Genome-Wide Associations of Signaling Pathways in Glioblastoma Multiforme

Background: eQTL analysis is a powerful method that allows the identification of causal genomic alterations, providing an explanation of expression changes of single genes. However, genes mediate their biological roles in groups rather than in isolation, prompting us to extend the concept of eQTLs to whole gene pathways. Methods: We combined matched genomic alteration and gene expression data of glioblastoma patients and determined associations between the expression of signaling pathways and genomic copy number alterations with a non-linear machine learning approach. Results: Expectedly, over-expressed pathways were largely associated to tag-loci on chromosomes with signature alterations. Surprisingly, tag-loci that were associated to under-expressed pathways were largely placed on other chromosomes, an observation that held for composite effects between chromosomes as well. Indicating their biological relevance, identified genomic regions were highly enriched with genes having a reported driving role in gliomas. Furthermore, we found pathways that were significantly enriched with such driver genes. Conclusions: Driver genes and their associated pathways may represent a functional core that drive the tumor emergence and govern the signaling apparatus in GBMs. In addition, such associations may be indicative of drug combinations for the treatment of brain tumors that follow similar patterns of common and diverging alterations

Involvement of MicroRNA Families in Cancer

Collecting representative sets of cancer microRNAs (miRs) from the literature we show that their corresponding families are enriched in sets of highly interacting miR families. Targeting cancer genes on a statistically significant level, such cancer miR families strongly intervene with signaling pathways that harbor numerous cancer genes. Clustering miR family-specific profiles of pathway intervention, we found that different miR families share similar interaction patterns. Resembling corresponding patterns of cancer miRs families, such interaction patterns may indicate a miR family’s potential role in cancer. As we find that the number of targeted cancer genes is a naı¨ve proxy for a cancer miR family, we design a simple method to predict candidate miR families based on gene-specific interaction profiles. Assessing the impact of miR families to distinguish between (non-)cancer genes, we predict a set of 84 potential candidate families, including 75% of initially collected cancer miR families. Further confirming their relevance, predicted cancer miR families are significantly indicated in increasing, non-random numbers of tumor types

All-reflective UV-VIS-NIR transmission and fluorescence spectrometer for mu m-sized samples

We report on an optical transmission spectrometer optimized for tiny samples. The setup is based on all-reflective parabolic optics and delivers broadband operation from 215 to 1030 nm. A fiber-coupled light source is used for illumination and a fiber-coupled miniature spectrometer for detection. The diameter of the probed area is less than 200 mu m for all wavelengths. We demonstrate the capability to record transmission, absorption, reflection, fluorescence and refractive indices of tiny and ultrathin sample flakes with this versatile device. The performance is validated with a solid state wavelength standard and with dye solutions

Pristine levels of suspended sediment in large German river channels during the Anthropocene?

Suspended sediment is an integral part of riverine transport and functioning that has been strongly altered during the Anthropocene due to the overwhelming human pressure on soils, sediments, and the water cycle. Understanding the controls of changing suspended sediment in rivers is therefore vital for effective management strategies. Here we present results from a trend analysis of suspended sediments covering 62 monitoring stations along the German waterways (catchment sizes range between 2000 and 160 000 km2) with more than 440 000 water samples taken between 1990 and 2010. Based on daily monitoring of suspended sediment concentration (SSC), we found significant declines in mean annual SSC and annual suspended sediment loads (SSLs) at 49 of 62 monitoring stations totaling −0.92 mg L−1 yr−1. At some stations decreases during the 20 years represent up to 50 % of the long-term average SSC. Significant decreases in SSC are associated with declining SSL despite an increase in sheet and rill erosion by almost 150 % derived from modeling due to changes in land use and management as well as rainfall erosivity. The contemporary suspended sediment loads of the Rhine at the German–Dutch border are approaching the natural base level of ∼1 Mt yr−1, which was reached by the Rhine during the mid-Holocene when the suspended sediment load was adjusted to the Holocene climatic conditions and before the onset of increased loads due to human-induced land use changes in the Rhine catchment. At this point we can only speculate regarding potential reasons for a decline in sediment transport in larger rivers despite erosion increase. We argue that increased sediment retention in upstream headwaters is presumably the major reason for declining SSC in the large river channels studied.</p

