Immunomodulatory and pro-oncologic effects of ketamine and isoflurane anesthetics in a murine model.

INTRODUCTION: Volatile and intravenous anesthetics may worsen oncologic outcomes in basic science animal models. These effects may be related to suppressed innate and adaptive immunity, decreased immunosurveillance, and disrupted cellular signaling. We hypothesized that anesthetics would promote lung tumor growth via altered immune function in a murine model and tested this using an immunological control group of immunodeficient mice. METHODS: Lewis lung carcinoma cells were injected via tail vein into C57BL/6 immunocompetent and NSG immunodeficient mice during exposure to isoflurane and ketamine versus controls without anesthesia. Mice were imaged on days 0, 3, 10, and 14 post-tumor cell injection. On day 14, mice were euthanized and organs fixed for metastasis quantification and immunohistochemistry staining. We compared growth of tumors measured from bioluminescent imaging and tumor metastasis in ex vivo bioluminescent imaging of lung and liver. RESULTS: Metastases were significantly greater for immunocompromised NSG mice than immunocompetent C57BL/6 mice over the 14-day experiment (partial η2 = 0.67, 95% CI = 0.54, 0.76). Among immunocompetent mice, metastases were greatest for mice receiving ketamine, intermediate for those receiving isoflurane, and least for control mice (partial η2 = 0.88, 95% CI = 0.82, 0.91). In immunocompetent mice, significantly decreased T lymphocyte (partial η2 = 0.83, 95% CI = 0.29, 0.93) and monocyte (partial η2 = 0.90, 95% CI = 0.52, 0.96) infiltration was observed in anesthetic-treated mice versus controls. CONCLUSIONS: The immune system appears central to the pro-metastatic effects of isoflurane and ketamine in a murine model, with decreased T lymphocytes and monocytes likely playing a role.

Balancing the management of powerline right-of-way corridors for humans and nature.

Green space in electric powerline rights of way (ROWs) can be a source of both ecosystem services and disservices in developed landscapes. Vegetation management within the ROW may influence tradeoffs that maximize potential services or disservices. Frequently mowed ROWs managed as lawn harbor less biodiversity than ROWs with taller vegetation, but may be preferred by people for aesthetic reasons and because they provide space for recreational activities. We conducted a survey of residents living by ROWs in the Chicago, Illinois USA metropolitan area to determine if residents prefer ROWs managed as lawn over those managed as native prairies or allowed to grow freely with only woody vegetation removed ("old-field ROWs"). We found that respondents did not prefer mowed over prairie or old-field ROWs. Furthermore, respondents living near mowed ROWs were least likely to think that the ROW is attractive, while those living near prairie ROWs were most likely to. Survey respondents tended to believe it was important for ROWs to provide habitat for wildlife, and wildlife observation was the most frequently reported activity conducted in the ROW. Finally, we found that a respondent's perception of biodiversity in the ROW was more closely correlated with positive feelings about the ROW than measured biodiversity levels. Our results suggest that managing ROWs for wildlife habitat is fully compatible with managing them for human enjoyment. We therefore recommend that where possible, ROW vegetation is managed in a more "natural" way than lawn because it has the potential to benefit both wildlife and people.

When a pest is not a pest: Birds indirectly increase defoliation but have no effect on yield of soybean crops.

Natural habitats near agricultural systems can be sources of both ecosystem services and disservices on farms. Ecosystem disservices, those aspects of an ecosystem that have negative impacts on humans, may disproportionately affect conservation decisions made by farmers. Birds, in particular, can have complex effects on crops, ranging from positive to neutral to negative. Therefore, it is important to quantify them in a meaningful way. Birds may be more abundant on farms near natural areas and may provide ecosystem services by consuming insect pests. However, when birds consume beneficial predatory arthropods rather than pest species (intraguild predation), they can provide a disservice to the farmer if the intraguild predation decreases crop yield. We studied bird intraguild predation in Illinois (USA) at six soybean fields adjacent to grasslands that provided source habitat for bird populations. We placed cages over soybean crops, which excluded birds but allowed access to arthropods, and measured differences in leaf damage and crop yield of plants in control and exclosure plots. We also conducted point counts at each site to quantify the bird communities. We found that plants within the bird exclosures had lower levels of leaf damage by pests than those in control plots, but there was no resulting effect on crop yield. We also found that sites with higher bird abundance had higher levels of leaf damage by pests, but bird species richness was not a significant predictor of leaf damage. These results suggest that although birds may have released pests through intraguild predation, there was no net disservice when considering crop yield, the variable most important to stakeholders.

Birds suppress pests in corn but release them in soybean crops within a mixed prairie/agriculture system.

Birds provide ecosystem services (pest control) in many agroecosystems and have neutral or negative ecological effects (disservices) in others. Large-scale, conventional row crop agriculture is extremely widespread globally, yet few studies of bird effects take place in these agroecosystems. We studied indirect effects of insectivorous birds on corn and soybean crops in fields adjacent to a prairie in Illinois (USA). We hypothesized that prairie birds would forage for arthropods in adjacent crop fields and that the magnitude of services or disservices would decrease with distance from the prairie. We used bird-excluding cages over crops to examine the net effect of birds on corn and soybean grain yield. We also conducted DNA metabarcoding to identify arthropod prey in fecal samples from captured birds. Our exclosure experiments revealed that birds provided net services in corn and net disservices in soybeans. Distance from prairie was not a significant predictor of exclosure treatment effect in either crop. Many bird fecal samples contained DNA from both beneficial arthropods and known economically significant pests of corn, but few economically significant pests of soybeans. Song Sparrows (Melospiza melodia), one of our most captured species, most commonly consumed corn rootworms, an economically significant pest of corn crops. We estimated that birds in this system provided a service worth approximately US $275 ha-1 in corn yield gain, and a disservice valued at approximately $348 ha-1 in soybean yield loss. Our study is the first to demonstrate that birds can provide substantial and economically valuable services in field corn, and disservices in soybean crops. The contrasting findings in the 2 crop systems suggest a range of bird impacts within widespread agroecosystems and demonstrate the importance of quantifying net trophic effects.

Las aves brindan servicios ecosistémicos (control de plagas) en muchos agro-ecosistemas y tienen efectos ecológicos neutrales o negativos (deservicios) en otros. La agricultura convencional a gran escala de cultivos en hilera está ampliamente distribuida a escala global, pero a pesar de esto se han realizado pocos estudios de los efectos de las aves en estos agro-ecosistemas. Estudiamos los efectos indirectos de las aves insectívoras en cultivos de maíz y soja en campos adyacentes a una pradera en Illinois (EEUU). Hipotetizamos que las aves de pradera forrajearían en busca de artrópodos en los campos de cultivo adyacentes y que la magnitud de los servicios o deservicios disminuiría con la distancia desde la pradera. Usamos jaulas de exclusión de aves sobre los cultivos para examinar el efecto neto de las aves en el rendimiento de granos de maíz y soja. También utilizamos el método de código de barras de ADN para identificar presas de artrópodos en las muestras de heces de las aves capturadas. Nuestros experimentos de exclusión revelaron que las aves brindaron servicios netos en el maíz y deservicios netos en la soja. La distancia a las praderas no fue un predictor significativo del efecto del tratamiento de exclusión en ninguno de los cultivos. Muchas muestras de heces de aves contuvieron ADN tanto de artrópodos benéficos como de plagas económicamente significativas de maíz, pero de pocas plagas económicamente significativas de soja. Melospiza melodia, una de nuestras especies más capturadas, mayormente consumió el gusano de la raíz del maíz, una plaga económicamente significativa de este cultivo. Estimamos que las aves en este sistema brindaron un servicio valuado en aproximadamente US $275 ha­1 de ganancias en rendimiento de maíz, y un deservicio valuado en aproximadamente $348 ha­1 de pérdidas en rendimiento de soja. Nuestro estudio es el primero en demostrar que las aves pueden brindar servicios substanciales y económicamente valiosos en los campos de maíz y deservicios en los cultivos de soja. Los hallazgos contrastantes en los dos sistemas de cultivo sugieren un rango de impactos de las aves dentro de los agro-ecosistemas ampliamente distribuidos y demuestra la importancia de cuantificar los efectos tróficos netos.

