Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome

The Hennekam lymphangiectasia–lymphedema syndrome is a genetically heterogeneous disorder. It can be caused by mutations in CCBE1 which are found in approximately 25 % of cases. We used homozygosity mapping and whole-exome sequencing in the original HS family with multiple affected individuals in whom no CCBE1 mutation had been detected, and identified a homozygous mutation in the FAT4 gene. Subsequent targeted mutation analysis of FAT4 in a cohort of 24 CCBE1 mutation-negative Hennekam syndrome patients identified homozygous or compound heterozygous mutations in four additional families. Mutations in FAT4 have been previously associated with Van Maldergem syndrome. Detailed clinical comparison between van Maldergem syndrome and Hennekam syndrome patients shows that there is a substantial overlap in phenotype, especially in facial appearance. We conclude that Hennekam syndrome can be caused by mutations in FAT4 and be allelic to Van Maldergem syndrome.     

Synthesis,Characterization and Evaluation of Cytotoxic Activities of Novel Aziridinyl Phosphonic Acid Derivatives

New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel?Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent.     

Ion-imprinted beads for molecular recognition based mercury removal from human serum

The aim of this study is to prepare ion-imprinted polymers which can be used for the selective removal of mercury ions [Hg(2+)] from human serum. N-Methacryloyl-(L)-cysteine (MAC) was chosen as the complexing monomer. In the first step, Hg(2+) was complexed with MAC and the Hg(2+)-imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-(l)-cysteine) (MIP) beads were synthesized by suspension polymerization. After that, the template ions (i.e., Hg(2+)) were removed using thiourea (0.5%, v/v) in 0.05 M HCl. The specific surface area of the MIP beads was found to be 59.04 m(2)/g with a size range of 63-140 micro m in diameter and the swelling ratio was 91.5%. According to the elemental analysis results, the MIP beads contained 87.0 micro mol MAC/g polymer. The maximum adsorption capacity was 0.45 mg Hg(2+)/g beads. The applicability of two kinetic models including pseudo-first order and pseudo-second order model was estimated on the basis of comparative analysis of the corresponding rate parameters, equilibrium capacity and correlation coefficients. Results suggest that chemisorption processes could be the rate-limiting step in the adsorption process. The relative selectivity coefficients of MIP beads for Hg(2+)/Cd(2+), Hg(2+)/Zn(2+) were 14.7 and 21.5 times greater than the non-imprinted (NIP) matrix, respectively. The MIP beads could be used many times without decreasing in their adsorption capacities significantly.     

Genotoxic and Histopathological Effects of Water Pollution on Two Fish Species, <Emphasis Type="Italic">Barbus capito pectoralis</Emphasis> and <Emphasis Type="Italic">Chondrostoma nasus</Emphasis> in the Büyük Menderes River,Turkey

The genotoxic and histopathological effects of water pollution were investigated on two fish species caught from the Buyuk Menderes River and from its tributary, the Cine Stream. The Buyuk Menderes basin is an important agricultural area in Turkey. The levels of copper, zinc, cadmium, cobalt, and lead were measured at the surface of the water and in gills, liver, and muscle tissue of Chondrostoma nasus and Barbus capito pectoralis. In some tissues, the concentrations of some of these metals exceeded acceptable levels for human consumption. Zinc was found to be the most abundant metal in water and tissues. Maximal metal accumulation was observed in the liver. To detect the genotoxic potential of contaminants, the formation of micronucleus in erythrocytes was used as indicator of chromosomal damage. The frequency of micronucleus formation did not show significant differences between locations and controls in B. capito pectoralis caught from three locations and C. nasus from two locations. The histological changes included significant decreases of the mean lengths of primary and secondary lamellae. In gills epithelia, we observed cellular proliferation that developed Because of secondary lamellae fusion, ballooning degenerations, or club deformation of secondary lamellae and cystic structures in secondary lamellae. In the liver, the changes included swollen and ruptured parenchymal cells, loss of cord structure, vacuoles filled with cellular debris, focal necrosis, and a significant increase in Kupffer cells.     

Neutrophil Gelatinase-Associated Lipocalin (NGAL) Predicts Response to Neoadjuvant Chemotherapy and Clinical Outcome in Primary Human Breast Cancer

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.     

Suppression of TLR4/MyD88/TAK1/NF-κB/COX-2 Signaling Pathway in the Central Nervous System by Bexarotene,a Selective RXR Agonist,Prevents Hyperalgesia in the Lipopolysaccharide-Induced Pain Mouse Model

Neurochemical Research - A selective RXR agonist, bexarotene, has been shown to have anti-inflammatory, anti-nociceptive, and neuroprotective effects in several models of numerous neurological...     

Antioxidant and antimicrobial actions of the clubmoss <Emphasis Type="Italic">Lycopodium clavatum</Emphasis> L.

Purpose of the present study was to evaluate antioxidant, antibacterial, antifungal, and antiviral activities of the petroleum ether, chloroform, ethyl acetate and methanol extracts as well as the alkaloid fraction of Lycopodium clavatum L. (LC) from Lycopodiaceae growing in Turkey. Antioxidant activity of the LC extracts was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging method at 0.2 mg/ml using microplate-reader assay. Antiviral assessment of LC extracts was evaluated towards the DNA virus Herpes simplex (HSV) and the RNA virus Parainfluenza (PI-3) using Madin-Darby Bovine Kidney (MDBK) and Vero cell lines. Antibacterial and antifungal activities of the extracts were tested against standard and isolated strains of the following bacteria; Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Acinobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis as well as the fungi; Candida albicans and C. parapsilosis. All of the extracts possessed noteworthy activity against ATCC strain of S. aureus (4 μg/ml), while the LC extracts showed reasonable antifungal effect. On the other hand, we found that only the chloroform extract was active against HSV (16–8 μg/ml), while petroleum ether and alkaloid extracts inhibited potently PI-3 (16–4 μg/ml and 32–4 μg/ml, respectively). However, all of the extracts had insignificant antiradical effect on DPPH. In addition, we also analyzed the content of the alkaloid fraction of the plant by capillary gas chromatography-mass spectrometry (GC-MS) and identified lycopodine as the major alkaloid.