The avian 'prefrontal cortex' and cognition

Both mammals and birds can flexibly organize their behavior over time. In mammals, the mental operations generating this ability are called executive functions and are associated with the prefrontal cortex. The corresponding structure in birds is the nidopallium caudolaterale. Anatomical, neurochemical, electrophysiological and behavioral studies show these structures to be highly similar. The avian forebrain displays no lamination that corresponds to the mammalian neocortex, hence lamination does not seem to be a requirement for higher cognitive functions. Because all other aspects of the neural architecture of the mammalian and the avian prefrontal areas are extremely comparable, the freedom to create different neural architectures that generate prefrontal functions seems to be very limited.     

Optimization based tumor classification from microarray gene expression data

Background

An important use of data obtained from microarray measurements is the classification of tumor types with respect to genes that are either up or down regulated in specific cancer types. A number of algorithms have been proposed to obtain such classifications. These algorithms usually require parameter optimization to obtain accurate results depending on the type of data. Additionally, it is highly critical to find an optimal set of markers among those up or down regulated genes that can be clinically utilized to build assays for the diagnosis or to follow progression of specific cancer types. In this paper, we employ a mixed integer programming based classification algorithm named hyper-box enclosure method (HBE) for the classification of some cancer types with a minimal set of predictor genes. This optimization based method which is a user friendly and efficient classifier may allow the clinicians to diagnose and follow progression of certain cancer types.

Methodology/Principal Findings

We apply HBE algorithm to some well known data sets such as leukemia, prostate cancer, diffuse large B-cell lymphoma (DLBCL), small round blue cell tumors (SRBCT) to find some predictor genes that can be utilized for diagnosis and prognosis in a robust manner with a high accuracy. Our approach does not require any modification or parameter optimization for each data set. Additionally, information gain attribute evaluator, relief attribute evaluator and correlation-based feature selection methods are employed for the gene selection. The results are compared with those from other studies and biological roles of selected genes in corresponding cancer type are described.

Conclusions/Significance

The performance of our algorithm overall was better than the other algorithms reported in the literature and classifiers found in WEKA data-mining package. Since it does not require a parameter optimization and it performs consistently very high prediction rate on different type of data sets, HBE method is an effective and consistent tool for cancer type prediction with a small number of gene markers.     

IL-7/anti-IL-7 mAb complexes restore T cell development and induce homeostatic T Cell expansion without lymphopenia

IL-7, a member of the common gamma-chain family of cytokines, is essential for B and T lymphocyte development and homeostasis of mature T cell subsets. Thus, naive and memory T cells are both dependent on IL-7 for survival and homeostatic proliferation under lymphopenic conditions. In line with prior findings with IL-2, we show in this study that the biological activity of IL-7 in vivo is greatly increased by association with anti-IL-7 mAb. Under in vivo conditions, IL-7/mAb complexes displayed 50- to 100-fold higher activity than free IL-7 and induced massive expansion of pre-B cells. IL-7/mAb complexes also increased thymopoiesis in normal mice and restored thymopoeisis in IL-7-deficient mice. For mature T cells, IL-7/mAb complexes induced marked homeostatic proliferation of both naive and memory CD4(+) and CD8(+) cell subsets even under normal T cell-replete conditions. Finally, IL-7/mAb complexes were able to enhance the magnitude of the primary response of Ag-specific naive CD8(+) cells. The strong stimulatory activity of IL-7/mAb complexes could be useful for treatment of immunodeficiency and cancer.     

FL3, a Synthetic Flavagline and Ligand of Prohibitins,Protects Cardiomyocytes via STAT3 from Doxorubicin Toxicity

Aims

The clinical use of doxorubicin for the treatment of cancer is limited by its cardiotoxicity. Flavaglines are natural products that have both potent anticancer and cardioprotective properties. A synthetic analog of flavaglines, FL3, efficiently protects mice from the cardiotoxicity of doxorubicin. The mechanism underlying this cardioprotective effect has yet to be elucidated.

Methods and Results

Here, we show that FL3 binds to the scaffold proteins prohibitins (PHBs) and thus promotes their translocation to mitochondria in the H9c2 cardiomyocytes. FL3 induces heterodimerization of PHB1 with STAT3, thereby ensuring cardioprotection from doxorubicin toxicity. This interaction is associated with phosphorylation of STAT3. A JAK2 inhibitor, WP1066, suppresses both the phosphorylation of STAT3 and the protective effect of FL3 in cardiomyocytes. The involvement of PHBs in the FL3-mediated cardioprotection was confirmed by means of small interfering RNAs (siRNAs) targeting PHB1 and PHB2. The siRNA knockdown of PHBs inhibits both phosphorylation of STAT3 and the cardioprotective effect of FL3.

Conclusion

Activation of mitochondrial STAT3/PHB1 complex by PHB ligands may be a new strategy against doxorubicin-induced cardiotoxicity and possibly other cardiac problems.     

The effect of melatonin on glycoprotein levels and oxidative liver injury in experimental diabetes

In this present study, the duration of melatonin (Mel) administered to diabetic rats was prolonged so as to examine its effects on the biochemical liver parameters of diabetic rats. In the experiment, Male Sprague Dawley rats were divided randomly into five groups; the control, diabetic + Mel, diabetic, diabetic + insulin, and diabetic + Mel + insulin. Diabetes mellitus was induced by administration of a single dose of streptozotocin (60 mg/kg) intraperitoneally and rats were given vehicle as a solvent for Mel every day for 12 weeks. In the diabetic + Mel group, diabetic rats were administered Mel (10 mg/kg/day) for 12 weeks to treat diabetes. The diabetic + insulin group were diabetic rats given insulin (6 U/kg) subcutaneously for 12 weeks. The diabetic + Mel + insulin rats received insulin and Mel at the same dose and time. At the end of the experiment, the animals were decapitated and liver tissues were taken. The protective effect of Mel on liver tissue of diabetic rats was investigated, total antioxidant status, total oxidant status, reactive oxygen species, oxidative stress index, adenosine deaminase, xanthine oxidase, paraoxonase 1, sodium/potassium ATPase, myeloperoxidase, γ-glutamyl transferase, sorbitol dehydrogenase, tumor necrosis factor-alpha, homocysteine, nitric oxide, glucose-6-phosphate dehydrogenase, and glycoprotein levels were determined in liver tissues. Treatment with Mel and/or insulin has been found to have a protective effect on biochemical parameters. The results showed that administration of Mel to diabetic rats prevented the distortion of the studied biochemical parameters of liver tissues.     

Fructans of the saline world

Saline and hypersaline environments make up the largest ecosystem on earth and the organisms living in such water-restricted environments have developed unique ways to cope with high salinity. As such these organisms not only carry significant industrial potential in a world where freshwater supplies are rapidly diminishing, but they also shed light upon the origins and extremes of life. One largely overlooked and potentially important feature of many salt-loving organisms is their ability to produce fructans, fructose polymers widely found in various mesophilic Eubacteria and plants, with potential functions as storage carbohydrates, aiding stress tolerance, and acting as virulence factors or signaling molecules. Intriguingly, within the whole archaeal domain of life, Archaea possessing putative fructan biosynthetic enzymes were found to belong to the extremely halophilic class of Halobacteria only, indicating a strong, yet unexplored link between the fructan syndrome and salinity. In fact, this link may indeed lead to novel strategies in fighting the global salinization problem. Hence this review explores the unknown world of fructanogenic salt-loving organisms, where water scarcity is the main stress factor for life. Within this scope, prokaryotes and plants of the saline world are discussed in detail, with special emphasis on their salt adaptation mechanisms, the potential roles of fructans and fructosyltransferase enzymes in adaptation and survival as well as future aspects for all fructanogenic salt-loving domains of life.     

Cytogenetic analysis of buccal cells from shoe-workers and pathology and anatomy laboratory workers exposed to n-hexane, toluene, methyl ethyl ketone and formaldehyde.

People employed in the shoe manufacture and repair industry are at an increased risk for cancer, the strongest evidence being for nasal cancer and leukaemia. A possible causal role for formaldehyde is likely for cancer of the buccal cavity and nasopharynx. Exfoliated buccal cells are good source of tissue for monitoring human exposure to inhaled and ingested occupational and environmental genotoxicants. To assess the cytogenetic damage related to occupational exposure to airborne chemicals during shoe-making and the processes in pathology and anatomy laboratories, the micronuclei (MN) count per 3000 cells was measured in buccal smears from shoe-workers (group I, n = 22) exposed to mainly n-hexane, toluene and methyl ethyl ketone (MEK) and from anatomy and pathology staff (group II, n = 28) exposed to formaldehyde (FA). Eighteen male university staff were used as controls. The mean time-weighted average (TWA) concentrations of n-hexane, toluene and MEK in 10 small shoe workshops were 58.07 p.p.m., 26.62 p.p.m. and 11.39 p.p.m., respectively. The measured air concentrations of FA in the breathing zone of the anatomy and pathology laboratory workers were between 2 and 4 p.p.m. Levels of 2,5-hexadione (2,5-HD) and hippuric acid (HA), metabolic markers of n-hexane and toluene exposure, respectively, were significantly higher in the urine of workers in group I than in control subjects (p < 0.001 and p < 0.01, respectively). The mean (+/- SD) MN (0/00) [corrected] frequencies in buccal mucosa cells from workers in group I, group II and controls were 0.62 +/- 0.45%, 0.71 +/- 0.56% and 0.33 +/- 0.30%, respectively (p < 0.05 and p < 0.05 compared with controls for group I and group II, respectively). The effects of smoking, age and duration of exposure on the frequency of micronucleated buccal cells from workers in all three groups studied were also evaluated. Overall, the results suggest that occupational exposure to organic solvents, mainly n-hexane, toluene, MEK and FA, may cause cytogenetic damage in buccal cells and that use of exfoliated buccal cells seems to be appropriate to measure exposure to organic solvents.