Competition and habitat quality influence age and sex distribution in wintering rusty blackbirds.

Bird habitat quality is often inferred from species abundance measures during the breeding and non-breeding season and used for conservation management decisions. However, during the non-breeding season age and sex classes often occupy different habitats which suggest a need for more habitat-specific data. Rusty Blackbird (Euphagus carolinus) is a forested wetland specialist wintering in bottomland hardwood forests in the south-eastern U. S. and belongs to the most steeply declining songbirds in the U.S. Little information is available to support priority birds such as the Rusty Blackbird wintering in this threatened habitat. We assessed age and sex distribution and body condition of Rusty Blackbirds among the three major habitats used by this species in the Lower Mississippi Alluvial Valley and also measured food availability. Overall, pecan groves had the highest biomass mainly driven by the amount of nuts. Invertebrate biomass was highest in forests but contributed only a small percentage to overall biomass. Age and sex classes were unevenly distributed among habitats with adult males primarily occupying pecan groves containing the highest nut biomass, females being found in forests which had the lowest nut biomass and young males primarily staying in forest fragments along creeks which had intermediate nut biomass. Males were in better body condition than females and were in slightly better condition in pecan groves. The results suggest that adult males occupy the highest quality habitat and may competitively exclude the other age and sex classes.

Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL.

Proteolytic resistance of Notch prior to ligand binding depends on the structural integrity of a negative regulatory region (NRR) of the receptor that immediately precedes the transmembrane segment. The NRR includes the 3 Lin12/Notch repeats and the juxtamembrane heterodimerization domain, the region of Notch1 most frequently mutated in T-cell acute lymphoblastic leukemia lymphoma (T-ALL). Here, we report the x-ray structure of the Notch1 NRR in its autoinhibited conformation. A key feature of the Notch1 structure that maintains its closed conformation is a conserved hydrophobic plug that sterically occludes the metalloprotease cleavage site. Crystal packing interactions involving a highly conserved, exposed face on the third Lin12/Notch repeat suggest that this site may normally be engaged in intermolecular or intramolecular protein-protein interactions. The majority of known T-ALL-associated point mutations map to residues in the hydrophobic interior of the Notch1 NRR. A novel mutation (H1545P), which alters a residue at the crystal-packing interface, leads to ligand-independent increases in signaling in reporter gene assays despite only mild destabilization of the NRR, suggesting that it releases the autoinhibitory clamp on the heterodimerization domain imposed by the Lin12/Notch repeats. The Notch1 NRR structure should facilitate a search for antibodies or compounds that stabilize the autoinhibited conformation.

Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly.

Human HIRA, ASF1a, ASF1b and CAF-1 are evolutionally conserved histone chaperones that form multiple functionally distinct chromatin-assembly complexes, with roles linked to diverse nuclear process, such as DNA replication and formation of heterochromatin in senescent cells. We report the crystal structure of an ASF1a-HIRA heterodimer and a biochemical dissection of ASF1a's mutually exclusive interactions with HIRA and the p60 subunit of CAF-1. The HIRA B domain forms an antiparallel beta-hairpin that binds perpendicular to the strands of the beta-sandwich of ASF1a, via beta-sheet, salt bridge and van der Waals contacts. The N- and C-terminal regions of ASF1a and ASF1b determine the different affinities of these two proteins for HIRA, by contacting regions outside the HIRA B domain. CAF-1 p60 also uses B domain-like motifs for binding to ASF1a, thereby competing with HIRA. Together, these studies begin to define the molecular determinants of assembly of functionally diverse macromolecular histone chaperone complexes.