Effects of an increase in summer precipitation on leaf, soil, and ecosystem fluxes of CO2 and H2O in a sotol grassland in Big Bend National Park, Texas

Global climate models predict that in the next century precipitation in desert regions of the USA will increase, which is anticipated to affect biosphere/atmosphere exchanges of both CO₂ and H₂O. In a sotol grassland ecosystem in the Chihuahuan Desert at Big Bend National Park, we measured the response of leaf-level fluxes of CO₂ and H₂O 1 day before and up to 7 days after three supplemental precipitation pulses in the summer (June, July, and August 2004). In addition, the responses of leaf, soil, and ecosystem fluxes of CO₂ and H₂O to these precipitation pulses were also evaluated in September, 1 month after the final seasonal supplemental watering event. We found that plant carbon fixation responded positively to supplemental precipitation throughout the summer. Both shrubs and grasses in watered plots had increased rates of photosynthesis following pulses in June and July. In September, only grasses in watered plots had higher rates of photosynthesis than plants in the control plots. Soil respiration decreased in supplementally watered plots at the end of the summer. Due to these increased rates of photosynthesis in grasses and decreased rates of daytime soil respiration, watered ecosystems were a sink for carbon in September, assimilating on average 31 mmol CO₂ m⁻² s⁻¹ ground area day⁻¹. As a result of a 25% increase in summer precipitation, watered plots fixed eightfold more CO₂ during a 24-h period than control plots. In June and July, there were greater rates of transpiration for both grasses and shrubs in the watered plots. In September, similar rates of transpiration and soil water evaporation led to no observed treatment differences in ecosystem evapotranspiration, even though grasses transpired significantly more than shrubs. In summary, greater amounts of summer precipitation may lead to short-term increased carbon uptake by this sotol grassland ecosystem.     

Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression

The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that expression of the coinhibitory molecule PD-1 predicts CD8+ antiviral T-cell exhaustion and may contribute to inadequate pathogen control. To investigate whether human CD8+ T cells express PD-1 and demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral and intrahepatic HCV-specific CD8+ T cells were examined. We found that in chronic HCV infection, peripheral HCV-specific T cells express high levels of PD-1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in contrast to those in the periphery, express not only high levels of PD-1 but also decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was HCV antigen specific and compartmentalized to the liver, the site of viral replication.     

Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.     

Chemoirradiation for Glioblastoma Multiforme: The National Cancer Institute Experience

Purpose

Standard treatment for glioblastoma (GBM) is surgery followed by radiation (RT) and temozolomide (TMZ). While there is variability in survival based on several established prognostic factors, the prognostic utility of other factors such as tumor size and location are not well established.

Experimental Design

The charts of ninety two patients with GBM treated with RT at the National Cancer Institute (NCI) between 1998 and 2012 were retrospectively reviewed. Most patients received RT with concurrent and adjuvant TMZ. Topographic locations were classified using preoperative imaging. Gross tumor volumes were contoured using treatment planning systems utilizing both pre-operative and post-operative MR imaging.

Results

At a median follow-up of 18.7 months, the median overall survival (OS) and progression-free survival (PFS) for all patients was 17.9 and 7.6 months. Patients with the smallest tumors had a median OS of 52.3 months compared to 16.3 months among patients with the largest tumors, P = 0.006. The patients who received bevacizumab after recurrence had a median OS of 23.3 months, compared to 16.3 months in patients who did not receive it, P = 0.0284. The median PFS and OS in patients with periventricular tumors was 5.7 and 17.5 months, versus 8.9 and 23.3 months in patients with non-periventricular tumors, P = 0.005.

Conclusions

Survival in our cohort was comparable to the outcome of the defining EORTC-NCIC trial establishing the use of RT+TMZ. This study also identifies several potential prognostic factors that may be useful in stratifying patients.     

Venous Thromboembolism in an Industrial North American City: Temporal Distribution and Association with Particulate Matter Air Pollution

Background

Emerging evidence, mainly from Europe and Asia, indicates that venous thromboembolism (VTE) occurs most often in winter. Factors implicated in such seasonality are low temperature-mediated exacerbation of coagulation and high levels of particulate matter (PM) air pollution. However, in contrast to most European and Asian cities, particulate matter pollution peaks in the summer in many North American cities.

