Positive Interactions between Desert Granivores: Localized Facilitation of Harvester Ants by Kangaroo Rats

Facilitation, when one species enhances the environment or performance of another species, can be highly localized in space. While facilitation in plant communities has been intensely studied, the role of facilitation in shaping animal communities is less well understood. In the Chihuahuan Desert, both kangaroo rats and harvester ants depend on the abundant seeds of annual plants. Kangaroo rats, however, are hypothesized to facilitate harvester ants through soil disturbance and selective seed predation rather than competing with them. I used a spatially explicit approach to examine whether a positive or negative interaction exists between banner-tailed kangaroo rat (Dipodomys spectabilis) mounds and rough harvester ant (Pogonomyrmex rugosus) colonies. The presence of a scale-dependent interaction between mounds and colonies was tested by comparing fitted spatial point process models with and without interspecific effects. Also, the effect of proximity to a mound on colony mortality and spatial patterns of surviving colonies was examined. The spatial pattern of kangaroo rat mounds and harvester ant colonies was consistent with a positive interspecific interaction at small scales (<10 m). Mortality risk of vulnerable, recently founded harvester ant colonies was lower when located close to a kangaroo rat mound and proximity to a mound partly predicted the spatial pattern of surviving colonies. My findings support localized facilitation of harvester ants by kangaroo rats, likely mediated through ecosystem engineering and foraging effects on plant cover and composition. The scale-dependent effect of kangaroo rats on abiotic and biotic factors appears to result in greater founding and survivorship of young colonies near mounds. These results suggest that soil disturbance and foraging by rodents can have subtle impacts on the distribution and demography of other species

Tick-, mosquito-, and rodent-borne parasite sampling designs for the National Ecological Observatory Network

Parasites and pathogens are increasingly recognized as significant drivers of ecological and evolutionary change in natural ecosystems. Concurrently, transmission of infectious agents among human, livestock, and wildlife populations represents a growing threat to veterinary and human health. In light of these trends and the scarcity of long-term time series data on infection rates among vectors and reservoirs, the National Ecological Observatory Network (NEON) will collect measurements and samples of a suite of tick-, mosquito-, and rodent-borne parasites through a continental-scale surveillance program. Here, we describe the sampling designs for these efforts, highlighting sampling priorities, field and analytical methods, and the data as well as archived samples to be made available to the research community. Insights generated by this sampling will advance current understanding of and ability to predict changes in infection and disease dynamics in novel, interdisciplinary, and collaborative ways. (Résumé d'auteur

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge";: Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma

CVE: an R package for interactive variant prioritisation in precision oncology

BACKGROUND: An increasing number of precision oncology programmes are being launched world-wide. To support this development, we present the Cancer Variant Explorer (CVE), an R package with an interactive Shiny web browser interface. RESULTS: Leveraging Oncotator and the Drug Gene Interaction Database, CVE offers exploration of variants within single or multiple tumour exomes to identify drivers, resistance mechanisms and to assess druggability. We present example applications including the analysis of an individual patient and a cohort-wide study, and provide a first extension of CVE by adding a tumour-specific co-expression network. CONCLUSIONS: The CVE package allows interactive variant prioritisation to expedite the analysis of cancer sequencing studies. Our framework also includes the prioritisation of druggable targets, allows exploratory analysis of tissue specific networks and is extendable for specific applications by virtue of its modular design. We encourage the use of CVE within translational research studies and molecular tumour boards. The CVE package is available via Bioconductor ( http://bioconductor.org/packages/CVE/).AM was supported by the National Institute for Health Research, Biomedical Research Centre (NIHR Cambridge BRC) and the German National Academic Foundation (Studienstiftung des deutschen Volkes). We would like also to acknowledge the support of The University of Cambridge, Cancer Research UK Cambridge Centre and Hutchison Whampoa Limited. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 337905. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The ERK and JNK pathways in the regulation of metabolic reprogramming.

Most tumor cells reprogram their glucose metabolism as a result of mutations in oncogenes and tumor suppressors, leading to the constitutive activation of signaling pathways involved in cell growth. This metabolic reprogramming, known as aerobic glycolysis or the Warburg effect, allows tumor cells to sustain their fast proliferation and evade apoptosis. Interfering with oncogenic signaling pathways that regulate the Warburg effect in cancer cells has therefore become an attractive anticancer strategy. However, evidence for the occurrence of the Warburg effect in physiological processes has also been documented. As such, close consideration of which signaling pathways are beneficial targets and the effect of their inhibition on physiological processes are essential. The MAPK/ERK and MAPK/JNK pathways, crucial for normal cellular responses to extracellular stimuli, have recently emerged as key regulators of the Warburg effect during tumorigenesis and normal cellular functions. In this review, we summarize our current understanding of the roles of the ERK and JNK pathways in controlling the Warburg effect in cancer and discuss their implication in controlling this metabolic reprogramming in physiological processes and opportunities for targeting their downstream effectors for therapeutic purposes.Brunel Research Initiative & Enterprise Fund, Brunel University of London (to CB), Kay Kendall Leukemia Fund (KKL443) (to CB), 250 Great Minds Fellowship, University of Leeds (to SP), AMMF Cholangiocarcinoma Charity (to SP and PMC), and Bloodwise (17014) (to SP and CB)

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints. These changes in the treatment landscape have dramatically improved patient outcomes, with the median overall survival of patients with advanced-stage melanoma increasing from approximately 9 months before 2011 to at least 2 years - and probably longer for those with BRAF-V600-mutant disease. Herein, we review the clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma. Mechanisms of resistance and biomarkers of response to BRAF-targeted treatments and immunotherapies are discussed, and the contrasting clinical benefits and limitations of these therapies are explored. We summarize the state of the field and outline a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma