, suggesting new therapeutic cotargeting strategies

CLU "in and out": looking for a link.

Cancer cells need to interact synergistically with their surrounding microenvironment to form a neoplasm and to progress further to colonize distant organs. The microenvironment can exert profound epigenetic effects on cells through cell-derived interactions between cells, or through cell-derived factors deposited into the microenvironment. Tumor progression implies immune-escaping and triggers several processes that synergistically induce a cooperation among transformed and stromal cells, that compete for space and resources such as oxygen and nutrients. Therefore, the extra cellular milieu and tissue microenvironment heterotypic interactions cooperate to promote tumor growth, angiogenesis, and cancer cell motility, through elevated secretion of pleiotropic cytokines and soluble factors. Clusterin (CLU), widely viewed as an enigmatic protein represents one of the numerous cellular factors sharing the intracellular information with the microenvironment and it has also a systemic diffusion, tightly joining the "In and the Out" of the cell with a still debated variety of antagonistic functions. The multiplicity of names for CLU is an indication of the complexity of the problem and could reflect, on one hand its multifunctionality, or alternatively could mask a commonality of function. The posited role for CLU, further supported as a cytoprotective prosurvival chaperone-like molecule, seems compelling, in contrast its tumor suppressor function, as a guide of the guardians of the genome (DNA-repair proteins Ku70/80, Bax cell death inducer), could really reflect the balanced expression of its different forms, most certainly depending on the intra- and extracellular microenvironment cross talk. The complicated balance of cytokines network and the regulation of CLU forms production in cancer and stromal cells undoubtedly represent a potential link among adaptative responses, genomic stability, and bystander effect after oxidative stresses and damage. This review focuses on the tumor-microenvironment interactions strictly involved in controlling local cancer growth, invasion, and distant metastases that play a decisive role in the regulation of CLU different forms expression and release. In addition, we focus on the pleiotropic action of the extracellular form of this protein, sCLU, that may play a crucial role in redirecting stromal changes, altering intercellular communications binding cell surface receptors and contributing to influence the secretion of chemokines in paracrine and autocrine fashion. Further elucidation of CLU functions inside and outside ("in and out") of cancer cell are warranted for a deeper understanding of the interplay between tumor and stroma, suggesting new therapeutic cotargeting strategies

On the Integrability, B\"Acklund Transformation and Symmetry Aspects of a Generalized Fisher Type Nonlinear Reaction-Diffusion Equation

The dynamics of nonlinear reaction-diffusion systems is dominated by the onset of patterns and Fisher equation is considered to be a prototype of such diffusive equations. Here we investigate the integrability properties of a generalized Fisher equation in both (1+1) and (2+1) dimensions. A Painlev\'e singularity structure analysis singles out a special case ($m=2$) as integrable. More interestingly, a B\"acklund transformation is shown to give rise to a linearizing transformation for the integrable case. A Lie symmetry analysis again separates out the same $m=2$ case as the integrable one and hence we report several physically interesting solutions via similarity reductions. Thus we give a group theoretical interpretation for the system under study. Explicit and numerical solutions for specific cases of nonintegrable systems are also given. In particular, the system is found to exhibit different types of travelling wave solutions and patterns, static structures and localized structures. Besides the Lie symmetry analysis, nonclassical and generalized conditional symmetry analysis are also carried out.Comment: 30 pages, 10 figures, to appear in Int. J. Bifur. Chaos (2004

Efficacy of atropine 0.01% for the treatment of childhood myopia in European patients

Purpose: To evaluate the efficacy and safety of atropine 0.01% in slowing myopia progression in European paediatric patients. Methods: Retrospective, medical records review study. Medical charts of paediatric patients with a myopia progression > 0.5 D/year treated with atropine 0.01% for at least 1 year were included. Patients receive a complete ophthalmic examination before and 12 months after initiation of atropine treatment. A group of myopic untreated children serves as a control group. The rate of myopia progression at baseline and 12 months after treatment with atropine was evaluated. The rate of myopia progression in treated and untreated patients was also compared. Adverse events were recorded. Results: Medical records of 52 treated and 50 control subjects were analysed. In the atropine group, the mean rate of myopia progression after 12 months of treatment ( 120.54 \ub1 0.61 D) was significantly slower compared with the baseline progression ( 121.20 \ub1 0.64 D; p < 0.0001) and to the progression in the control group ( 121.09 \ub1 0.64; p < 0.0001). The responders patients were 41/52 (79%), whereas 11/52 patients (21%) showed a progression > 0.50 D despite treatment. The only adverse event was temporary photophobia in five patients (9.6%), severe adverse events were not reported, and none of the patients discontinued the treatment. Conclusion: Low-dose atropine significantly slowed the rate of myopia progression in European paediatric patients with a favourable safety profile

Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation

Background: Stickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients. Methods: Herein, we report a case of an 8-year- old child with Stickler Syndrome, presenting with early-onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene. Results: A novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing. Conclusion: We reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early-onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene-related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease

Color fundus autofluorescence to determine activity of macular neovascularization in age-related macular degeneration

Purpose: To evaluate with color fundus autofluorescence (FAF) different lesion components of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) and to assess its activity. Methods: In total, 137 eyes (102 patients) with MNV underwent a complete eye exami-nation, including color fundus photography, optical coherence tomography (OCT), OCT angiography, and confocal color FAF, with an excitation wavelength at 450 nm. Each image was imported into a custom-image analysis software for quantitative estimation of emission wavelength and green and red emission fluorescence (GEFC/REFC) inten-sity, considering both single components of neovascular AMD and different MNV types (type 1 and type 2 MNV, active and inactive MNV). Results: Subretinal fluid (SRF) had significantly higher values of GEFC (P = 0.008 and P = 0.0004) and REFC intensity (P = 0.005 and P = 0.0003) versus fibrosis and atrophy. The emission wavelength from SRF was lower compared to atrophy (P = 0.024) but not to fibrosis (P = 0.46). No significant differences were detected between type 1 and 2 MNV. Considering active versus inactive MNVs, a difference was detected for all evaluated parameters (P < 0.001). Mean FAF wavelength of both MNV with SRF and intrareti-nal fluid (IRF) was lower versus inactive MNV (P < 0.001 and P = 0.005). MNV with SRF (P < 0.001) had higher values of GEFC and REFC versus inactive MNV (P < 0.001). MNV with IRF had higher values of GEFC versus inactive MNV (P = 0.05). Conclusions: Quantitative color FAF can differentiate active versus inactive MNV, whereas no differences were found between type 1 and type 2 MNV. If these data can be further confirmed, color FAF may be useful for automatic detection of active MNV in AMD and as a guide for treatment. Translational Relevance: Automatic quantitative evaluation of green and red emission components of FAF in AMD can help determine the activity of MNV and guide the treatment

Subclinical signs of retinal involvement in hereditary angioedema

To explore retinal abnormalities using spectral domain optical coherence tomography (SD‐OCT) and OCT‐angiography (OCT‐A) in a highly selective cohort of patients with type I hereditary angioedema (HAE). This prospective case‐control study included 40 type I HAE patients and 40 age‐/sex‐matched healthy subjects (HC). All participants underwent SD‐OCT‐scanning of retinal posterior pole (PP), peripapillary retinal nerve fiber layer (pRNFL), and optic nerve head (ONH). Superficial/deep capillary density was analyzed by OCT‐A. A total of 80 eyes from 40 HAE and 40 eyes from HC were evaluated. The pRNFL was thicker in HAE than in HC in nasal superior (p &lt; 0.0001) and temporal quadrants (p = 0.0005 left, p = 0.003 right). The ONH thickness in HAE patients was greater than in HC in the nasal (p = 0.008 left, p = 0.01 right), temporal (p = 0.0005 left, p = 0.003 right), temporal inferior (p = 0.007 left, p = 0.0008 right), and global (p = 0.005 left, p = 0.007 right) scans. Compared to HC, HAE showed a lower capillary density in both superficial (p = 0.001 left, p = 0.006 right) and deep (p = 0.008 left, p = 0.004 right) whole images, and superficial (p = 0.03 left) and deep parafoveal (p = 0.007 left, p = 0.005 right) areas. Our findings documented subclinical retinal abnormalities in type I HAE, supporting a potential role of the retinal assessment by SD‐ OCT/OCT‐A as a useful tool in the comprehensive care of HAE patients

Candidemia Surveillance in Brazil: Evidence for a Geographical Boundary Defining an Area Exhibiting an Abatement of Infections by Candida albicans Group 2 Strains

Prospective population surveillance has been conducted for candidemia in Brazil (A. L. Colombo, M. Nucci, B. J. Park, et al., J. Clin. Microbiol. 44:2816-2823, 2006). in the present study, a total of 63 isolates from 61 patients, representing 11 medical centers from nine geographic regions, were characterized by multilocus sequence typing (MLST). A total of 48 unique profiles or diploid sequence types (DSTs) were observed, with nine new sequence types (STs) and 32 new DSTs. There were no apparent correlations between center/region and DST patterns. Subtypes were compared to those in a known characterized reference set, including a large database of strains obtained worldwide. Significantly, only one C. albicans group 2 isolate was found in our collection, although isolates from this particular group are commonly found worldwide. These data, combined with information from other previously reported studies, establish a statistically significant diminishment of group 2 strains in Central and South America, including Mexico and portions of the Southwestern United States.Centers for Disease Control and Prevention (CDC)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilWeb of Scienc