Nitric oxide modulates glutathione synthesis during endotoxemia

Nitric oxide is known to modulate intracellular glutathione levels, but the relationship between nitric oxide synthesis and glutathione metabolism during endotoxemia is unknown. The present study was designed to examine the effects of increased nitric oxide formation on hepatic glutathione synthesis and antioxidant defense in endotoxemic mice. Our results demonstrate that hepatic glutathione synthesis is decreased for 24 h following injection of lipopolysaccharide (LPS). Administration of the cysteine precursor, L-2-oxothiazolidine-4-carboxylic acid (OTZ), failed to normalize hepatic glutathione concentration, and suggests that decreased γ-glutamylcysteine ligase activity is primarily responsible for the decrease in hepatic glutathione levels during endotoxemia. Inhibition of nitric oxide synthesis prevented the endotoxin-induced changes in hepatic and plasma glutathione status and up-regulated liver glutathione and cysteine synthesis pathways at the level of gene expression. Furthermore, whereas the activity of glutathione peroxidase and glutathione S-transferase decreased during endotoxemia, both of these changes were prevented by inhibition of nitric oxide synthesis. In conclusion, increased nitric oxide synthesis during endotoxemia causes marked changes in glutathione flux and defenses against oxidative stress in the liver.     

Bi-directional PCR allele-specific amplification (bi-PASA) for detection of caspase-8 -652 6N ins/del promoter polymorphism (rs3834129) in breast cancer

Caspase-8 (CASP8) plays a critical role in regulating apoptosis, and its functional polymorphisms may modify cancer risk. We investigated the possible association between CASP8 -652 6N ins/del (rs3834129) and the risk of breast cancer in a sample of Iranian population. This case-control study was done on 236 breast cancer patients and 203 cancer free healthy female. We designed a rapid and simple bi-directional PCR allele-specific amplification (bi-PASA) for detection of CASP8 -652 6N ins/del polymorphism. The results showed that the CASP8 -652 6N del/dl genotype was inversely associated with breast cancer risk (OR=0.33, 95% CI=0.17-0.65, p=0.001). The frequencies of the del allele in cases and controls were 29.1% and 38.6%, respectively. An inverse association between CASP8 6N del variant and the risk of breast cancer (OR=0.66, 95% CI=0.66-0.87, p=0.002) was found. In conclusion, the result suggests that the CASP8 -652 6N del polymorphism plays a protective role in susceptibility to breast cancer in our population. Further studies in other populations with larger samples are needed to confirm these findings.     

Science of breeding and heredity from ancient Persia to modern Iran

About 1700 years BC, the prophet Zoroaster declared equal right for women and men to choose their "own ways." There is much evidence that ancient Persians believed in the equal contribution of women and men toward producing a child, and all its hereditary characteristics.Even more surprising are the phrases in Vandidad book, which were gathered by Mobedans in the Mad dynasty about egg extraction (gametes) from animal reproductive organs (gonads) and their storage for future conception.Centuries later, Western philosopher beliefs in regard to reproduction were contrary to Persian knowledge. The Greek philosophers believed that man's water (semen) contains all human characteristics, and the female uterus is only responsible for nurturing and development of fetus. After detection of the ovum (de Graaf 2(nd) half 17 century) Malpigy proposed the preformation theory (ovist) which means there is a miniature human inside ovum, that grows after Semen has entered the uterus and grow into a well-developed fetus. This hypothesis was later delegated to spermatozoa. These contradictory and inappropriate beliefs were subject to discussions and dispute, until C.E. Wolf demonstrated that the embryo is a product of the fertilization of ovum by spermatozoa.800 years prior this the sage Ferdowsi "The Great Iranian Poet" explains nicely the equal participation of man and woman in the production of the fetus and transmission of characters.After the renaissance and especially in recent years, tremendous achievements have been made in unraveling biological secrets of reproduction. There was no work o n genetics in Iran until 1936, when a genetic course was added to the biology curriculum in related colleges and universities; Iranian Genetics Society was founded in 1966, initiating a steady movement in this field.Although there was an inevitable gap during the revolution and war in our country, now there is great effort by researchers to eliminate the gap and bring us into the mainstream of world science, and development in biomedical sciences in the third millennium.     

Environmental Impact Assessment of the Heterogeneity in Consumers’ Usage Behavior: An Agent‐Based Modeling Approach

The aim of this study is to develop a framework for understanding the heterogeneity and uncertainties present in the usage phase of the product life cycle through utilizing the capabilities of an agent‐based modeling (ABM) technique. An ABM framework is presented to model consumers’ daily product usage decisions and to assess the corresponding electricity consumption patterns. The theory of planned behavior (TPB), with the addition of the habit construct, is used to model agents’ decision‐making criteria. A case study is presented on the power management behavior of personal computer users and the possible benefits of using smart metering and feedback systems. The results of the simulation demonstrate that the utilization of smart metering and feedback systems can promote the energy conservation behaviors and reduce the total PC electricity consumption of households by 20%.     

Identification and characterization of an archaeon-specific riboflavin kinase

The riboflavin kinase in Methanocaldococcus jannaschii has been identified as the product of the MJ0056 gene. Recombinant expression of the MJ0056 gene in Escherichia coli led to a large increase in the amount of flavin mononucleotide (FMN) in the E. coli cell extract. The unexpected features of the purified recombinant enzyme were its use of CTP as the phosphoryl donor and the absence of a requirement for added metal ion to catalyze the formation of FMN. Identification of this riboflavin kinase fills another gap in the archaeal flavin biosynthetic pathway. Some divalent metals were found to be potent inhibitors of the reaction. The enzyme represents a unique CTP-dependent family of kinases.     

Cryopreservation of Cortical Tissue Blocks for the Generation of Highly Enriched Neuronal Cultures

In this study, we outline a standardized protocol for the successful cryopreservation and thawing of cortical brain tissue blocks to generate highly enriched neuronal cultures. For this protocol the freezing medium used is 10% dimethyl sulfoxide (DMSO) diluted in Hank''s Buffered Salt Solution (HBSS). Blocks of cortical tissue are transferred to cryovials containing the freezing medium and slowly frozen at -1°C/min in a rate-controlled freezing container. Post-thaw processing and dissociation of frozen tissue blocks consistently produced neuronal-enriched cultures which exhibited rapid neuritic growth during the first 5 days in culture and significant expansion of the neuronal network within 10 days. Immunocytochemical staining with the astrocytic marker glial fibrillary acidic protein (GFAP) and the neuronal marker beta-tubulin class III, revealed high numbers of neurons and astrocytes in the cultures. Generation of neural precursor cell cultures after tissue block dissociation resulted in rapidly expanding neurospheres, which produced large numbers of neurons and astrocytes under differentiating conditions. This simple cryopreservation protocol allows for the rapid, efficient, and inexpensive preservation of cortical brain tissue blocks, which grants increased flexibility for later generation of neuronal, astrocyte, and neuronal precursor cell cultures.     

Induced in vitro differentiation of neural-like cells from human exfoliated deciduous teeth-derived stem cells

Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic and multipotent stem cells with a neural crest cell origin. Additionally, they can be collected with minimal invasiveness in comparison with other sources of mesenchymal stem cells (MSCs). Therefore, SHED could be a desirable option for potential therapeutic applications. In this study, SHEDs were established from enzyme-disaggregated deciduous dental pulp obtained from 6 to 9 year-old children. The cells had typical fibroblastoid morphology and expressed antigens characteristic of MSCs, STRO1, CD146, CD45, CD90, CD106 and CD166, but not the hematopoietic and endothelial markers, CD34 and CD31, as assessed by FACS analysis. Differentiation assessment revealed a strong osteogenic and adipogenic potential of SHEDs. In order to further evaluate the in vitro differentiation potential of SHED into neural cells, a simple short time growth factor-mediated induction was used. Immunofluorescence staining and flow cytometric analysis revealed that SHED rapidly expressed nestin and b-III tubulin, and later expressed intermediate neural markers. In addition, the intensity and percentages of nestin and b-III tubulin and mature neural markers (PSA-NCAM, NeuN, Tau, TH, or GFAP) increased significantly following treatment. Moreover, RT-PCR and Western blot analyses showed that the neural markers were strongly up-regulated after induction. In conclusion, these results provide evidence that SHED can differentiate into neural cells by the expression of a comprehensive set of genes and proteins that define neural-like cells in vitro. SHED cells might be considered as new candidates for the autologous transplantation of a wide variety of neurological diseases and neurotraumatic injuries.