Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology.

Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs

Gravitational Influence on Human Living Systems and the Evolution of Species on Earth

Gravity constituted the only constant environmental parameter, during the evolutionary period of living matter on Earth. However, whether gravity has affected the evolution of species, and its impact is still ongoing. The topic has not been investigated in depth, as this would require frequent and long-term experimentations in space or an environment of altered gravity. In addition, each organism should be studied throughout numerous generations to determine the profound biological changes in evolution. Here, we review the significant abnormalities presented in the cardiovascular, immune, vestibular and musculoskeletal systems, due to altered gravity conditions. We also review the impact that gravity played in the anatomy of snakes and amphibians, during their evolution. Overall, it appears that gravity does not only curve the space–time continuum but the biological continuum, as well

The role of CXC-chemokine receptor CXCR2 and suppressor of cytokine signaling-3 (SOCS-3) in renal cell carcinoma

BACKGROUND: Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC. METHODS: In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases. RESULTS: Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis. CONCLUSIONS: Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its therapeutic targeting. IL-8/CXCR2 signaling also contributes to the metastatic phenotype of RCC cells but appears of lesser prognostic utility. Both CXCR2 and SOCS-3 appear to be related to transcription factors induced under hypoxia

Poincaré Maps and Aperiodic Oscillations in Leukemic Cell Proliferation Reveal Chaotic Dynamics

Biological systems are dynamic systems featuring two very common characteristics; Initial conditions and progression over time. Conceptualizing this on tumour models it can lead to important conclusions about disease progression, as well as the disease’s “starting point”. In the present study we tried to answer two questions: (a) which are the evolving properties of proliferating tumour cells that started from different initial conditions and (b) we have attempted to prove that cell proliferation follows chaotic orbits and it can be described by the use of Poincaré maps. As a model we have used the acute lymphoblastic leukemia cell line CCRF-CEM. Measurements of cell population were taken at certain time points every 24 h or 48 h. In addition to the population measurements flow cytometry studies have been conducted in order to examine the apoptotic and necrotic rate of the system and also the DNA content of the cells as they progress through. The cells exhibited a proliferation rate of nonlinear nature with aperiodic oscillatory behavior. In addition to that, the (positive) Lyapunov indices and the Poincaré representations in phase-space that we performed confirmed the presence of chaotic orbits. Several studies have dealt with the complex dynamic behaviour of animal populations, but few with cellular systems. This type of approach could prove useful towards the understanding of leukemia dynamics, with particular interest in the understanding of leukemia onset and progression

A lightweight anonymity & location privacy service

Abstract-As embedded systems, in their various forms, become ubiquitous, new types of services are offered, aiming to enhance every aspect of the everyday life and allowing users to enjoy pervasive and personalized access to information. Along with the benefits come considerable threats to users' privacy, as these enhanced services operate on private sensitive information, such as the true identity and location of users. This paper proposes a lightweight, distributed anonymity and location privacy service which can be deployed on mobile embedded systems (e.g. smart clothing, smart phones), even heterogeneous in nature, allowing users to form communities which help them hide their identities and exact location. Acting as a proxy the proposed service can sanitize users' requests prior to forwarding them to a location-based service (LBS). The deployment of this type of information sanitization proxy would facilitate the wider adoption of the new generation of enhanced reality applications and services, alleviating the justified concerns regarding users' privacy