Objectives

We aimed to exploit this geographical difference and examine the temporal distribution of VTE in a cold-weather, North American city, Detroit, with a summer PM peak. Our goal was thereby to resolve the influence of temperature and PM levels on VTE.

Methods

Our retrospective, analytical semi-ecological study used chart review to confirm 1,907 acute, ambulatory VTE cases, divided them by location (Detroit versus suburban), and plotted monthly VTE frequency distributions. We used Environmental Protection Agency data to determine the temporal distribution of PM pollution components in Detroit. Suburban PM air pollution is presumed negligible and therefore not monitored.

Results

Acute VTE cases in Detroit (1,490) exhibited a summer peak (June 24^th) and differed from both a uniform distribution (P<0.01) and also that of 1,123 no-VTE cases (P<0.02). Levels of 10 µm diameter PM and coarse particle (2.5 to 10 µm) PM also exhibited summer peaks versus a winter peak for 2.5 µm diameter PM. Contrary to their urban counterparts, suburban cases of acute VTE (417) showed no monthly variation.

Conclusions

The summer peak of acute VTE in Detroit indicates that low temperature is not a major factor in VTE pathogenesis. In contrast, concordance of the 10 µm diameter PM, coarse particle, and the Detroit VTE monthly distributions, combined with no monthly suburban VTE variation, is consistent with a role for PM pollution. Furthermore, divergence of the VTE and 2.5 µm PM distributions suggests that particle size may play a role.     

A review of the world's active seabird restoration projects

Within the past several decades, seabird populations have been actively restored in locales where they were reduced or extirpated. Chick translocation, acoustic vocalization playbacks, and decoys are now used widely to lure breeding seabirds to restoration sites. In this first worldwide review of seabird restoration projects we evaluate the factors affecting project success or failure and recommend future directions for management. We identified 128 active restoration projects that were implemented to protect 47 seabird species in 100 locales spanning 14 countries since active restoration methods were pioneered in 1973. Active seabird restoration can achieve conservation goals for threatened and endangered species, and for species affected by anthropogenic impacts (e.g., oil spills, invasive species, fisheries). It also can be used to relocate populations from undesired breeding locales to more favorable locations, and to establish multiple breeding locations to reduce risks posed by catastrophic events. Active restoration can help to restore ecological processes, as large seabird colonies function to cycle marine nutrients to terrestrial ecosystems and create habitats for commensal species. Active restoration is especially appropriate where the original causes of decline are no longer working to suppress colony establishment and growth. Successful restoration efforts require careful planning and long-term commitments. We introduce the different forms of active seabird restoration techniques, review their utility for different seabird species, and use case studies to suggest how to optimize this technique to restore seabird species globally. Wildlife managers can use this review to guide their seabird restoration projects in the planning, implementation, and monitoring stages; tailor their restoration to seabird-specific life histories; and identify areas for further research to improve restoration utility in the future. © 2011 The Wildlife Society.     

Using Sequence Similarity Networks for Visualization of Relationships Across Diverse Protein Superfamilies

The dramatic increase in heterogeneous types of biological data—in particular, the abundance of new protein sequences—requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity—GPCRs and kinases from humans, and the crotonase superfamily of enzymes—we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships.     

Methanogens with pseudomurein use diaminopimelate aminotransferase in lysine biosynthesis

Methanothermobacter thermautotrophicus uses lysine for both protein synthesis and cross-linking pseudomurein in its cell wall. A diaminopimelate aminotransferase enzyme from this methanogen (MTH0052) converts tetrahydrodipicolinate to l,l-diaminopimelate, a lysine precursor. This gene complemented an Escherichia coli diaminopimelate auxotrophy, and the purified protein catalyzed the transamination of diaminopimelate to tetrahydrodipicolinate. Phylogenetic analysis indicated this gene was recruited from anaerobic Gram-positive bacteria. These results expand the family of diaminopimelate aminotransferases to a diverse set of plant, bacterial and archaeal homologs. In contrast marine methanogens from the Methanococcales, which lack pseudomurein, appear to use a different diaminopimelate pathway for lysine biosynthesis.