Mesenchymal Stem Cells Promote Oligodendroglial Differentiation in Hippocampal Slice Cultures

We have previously shown that soluble factors derived from mesenchymal stem cells (MSCs) induce oligodendrogenic fate and differentiation in adult rat neural progenitors (NPCs) in vitro. Here, we investigated if this pro-oligodendrogenic effect is maintained after cells have been transplanted onto rat hippocampal slice cultures, a CNS-organotypic environment. We first tested whether NPCs, that were pre-differentiated in vitro by MSC-derived conditioned medium, would generate oligodendrocytes after transplantation. This approach resulted in the loss of grafted NPCs, suggesting that oligodendroglial pre-differentiated cells could not integrate in the tissue and therefore did not survive grafting. However, when NPCs together with MSCs were transplanted in situ into hippocampal slice cultures, the grafted NPCs survived and the majority of them differentiated into oligodendrocytes. In contrast to the prevalent oligodendroglial differentiation in case of the NPC/MSC co-transplantation, naive NPCs transplanted in the absence of MSCs differentiated predominantly into astrocytes. In summary, the pro-oligodendrogenic activity of MSCs was maintained only after co-transplantation into hippocampal slice cultures. Therefore, in the otherwise astrogenic milieu, MSCs established an oligodendrogenic niche for transplanted NPCs, and thus, co-transplantation of MSCs with NPCs might provide an attractive approach to re-myelinate the various regions of the diseased CNS. Copyright (C) 2009 S. Karger AG, Base

Critical Infrastructure Automated Immuno-Response System (CIAIRS)

Critical Infrastructures play a central role in the world around us and are the backbone of everyday life. Their service provision has become more widespread, to the point where it is now practically ubiquitous in many societies. Critical Infrastructure assets contribute to the economy and society as a whole. Their impact on the security, economy and health sector are extremely vital. Critical Infrastructures now possess levels of automation that require the integration of, often, mutually incompatible technologies. Their increasing complexity has led to the creation of direct and indirect interdependent connections amongst the infrastructure groupings. In addition, the data generated is vast as the intricate level of interdependency between infrastructures has grown. Since Critical Infrastructures are the backbone of everyday life, their protection from cyber-threats is an increasingly pressing issue for governments and private industries. Any failures, caused by cyber-attacks, have the ability to spread through interconnected systems and are a challenge to detect; especially as the Internet is now heavily reliant on Critical Infrastructures. This has led to different security threats facing interconnected security systems. Understanding the complexity of Critical Infrastructure interdependencies, how to take advantage of it in order to minimize the cascading problem, enables the prediction of potential problems before they happen. Therefore, this work firstly discusses the interdependency challenges facing Critical Infrastructures; and how it can be used to create a support network against cyber-attacks. In much, the same way as the human immune system is able to respond to intrusion. Next, the development of a distributed support system is presented. The system employs behaviour analysis techniques to support interconnected infrastructures and distribute security advice throughout a distributed system of systems. The approach put forward is tested through a statistical analysis methodology, in order to investigate the cascading failure effect whilst taking into account the independent variables. Moreover, our proposed system is able to detect cyber-attacks and share the knowledge with interconnected partners to create an immune system network. The development of the ‘Critical Infrastructure Auto-Immune Response System’ (CIAIRS) is presented with a detailed discussion on the main segments that comprise the framework and illustrates the functioning of the system. A semi-structured interview helped to demonstrate our approach by using a realistic simulation to construct data and evaluate the system output

Effect of Edwardsiella ictaluri Infection on Plasma Corticosterone Levels in Channel Catfish (Ictalurus punctatus)

Channel catfish (Ictalurus punctatus) were innoculated with a new host specific bacterium, Edwardsiella ictaluri, to observe the influence of bacterial infection on plasma corticosterone levels at various temperatures. The fish were innoculated intraperitoneally. The infected fish were separated from the controls. Plasma corticosterone concentrations were determined by radioimmunoassay. The plasma corticosterone concentrations in non-innoculated catfish were about 6.15 ng/ml and nearly 5.63 ng/ml in the infected fish. The lower level of the hormone in the infected catfish was not significantly different from the control level. High temperature was a stress factor which increased plasma corticosterone levels whereas E. ictaluri retarded the response of corticosterone secreting cells of the fish kidneys

Colorectal cancer defeating? Challenge accepted!

Colorectal tumours are actually considered as aberrant organs, within it is possible to notice a different stage of cell growth and differentiation. Their origin is reported to arise from a subpopulation of tumour cells endowed with, just like the healthy stem cells, self-renewal and aberrant multi-lineage differentiation capacity likely to be called colorectal cancer stem cells (CCSCs). Cancer stem cells (CSCs) fate, since their origin, reflects the influences from their microenvironment (or niche) both in the maintenance of stemness, in promoting their differentiation, and in inducing epithelial-mesenchymal transition, responsible of CSCs dissemination and subsequent formation of metastatic lesions. The tumour cells heterogeneity and their immuno-response resistance nowadays probably responsible of the failure of the conventional therapies, make this research field an open issue. Even more importantly, our increasing understanding of the cellular and molecular mechanisms that regulate CSC quiescence and cell cycle regulation, self-renewal, chemotaxis and resistance to cytotoxic agents, is expected to eventually result in tailor-made therapies with a significant impact on the morbidity and overall survival of colorectal cancer patients

Gender Differences in Survival in Idiopathic Pulmonary Fibrosis and Following Lung Transplant

Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive form of interstitial lung disease characterized by inflammation and abnormal tissue repair ultimately leading to decreased pulmonary function and death. Risk factors for IPF are largely unknown and medical treatment offers a poor prognosis due to the lack of effective treatment options. Survival outcomes were analyzed for a cohort of 331 patients. The median age at clinical evaluation for IPF was 69 years. Subjects survived an average of 21.82 months after diagnosis, with a higher survival in females than in males. Males had a risk 2.85 times higher than females of death. Subjects older than 69 years of age had a relative risk of dying of 1.6 in comparison to subjects younger than 69 years. Predictors of survival after lung transplant were also analyzed in a cohort of 990 lung transplanted patients. The overall survival was 41.6%, (41.5 % in males, and 41.8 % in females), the average length of the follow up was 45.84 plus or minus 51.98 months (range 0 to 282.47 months). Females tend to live longer than males: 50.75 plus or minus 55.41 months versus 40.64 plus or minus 47.60 months, respectively. Males had a risk of dying during the follow up that was 1.18 (95% CI 1.01-1.40) relative to females, after adjusting for ethnicity, age, smoking status, diagnosis and donor characteristics. Females who had at least one full term pregnancy during their life had better survival rates than females who had no full term pregnancies.Our results of a better survival after lung transplant in females (particularly females with at least one pregnancy) support the hypothesis of a hormonal contribution to survival and of the development of immunotolerance after pregnancy.The public health significance includes the use of the current study as a model in understanding the role of immunity in cancer development. The age-adjusted incidence rate is 555.8 per 100,000 men and 411.3 per 100,000 women per year (2000-2004), and the combined lifetime risk of cancer is approximately 1 in 2. Thus, any further understanding of cancer causes would be worthwhile in cancer prevention and treatment efforts

A machine learning pipeline for discriminant pathways identification

Motivation: Identifying the molecular pathways more prone to disruption during a pathological process is a key task in network medicine and, more in general, in systems biology. Results: In this work we propose a pipeline that couples a machine learning solution for molecular profiling with a recent network comparison method. The pipeline can identify changes occurring between specific sub-modules of networks built in a case-control biomarker study, discriminating key groups of genes whose interactions are modified by an underlying condition. The proposal is independent from the classification algorithm used. Three applications on genomewide data are presented regarding children susceptibility to air pollution and two neurodegenerative diseases: Parkinson's and Alzheimer's. Availability: Details about the software used for the experiments discussed in this paper are provided in the Appendix

New insights on metal allergy in total joint arthroplasty

Metal allergy is an uncommon and not completely understood cause of failure in total joint arthroplasty (TJA). However, either immunopathology neither histologic studies clarified the mechanisms through which the metal ions could lead to the complications related to them. The lack of evidence around this topic also reflects the difficulties to diagnose the MRP in TJA. In fact, the diagnosis is generally based on the exclusion of other causes. Currently, skin-patch testing and lymphocyte transformation test (LTT) are being commonly used to investigate about metal hypersensitivity and a delayed type-IV hypersensitivity is the immuno-histologic response to metals involved in TJA loosening. A review of the recent publications about this topic has been made focusing on immunology, histopathology, and clinics to better understand a still debated topic in orthopedic practice

Directed Irradiation Synthesis as an Advanced Plasma Technology for Surface Modification to Activate Porous and “as-received” Titanium Surfaces

For the design of smart titanium implants, it is essential to balance the surface properties without any detrimental effect on the bulk properties of the material. Therefore, in this study, an irradiation-driven surface modification called directed irradiation synthesis (DIS) has been developed to nanopattern porousand“as-received”c.p. Tisur faces with the aim of improving cellular viability. Nano features were developed using singly-charged argon ions at 0.5 and 1.0 keV energies, incident angles from 0◦ to 75◦ degrees, and fluences up to 5.0×1017 cm−2. Irradiated surfaces were evaluated by scanning electron microscopy, atomic force microscopy and contact angle, observing an increased hydrophilicity (a contact angle reduction of 73.4% and 49.3%) and a higher roughness on both surfaces except for higher incident angles, which showed the smoothest surface. In-vitro studies demonstrated the biocompatibility of directed irradiation synthesis (DIS) reaching 84% and 87% cell viability levels at 1 and 7 days respectively, and a lower percentage of damaged DNA in tail compared to the control c.p. Ti. All these results confirm the potential of the DIS technique to modify complex surfaces at the nanoscale level promoting their biological performance.Department of Defense (Spain) contract W81XWH-11-2-0067Ministry of Economy and Competitiveness of Spain grant MAT2015-71284-