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Short rotation coppices (SRCs) are a promising alternative for environmental-friendly biomass production. However, profound understanding of nitrogen (N) uptake and allocation dynamics and their interaction with biomass production of individual tree species is required for their sustainable management. In-situ 15 N soil pulse labeling of the widely applied willow cv. Tordis and poplar cv. Max 1 allowed tracing their uptake of N min and to evaluate the effect of N nutrition on their growth. A pulse of either 15 NH 4 NO 3 or NH 4 15 NO 3 was applied to the soil of four replicate trees of each species in a pot experiment. Leaf, twigs, stem, root were analyzed to quantify the uptake and allocation of 15 N after labeling. Summarizing all compartments of poplar, almost all of 15 NO 3 − (97%) from the N soil pool could be recovered, but only a third of the 15 NH 4 + (34%). In contrast, willow incorporated exactly the same amount of 15 N (49%) from both tracers i.e. showing no preference for a certain N min species. Poplar did not only have the higher N min uptake but also showed a higher total biomass (12.2 g·tree −1 ) production than willow (10.2 g·tree −1 ) in first 56 days, which goes along which its higher allocation of N into leaves. We conclude that the poplar cv. Max 1 might be a better choice for biomass production, especially at arable sites with high N contents as well as for protecting from all negative impacts of non-closed N cycles as typical for classical agricultural managed sites (e.g. nitrate leaching or N 2 O emissions). [ABSTRACT FROM AUTHOR]

During the last few decades, improvements in the planning and application of radiotherapy in combination with surgery and chemotherapy resulted in increased survival rates of tumor patients. However, the success of radiotherapy is impaired by two reasons: firstly, the radioresistance of tumor cells and, secondly, the radiation-induced damage of normal tissue cells located in the field of ionizing radiation. These limitations demand the development of drugs for either radiosensitization of tumor cells or radioprotection of normal tissue cells. In order to identify potential targets, a detailed understanding of the cellular pathways involved in radiation response is an absolute requirement. This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization. [ABSTRACT FROM AUTHOR]

The U1 small nuclear RNA (U1 snRNA) as a component of the major U2-dependent spliceosome recognizes 5′ splice sites (5′ss) containing GT as the canonical dinucleotide in the intronic positions +1 and +2. The c.165+1G>T germline mutation in the 5′ss of exon 2 of the Fanconi anemia C (FANCC) gene commonly predicted to prevent correct splicing was identified in nine FA patients from three pedigrees. RT-PCR analysis of the endogenous FANCC mRNA splicing pattern of patient-derived fibroblasts revealed aberrant mRNA processing, but surprisingly also correct splicing at the TT dinucleotide, albeit with lower efficiency. This consequently resulted in low levels of correctly spliced transcript and minute levels of normal posttranslationally processed FANCD2 protein, indicating that this naturally occurring TT splicing might contribute to the milder clinical manifestations of the disease in these patients. Functional analysis of this FANCC 5′ss within splicing reporters revealed that both the noncanonical TT dinucleotide and the genomic context of FANCC were required for the residual correct splicing at this mutant 5′ss. Finally, use of lentiviral vectors as a delivery system to introduce expression cassettes for TT-adapted U1 snRNAs into primary FANCC patient fibroblasts allowed the correction of the DNA-damage-induced G2 cell-cycle arrest in these cells, thus representing an alternative transcript-targeting approach for genetic therapy of inherited splice-site mutations. [ABSTRACT FROM AUTHOR]

The ability to fix nitrogen is widely, but sporadically distributed among the Bacteria and Archaea suggesting either a vertically inherited, ancient function with widespread loss across genera or an adaptive feature transferred laterally between co-inhabitants of nitrogen-poor environments. As previous phylogenetic studies of nifH and nifD have not completely resolved the evolutionary history of nitrogenase, sixty nifD, nifK, and combined nifDK genes were analyzed using Bayesian, maximum likelihood, and parsimony algorithms to determine whether the individual and combined datasets could provide additional information. The results show congruence between the 16S and nifDK phylogenies at the phyla level and generally support vertical descent with loss. However, statistically significant differences between tree topographies suggest a complex evolutionary history with the underlying pattern of vertical descent obscured by recurring lateral transfer events and different patterns of evolution between the genes. Results support inheritance from the Last Common ancestor or an ancient lateral transfer of the nif genes between Bacteria and Archaea, ongoing gene transfer between cohabitants of similar biogeographic regions, acquisition of nitrogen-fixing capability via symbiosis islands, possible xenologous displacement of one gene in the operon, and possible retention of ancestral genes in heterocystous cyanobacteria. Analyses support the monophyly of the Cyanobacteria, αβγ-Proteobacteria, and Actinobacteria ( Frankia) and provide strong support for the placement of Frankia nif genes at the base of combined the Cyanobacteria/Proteobacteria clades. [ABSTRACT FROM AUTHOR]

Purpose/Objective: Although radiotherapy is a key component of cancer treatment, its implementation into pre-clinical in vivo models with relatively small target volumes is frequently omitted either due to technical complexity or expected side effects hampering long-term observational studies. We here demonstrate how an affordable industrial micro-CT can be converted into a small animal IGRT device at very low costs. We also demonstrate the proof of principle for the case of partial brain irradiation of mice carrying orthotopic glioblastoma implants. Methods/Materials: A commercially available micro-CT originally designed for non-destructive material analysis was used. It consists of a CNC manipulator, a transmission X-ray tube (10–160 kV) and a flat-panel detector, which was used together with custom-made steel collimators (1–5 mm aperture size). For radiation field characterization, an ionization chamber, water-equivalent slab phantoms and radiochromic films were used. A treatment planning tool was implemented using a C++ application. For proof of principle, NOD/SCID/γc−/− mice were orthotopically implanted with U87MG high-grade glioma cells and irradiated using the novel setup. Results: The overall symmetry of the radiation field at 150 kV was 1.04±0.02%. The flatness was 4.99±0.63% and the penumbra widths were between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve along the central axis followed a typical shape of keV photons. Dose rates measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well and resulted in central tumor necrosis consistent with therapeutic efficacy. Conclusion: A conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and other cancers. We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination–mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome. [ABSTRACT FROM AUTHOR]

Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia–like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian cancer. These include two frameshift-causing insertions, two splice-site mutations and two nonfunctional missense mutations. The mutations were found exclusively within 480 pedigrees with the occurrence of both breast and ovarian tumors (BC/OC; 1.3%) and not in 620 pedigrees with breast cancer only or in 2,912 healthy German controls. These results provide the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog and support the 'common disease, rare allele' hypothesis. [ABSTRACT FROM AUTHOR]

The prevalence of attentional problems, and the effect of methylphenidate was evaluated in a clinic population of children with myelomeningocele. Families of 79 children between the ages of 6 and 15 years were screened for the presence of attention problems in their children, using Conners' questionnaires for parents and teachers, and/or the DSM-IV checklist. Thirty-nine per cent of the children exhibited attention problems, primarily without hyperactivity. Fourteen children with attentional problems were enrolled in a double-blind placebocontrolled trial methylphenidate. Response to methylphenidate was assessed with Conners' questionnaires, Conners' Continuous Performance Test, and a battery of selected neuropsychological tests. No statistically significant response was measured for the group while on methylphenidate. Four children were clinical responders to methylphenidate. The prevalence of attentional problems in children with myelomeningocele is high, and effective medication therapy needs to be studied further. [ABSTRACT FROM AUTHOR]