Inhibitory ITAM signaling by Fc alpha RI-FcR gamma chain controls multiple activating responses and prevents renal inflammation

Inhibitory signaling is an emerging function of ITAM-bearing immunoreceptors in the maintenance of homeostasis. Monovalent targeting of the IgA Fc receptor (FcalphaRI or CD89) by anti-FcalphaRI Fab triggers potent inhibitory ITAM (ITAM(i)) signaling through the associated FcRgamma chain (FcalphaRI-FcRgamma ITAM(i)) that prevents IgG phagocytosis and IgE-mediated asthma. It is not known whether FcalphaRI-FcRgamma ITAM(i) signaling controls receptors that do not function through an ITAM and whether this inhibition requires Src homology protein 1 phosphatase. We show in this study that FcalphaRI-Fcgamma ITAM(i) signals depend on Src homology protein 1 phosphatase to target multiple non-ITAM-bearing receptors such as chemotactic receptors, cytokine receptors, and TLRs. We found that anti-FcalphaRI Fab treatment in vivo reduced kidney inflammation in models of immune-mediated glomerulonephritis and nonimmune obstructive nephropathy by a mechanism that involved decreased inflammatory cell infiltration and fibrosis development. This treatment also prevented ex vivo LPS activation of monocytes from patients with lupus nephritis or vasculitis, as well as receptor activation through serum IgA complexes from IgA nephropathy patients. These findings point to a crucial role of FcalphaRI-FcRgamma ITAM(i) signaling in the control of multiple heterologous or autologous inflammatory responses. They also identify anti-FcalphaRI Fab as a new potential therapeutic tool for preventing progression of renal inflammatory diseases.     

The effects of magnesium, calcium and EDTA on slime production byStaphylococcus epidermidis strains

Effect of magnesium, calcium and EDTA on slime production by 15 slime-positive and 13 slime-negative Staphylococcus epidermidis strains isolated from various clinical specimens was determined. The slime production on tryptic soy broth was significantly enhanced after addition of 128 mumol/L Mg2+. Similarly, the addition of Ca2+ caused a significant increase in slime production of all tested strains when concentration of Ca2+ exceeded 64 mumol/L. In contrast, in the presence of EDTA the slime production by all strains was significantly reduced. Hence Ca2+ and Mg2+ increase slime production of S. epidermidis. This finding is important in the context of the pathogenesis of biomedical implant infections caused by S. epidermidis.     

Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis

There are two isoforms of sphingosine kinase (SphK) that catalyze the formation of sphingosine 1-phosphate, a potent sphingolipid mediator. Whereas SphK1 stimulates growth and survival, here we show that SphK2 enhanced apoptosis in diverse cell types and also suppressed cellular proliferation. Apoptosis was preceded by cytochrome c release and activation of caspase-3. SphK2-induced apoptosis was independent of activation of sphingosine 1-phosphate receptors. Sequence analysis revealed that SphK2 contains a 9-amino acid motif similar to that present in BH3-only proteins, a pro-apoptotic subgroup of the Bcl-2 family. As with other BH3-only proteins, co-immunoprecipitation demonstrated that SphK2 interacted with Bcl-xL. Moreover, site-directed mutation of Leu-219, the conserved leucine residue present in all BH3 domains, markedly suppressed SphK2-induced apoptosis. Hence, the apoptotic effect of SphK2 might be because of its putative BH3 domain.     

Melatonin prevents formaldehyde-induced neurotoxicity in prefrontal cortex of rats: an immunohistochemical and biochemical study

This study was undertaken to investigate the protective effects of melatonin against formaldehyde-induced neurotoxicity in prefrontal cortex of rats. For this purpose, 21 male Wistar rats were divided into three groups. The rats in Group I were used as a control, while the rats in Group II were injected every other day with formaldehyde. The rats in Group III received melatonin daily while exposed to formaldehyde. At the end of 14-day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for immunohistochemical evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels, were significantly increased in rats treated with formaldehyde compared with those of the controls. In the immunohistochemical evaluation of this group, apoptotic cells were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels, were detected in the rats administered melatonin while exposed to formaldehyde. Furthermore, apoptotic changes caused by formaldehyde were decreased in these rats. The results of our study suggest that melatonin treatment prevents formaldehyde-induced neuronal damage in prefrontal cortex.     

Comparison of fatty acids and some mineral matter profiles of wild and farmed snails,Cornu aspersum Müller, 1774

ABSTRACT

The fatty acid and mineral matter compositions of the visceral mass and pedal mass of wild and farmed Cornu aspersum were compared. The relative fatty acid amounts of the visceral and pedal masses of wild and farmed snails are: polyunsaturated fatty acid (PUFA) > saturated fatty acid (SFA) > monounsaturated fatty acid (MUFA), PUFA?>?SFA?>?MUFA, MUFA?>?PUFA?>?SFA and PUFA?>?MUFA?>?SFA, respectively. Wild snails had a higher concentration of iron and zinc than farmed snails. Selenium was 2.82 times higher in the pedal mass of farmed snails than the pedal mass of wild snails. Ca:P ratios in the visceral mass of wild snails, visceral mass and pedal mass of farmed snails were 1.76:1, 1.12:1 and 3.87:1 respectively. Both wild and farmed snails have high contents of oleic, linoleic, eicosapentaenoic and docosahexaenoic fatty acids and are a good source of minerals. Careful attention should be paid, however, as to which diet will be used during farming because the composition of fatty acid in the snail is affected by diet.     

GPCRs and EGFR – Cross-talk of membrane receptors in cancer

G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) are two important classes of cell surface receptors proven to be highly tractable as drug targets. Both receptor classes are involved in various complex (patho-) physiological processes in the human body including cellular growth and differentiation. More recently, accumulating data suggest that GPCR-induced activation of EGFR, the prototyp of RTKs represents a major mechanism in various cancers. The present review will focus on this cross-talk with particular emphasis on intracellular scaffold proteins regulating EGFR transactivation. It will give an overview about the current status of the research and future directions, highlight recent trends in the field, and discuss the potential of therapeutic strategies combining GPCR and EGFR targeting on the one hand and specific targeting of the cross-talk on the other hand in cancer therapy.     

Absence of typical diel vertical migration in Daphnia: varying role of water clarity, food, and dissolved oxygen in Lake Eymir, Turkey

Diel vertical migration (DVM) is a complex and dynamic behaviour against predation because the reaction of migrating organisms to light intensity plays a primary role, but is modified by other factors. In the relatively shallow but thermally stratified Lake Eymir, Daphnia pulex de Geers utilized vertical refugia afforded by the hypolimnion during both day and night. Differences in general vulnerability to fish predation determined the differences in their mean residence depths (MRDs) of different population categories such as most conspicuous and vulnerable individuals of adult with eggs inhabited the deepest depth, whereas juveniles stayed close the thermocline. In late spring, profoundly high amplitude of displacement within the hypolimnion, probably due to the hypolimnion being well-lit and relatively well-oxygenated for the fish and rather unsafe for the large-sized daphnids, was recorded. Therefore, the large-sized daphnids daytime refuge was close to the bottom whereas at night they moved upward to benefit from warmer water temperature along with food availability in the presence of fish predation but still remained below the thermocline. In summer, the insignificant amplitude of the hypolimnetic, which later became epilimnetic, displacements were probably due to the near-anoxic condition found below the thermocline. This might have deterred the fish, thus providing a safer refuge for daphnids in the below thermocline, which afterwards became the above thermocline. Low oxygen availability was regarded as the summer proximate factor. The abundant food and warmer water conditions found in the below/above thermocline also accounted for absence of DVM in summer. Consequently, this study suggests that DVM by Daphnia is an adaptation that is plastic to changing environmental conditions.     

Influence of Dietary Copper Proteinate on Performance,Selected Biochemical Parameters,Lipid Peroxidation,Liver, and Egg Copper Content in Laying Hens

This study was performed to determine the effects of copper proteinate on performance, blood chemistry, lipid peroxidation status, and organs as well as copper deposition in the liver and eggs of laying hens. Seventy-two 30-week-old Bovans laying hens were distributed into four groups with three replicates. Animals were fed basal diet containing at least 17% crude protein and 2,800 kcal/kg metabolizable energy supplemented with either 0, 150, 300, or 450 mg/kg copper as copper proteinate. Supplementation of 150 and 300 mg/kg copper increased egg production, whereas 450 mg/kg copper decreased (p < 0.001). Liver copper levels were elevated in 300 and 450 mg/kg copper-supplemented groups (p < 0.001). Egg copper contents increased in all treatment groups (p < 0.01). An increase in glucose (p < 0.001) and decreases in albumin (p < 0.01) and total cholesterol (p < 0.05) levels were determined with 300 and 450 mg/kg copper. Supplementation of 450 mg/kg copper increased alkaline phosphatase and gamma glutamyl transpeptidase activities (p < 0.05), malondialdehyde, and high-density lipoprotein levels (p < 0.01) but decreased alanine aminotransferase and lactate dehydrogenase activities (p < 0.01). No gross and microscopic changes were observed in the liver and kidneys. These results indicated that 150 and 300 mg/kg copper increased egg production without having marked adverse effects, but 450 mg/kg copper altered some blood chemistry variables and reduced egg production in laying hens.