Phenotypic correlations in a patient with ring chromosome 22

Ring chromosome 22, a rare cytogenetic anomaly, has been described in over 60 cases in the medical literature. The aim of this report was to present a case carrying ring chromosome 22, and her family.It is a case report of a patient presented at Medical Faculty of ?ukurova University in Turkey.An 8-year-old girl with ring chromosome 22 and her family were evaluated cytogenetically and clinically.A chromosome analysis of the proband revealed a de novo 46, XX, r(22)(p11.2;q13) karyotype. Our subject demonstrated the prominent features of this syndrome including profound mental retardation, language impairment, dysmorphic features, lack of speech, hyperactivity, and behavioral disorders.There is lack of consistency between the physical abnormalities that we observed in our subject and those observed for such patients in the literature. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region.     

p38MAPK Signaling and Desmoglein-3 Internalization Are Linked Events in Pemphigus Acantholysis

Pemphigus vulgaris (PV) is an autoimmune blistering disease in which antibodies against the desmosomal cadherin, DSG3 (desmoglein-3), cause acantholysis. It has become increasingly clear that loss of cell-cell adhesion in PV is a complex and active process involving multiple signaling events such as activation of p38MAPK. It has also been demonstrated that incubating keratinocytes with PV IgG causes a redistribution of DSG3 from the cell surface to endosomes, which target these proteins for degradation. This study was undertaken to determine the relationship between p38MAPK and DSG3 endocytosis in pemphigus. In this work, we confirm that PV IgG causes internalization of cell-surface DSG3 into endosomes (as early as 4 h), which are then depleted from both detergent-soluble and detergent-insoluble pools. Cell-surface DSG3 internalization and depletion from both the detergent-soluble and detergent-insoluble fractions were blocked by the p38MAPK inhibitor SB202190. These data suggest that p38MAPK is capable of regulating PV IgG-mediated DSG3 internalization and that previously isolated mechanistic observations may be linked to a common pathway by which pemphigus autoantibodies lead to acantholysis.     

Drought-induced changes in nutrient concentrations and retention in two shallow Mediterranean lakes subjected to different degrees of management

While extensive knowledge exists on the relationship between nutrient loading and nutrient concentrations in lakes in the cold temperate region, few studies have been conducted in warm lakes, not least in warm arid lakes. This is unfortunate as a larger proportion of the world’s lakes will be situated in arid climates in the future due to climate change and a larger proportion will suffer from a higher frequency of intensive drought. We conducted a comprehensive 11–13 year mass balance study in two interconnected shallow Mediterranean lakes in Turkey, covering a period with substantial changes in climate conditions. The upstream lake was only affected by natural changes in nutrient loading, while the downstream lake was additionally influenced by sewage diversion and restoration by fish removal. Contrasting to experience from north temperate lakes we found an increase in in-lake concentrations of total phosphorus and inorganic nitrogen (ammonia as well as nitrate) in dry years despite lower external nutrient loading, and submerged macrophytes did not increase the nitrogen retention capacity of the lakes. In contrast, fish removal modulated the nitrogen concentration as in north temperate lakes, but the effect was not long-lasting. Our results suggest that climate warming reduces the nutrient retention capacity of shallow lakes in the Mediterranean and exacerbates eutrophication. Lower thresholds of nutrient loading for shifting turbid shallow lakes to a clear water state are therefore to be expected in arid zones in a future warmer climate, with important management implications.     

Neo-clerodane diterpenoids and phenylethanoid glycosides from Teucrium chamaedrys L

A neo-clerodane type diterpenoid, 12(S)-15,16-epoxy-19-hydroxy-neo-cleroda-13(16),14-dien-18,6alpha:20,12-diolide, and two phenylethanoid glycosides, teucrioside-3(IIII)-O-methylether and teucrioside-3(IIII),4(IIII)-O-dimethylether were isolated from the aerial parts of Teucrium chamaedrys. Their structures were identified on the basis of extensive NMR spectra, LC-ESIMS analysis, and molecular modeling studies.     

Effects of zinc deficiency and supplementation on some hematologic parameters of rats performing acute swimming exercise

The aim of the study was to investigate how zinc deficiency and supplementation effect some hematologic parameters of rats performing swimming exercise. Forty adult male Spraque-Dawley rats were divided into 4 groups, zinc deficient swimming group (Group 1, n=10, zinc supplemented swimming group (Group 2, n=10), swimming control group (Group 3, n=10), and control group (Group 4, n=10). Blood samples were taken by decapitation and analyzed for the determination of erythrocyte, hemoglobin level, hematocrit, leukocyte, lymphocyte, platelet count and plasma zinc level at the end of the 4 week experiment. Erythrocyte count of group 1 was the lowest whereas erythrocyte count in group 3 was significantly lower than that in group 2 and 4 (p<0.05). Hemoglobin level of group 1 was significantly lower than that of groups 2 and 4 (p<0.05). Hematocrit was significantly lower in both group 1 and group 3 than both groups 2 and 4 (p<0.05). Lymphocyte count in group 2 was significantly higher than in all other groups (p<0.05). Platelet counts in group 2 was significantly lower than in all other groups (p<0.05). Our findings suggest that zinc deficiency effects the hematologic parameters mentioned negatively whereas zinc supplementation has a positive influence.     

