European earwig, Forficula auricularia L. (Dermaptera: Forficulidae), at the Hanford Reach National Monument, Washington State

The European earwig, Forficula auricularia L., was surveyed using pitfall traps at 3 sites at the Hanford Reach National Monument in south central Washington State. Pitfall traps were collected weekly from April 2002 through April 2003. The earwig was consistently taken during all months of the year at a disturbed, weedy site along the Columbia River (White Bluffs Ferry site) but was rare or not collected in 2 less-disturbed shrubsteppe habitats. Highest numbers occurred during April–May, when immatures accounted for the majority of the catch; immatures reached the adult stage during mid-July, and the species is univoltine at the site. Possible reasons why earwigs have not colonized the monument’s shrubsteppe habitat include the arid climate with lack of available moisture, especially for breeding purposes, and a lack of burrow sites. La tijereta Europea, Forficula auricularia L., fue estudiada usando trampas de caída en tres sitios del Hanford Reach National Monument en el sur del estado de Washington. Se colectaron los contenidos de las trampas de caída semanalmente desde abril de 2002 hasta abril de 2003. La tijereta apareció constantemente durante todos los meses del año en un sitio perturbado de vegetación herbácea en la orilla del Río Columbia (el lugar del antiguo transbordador White Bluffs) pero su colecta fue escasa o nula en dos hábitats de estepa arbustiva menos perturbados. Los mayores números ocurrieron durante abril y mayo cuando los organismos inmaduros representaron la mayoría de los especímenes capturados; éstos alcanzaron la etapa adulta a mediados de julio y la especie es univoltina en este sitio. Posibles causas de que las tijeretas no hayan colonizado el hábitat de estepa arbustiva del Monumento podrían incluir su clima árido carente de agua disponible, especialmente para la reproducción, y una falta de sitios para madrigueras.     

Initial survey of acetylene reduction and selected microorganisms in the feces of 19 species of mammals

Nitrogen-fixing bacteria, as demonstrated by the acetylene reduction method; yeasts, and actinomycetes were found in feces of mammals collected from St. Lawrence Island, Alaska, to the North Carolina-Tennessee border. The mammals, representing four orders and 19 species, occupy a wide variety of habitats and may play an important role in dispersing microorganisms vital to the ecosystem.     

Mycophagy of red-backed voles, Clethrionomys californicus and C. gapperi

We examined stomach contents of 426 Clethrionomys , 217 C. californicus from western Oregon and 209 C. gapperi from widely scattered areas across North America. Clethrionomys californicus consumed fungi of 28 genera. Clethrionomys gapperi from the Rocky Mountains westward consumed fungi of 23 genera, whereas C. gapperi east of the Rocky Mountains consumed fungi of 7 genera. This study supports the conclusions of an earlier study, limited to Oregon and Washington, that food habits of C. californicus and C. gapperi are more closely related to habitat than to species or subspecies of vole.     

Novel recursive inference algorithm for discrete dynamic Bayesian networks

Dynamic Bayesian networks (DBNs) can effectively perform modeling and qualitative reasoning for many dynamic systems. However, most of its inference algorithms involve complicated graphical transformations that are hard to program and time-consuming to compute. This article proposes a new recursive inference algorithm, which is a purely numerical method derived from probability theory and the characteristics of Bayesian networks to do both on-line and off-line inferences in discrete DBNs. The most prominent advantages of this novel approach include: (1) it is an exact inference algorithm, thus its accuracy and stability can be guaranteed, (2) it avoids the complex graphical transformation so as to remarkably improve the inference speed, and (3) its concise recursive formulae facilitate programming of both forwards and backwards pass. All of these issues are verified by accurate mathematical derivation as well as a couple of application examples with comparison between the new algorithm and the two most prevailing inference approaches of discrete DBNs – the interface algorithm and the forwards–backwards algorithm.     

Hsp72 preserves muscle function and slows progression of severe muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.     

Systematic identification of genomic markers of drug sensitivity in cancer cells

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.     

Dissecting the genomic complexity underlying medulloblastoma

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.     

APJ acts as a dual receptor in cardiac hypertrophy

Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Gαi and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of β-arrestins or by pharmacological doses of apelin acting through Gαi. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy.