Fluorination of BC3 nanotubes: DFT studies

We have studied the adsorption of atomic and molecular fluorines on a BC₃ nanotube by using density functional calculations. It was found that the adsorption of atomic fluorine on a C atom of the tube surface is energetically more favorable than that on a B atom by about 0.97 eV. The adsorption of atomic fluorine on both C and B atoms significantly affects the electronic properties of the BC₃ tube. The HOMO-LUMO energy gap is considerably reduced from 2.37 to 1.50 and 1.14 eV upon atomic F adsorption on B and C atoms, respectively. Molecular fluorine energetically tends to be dissociated on B atoms of the tube surface. The associative and dissociative adsorption energies of F₂ were calculated to be about ?0.42 and ?4.79 eV, respectively. Electron emission density from BC₃ nanotube surface will be increased upon both atomic and molecular fluorine adsorptions due to work function decrement.     

Does Dietary vitamin E or C Decrease Egg Yolk Cholesterol?

An experiment was conducted to determine the effect of dietary vitamin E and C on serum metabolites, yolk cholesterol, egg quality, and performance of layer hens. One hundred sixty-eight commercial Hy-Line W-36 layer hens were randomly divided into seven groups and six replicates with four hens in each. Dietary treatments were introduced after the pre-experimental period (10 days) to adjust egg production. Treatments were levels of vitamin E or C (100, 200, and 400 mg/kg diet) supplementation to the basal diet for 4 weeks, whereas the control group received no supplementation. Egg production, egg weight, and feed consumption were recorded during the study. Shell thickness, Haugh unit score, yolk color, yolk weight, yolk cholesterol, and blood parameters were measured at the end of experiment. There was no significant effect of dietary vitamin E or C on hen performance. Egg yolk cholesterol concentrations decreased linearly by antioxidant vitamin supplementation (P?<?0.01). Egg yolk cholesterol reduction did not have any negative effect on egg production rate. Antioxidants, especially vitamin C, increased serum glucose concentration (P?<?0.05). Serum total cholesterol content did not change by vitamin supplementation but cholesterol in high-density lipoprotein (HDL-C) decreased and cholesterol in low-density lipoprotein (LDL-C) increased (P?<?0.05), as dietary vitamin E or C supplementation increased in diets. These results are in conflict with the previous hypothesis that antioxidants have a role in LDL-C removal from the blood or increasing HDL-C. Vitamin E was more effective than vitamin C in this case and if these results are confirmed by further studies, they may result to revision in researchers’ point of view about antioxidant especially in human medicine.     

Critical negative regulation of type 1 T cell immunity and immunopathology by signaling adaptor DAP12 during intracellular infection

Transmembrane signaling adaptor DAP12 has increasingly been recognized for its important role in innate responses. However, its role in the regulation of antimicrobial T cell responses has remained unknown. In our current study, we have examined host defense, T cell responses, and tissue immunopathology in models of intracellular infection established in wild-type and DAP12-deficient mice. During mycobacterial infection, lack of DAP12 leads to pronounced proinflammatory and Th1 cytokine responses, overactivation of Ag-specific CD4 and CD8 T cells of type 1 phenotype, and heightened immunopathology both in the lung and lymphoid organs. DAP12-deficient airway APC display enhanced NF-kappaB activation and cytokine responses upon TLR stimulation or mycobacterial infection in vitro. Of importance, adoptive transfer of Ag-loaded DAP12-deficient APC alone could lead to overactivation of transferred transgenic or endogenous wild-type T cells in vivo. We have further found that the immune regulatory role by DAP12 is not restricted only to intracellular bacterial infection, since lack of this molecule also leads to uncontrolled type 1 T cell activation and severe immunopathology and tissue injury during intracellular viral infection. Our study thus identifies DAP12 as an important novel immune regulatory molecule that acts, via APC, to control the level of antimicrobial type 1 T cell activation and immunopathology.     

Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter

Versican, one of the key components of prostatic stroma, plays a central role in tumor initiation and progression. Here, we investigated promoter elements and mechanisms of androgen receptor (AR)-mediated regulation of the versican gene in prostate cancer cells. Using transient transfection assays in prostate cancer LNCaP and cervical cancer HeLa cells engineered to express the AR, we demonstrate that the synthetic androgen R1881 and dihydrotestosterone stimulate expression of a versican promoter-driven luciferase reporter vector (versican-Luc). Further, both basal and androgen-stimulated versican-Luc activities were significantly diminished in LNCaP cells, when AR gene expression was knocked down using a short hairpin RNA. Methylation-protection footprinting analysis revealed an AR-protected element between positions +75 and +102 of the proximal versican promoter, which strongly resembled a consensus steroid receptor element. Electrophoretic mobility shift and supershift assays revealed strong and specific binding of the recombinant AR DNA binding domain to oligonucleotides corresponding to this protected DNA sequence. Site-directed mutagenesis of the steroid receptor element site markedly diminished R1881-stimulated versican-Luc activity. In contrast to the response seen using LNCaP cells, R1881 did not significantly induce versican promoter activity and mRNA levels in AR-positive prostate stromal fibroblasts. Interestingly, overexpression of beta-catenin in the presence of androgen augmented versican promoter activity 10- and 30-fold and enhanced versican mRNA levels 2.8-fold in fibroblasts. In conclusion, we demonstrate that AR transactivates versican expression, which may augment tumor-stromal interactions and may contribute to prostate cancer progression.     

Tenascin-C as a noninvasive biomarker of coronary artery disease

Molecular Biology Reports - Coronary artery disease (CAD), is the leading cause of mortality and morbidity worldwide. Tenascin-C (TNC) with high expression levels in inflammatory and cardiovascular...     

Afghanistan's ethnic groups share a Y-chromosomal heritage structured by historical events

Afghanistan has held a strategic position throughout history. It has been inhabited since the Paleolithic and later became a crossroad for expanding civilizations and empires. Afghanistan's location, history, and diverse ethnic groups present a unique opportunity to explore how nations and ethnic groups emerged, and how major cultural evolutions and technological developments in human history have influenced modern population structures. In this study we have analyzed, for the first time, the four major ethnic groups in present-day Afghanistan: Hazara, Pashtun, Tajik, and Uzbek, using 52 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y-chromosome. A total of 204 Afghan samples were investigated along with more than 8,500 samples from surrounding populations important to Afghanistan's history through migrations and conquests, including Iranians, Greeks, Indians, Middle Easterners, East Europeans, and East Asians. Our results suggest that all current Afghans largely share a heritage derived from a common unstructured ancestral population that could have emerged during the Neolithic revolution and the formation of the first farming communities. Our results also indicate that inter-Afghan differentiation started during the Bronze Age, probably driven by the formation of the first civilizations in the region. Later migrations and invasions into the region have been assimilated differentially among the ethnic groups, increasing inter-population genetic differences, and giving the Afghans a unique genetic diversity in Central Asia.     

Airway delivery of soluble mycobacterial antigens restores protective mucosal immunity by single intramuscular plasmid DNA tuberculosis vaccination: role of proinflammatory signals in the lung

Protection by parenteral immunization with plasmid DNA vaccines against pulmonary tuberculosis (TB) is very modest. In this study, we have investigated the underlying mechanisms for the poor mucosal protective efficacy and the avenues and mechanisms to improve the efficacy of a single i.m. immunization with a monogenic plasmid DNA TB vaccine in a murine model. We show that i.m. DNA immunization fails to elicit accumulation of Ag-specific T cells in the airway lumen despite robust T cell responses in the spleen. Such systemically activated T cells cannot be rapidly mobilized into the airway lumen upon Mycobacterium tuberculosis exposure. However, airway deposition of low doses of soluble mycobacterial Ags in previously immunized mice effectively mobilizes the systemically activated T cells into the airway lumen. A fraction of such airway luminal T cells can persist in the airway lumen, undergo quick, robust expansion and activation and provide marked immune protection upon airway M. tuberculosis exposure. Airway mucosal deposition of soluble mycobacterial Ags was found to create a tissue microenvironment rich in proinflammatory molecules including chemokines and hence conducive to T cell recruitment. Thus, in vivo neutralization of MIP-1alpha or IFN-inducible protein-10 markedly inhibited the accumulation of Ag-specific T cells in the airway lumen. Our data suggest that immunoprotective efficacy on the mucosal surface by i.m. plasmid DNA immunization could be substantially improved by simple mucosal soluble Ag inoculation and restoration of mucosal luminal T cells. Our study holds implication for the future design of DNA vaccination strategies against intracellular infections.