Modulation of tumour colony growth by irradiated accessory cells.

The ability of human tumour cells to form colonies in soft agar is enhanced by the presence of autologous phagocytic/adherent cells. We investigated the effect of irradiation on the ability of the adherent cells to support human tumour colony formation. Relatively low doses of irradiation significantly increased the growth enhancing ability of adherent cells in 17/19 cases. The possibility that the enhancement was mediated by inactivation of radiosensitive contaminating lymphocytes was explored. Depletion of T lymphocytes from unirradiated adherent cells by a monoclonal antibody and complement resulted in little overall change in tumour colony growth. However, elimination of only the suppressor subset (OKT8+) of T lymphocytes resulted in increased colony growth relative to control values obtained with unirradiated adherent cells. In contrast, depletion of T lymphocytes from irradiated adherent cells by a pan T monoclonal antibody and complement decreased colony formation. Thus, the ability of irradiated macrophages to enhance tumour colony growth appeared to be mediated by a T lymphocyte. The effect of irradiation on isolated populations of macrophages and T lymphocytes was also examined. The enhanced ability of irradiated adherent cells to support tumor colony growth appeared to have been due to treatment of T lymphocytes alone. The results indicate that both adherent macrophages and lymphocytes may influence the growth of clonogenic human tumour cells

Inversion of Randomly Corrugated Surfaces Structure from Atom Scattering Data

The Sudden Approximation is applied to invert structural data on randomly corrugated surfaces from inert atom scattering intensities. Several expressions relating experimental observables to surface statistical features are derived. The results suggest that atom (and in particular He) scattering can be used profitably to study hitherto unexplored forms of complex surface disorder.Comment: 10 pages, no figures. Related papers available at http://neon.cchem.berkeley.edu/~dan

Identification of plant-derived alkaloids with therapeutic potential for myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3 UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of availableMBNL1leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequesteredMBNL1from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1.We identified several alkaloids, including the -carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of theDM1pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases

Hopping Conductivity of a Nearly-1d Fractal: a Model for Conducting Polymers

We suggest treating a conducting network of oriented polymer chains as an anisotropic fractal whose dimensionality D=1+\epsilon is close to one. Percolation on such a fractal is studied within the real space renormalization group of Migdal and Kadanoff. We find that the threshold value and all the critical exponents are strongly nonanalytic functions of \epsilon as \epsilon tends to zero, e.g., the critical exponent of conductivity is \epsilon^{-2}\exp (-1-1/\epsilon). The distribution function for conductivity of finite samples at the percolation threshold is established. It is shown that the central body of the distribution is given by a universal scaling function and only the low-conductivity tail of distribution remains $\epsilon$-dependent. Variable range hopping conductivity in the polymer network is studied: both DC conductivity and AC conductivity in the multiple hopping regime are found to obey a quasi-1d Mott law. The present results are consistent with electrical properties of poorly conducting polymers.Comment: 27 pages, RevTeX, epsf, 5 .eps figures, to be published in Phys. Rev.

Deoxyribonucleic Acid as a Universal Electrolyte for Bio-Friendly Light-Emitting Electrochemical Cells [in press]

In the search for bio and eco‐friendly light sources, light‐emitting electrochemical cells (LECs) are promising candidates for the implementation of biomaterials in their device architecture thanks to their low fabrication complexity and wide range of potential technological applications. In this work, the use of the DNA derivative DNA‐cetyltrimethylammonium (DNA‐CTMA) is introduced as the ion‐solvating component of the solid polymer electrolyte (SPE) in the active layer of solution‐processed LECs. The focus is particularly on the investigation of its electrochemical and ionic conductivity properties demonstrating its suitability for device fabrication and correlation with thin film morphology. Furthermore, upon blending with the commercially available emissive polymer Super Yellow, the structure property relationship between the microstructure and the ionic conductivity is investigated and yields an optimized LEC performance. The large electrochemical stability window of DNA‐CTMA enables a stable device performance for a variety of emitters covering the complete visible spectral range, thus highlighting the universal character of this naturally sourced SPE

Administration of Silver Fir (Abies alba Mill.) to goats and its potential to control gastro-intestinal parasites

Gastrointestinal nematodes (GIN) substantially impact on goat health. Because of the widespread development of GIN, resistant to allopathic drugs, further research into alternative parasite control methods is required [1]. Silver fir, Abies alba MILL (SF), is traditionally used by Swiss farmers in order to control GIN infections of goats but also to improve animal welfare. A survey among goat farmers revealed that goat farmers use SF in winter during a period of approximately five months. The SF-ration per animal and day differ between approximately 8.2 g dry matter (DM) to 600 g DM [2]. As there is scientific evidence neither for an anthelmintic potential nor for the feed intake and milk performance of SF, we conducted a study with 30 goats. For a 20 days feeding experiment one group of 15 goats (A) was, additionally to their basic ration, daily fed with SF. The remaining 15 goats (group B) were fed with the basic ration only. Individual faecal egg counts (FEC) were conducted of all goats. Furthermore the effects of SF on the intake of the basic ration, milk yield and ingredients were tested. Total phenols (TP) and essential oils (EO) of 12 representative samples of the administered SF were determined by steam distillation and GS-MS-Analytic, respectively. SF contained 1,8 % TP. Limonene, bornyl acetate and beta caryophyllene were identified as the main EO. SF-feeding did not result in a reduction of GIN FEC (Fig 1). The intake of SF per animal and day was 261 +/- 0.22 g DM. Although SF reduced the basic forage intake significantly, SF increased the total DM intake significantly (A: 1948 +/- 93 g DM; B: 1797 +/- 93 g DM). SF feeding showed no effect on milk yield and milk components (Tab 1) [2]. Although farmers are convinced of the anthelmintic potential of SF, our short term study could not point to such an effect. It is possible that a prolonged period of SF administration is necessary in order for such effects to become apparent. [1] Jackson, N. F. und Coop, R. L. (2000). The development of anthelmintic resistance in sheep nematodes. Parasitology, 120(07):95 [2] Giebler-Schubert, Frauke (2013). Einsatz von Weißtanne zur Reduktion des Magen-Darm-Strongyliden-Befalls bei Ziegen: In-vivo-Versuche und Erfahrungswissen, Universität Hohenhei

Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure

Hamlet and the fall of the Berlin wall : the myth of interventionist Shakespeare performance

The critical reception of Heiner Müller’s 1990 Hamlet/Maschine at the Deutsches Theater in East Berlin epitomizes a trend of crediting GDR Shakespeare performance with political influence. Drawing on rehearsal notes and reviews, Oliver challenges the interventionist Shakespeare myth, contrasting the Deutsches Theater’s political involvement with the impact of its Hamlet production on events surrounding the fall of the Berlin Wall. Shakespeare’s capacity for political intervention at this point was limited by theater practitioners’ reliance on public funding, their close relationships with governmental authority, and an underlying distrust of the masses. Ultimately, GDR artists proved useful to the 1989 protest movement because they occupied a unique position at the interface of dissidence and power