Mutation Analysis of BRCA1, BRCA2, PALB2 and BRD7 in a Hospital-Based Series of German Patients with Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive form of breast carcinoma with a poor prognosis. Recent evidence suggests that some patients with TNBC harbour germ-line mutations in DNA repair genes which may render their tumours susceptible to novel therapies such as treatment with PARP inhibitors. In the present study, we have investigated a hospital-based series of 40 German patients with TNBC for the presence of germ-line mutations in BRCA1, BRCA2, PALB2, and BRD7 genes. Microfluidic array PCR and next-generation sequencing was used for BRCA1 and BRCA2 analysis while conventional high-resolution melting and Sanger sequencing was applied to study the coding regions of PALB2 and BRD7, respectively. Truncating mutations in BRCA1 were found in six patients, and truncating mutations in BRCA2 and PALB2 were detected in one patient each, whereas no truncating mutation was identified in BRD7. One patient was a double heterozygote for the PALB2 mutation, c.758insT, and a BRCA1 mutation, c.927delA. Our results confirm in a hospital-based setting that a substantial proportion of German TNBC patients (17.5%) harbour germ-line mutations in genes involved in homology-directed DNA repair, with a preponderance of BRCA1 mutations. Triple-negative breast cancer should be considered as an additional criterion for future genetic counselling and diagnostic sequencing.     

Similarity between contemporary vegetation and plant remains in the surface sediment in Mediterranean lakes

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Parasitic Bacteria and Fungi on Common Mistletoe (Viscum album L.) and Their Potential Application in Biocontrol

This study was carried out to identify pathogenic bacteria and fungi on mistletoe (Viscum album L.) and investigate their potential use in biological control of this parasitic plant. For this purpose, a total of 48 fungal isolate and 193 bacterial strains were isolated from contaminated V. album during the summers 2005–2006. The isolated bacterial strains and fungal isolates were identified by using the Sherlock Microbial Identification System (MIS; Microbial ID, Newark) and microscopic methods, respectively. The bacterial strains that induced hypersensitive reaction (HR) on tobacco (Nicotiana tabacum L.) and fungal isolates were tested for pathogenicity on young shoots of mistletoe by using injection methods. The pathogenic bacterial strains and fungal isolates were also tested for their activity against mistletoe using spray methods. Five bacterial strains (two Burkholderia cepacia, one each of Bacillus megaterium, Bacillus pumilus and Pandoraea pulminicola) were HR and pathogenicity positive when injected but none of them when sprayed on mistletoe. When fungi were injected, 32 isolates were pathogenic but only thirteen when sprayed on mistletoe. Alternaria alternata VA?‐202, VA?‐205, VA?‐217 and Acremonium kiliense VA‐11 fungal isolates were the most effective ones and caused strong disease symptoms on mistletoe. The present study is the first report on the efficiency of potential biocontrol agents against mistletoe in Turkey.     

<Emphasis Type="Italic">Nonomuraea insulae</Emphasis> sp. nov., isolated from forest soil

Strain H2R21^T, a novel actinobacterium, isolated from a forest soil sample collected from Heybeliada, Istanbul, Turkey, and a polyphasic approach was used for characterisation of the strain. Chemotaxonomic and morphological characterisation of strain H2R21^T indicated that it belongs to the genus Nonomuraea. 16S rRNA gene sequence similarity showed that the strain is closely related to Nonomuraea purpurea 1SM4-01^T (99.1%) and Nonomuraea solani CGMCC 4.7037^T (98.4%). DNA–DNA relatedness values were found to be lower than 70% between the isolate and its phylogenetic neighbours N. purpurea 1SM4-01^T, N. solani CGMCC 4.7037^T and Nonomuraea rhizophila YIM 67092^T. The whole cell hydrolysates of strain H2R21^T were found to contain meso-diaminopimelic acid as the diagnostic diamino acid and glucose, madurose, mannose and ribose as the cell sugars. The polar lipids were identified as phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, dihydroxy-phosphatidylethanolamine, phosphatidylinositol, glycophosphatidylinositol, two glycophospholipids and two unidentified lipids. The predominant menaquinones were identified as MK-9(H₄) and MK-9(H₆). The major fatty acids were found to be iso-C_16:0, iso-C_16:0 2OH and C_17:0 10-methyl. On the basis of DNA–DNA relatedness data and some phenotypic characteristics, it is evident that strain H2R21^T can be distinguished from the closely related species in the genus Nonomuraea. Thus, it is concluded that strain H2R21^T represents a novel species of the genus Nonomuraea, for which the name Nonomuraea insulae sp. nov. is proposed. The type strain is H2R21^T (= DSM 102915^T = CGMCC 4.7338^T = KCTC 39769^T).     

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in f?broblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.     

Selectively Modulating Conformational States of USP7 Catalytic Domain for Activation

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Protective effect of magnesium supplementation on experimental 3-methyl cholantrene-induced fibrosarcoma and changes in tissue magnesium distribution during carcinogenesis in rats

In this study, we wanted to examine the effect of magnesium (Mg²⁺) supplementation on the experimental 3-methyl cholantrene (3-MC)-induced fibrosarcoma and alterations in (Mg²⁺) distribution in several tissues of the rats, during carcinogenesis. It was determined that serum and tissue (Mg²⁺) levels of the rats in (Mg²⁺)-supplemented diet group were higher than those of the rats in the (Mg²⁺)-nonsupplemented and control groups. The mean time of fibrosarcoma development for (Mg²⁺)-supplemented group was longer than (Mg²⁺)-nonsupplemented group (p<0.05). Symptoms of hypermagnesemia were not observed in any of the rats. These results suggests that dietary (Mg²⁺) supplementation may have a partial anticarcinogenic effect on experimental 3-MC-induced fibrosarcoma by prolongation of the latent period of carcinogenesis.