Effects of Different Geographical Aspects and Ontogenetic Variability on Total Hypericin Content of <i>Hypericum triquetrifolium</i> Turra. and <i>Hypericum scabrum</i> L.

The present study was conducted to determine the total hypericin contents of Hypericum triquetrifolium Turra. and Hypericum scabrum L. species which are naturally distributed in the flora of Siirt province, Turkey. Hypericin contents of Hypericum species grown in different geographical aspects (North, South, East, and West), and it was measured at different harvest times (full blooming and post blooming period). In the current study, it has been determined that total hypericin content varies considerably according to aspects, plant developmental stages (ontogenetic variance), and species. According to species x aspect interaction, the highest total hypericin content was recorded from the west aspect (3.13 mg/g) in Hypericum triquetrifolium, while, the lowest hypericin content was also obtained from the west aspect (1.22 mg/g) in Hypericum scabrum. When the highest total hypericin content was analyzed according to aspect x species x harvest time interaction, the highest total hypericin content was produced from Hypericum triquetrifolium at the harvest of west aspect with 5.28 mg/g, while the minimum amount of hypericin was obtained from the same aspect in Hypericum scabrum with 0.50 mg/g. In species x harvest time interaction, the highest total hypericin content was obtained from the full bloom (3.10 mg/g) harvest in Hypericum triquetrifolium, while the lowest hypericin was obtained from the full bloom (1.26 mg/g) harvest in Hypericum scabrum. The data suggest that the average total hypericin content was 2.26 mg/g in Hypericum triquetrifolium and 1.28 mg/g in Hypericum scabrum.     

Pollen counts and their relationship to meteorological factors in Ankara,Turkey during 2005–2008

Pollen plays an important role in the development and exacerbation of allergic diseases. We aimed to investigate the days with highest counts of the most allergenic pollens and to identify the meteorological factors affecting pollen counts in the atmosphere of Ankara, Turkey. Airborne pollen measurements were carried out from 2005 to 2008 with a Burkard volumetric 7-day spore trap. Microscope counts were converted into atmospheric concentrations and expressed as pollen grains/m³. Meteorological parameters were obtained from the State Meteorological Service. All statistical analyses were done with pollen counts obtained from March to October for each year. The percentages of tree, grass and weed pollens were 72.1% (n = 24,923), 12.8% (n = 4,433) and 15.1% (n = 5,219), respectively. The Pinaceae family from tree taxa (39% to 57%) and the Chenopodiaceae/Amaranthaceae family from weed taxa, contributed the highest percentage of pollen (25% to 43%), while from the grass taxa, only the Poaceae family was detected from 2005 to 2008. Poaceae and Chenopodiaceae/Amaranthaceae families, which are the most allergenic pollens, were found in high numbers from May to August in Ankara. In multiple logistic regression analysis, wind speed (OR = 1.18, CI95% = 1.02–1.36, P = 0.023) for tree pollen, daily mean temperature (OR = 1.10, CI95% = 1.04–1.17, P = 0.001) and sunshine hours (OR = 1.15, CI95% = 1.01–1.30, P = 0.033) for grass pollen, and sunshine hours (OR = 3.79, CI95% = 1.03–13.92, P = 0.044) for weed pollen were found as significant risk factors for high pollen count. The pollen calendar and its association with meteorological factors depend mainly on daily temperature, sunshine hours and wind speed, which may help draw the attention of physicians and allergic patients to days with high pollen counts.     

Axial stretch: A novel mechanism of the lower esophageal sphincter relaxation

Swallow and esophageal distension-induced relaxations of the lower esophageal sphincter (LES) are associated with an orad movement of the LES because of a concurrent esophageal longitudinal muscle contraction. We hypothesized that the esophageal longitudinal muscle contraction induces a cranially directed mechanical stretch on the LES and therefore studied the effects of a mechanical stretch on the LES pressure. In adult opossums, a silicon tube was placed via mouth into the esophagus and laparotomy was performed. Two needles with silk sutures were passed, 90 degrees apart, through the esophageal walls and silicon tube, 2 cm above the LES. The tube was withdrawn, and one end of each of the four sutures was anchored to the esophageal wall and the other end exited through the mouth to exert graded cranially directed stretch on the LES by using pulley and weights. A cranially directed stretch caused LES relaxation, and with the cessation of stretch there was recovery of the LES pressure. The degree an d duration of LES relaxation increased with the weight and the duration of stretch, respectively. The mean LES relaxation in all animals was 77.7 +/- 4.7%. The required weight to induce maximal LES relaxation differed in animals (714 +/- 348 g). N(G)-nitro-L-arginine, a nitric oxide inhibitor, blocked the axial stretch-induced LES relaxation almost completely (from 78 to 19%). Our data support the presence of an axial stretch-activated inhibitory mechanism in the LES. The role of axial stretch in the LES relaxation induced by swallow and esophageal distension requires further investigation.     

Dynamic and Thermodynamic Response of the Ras Protein Cdc42Hs upon Association with the Effector Domain of PAK3

Human cell division cycle protein 42 (Cdc42Hs) is a small, Rho-type guanosine triphosphatase involved in multiple cellular processes through its interactions with downstream effectors. The binding domain of one such effector, the actin cytoskeleton-regulating p21-activated kinase 3, is known as PBD46. Nitrogen-15 backbone and carbon-13 methyl NMR relaxation was measured to investigate the dynamical changes in activated GMPPCP·Cdc42Hs upon PBD46 binding. Changes in internal motion of the Cdc42Hs, as revealed by methyl axis order parameters, were observed not only near the Cdc42Hs–PBD46 interface but also in remote sites on the Cdc42Hs molecule. The binding-induced changes in side-chain dynamics propagate along the long axis of Cdc42Hs away from the site of PBD46 binding with sharp distance dependence. Overall, the binding of the PBD46 effector domain on the dynamics of methyl-bearing side chains of Cdc42Hs results in a modest rigidification, which is estimated to correspond to an unfavorable change in conformational entropy of approximately − 10 kcal mol^− 1 at 298 K. A cluster of methyl probes closest to the nucleotide-binding pocket of Cdc42Hs becomes more rigid upon binding of PBD46 and is proposed to slow the catalytic hydrolysis of the γ phosphate moiety. An additional cluster of methyl probes surrounding the guanine ring becomes more flexible on binding of PBD46, presumably facilitating nucleotide exchange mediated by a guanosine exchange factor. In addition, the Rho insert helix, which is located at a site remote from the PBD46 binding interface, shows a significant dynamic response to PBD46 binding.     

Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma

Tunneling nanotubes are long, non-adherent F-actin-based cytoplasmic extensions which connect proximal or distant cells and facilitate intercellular transfer. The identification of nanotubes has been limited to cell lines, and their role in cancer remains unclear. We detected tunneling nanotubes in mesothelioma cell lines and primary human mesothelioma cells. Using a low serum, hyperglycemic, acidic growth medium, we stimulated nanotube formation and bidirectional transfer of vesicles, proteins, and mitochondria between cells. Notably, nanotubes developed between malignant cells or between normal mesothelial cells, but not between malignant and normal cells. Immunofluorescent staining revealed their actin-based assembly and structure. Metformin and an mTor inhibitor, Everolimus, effectively suppressed nanotube formation. Confocal microscopy with 3-dimensional reconstructions of sectioned surgical specimens demonstrated for the first time the presence of nanotubes in human mesothelioma and lung adenocarcinoma tumor specimens. We provide the first evidence of tunneling nanotubes in human primary tumors and cancer cells and propose that these structures play an important role in cancer cell pathogenesis and invasion.     

Human immunodeficiency virus type 1 superinfection occurs despite relatively robust neutralizing antibody responses

Superinfection by a second human immunodeficiency virus type 1 (HIV-1) strain indicates that gaps in protective immunity occur during natural infection. To define the role of HIV-1-specific neutralizing antibodies (NAbs) in this setting, we examined NAb responses in 6 women who became superinfected between ~1 to 5 years following initial infection compared to 18 women with similar risk factors who did not. Although superinfected individuals had less NAb breadth than matched controls at ~1 year postinfection, no significant differences in the breadth or potency of NAb responses were observed just prior to the second infection. In fact, four of the six subjects had relatively broad and potent NAb responses prior to infection by the second strain. To more specifically examine the specificity of the NAbs against the superinfecting virus, these variants were cloned from five of the six individuals. The superinfecting variants did not appear to be inherently neutralization resistant, as measured against a pool of plasma from unrelated HIV-infected individuals. Moreover, the superinfected individuals were able to mount autologous NAb responses to these variants following reinfection. In addition, most superinfected individuals had NAbs that could neutralize their second viral strains prior to their reinfection, suggesting that the level of NAbs elicited during natural infection was not sufficient to block infection. These data indicate that preventing infection by vaccination will likely require broader and more potent NAb responses than those found in HIV-1-infected individuals.     

The use of wild edible plants in western and central Anatolia (Turkey)

In this study, 121 wild edible plants used as food in Anatolia were surveyed to determine the plant parts used and their detailed preparation methods. The results of this study show that the plants may be boiled, fried in fat, and eaten raw or as rolled vegetables. They may also be consumed as pickles, fruits, sweets and spices, and drunk as cold and hot drinks. Thirty species (8 genera) were identified as belonging to the Lamiaceae family, 15 species (15 genera) belong to the Asteraceae family, 13 species (5 genera) belong to the Rosaceae family, 8 species (7 genera) belong to the Brassicaceae family, 6 species (3 genera) belong to the Orchidaceae family and 5 species (5 genera) belong to the Apiaceae family. The genera represented by the highest number of species in the study are as follows:Sideritis L. is represented by 13 species, Origanum L. by 7 species,Rubus L. by 5 species,Thymus L. by 4 species andRumex L. by 4 species.     

Effects of ciprofloxacin on fetal rat liver during pregnancy and protective effects of quercetin

Urinary tract infections are common in pregnant women and ciprofloxacin frequently is used as a broad spectrum antibiotic. It has been suggested that ciprofloxacin causes liver damage in fetuses. Quercetin is a flavonoid with antioxidant properties. We investigated the efficacy of quercetin treatment for preventing fetal liver damage caused by ciprofloxacin. Pregnant rats were divided into four groups: untreated control group (C), 20 mg/kg quercetin for 21 days group (Q), 20 mg/kg twice/day ciprofloxacin for 10 days group (CP), and 20 mg/kg, ciprofloxacin + quercetin for 21 days group (CP + Q). Fetal livers were removed on day 21 of gestation to measure antioxidants and for histological observation. Malondialdehyde (MDA) and glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in tissue samples. GSH-Px, SOD and CAT activities were significantly lower in the CP group compared to group C. A significant increase in MDA was observed in the CP group compared to group C. There was no significant difference in GSH levels in any group. MDA levels were lower and CAT, SOD and GSH-Px enzyme activities were higher in the CP + Q group compared to group CP. Liver samples of the CP group exhibited central vein dilation, portal vein congestion, pyknotic nuclei and cytoplasmic vacuolization in some hepatocytes. Histological changes were less prominent in the rats treated with quercetin. Use of ciprofloxacin during pregnancy caused oxidative damage in fetal liver tissue. Oxidative stress was ameliorated by quercetin. Quercetin supports the antioxidant defense mechanism and it is beneficial for treating fetal liver damage caused by ciprofloxacin.