Effects of chronic treatment with sodium tetrachloroaurate(III) in mice and membrane models

Gold is a nonessential element with a variety of applications in medicine. A few gold(I) compounds are used in the clinics for treatment of rheumatoid arthritis and of discoid lupus. Some novel gold(III) compounds are under evaluation as anticancer agents. It is known that gold compounds generally produce toxic effects on the kidneys and characteristic lesions in the brain. However, information concerning the neurotoxicity of gold derivatives in humans as well as in experimental toxicology is rather scarce. For this reason we tried to shed some further light on this aspect of gold neurotoxicity by chronic treatment of mice with sodium tetrachloroaurate(III) in order to observe possible biophysical and morphological alterations that may occur in the brain. Chronic gold treatment resulted in a markedly decreased expression of metallothioneins and of glial fibrillary acidic protein in astrocytes of different brain areas. To examine its effects on cell membranes, interactions of sodium tetrachloroaurate(III) with molecular models were also evaluated. The models consisted in bilayers built-up of classes of phospholipids located in the outer and inner monolayers of biological membranes. Structural perturbation of cell membrane models was observed only at concentrations 10(5) times higher than those detected in the brains of animals after three months' treatment. These results show that toxic effects on animal brain upon treatment with sodium tetrachloroaurate develop with difficulty and may be observed only at high doses.     

Determination of degradation of radioactivity and its kinetics in aerobic composting

In this study, the kinetics of disappearance of radioactivity in aerobic composting was investigated. For this purpose, compost materials were prepared by mixing sugar beet wastes, wine factory wastes (grape wastes), straw and biological treatment sludge in different amounts. While alpha-radioactivity was not initially detected in all composting materials, the composting materials had some beta-radioactivity. In the mixtures of sugar beet wastes--straw-biological treatment sludge (1), sugar beet wastes-wine factory wastes (grape wastes)-biological treatment sludge (II) and wine factory wastes (grape wastes)-biological treatment sludge (III), the beta-radioactivity reduced by 82%, 58%, 85% respectively of initial values after 52 d. The beta-radioactivity degradation in the composting process could be represented by first-order kinetics and reaction rate constants of mixtures of I, II and III were k = 0.0693 d(-1) (R2 - 0.84), k = 0.0453 d(-1) (R2 = 0.98), k = 0.0234 d(-1) (R2 = 0.97), respectively.     

Tryptophan (W) at position 37 of murine IL-12/IL-23 p40 is mandatory for binding to IL-12Rβ1 and subsequent signal transduction

Interleukin (IL)-12 and IL-23 are composite cytokines consisting of p35/p40 and p19/p40, respectively, which signal via the common IL-12 receptor β1 (IL-12Rβ1) and the cytokine-specific receptors IL-12Rβ2 and IL-23R. Previous data showed that the p40 component interacts with IL-12Rβ1, whereas p19 and p35 subunits solely bind to IL-23R and IL-12Rβ2, resulting in tetrameric signaling complexes. In the absence of p19 and p35, p40 forms homodimers and may induce signaling via IL-12Rβ1 homodimers. The critical amino acids of p19 and p35 required for binding to IL-23R and IL-12Rβ2 are known, and two regions of p40 critical for binding to IL-12Rβ1 have recently been identified. In order to characterize the involvement of the N-terminal region of p40 in binding to IL-12Rβ1, we generated deletion variants of the p40-p19 fusion cytokine. We found that an N-terminal deletion variant missing amino acids M23 to P39 failed to induce IL-23-dependent signaling and did not bind to IL-12Rβ1, whereas binding to IL-23R was maintained. Amino acid replacements showed that p40W37K largely abolished IL-23-induced signal transduction and binding to IL-12Rβ1, but not binding to IL-23R. Combining p40W37K with D36K and T38K mutations eliminated the biological activity of IL-23. Finally, homodimeric p40D36K/W37K/T38K did not interact with IL-12Rβ1, indicating binding of homodimeric p40 to IL-12Rβ1 is comparable to the interaction of IL-23/IL-12 and IL-12Rβ1. In summary, we have defined D36, W37, and T38 as hotspot amino acids for the interaction of IL-12/IL-23 p40 with IL-12Rβ1. Structural insights into cytokine–cytokine receptor binding are important to develop novel therapeutic strategies.     

Bone mass toxicity associated with inhalation exposure to toluene

The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly used solvents in industry; it is easily available and conventient to use. Many toxicologic effects on biological systems secondary to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation. Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant abuse is endemic.     

The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is the ligand for five specific G protein-coupled receptors, named S1P(1) to S1P(5). In this study, we found that cross-communication between platelet-derived growth factor receptor and S1P(2) serves as a negative damper of PDGF functions. Deletion of the S1P(2) receptor dramatically increased migration of mouse embryonic fibroblasts toward S1P, serum, and PDGF but not fibronectin. This enhanced migration was dependent on expression of S1P(1) and sphingosine kinase 1 (SphK1), the enzyme that produces S1P, as revealed by downregulation of their expression with antisense RNA and small interfering RNA, respectively. Although S1P(2) deletion had no significant effect on tyrosine phosphorylation of the PDGF receptors or activation of extracellular signal-regulated kinase 1/2 or Akt induced by PDGF, it reduced sustained PDGF-dependent p38 phosphorylation and markedly enhanced Rac activation. Surprisingly, S1P(2)-null cells not only exhibited enhanced proliferation but also markedly increased SphK1 expression and activity. Conversely, reintroduction of S1P(2) reduced DNA synthesis and expression of SphK1. Thus, S1P(2) serves as a negative regulator of PDGF-induced migration and proliferation as well as SphK1 expression. Our results suggest that a complex interplay between PDGFR and S1P receptors determines their functions.