Behavioral testing and preliminary analysis of the hamster visual system

The dependence of visual orienting ability in hamsters on the axonal projections from retina to midbrain tectum provides experimenters with a good model for assessing the functional regeneration of this central nervous system axonal pathway. For reliable testing of this behavior, male animals at least 10-12 weeks old are prepared by regular pretesting, with all procedures carried out during the less active portion of the daily activity cycle. Using a sunflower seed attached to a small black ball held at the end of a stiff wire, and avoiding whisker contact, turning movements toward visual stimuli are video recorded from above. Because at the eye level, the nasal-most 30° of the visual field can be seen by both the eyes, this part of the field is avoided in assessments of a single side. Daily sessions consist of ten presentations per side. Measures are frequency of responding and detailed turning trajectories. Complete assessment of the functional return of behavior in this testing paradigm takes 3-6 months to complete.postprin

Comparison of sapwood invasion by three Phytophthora spp.in different hosts

Many Phytophthora spp. have recently been isolated from native vegetation in Western Australia. As their pathogenicity is often unknown, it is not possible to provide advice to land managers on the impact of site infestation on native plants and how these infestations should be managed. We describe a rapid screening method based on sapwood invasion that has been used to compare the pathogenicity of Phytophthora arenaria, P. cinnamomi and P. multivora. Radial invasion into the xylem of six banksias and three eucalypts was assessed in an excised branch assay in summer and winter. Branches were wound inoculated and invasion was assessed by plating from a strip of tissue cut across the stem at the inoculation point and at 40 mm above and below. A symptomless infection had established in both the bark and sapwood within 6 days. P. arenaria was only isolated from the strip of tissue at the inoculation point. P. cinnamomi was isolated from the sapwood of Banksia attenuata, B. burdettii, B. menziesii and B. speciosa 40 mm above or below the inoculation point in some experiments. P. multivora was isolated from B. speciosa 40 mm below the inoculation point in one experiment. Hyphae of both species were seen in both ray parenchyma cells and xylem vessels. The invasiveness of the Phytophthora spp. was compared on the two groups of hosts using scores for sapwood invasion at the inoculation point. For banksias, P. cinnamomi and P. multivora had significantly higher invasion scores on banksias than P. arenaria but were not significantly different to one another. There was no significant difference between the three Phytophthora spp. on the eucalypt hosts. Assessing sapwood invasion provides a rapid, inexpensive and biologically meaningful way of screening the many Phytophthora spp. that have been isolated from native vegetation

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.United States. National Institutes of Health (R01GM107536)Alex's Lemonade Stand FoundationHoward Hughes Medical InstituteBoston Children's Hospital. Manton Center for Orphan Disease ResearchNational Institute of General Medical Sciences (U.S.) (T32GM007753

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms