SHORT COMMUNICATION: Complementary tumor induction in neural grafts exposed to N-ethyl-N-nitrosourea and an activated myc gene

Using a combination of transplacental carcinogen exposure and retrovirus-mediated oncogene transfer into fetal brain transplants, we have studied complementary transformation by N-ethyl-N-nitrosourea (NEU) and the v-myc oncogene in the nervous system. Previous experiments had demonstrated that both agents will not induce tumors independently whereas simultaneous expression of v-H-ras and v-gag/myc exerted a powerful transforming potential in neural grafts. In order to identify other genetic alterations that co-operate with an activated myc gene, the neurotropic carcinogen NEU was used to generate mutations of cellular genes. On embryonic day 14 (ED14), pregnant donor animals (F344 rats) received a single i.v. dose of NEU (50 mg/kg). Twenty-four hours later (ED15), the fetal brains were removed, triturated and incubated with a retroviral vector carrying the v-gag/myc oncogene. Subsequently, these primary cell suspensions were transplanted stereotactically into the caudate-putamen of syngenic adult recipients. After latency periods of 3-6 months, 5 of 10 recipients harboring ED15 fetal brain transplants developed malignant, poorly differentiated neuroectodermal tumors in the grafts. No tumor development was observed in seven recipients harboring ED16 neural grafts. Cell lines were established from three tumors and the 110 kd gag/myc fusion protein encoded by the retroviral construct was identified in the tumors by Western blotting. Several candidate genes for mutational activation by NEU including the H-ras, K-ras and neu oncogenes were analyzed for specific point mutations by polymerase chain reaction (PCR) and direct DNA sequencing of the PCR products. However, no mutations were found in any of these genes. These findings lend further support to the multistep hypothesis of neoplastic transformation in the brain. The tumors induced in this model provide an interesting tool for the identification of genes that co-operate with an activated myc gene in neurocarcinogenesi

Quark-gluon vertex in arbitrary kinematics

We compute the quark-gluon vertex in quenched lattice QCD, in the Landau gauge using an off-shell mean-field O(a)-improved fermion action. The complete vertex is computed in two specific kinematical limits, while the Dirac-vector part is computed for arbitrary kinematics. We find a nontrivial and rich tensor structure, including a substantial infrared enhancement of the interaction strength regardless of kinematics.Comment: 6 pages, 8 figures, talk by JIS at QCD Down Under, Adelaide, 10-19 March 200

Current quark mass effects on chiral phase transition of QCD in the improved ladder approximation

Current quark mass effects on the chiral phase transition of QCD is studied in the improved ladder approximation. An infrared behavior of the gluon propagator is modified in terms of an effective running coupling. The analysis is based on a composite operator formalism and a variational approach. We use the Schwinger-Dyson equation to give a ``normalization condition'' for the Cornwall-Jackiw-Tomboulis effective potential and to isolate the ultraviolet divergence which appears in an expression for the quark-antiquark condensate. We study the current quark mass effects on the order parameter at zero temperature and density. We then calculate the effective potential at finite temperature and density and investigate the current quark mass effects on the chiral phase transition. We find a smooth crossover for $T>0$, $\mu=0$ and a first-order phase transition for $\mu>0$, T=0. Critical exponents are also studied and our model gives the classical mean-field values. We also study the temperature dependence of masses of scalar and pseudoscalar bosons. A critical end point in the $T$-$\mu$ plane is found at $T \sim 100$ MeV, $\mu \sim 300$ MeV.Comment: 19 pages, 13 figure

State sampling dependence of the Hopfield network inference

The fully connected Hopfield network is inferred based on observed magnetizations and pairwise correlations. We present the system in the glassy phase with low temperature and high memory load. We find that the inference error is very sensitive to the form of state sampling. When a single state is sampled to compute magnetizations and correlations, the inference error is almost indistinguishable irrespective of the sampled state. However, the error can be greatly reduced if the data is collected with state transitions. Our result holds for different disorder samples and accounts for the previously observed large fluctuations of inference error at low temperatures.Comment: 4 pages, 1 figure, further discussions added and relevant references adde

Maturation of the gastric microvasculature in Xenopus laevis (Lissamphibia, Anura) occurs at the transition from the herbivorous to the carnivorous lifestyle, predominantly by intussuceptive microvascular growth (IMG): a scanning electron microscope study of microvascular corrosion casts and correlative light microscopy

The microvascular bed of the stomach of Xenopus laevis and the changes it undergoes when the herbivorous tadpole becomes a carnivorous adult were studied by scanning electron microscopy of vascular corrosion casts and light microscopy of stained tissue sections. In tadpoles an upper and a lower gastric artery supplied, and upper, middle and lower medial and lateral gastric veins drained the vertically extending stomach. During metamorphosis, the stomach gained a horizontal cranio-caudal extension and vessels accordingly become dorsal and ventral gastric arteries, and anterior, middle and posterior gastric veins, respectively. Up to stage 64 (late climax) mucosal capillaries formed a polygonal network of wide immature-looking capillaries ensheathing gastric glands in a basket-like manner. From stage 64 onwards, blood vessels of the stomach appeared mature, revealed a clear hierarchy and were correlated closely with the histomorphology of the stomach, which had also gained the adult pattern. Within the gastric mucosa, ascending arterioles branched in a fountain-like pattern into wide subepithelial capillaries establishing a centripetal blood flow along the gastric glands, which makes an ultrashort control loop of glandular cells within the branched tubular gastric glands very unlikely. Formation of the stomach external muscular layer started at stage 57 when smooth muscle cells locally formed a single longitudinal and one-to-two single circular layers. Abundant signs of intussusceptive microvascular growth and rare vascular sprouts in vascular corrosion casts indicated that the larval-to-adult microvascular pattern formation of the stomach of Xenopus laevis Daudin occurs predominantly by non-sprouting angiogenesis

Phylogenetic placement of environmental sequences using taxonomically reliable databases helps to rigorously assess dinophyte biodiversity in Bavarian lakes (Germany).

1. Reliable determination of organisms is a prerequisite to explore their spatial and temporal occurrence and to study their evolution, ecology, and dispersal. In Europe, Bavaria (Germany) provides an excellent study system for research on the origin and diversification of freshwater organisms including dinophytes, due to the presence of extensive lake districts and ice age river valleys. Bavarian freshwater environments are ecologically diverse and range from deep nutrient‐poor mountain lakes to shallow nutrient‐rich lakes and ponds. 2. We obtained amplicon sequence data (V4 region of small subunit‐rRNA, c. 410 bp long) from environmental samples collected at 11 sites in Upper Bavaria. We found 186 operational taxonomic units (OTUs) associated with Dinophyceae that were further classified by means of a phylogenetic placement approach. 3. The maximum likelihood tree inferred from a well‐curated reference alignment comprised a systematically representative set of 251 dinophytes, covering the currently known molecular diversity and OTUs linked to type material if possible. Environmental OTUs were scattered across the reference tree, but accumulated mostly in freshwater lineages, with 79% of OTUs placed in either Apocalathium, Ceratium, or Peridinium, the most frequently encountered taxa in Bavaria based on morphology. 4. Twenty‐one Bavarian OTUs showed identical sequences to already known and vouchered accessions, two of which are linked to type material, namely Palatinus apiculatus and Theleodinium calcisporum. Particularly within Peridiniaceae, delimitation of Peridinium species was based on the intraspecific sequence variation. 5. Our approach indicates that high‐throughput sequencing of environmental samples is effective for reliable determination of dinophyte species in Bavarian lakes. We further discuss the importance of well‐curated reference databases that remain to be developed in the future

Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.

TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease

Collective perspective on advances in Dyson-Schwinger Equation QCD

We survey contemporary studies of hadrons and strongly interacting quarks using QCD's Dyson-Schwinger equations, addressing: aspects of confinement and dynamical chiral symmetry breaking; the hadron spectrum; hadron elastic and transition form factors, from small- to large-Q^2; parton distribution functions; the physics of hadrons containing one or more heavy quarks; and properties of the quark gluon plasma.Comment: 56 pages. Summary of lectures delivered by the authors at the "Workshop on AdS/CFT and Novel Approaches to Hadron and Heavy Ion Physics," 2010-10-11 to 2010-12-03, hosted by the Kavli Institute for Theoretical Physics, China, at the Chinese Academy of Science