CD4+CD25highCD127low Regulatory T Cells in Peripheral Blood Are Not an Independent Factor for Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

Background. The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT) largely relies on the graft-versus-leukemia (GVL) effect. Uncontrolled graft-versus-host disease (GVHD) is a feared complication of HSCT. Regulatory T cells (Treg) are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD) and chronic GVHD (cGVHD). Methods. In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls. Results. Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD. Conclusions. This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity

Homeologous Plastid DNA Transformation in Tobacco Is Mediated by Multiple Recombination Events

Efficient plastid transformation has been achieved in Nicotiana tabacum using cloned plastid DNA of Solanum nigrum carrying mutations conferring spectinomycin and streptomycin resistance. The use of the incompletely homologous (homeologous) Solanum plastid DNA as donor resulted in a Nicotiana plastid transformation frequency comparable with that of other experiments where completely homologous plastid DNA was introduced. Physical mapping and nucleotide sequence analysis of the targeted plastid DNA region in the transformants demonstrated efficient site-specific integration of the 7.8-kb Solanum plastid DNA and the exclusion of the vector DNA. The integration of the cloned Solanum plastid DNA into the Nicotiana plastid genome involved multiple recombination events as revealed by the presence of discontinuous tracts of Solanum-specific sequences that were interspersed between Nicotiana-specific markers. Marked position effects resulted in very frequent cointegration of the nonselected peripheral donor markers located adjacent to the vector DNA. Data presented here on the efficiency and features of homeologous plastid DNA recombination are consistent with the existence of an active RecA-mediated, but a diminished mismatch, recombination/repair system in higher-plant plastids

An Introduction to PYTHIA 8.2

The PYTHIA program is a standard tool for the generation of events in high-energy collisions, comprising a coherent set of physics models for the evolution from a few-body hard process to a complex multiparticle final state. It contains a library of hard processes, models for initial- and final-state parton showers, matching and merging methods between hard processes and parton showers, multiparton interactions, beam remnants, string fragmentation and particle decays. It also has a set of utilities and several interfaces to external programs. PYTHIA 8.2 is the second main release after the complete rewrite from Fortran to C++, and now has reached such a maturity that it offers a complete replacement for most applications, notably for LHC physics studies. The many new features should allow an improved description of data.Comment: 45 page

Superficial Soft-Tissue Sarcomas Rarely Require Advanced Soft-Tissue Reconstruction Following Resection

Objective: Soft-tissue sarcomas are most frequently located deep within myofascial compartments. Superficial soft-tissue sarcomas (S-STS) are relatively less common and may be managed differently than deep sarcomas because generous resection margins are often possible without sacrificing critical structures. We sought to investigate the frequency and types of soft-tissue reconstructive procedures that are required following excision of S-STS. Methods: We reviewed 457 consecutively treated patients with S-STS with a minimum 2-year follow-up from our prospectively maintained database between 1989 and 2009. Results: Mean follow-up was 10.5 years (range, 2–23). Four hundred twenty-one tumors (91%) were excised with negative margins, 38 (8.3%) had microscopically positive margins, and three (0.7%) had grossly positive margins. One patient required an amputation. In 271 (58%) patients, the wounds were closed primarily. In comparison, 93 patients (20%) required a rotation flap, 70 (15%) required a split-thickness skin graft, and 23 (5%) underwent a free tissue transfer (ie, advanced reconstructive procedure). The overall complication rate was 12%, although 43% of patients undergoing free tissue transfer developed complications (P = 0.04). An unplanned excision before referral to our center was a risk factor for local recurrence (P = 0.03) when residual tumor was recovered in the reexcision specimen pathologically. Conclusions: Although concern about the morbidity associated with a free tissue transfer (ie, advanced reconstructive procedure) may potentially limit the adequacy of resection in some patients with S-STS, the results of this study showed that the majority of patients had complete excisions with negative margins and primary closure. Obtaining a negative margin when excising a known or suspected S-STS rarely requires an advanced reconstructive procedure and almost never results in loss of limb