sFas levels increase in response to cisplatin-based chemotherapy in lung cancer patients

The Fas/Fas Ligand (FasL) system and survivin have counteracting roles in cell survival. Therefore, we explored the role of circulating soluble Fas (sFas) and the tissue levels of Fas and survivin with regard to response to chemotherapy in lung cancer patients. Serum samples from 52 lung cancer patients and 54 control subjects (19 benign lung disease and 35 healthy control subjects) were collected prior to and 24 and 48 h after chemotherapy. sFas was statistically significantly higher in the cancer group than that in the control groups (p < 0.001). Baseline (before chemotherapy) sFas values showed a statistically significant inverse correlation with overall survival (r = ?0.599, p < 0.001). There was a significant increase in serum sFas levels 24 h after treatment (p < 0.05). Contrarily, tissue levels of Fas and survivin were not changed following the chemotherapy (p > 0,05). In conclusion, increased sFas may be an indicator of poor outcome in lung cancer patients. However, cisplatin‐based chemotherapy may not be effective via neither the Fas/FasL system nor survivin pathway. Indeed, larger sample size is required for further evaluation. Copyright © 2010 John Wiley & Sons, Ltd.     

CD16 promotes Escherichia coli sepsis through an FcR gamma inhibitory pathway that prevents phagocytosis and facilitates inflammation

Sepsis, a leading cause of death worldwide, involves proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here we show that the FcRgamma adaptor, an immunoreceptor tyrosine-based activation motif (ITAM)-bearing signal transduction subunit of the Fc receptor family, has a deleterious effect on sepsis. FcRgamma(-/-) mice show increased survival during peritonitis, owing to markedly increased E. coli phagocytosis and killing and to lower production of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. The FcRgamma-associated receptor that inhibits E. coli phagocytosis is FcgammaRIII (also called CD16), and its absence protects mice from sepsis. FcgammaRIII binds E. coli, and this interaction induces FcRgamma phosphorylation, recruitment of the tyrosine phosphatase SHP-1 and phosphatidylinositide-3 kinase (PI3K) dephosphorylation. Decreased PI3K activity inhibits E. coli phagocytosis and increases TNF-alpha production through Toll-like receptor 4. We identified the phagocytic receptor negatively regulated by FcRgamma on macrophages as the class A scavenger receptor MARCO. E. coli-FcgammaRIII interaction induces the recruitment of SHP-1 to MARCO, thereby inhibiting E. coli phagocytosis. Thus, by binding FcgammaRIII, E. coli triggers an inhibitory FcRgamma pathway that both impairs MARCO-mediated bacterial clearance and activates TNF-alpha secretion.     

Rheological Behaviour of Instant Hot Chocolate Beverage: Part 1. Optimization of the Effect of Different Starches and Gums

In this study, effects of different starches (tapioca (TS), wheat (WS), corn (CS), potato (PS), modified corn (MCS) and modified potato (MPS)) and gums (xanthan gum (XG), guar gum (GG), alginate (A), salep (S), locust bean gum (LBG) and carrageen (C)) on the rheological properties of model hot chocolate beverage were studied. Swelling power (SP) of the starches and water absorption capacity (WAC) of the gums were determined. Hot chocolate beverages showed pseudoplastic behaviour. Ostwald de Waele model accurately described flow behaviour of each beverage sample. K, n, R ² values for Ostwald model were in the range of 4.8–160.3 mPa.sⁿ, 0.5117–0.9745, 0.9972–0.9998, respectively. The highest synergic effect in the model was observed between the interaction of MCS and XG. The XG-PS, XG-TS, XG-CS combinations showed the highest K and viscosity values, respectively.     

The Saccharomyces cerevisiae W303-K6001 cross-platform genome sequence: insights into ancestry and physiology of a laboratory mutt

Saccharomyces cerevisiae strain W303 is a widely used model organism. However, little is known about its genetic origins, as it was created in the 1970s from crossing yeast strains of uncertain genealogy. To obtain insights into its ancestry and physiology, we sequenced the genome of its variant W303-K6001, a yeast model of ageing research. The combination of two next-generation sequencing (NGS) technologies (Illumina and Roche/454 sequencing) yielded an 11.8 Mb genome assembly at an N50 contig length of 262 kb. Although sequencing was substantially more precise and sensitive than whole-genome tiling arrays, both NGS platforms produced a number of false positives. At a 378× average coverage, only 74 per cent of called differences to the S288c reference genome were confirmed by both techniques. The consensus W303-K6001 genome differs in 8133 positions from S288c, predicting altered amino acid sequence in 799 proteins, including factors of ageing and stress resistance. The W303-K6001 (85.4%) genome is virtually identical (less than equal to 0.5 variations per kb) to S288c, and thus originates in the same ancestor. Non-S288c regions distribute unequally over the genome, with chromosome XVI the most (99.6%) and chromosome XI the least (54.5%) S288c-like. Several of these clusters are shared with Σ1278B, another widely used S288c-related model, indicating that these strains share a second ancestor. Thus, the W303-K6001 genome pictures details of complex genetic relationships between the model strains that date back to the early days of experimental yeast genetics. Moreover, this study underlines the necessity of combining multiple NGS and genome-assembling techniques for achieving accurate variant calling in genomic studies.     

Acute inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alfa-2a in a patient with chronic hepatitis C virus infection: a case report

ABSTRACT: INTRODUCTION: The combination of polyethylene glycol (PEG)ylated interferon (pegylated interferon) and ribavirin has been shown to be an effective treatment for chronic hepatitis C virus. In general, common side effects related to this combination therapy are mild and are well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to PEG-interferon alpha2a (pegylated interferon alfa-2a) is extremely rare. In the literature, only one case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon alpha2a has been published previously. CASE PRESENTATION: To the best of our knowledge we present only the second case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon alpha2a, occurring in a 63-year-old Caucasian man. He developed tingling, numbness, and weakness of his upper and lower extremities with acute neurological deficits after five weeks of a combination therapy with PEG-interferon alpha2a and ribavirin for chronic hepatitis C virus infection. His clinical course, neurological findings, and his electromyogram results were all consistent with acute inflammatory demyelinating polyneuropathy. Our patient recovered completely after interferon was stopped and symptomatic treatment and a further electromyogram showed a disappearance of neuropathy. Four weeks later, PEG-interferon alpha2a was reintroduced with a gradually increasing dose without any reappearance of neurological symptoms allowing hepatitis C seroconversion. CONCLUSIONS: Recognition of this rare yet possible presentation is important for early and accurate diagnosis and treatment. This case report also suggests that the reintroduction of PEGylated interferon in patients who had presented with acute inflammatory demyelinating polyneuropathy related to interferon alpha may be safe, but this must be confirmed by further studies.     

Topotecan Treatment and Its Toxic Effects on Hematologic Parameters and Trace Elements

The aim of this study was to investigate the effects of topotecan, a topoisomerase I-inhibiting anticancer agent, on hematologic parameters and serum levels of trace elements. The study was conducted on three groups consisting of 16 and 18 rabbits in the study groups and 15 rabbits in the control group. Rabbits in group I (n = 16) received high-dose topotecan intravenously (i.v.; 0.5 mg/kg once daily), while rabbits in group II (n = 18) received low-dose topotecan i.v. (0.25 mg/kg once daily) for 3 days. The 15 rabbits comprising the control group did not receive topotecan. Serum samples were collected from each rabbit on the first day, before the treatment, and on the 15th day of treatment. Erithrocytes, hemoglobin, white blood cell count, thrombocyte count, and trace elements such as selenium, copper, lead, zinc, and cobalt were analyzed. Hemoglobin levels and erythrocyte counts were lower in both study groups than in the control group. However, thrombocyte and leukocyte counts were similar in all three groups (p > 0.005). Serum trace element levels (copper, lead, zinc, and cobalt) did not differ significantly between groups. However, serum selenium levels were significantly lower in both study groups than the control group (p < 0.001). The results revealed that topotecan treatment causes a decrease in erythrocyte counts and hemoglobin levels due to bone marrow suppression, and these effects must be taken into account during treatment. In addition, selenium supplementation might be helpful in cancer patients receiving topotecan to increase the effect of the chemotherapeutic agent.     

Anatomy, palynology and nutlet micromorphology of Turkish endemic Teucrium sandrasicum (Lamiaceae)

In this study, the anatomical features of the leaf and stem, besides the pollen and nutlet characteristics of Teucrium sandrasicum are investigated. T. sandrasicum, belonging to sect. Teucrium, is an endemic perennial herb growing on serpentine around Muğla province. The anatomical studies on T. sandrasicum revealed that the stem shares the general characteristics of the Labiatae family. The leaves clearly exhibit xeromorphy due to features such as the distribution of stomata on the lower surface (hipostomatic), the occurrence of guard cells below the epidermis (xeromorphic type), inrolled margins, thick cuticle layer, thick outer epidermal cell wall, a high density of trichomes and thick palisade layer of the mesophyll. The anatomical studies showed that the upper epidermal cells of the leaf include many spherocrystals. The pollen grains are prolate, medium in size, 3-colpate with verrucate ornamentation. The nutlets are ellipsoid with a reticulate-verrucate surface. The results have proven that T. sandrasicum is different from the other species of the sect. Teucrium because of the branched trichomes on the stem and the lack of eglandular trichomes on the nutlets.     

Magnetic Alignment in Carps: Evidence from the Czech Christmas Fish Market

While magnetoreception in birds has been studied intensively, the literature on magnetoreception in bony fish, and particularly in non-migratory fish, is quite scarce. We examined alignment of common carps (Cyprinus carpio) at traditional Christmas sale in the Czech Republic. The sample comprised measurements of the directional bearings in 14,537 individual fish, distributed among 80 large circular plastic tubs, at 25 localities in the Czech Republic, during 817 sampling sessions, on seven subsequent days in December 2011. We found that carps displayed a statistically highly significant spontaneous preference to align their bodies along the North-South axis. In the absence of any other common orientation cues which could explain this directional preference, we attribute the alignment of the fish to the geomagnetic field lines. It is apparent that the display of magnetic alignment is a simple experimental paradigm of great heuristic potential.