De novo 18q deletion with mitral valve insufficiency

We report an 18-year-old Turkish girl with an 18q- deletion and abnormalities of face, mental and growth retardation, mitral deficiency and hypothyroidism. Mitral deficiency has not been reported in 18q deletion syndrome cases previously. We performed cytogenetic and molecular cytogenetic analysis, and brain MRI. Her karyotype was 46,XX,del(18)(q21.2-->qter). This report compares the symptoms and features of the present patient with previously reported cases with 18q syndrome.     

Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720

Immunotherapeutic drugs that mimic sphingosine 1-phosphate (S1P) disrupt lymphocyte trafficking and cause T helper and T effector cells to be retained in secondary lymphoid tissue and away from sites of inflammation. The prototypical therapeutic agent, 2-alkyl-2-amino-1,3-propanediol (FTY720), stimulates S1P signaling pathways only after it is phosphorylated by one or more unknown kinases. We generated sphingosine kinase 2 (SPHK2) null mice to demonstrate that this kinase is responsible for FTY720 phosphorylation and thereby its subsequent actions on the immune system. Both systemic and lymphocyte-localized sources of SPHK2 contributed to FTY720 induced lymphopenia. Although FTY720 was selectively activated in vivo by SPHK2, other S1P pro-drugs can be phosphorylated to cause lymphopenia through the action of additional sphingosine kinases. Our results emphasize the importance of SPHK2 expression in both lymphocytes and other tissues for immune modulation and drug metabolism.     

Antioxidant system activation in prostate cancer

The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the levels of copper, zinc, and malondialdehyde were determined in 21 age-, sex-, and body-mass-index-matched prostate cancer patients; 50 patients diagnosed with benign prostatic obstruction (BPO) were compared to 50 healthy male subjects acting as controls. The patients were divided into two groups depending on the stage of the disease (group 1 [organ-confined] and group II [advanced disease]) and into three subgroups according to differentiation criteria: subgroup A (n=5, Gleason sum 2–4, well differentiated); subgroup B (n=9, Gleason sum 5–7, moderately differentiated), and subgroup C (n=7, Gleason sum 8–10, poorly differentiated). The MDA levels were higher and the antioxidant activity and Zn levels lower in the prostate cancer groups than in the healthy control and BPO groups. These results confirm the value of therapies aimed at increasing the antioxidant capacity and encourage the use of plasma and erythrocyte Zn levels in the differential diagnosis of BPO and prostate cancer. The MDA levels can be used in the diagnosis and follow-up of prostate cancer.     

Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo

Background aimsDifferentiation or reprogramming of stem cells could be achieved by remodulating the microenvironment, which regulates the fate of cells by soluble factors and contacts. By providing an in vivo-like microenvironment, directional and functional differentiation of stem cells could be achieved in vitro. In this study, the differentiation of mesenchymal stromal cells (MSCs) derived from rat tissues (adipose, rAT; bone marrow, rBM) were analyzed by in vitro and in vivo co-culture experiments. The insulin-producing capacities of islets transplanted under the renal kidney capsule with rAT- and rBM-MSCs were compared and the reduction of hyperglycemia symptoms in rat models was examined.MethodsMSCs prelabeled with green fluorescence protein were co-cultured with islets directly. The insulin production of cells was determined by immunostaining and ELISA. Streptozotocin-induced diabetic rat models were created and MSCs were co-transplanted with the islets under the kidney capsule to confirm the in vitro results.ResultsMSCs were differentiated into insulin-producing cells after 38 days of co-culture, confirmed by insulin and C-peptide stainings. In vivo functional studies revealed that the co-culture of islets with MSCs provided higher differentiation efficiency. The weight gain measurement and glucose tolerance test in the rat group co-transplanted of rAT-MSCs and islets indicate a better recovery than islet-alone transplants and co-transplants of islets and rBM-MSCs.ConclusionsrAT-MSCs could be considered as the cell of choice for cell-based treatment of type 1 diabetes. Because the co-transplantation of islets with MSCs increases the number of insulin-producing cells, this method was suggested for clinical applications.     

IL-23 is required for neutrophil homeostasis in normal and neutrophilic mice

IL-23 is secreted by macrophages and dendritic cells in response to microbial products and inflammatory cytokines. IL-23 is a heterodimer composed of the unique IL-23p19 subunit linked to the common p40 subunit that it shares with IL-12. IL-23 is implicated in autoimmune diseases, where it supports the expansion of IL-17A-producing CD4+ Th17 cells. IL-23 also regulates granulopoiesis in a neutrostat regulatory feedback loop through IL-17A-producing neutrophil regulatory (Tn) cells, most of which express gammadelta TCR. This homeostatic system is disrupted in mice lacking adhesion molecules like beta2-integrins (Itgb2-/-) which have defective neutrophil trafficking and neutrophilia. To test the role of IL-23 in the homeostatic regulation of circulating neutrophil numbers, we measured blood neutrophil numbers in p40-deficient (IL12b-/-) mice and found them reduced compared with wild-type mice. IL12b-/-Itgb2-/- mice, lacking beta2-integrins, IL-12, and IL-23 showed significantly blunted neutrophilia compared with Itgb2-/- mice. Treatment of both IL12b-/- and IL12b-/-Itgb2-/- mice with IL-23, but not IL-12, restored circulating neutrophil counts. Serum levels of IL-17A were readily detectable in Itgb2-/- mice, but not in IL12b-/-Itgb2-/- mice, suggesting that IL-17A production is reduced when IL-23 is absent. Similarly, tissue mRNA expression of IL-17A was reduced in IL12b-/-Itgb2-/-mice compared with Itgb2-/- controls. The total number of CD3+ IL-17A-producing Tn cells were significantly reduced in the spleen and lamina propria of IL12b-/-Itgb2-/- mice, with the largest reduction found in gammadelta+ T cells. Our results suggest a prominent role of IL-23 in the regulation of granulopoiesis and the prevalence of IL-17A-producing Tn cells.     

Determination of antimicrobial and antiviral properties of IR3535

Insect repellent is a substance directly applied to skin or clothing in order to repel flies, mosquitoes, ticks etc. IR3535 or Ethyl butylacetylaminopropionate (EBAAP) is a relatively new repellent which is classified as a biopesticide due to exceptional skin tolerance and overall safety. The repellency against various insect and ticks, and the low toxicity of IR3535 are well acknowledged. However, there has been no attempt to investigate the effects on microorganisms or viruses up to now. In the present study, antimicrobial activity was investigated based on disc diffusion and micro-well dilution assays. Disc diffusion assays revealed IR3535 displayed remarkable antimicrobial activity on the microorganisms tested. MIC results showed that the antifungal efficiency of IR3535 is higher with respect to its antibacterial and anticandidal efficiency. Moreover, antiviral test results revealed that IR3535 showed antiviral effects against Poliovirus and Adenovirus. This is the first study that reveals IR3535’s antimicrobial and antiviral properties against a broad range of microorganisms and viruses. In consideration of the antimicrobial and antiviral properties, IR3535 is a promising agent that could be used to develop novel therapeutic approaches, new application areas and formulations in the future.

     

Removal of cadmium by Pleurotus sajor-caju basidiomycetes

The bioaccumulation of cadmium by the white rot fungus Pleurotus sajor-caju onto dry biomass was investigated using aqueous media with concentrations in the range of 0.125 mM–1.0 mM The highest cadmium uptake (between 88.9 and 91.8%) was observed with aerobic fungal biomass from the exponential growth phase. Up to 1.0 mM cadmium gradually inhibited mycelium development, but never blocked it completely. Freeze-dried, oven-dried and non-metabolizing live Pleurotus sajor-caju biomass types were tested for their capacity to adsorb the test ion Cd²⁺ within the pH range of 4.5 to 6.0. Freeze–dried biomass proved to be the most efficient biomass type for Cd²⁺ metal adsorption. Therefore, Pleurotus sajor-caju may be used for heavy metal removal and bioremediation.     

Elaborate ultrastructure of the Hirudo (Annelida: Hirudinae) cocoon surface

Species of medicinal leeches (Hirudo medicinalis, H. verbana, and H. sulukii) secrete hard‐shelled cocoons. When initially deposited, a cocoon is surrounded by a foam. Over a short time, the foam is transformed into a three‐dimensional structure. We show here that this peripheral structure likely forms by the solidification and dehydration of a moderately viscous, proteinaceous substance that surrounds bubbles of various sizes. The resulting matrix‐like structure comprises a network of curved branches juxtaposed at ～120° and taper in width as a function of distance from the outer cocoon wall. The material is proteinaceous, and traps environmental material in its composition, especially silicon. The geometry of compartments and abundance of silicon on branch surfaces suggest a mechanism for trapping water to prevent desiccation in a terrestrial environment.     

Heliotropium thermophilum,an extreme heat tolerant species,promises plants about adaptation to high soil temperature conditions

To understand high temperature tolerance, Heliotropium thermophilum, a flowering plant thriving in a geothermal field with a soil temperature ranging between 55 and 65 °C, was grown in controlled laboratory conditions and two different soil temperatures were applied to the plants. One of them was the control group (CT 25 ± 3 °C) and the other was the high temperature group (HT 60 ± 4 °C). Water potential, dry weight, cell membrane injury (CMI), lipid peroxidation, hydrogen peroxide, chlorophylls, carotenoids, flavonoids, anthocyanins, proline and total soluble sugar contents were measured. Contents of total soluble sugars, phenolics, flavonoids, anthocyanins, proline were found to be higher in HT group than CT while CMI was opposite. Moreover, no difference was determined in water potential, dry weight, lipid peroxidation, total chlorophyll and carotenoids between CT and HT. H. thermophilum plants adapted to high temperature under laboratory conditions through changing membrane lipid saturation, accumulating osmotically active compounds to save water or increase its uptake and inducing antioxidants such as phenolic compounds to keep reactive oxygen species under control. In conclusion, this study showed that H. thermophilum plant was highly resistant to high soil temperature under optimized laboratory conditions. Moreover, a plant that can withstand 60 °C for a long period of time up to 60 days under laboratory conditions was reported for the first time.