Aspergillus piperis a/5 from plum-distilling waste compost produces a complex of antifungal metabolites active against the phytopathogen pythium aphanidermatum

Adding compost to soil can result in plant disease suppression through the mechanisms of antagonistic action of compost microflora against plant pathogens. The aim of the study was to select effective antagonists of Pythium aphanidermatum from compost, to assess the effect of its extracellular metabolites on the plant pathogen, and to characterize antifungal metabolites. The fungal isolate selected by a confrontation test was identified as Aspergillus piperis A/5 on the basis of morphological features and the internal transcribed spacer (ITS) region, beta-tubulin and calmodulin partial sequences. Liquid chromatography-mass spectroscopy (LC-MS) analysis showed that gluconic and citric acid were the most abundant in the organic culture extract. However, the main antifungal activity was contained in the aqueous phase remaining after the organic solvent extraction. The presence of considerable amounts of proteins in both the crude culture extract as well as the aqueous phase remaining after solvent extraction was confirmed by SDS-PAGE. Isolated Aspergillus piperis A/ 5 exhibits strong antifungal activity against the phytopathogen Pythium aphanidermatum. It secretes a complex mixture of metabolites consisting of small molecules, including gluconic acid, citric acid and itaconic acid derivatives, but the most potent antifungal activity was associated with proteins resistant to heat and organic solvents. Our findings about the activity and characterization of antagonistic strain metabolites contribute to the understanding of the mechanism of interaction of antifungal metabolites as well as fungal-fungal interaction. The obtained results provide a basis for further application development in agriculture and food processing

Clinical case seminar - familial intracranial germinoma

Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood

Thermal constraints on the reionisation of hydrogen by population-II stellar sources

Measurements of the intergalactic medium (IGM) temperature provide a potentially powerful constraint on the reionisation history due to the thermal imprint left by the photo-ionisation of neutral hydrogen. However, until recently IGM temperature measurements were limited to redshifts 2 < z < 4.8, restricting the ability of these data to probe the reionisation history at z > 6. In this work, we use recent measurements of the IGM temperature in the near-zones of seven quasars at z ~ 5.8 - 6.4, combined with a semi-numerical model for inhomogeneous reionisation, to establish new constraints on the redshift at which hydrogen reionisation completed. We calibrate the model to reproduce observational constraints on the electron scattering optical depth and the HI photo-ionisation rate, and compute the resulting spatially inhomogeneous temperature distribution at z ~ 6 for a variety of reionisation scenarios. Under standard assumptions for the ionising spectra of population-II sources, the near-zone temperature measurements constrain the redshift by which hydrogen reionisation was complete to be z > 7.9 (6.5) at 68 (95) per cent confidence. We conclude that future temperature measurements around other high redshift quasars will significantly increase the power of this technique, enabling these results to be tightened and generalised.Comment: 15 pages, 8 figures, accepted for publication in MNRA

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach

Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction

Background: In the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addition, to our knowledge, serum MMP-9, MMP-10 and TIMP-1 levels in patients with malignant middle cerebral artery infarction (MMCAI) for mortality prediction have not been studied, and these were the objectives of this study. Methods: This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We included patients with severe MMCAI defined as Glasgow Coma Scale (GCS) lower than 9. We measured circulating levels of MMP-9, MMP-10, TIMP-1, in 50 patients with severe MMCAI at diagnosis and in 50 healthy subjects. Endpoint was 30-day mortality. Results: Patients with severe MMCAI showed higher serum levels of MMP-9 (p = 0.001), MMP-10 (p 239 ng/mL are associated with 30-day mortality (OR = 5.82; 95 % CI = 1.37-24.73; P = 0.02) controlling for GCS and age. The area under the curve for TIMP-1 as predictor of 30-day mortality was 0.81 (95 % CI = 0.67-0.91; P < 0.001). We found an association between circulating levels of TIMP-1 and MMP-10 (rho = 0.45; P = 0.001), plasminogen activator inhibitor (PAI)-1 (rho = 0.53; P < 0.001), and tumor necrosis factor (TNF)-alpha (rho = 0.70; P < 0.001). Conclusions: The most relevant and new findings of our study, were that serum TIMP-1 levels in MMCAI patients were associated with mortality, and could be used as a prognostic biomarker of mortality in MMCAI patients

Modelling recombinations during cosmological reionization

An ionization front expanding into a neutral medium can be slowed-down significantly by recombinations. In cosmological numerical simulations the recombination rate is often computed using a 'clumping factor', that takes into account that not all scales in the simulated density field are resolved. Here we demonstrate that using a single value of the clumping factor significantly overestimates the recombination rate, and how a local estimate of the clumping factor is both easy to compute, and gives significantly better numerical convergence. We argue that this lower value of the recombination rate is more relevant during the reionization process and hence that the importance of recombinations during reionization has been overestimated.Comment: 5 pages, 3 figures, accepted for publication in MNRAS Letter

Germline mutation analysis of BRCA1 and BRCA2 genes in Yugoslav breast/ovarian cancer families

The frequency of germline BRCA1 and BRCA2 mutations was tested in Yugoslav breast and breast/ovarian cancer families using combined heteroduplex/single-strand conformation polymorphism analysis for the entire coding region of both genes. Three different recurrent BRCA1 mutations (one 185delAG, one 3447del4 and two 5382insC) were identified in 4 of 12 families (33%), whereas no definite disease-causing alterations of BRCA2 was detected. Genotype analysis revealed a possible common founder effect for each 185delAG and 5382insC. The relatively high frequency of germline BRCA1 mutations determined in this panel of families confirms the important role of BRCA1 in disease predisposition in the Yugoslav population, while the lack of population specific founder and/or unique mutations show the need of further analysis of samples from this yet unexamined region of Europe

The mechanisms of 6-hydroxydopamineInduced astrocyte death

Treatment with 6-hydroxydopamine significantly reduced the viability of cultured rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. 6-Hydroxydopamine-treated astrocytes exhibited altered nuclear morphology, DNA fragmentation, and reduced intracellular esterase activity, which indicated apoptotic cell death. Astrocytes were protected by neutralization of 6-hydroxydopamine autooxidation products H2O2, O-2, and -OH, but not by cell-derived or chemically generated anti-apoptotic free radical nitric oxide. Finally, 6-hydroxydopamine activated extracellular signal-regulated kinase in astrocytes and selective inhibitor of extracellular signal-regulated kinase activation partially prevented astrocyte death. Taken together, these data indicate that 6-hydroxydopamine-triggered oxidative stress induces extracellular signal-regulated kinase-dependent apoptotic death of astrocytes.nul

The mechanisms of 6-hydroxydopamineInduced astrocyte death

Treatment with 6-hydroxydopamine significantly reduced the viability of cultured rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. 6-Hydroxydopamine-treated astrocytes exhibited altered nuclear morphology, DNA fragmentation, and reduced intracellular esterase activity, which indicated apoptotic cell death. Astrocytes were protected by neutralization of 6-hydroxydopamine autooxidation products H2O2, O-2, and -OH, but not by cell-derived or chemically generated anti-apoptotic free radical nitric oxide. Finally, 6-hydroxydopamine activated extracellular signal-regulated kinase in astrocytes and selective inhibitor of extracellular signal-regulated kinase activation partially prevented astrocyte death. Taken together, these data indicate that 6-hydroxydopamine-triggered oxidative stress induces extracellular signal-regulated kinase-dependent apoptotic death of astrocytes.nul