Prevalence of \u3ci\u3eEimeria\u3c/i\u3e (Apicomplexa: Eimeriidae) in Reintroduced Gunnison\u27s Prairie Dogs (\u3ci\u3eCynomys gunnisoni\u3c/i\u3e)

Fecal samples from 54 Gunnison’s prairie dogs (Cynomys gunnisoni) from Albuquerque, NM were analyzed for the presence of coccidia and all were positive. They were then relocated to an abandoned prairie dog town on the Sevilleta Long Term Ecological Research (LTER) site. Six Eimeria species, E. callospermophili, E. cynomysis, E. pseudospermophili (new host record), E. spermophili, E. ludoviciani and E. vilasi (new host record) were found in Albuquerque animals, but only two species, E. callospermophili and E. vilasi were present in relocated hosts. A significant (P \u3c 0.05) reduction was seen in the prevalence of E. vilasi (72% vs. 13%) and in the prevalence of infections (P \u3c 0.05) with two or more Eimeria species (39% vs. 4%) in pre- and postrelocation animals. To assess the impact of the introduction of C. gunnisoni on the resident rodent population, feces were collected from 6 species of rodents. Five Eimeria species, E. arizonensis (Reithrodontomys), E. chobotari (Dipodomys, Perognathus), E. liomysis (Dipodomys), E. mohavensis (Dipodomys) and E. reedi (Perognathus) were found. We found no evidence of coccidia transfer among introduced and resident rodent species

Quantitative Intravital Microscopy of Liver Transport

poster abstractBecause if its unique ability to collect fluorescence images from deep in biological tissues, intravital multiphoton microscopy has become a valuable tool in several areas of biological research, including neurobiology, cancer biology and immunology. Here we describe methods of quantitative intravital microscopy that we have developed to characterize cholestatic liver injury. Special methods of tissue immobilization, multiphoton microscopy and digital image analysis were developed to support dynamic measurements of the kinetics of transport from the sinusoids into the cytosol and from the cytosol into the bile canaliculi in individual hepatocytes in vivo. Using a combination of different fluorescent probes, we have combined transport assays with measures of microvascular function, inflammation and cell viability to provide integrated measures of liver injury. The sensitivity of this approach is demonstrated in quantitative analyses of the acute effects of cholestatic drugs and the effects of chronic kidney disease

Immune evasion in cancer: mechanistic basis and therapeutic strategies

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through “equilibrium” and “senescence” before re- emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, deregulated metabolism etc. In this review, we will discuss the advances made towards understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7

Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability. Previously, we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inherited metastasis susceptibility gene. In this study, using orthotopic metastasis assays and genetically engineered mouse models, we show that one of the enzymatic subunits of the CCR4-NOT complex, Cnot7, is also a metastasis modifying gene. We demonstrate that higher expression of Cnot7 drives tumor cell autonomous metastatic potential, which requires its deadenylase activity. Furthermore, metastasis promotion by CNOT7 is dependent on interaction with CNOT1 and TOB1. CNOT7 ribonucleoprotein-immunoprecipitation (RIP) and integrated transcriptome wide analyses reveal that CNOT7-regulated transcripts are enriched for a tripartite 3’UTR motif bound by RNA-binding proteins known to complex with CNOT7, TOB1, and CNOT1. Collectively, our data support a model of CNOT7, TOB1, CNOT1, and RNA-binding proteins collectively exerting post-transcriptional control on a metastasis suppressive transcriptional program to drive tumor cell metastasis

Femtosecond Operation of the LCLS for User Experiments

In addition to its normal operation at 250pC, the LCLS has operated with 20pC bunches delivering X-ray beams to users with energies between 800eV and 2 keV and with bunch lengths below 10 fs FWHM. A bunch arrival time monitor and timing transmission system provide users with sub 50 fs synchronization between a laser and the X-rays for pump/probe experiments. We describe the performance and operational experience of the LCLS for short bunch experiments

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure