Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

Trends in Hydrological Parameters of a Southern Brazilian Watershed and its Relation to Human Induced Changes

The Piracicaba river basin is a subtropical watershed located in the southeastern region of Brazil. With an area of 12 400 km², the basin is a typical example of new landscape resulting from development in tropical and sub-tropical regions: establishment of intensive industrial and agricultural processes were followed by significant population growth and water management. This scenario has led to significant increase in water demand and decrease in water quality. The main objective of this study is the detection of changes in the patterns of flow and precipitation in the basin, and its possible relation to man-induced changes. Statistical analyses were performed on records of precipitation, evapotranspiration and streamflow, from 1947 to 1991. Precipitation and evapotranspiration totals showed significant increasing trends for the entire basin. From eight streamflow gauge stations, half showed significant decreasing trend. The most probable cause of such trends is the export of water from the basin to the metropolitan region of São Paulo city.     

Play therapy for multicultural populations: Guidelines for mental health professionals.

Describes methods and techniques of play therapy for use with multicultural and diverse populations. Barriers to counseling multicultural children and Eurocentric play therapy techniques with multicultural populations are highlighted. Specific guidelines and examples for play therapy with multicultural children are provided. Recommendations and implications for mental health professionals are also discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A variable rate multipulse speech coder for CDMA cellular systems

Variable Rate (VR) speech coders are classified into: source-controlled VR coders where the rate is selected depending on the local character of the speech, and network-controlled VR coders where an external control signal selects the coding rate. The first category benefits from the variable rate channels used by Code Division Multiple Access (CDMA) mobile communications. The second category is indispensable for the right behaviour of the CDMA systems under conditions as high traffic levels. The VR speech coder presented in this communication exhibits both types of control. The source control is achieved by means of a Voice Activity Detector (VAD) and a phonetic classifier. The network control acts on the selection procedure of the multipulse excitation sequence to the synthesis filter. This is the main advantage of our VR MultiPulse speech coder because by means of an external signal the bit rate can be changed only every 4 msec, without transitions or distortions. Considering one-way communication, six different operating rates can be externally selected ranging from 4.8 to 9.1 kbps for the active frames; an average bit rate of 380 bps is required for the noise frames.This work has been partly funded by the Spanish Research National Plan under grant no. TIC92-0800-C05-02 and by Northern Telecom.     

Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats

Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.     

Visualizing Extracellular Vesicles and Their Function in 3D Tumor Microenvironment Models

Extracellular vesicles (EVs) are cell-derived nanostructures that mediate intercellular communication by delivering complex signals in normal tissues and cancer. The cellular coordination required for tumor development and maintenance is mediated, in part, through EV transport of molecular cargo to resident and distant cells. Most studies on EV-mediated signaling have been performed in two-dimensional (2D) monolayer cell cultures, largely because of their simplicity and high-throughput screening capacity. Three-dimensional (3D) cell cultures can be used to study cell-to-cell and cell-to-matrix interactions, enabling the study of EV-mediated cellular communication. 3D cultures may best model the role of EVs in formation of the tumor microenvironment (TME) and cancer cell-stromal interactions that sustain tumor growth. In this review, we discuss EV biology in 3D culture correlates of the TME. This includes EV communication between cell types of the TME, differences in EV biogenesis and signaling associated with differing scaffold choices and in scaffold-free 3D cultures and cultivation of the premetastatic niche. An understanding of EV biogenesis and signaling within a 3D TME will improve culture correlates of oncogenesis, enable molecular control of the TME and aid development of drug delivery tools based on EV-mediated signaling.