Impairment of placental growth is a major factor contributing to intrauterine growth retardation (IUGR) in both human pregnancy and animal production. Results of recent studies indicate that ...administration of l-arginine (Arg) to gestating pigs or sheep with IUGR fetuses can enhance fetal growth. However, the underlying mechanisms are largely unknown. The present study tested the hypothesis that Arg stimulates the mammalian target of rapamycin (mTOR) signaling pathway and protein synthesis in porcine conceptus trophectoderm (pTr2) cells. The cells were cultured for 4 days in Arg-free Dulbecco's modified Eagle's Ham medium containing 10, 50, 100, 200, 350 or 500 μM Arg. Cell numbers, protein synthesis and degradation, as well as total and phosphorylated levels of mTOR, ribosomal protein S6 kinase 1 (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4EBP1), were determined. The pTr2 cells exhibited time (0–6 days)- and Arg concentration (10–350 μM)-dependent increases in proliferation. Addition of 100 and 350 μM Arg to culture medium dose-dependently increased (a) protein synthesis and decreased protein degradation and (b) the abundance of total and phosphorylated mTOR, p70S6K and 4EBP1 proteins. Effects of 350 μM Arg on intracellular protein turnover were only modestly affected when nitric oxide synthesis was inhibited. Collectively, these results indicate a novel and important role for Arg in promoting growth of porcine placental cells largely via a nitric-oxide-independent pathway. Additionally, these findings help to explain beneficial effects of Arg supplementation on improving survival and growth of embryos/fetuses in mammals.
The negative effects of roads on wildlife populations are a growing concern. Movement corridors and road-kill data are typically used to prioritize road segments for mitigation measures. Some ...research suggests that locations where animals move across roads following corridors coincide with locations where they are often killed by vehicles. Other research indicates that corridors and road-kill rarely occur in the same locations. We compared movement corridor and road mortality models as means of prioritizing road segments for mitigation for five species of felids in Brazil: tiger cats (
Leopardus tigrinus
and
Leopardus
guttulus
were analyzed together), ocelot (
Leopardus pardalis
), jaguarundi (
Herpailurus yagouaroundi
), and puma (
Puma concolor
). We used occurrence data for each species and applied circuit theory to identify potential movement corridors crossed by roads. We used road-kill records for each species and applied maximum entropy to determine where mortality was most likely to occur on roads. Our findings suggest that movement corridors and high road mortality are not spatially associated. We suggest that differences in the behavioral state of the individuals in the species occurrence and road-kill data may explain these results. We recommend that the road segments for which the results from the two methods agree (~5300 km for all studied species combined at 95th percentile) should be high-priority candidates for mitigation together with road segments identified by at least one method in areas where felids occur in low population densities or are threatened by isolation effects.
This paper examines the dynamics of violence in the Palestinian-Israeli conflict during the Second Intifada. Using data on the daily number of fatalities between September 2000 and January 2005, we ...estimate reaction functions for both Israelis and Palestinians and find evidence of Granger causality from Palestinian to Israeli violence, but not vice versa. This finding is consistent using either the incidence or level of fatalities and is robust to the specification of the lag structure and the level of time aggregation. We find no evidence that the Palestinians and Israelis are engaged in a predictable “tit-for-tat” cycle of violence. (JEL D74, H56, O17)
We present the design, fabrication, and characterization of integrated Bragg gratings in silicon-on-insulator slot waveguides. The Bragg gratings are formed with sidewall corrugations, either on the ...inside or on the outside of the waveguide. We demonstrate resonators implemented using phase-shifted Bragg gratings in slot waveguides, showing quality factors up to 3 × 10(4). Due to the strong optical confinement in the slot, these devices are promising for optical sensing applications. The devices were fabricated using a CMOS-compatible process, facilitating high-volume and low-cost production.
Metastatic renal cell carcinoma (RCC) remains an incurable disease for most patients highlighting an urgent need for new treatments. However, the preclinical investigation of new therapies is limited ...by traditional two-dimensional (2D) cultures which do not recapitulate the properties of tumor cells within a collagen extracellular matrix (ECM), while human tumor xenografts are time-consuming, expensive and lack adaptive immune cells. We report a rapid and economical human microphysiological system ("RCC-on-a-chip") to investigate therapies targeting RCC spheroids in a 3D collagen ECM. We first demonstrate that culture of RCC cell lines A498 and RCC4 in a 3D collagen ECM more faithfully reproduces the gene expression program of primary RCC tumors compared to 2D culture. We next used bortezomib as a cytotoxin to develop automated quantification of dose-dependent tumor spheroid killing. We observed that viable RCC spheroids exhibited collective migration within the ECM and demonstrated that our 3D system can be used to identify compounds that inhibit spheroid collective migration without inducing cell death. Finally, we demonstrate the RCC-on-a-chip as a platform to model the trafficking of tumor-reactive T cells into the ECM and observed antigen-specific A498 spheroid killing by engineered human CD8
T cells expressing an ROR1-specific chimeric antigen receptor. In summary, the phenotypic differences between the 3D versus 2D environments, rapid imaging-based readout, and the ability to carefully study the impact of individual variables with quantitative rigor will encourage adoption of the RCC-on-a-chip system for testing a wide range of emerging therapies for RCC.
Increasing fragmentation of grassland habitats by human activities is a major threat to biodiversity and landscape quality. Monitoring their degree of fragmentation has been identified as an urgent ...need. This study quantifies for the first time the current degree of grassland fragmentation in the Canadian Prairies using four fragmentation geometries (FGs) of increasing specificity (i.e. more restrictive grassland classification) and five types of reporting units (7 ecoregions, 50 census divisions, 1,166 municipalities, 17 sub-basins, and 108 watersheds). We evaluated the suitability of 11 datasets based on 8 suitability criteria and applied the effective mesh size (
m
eff
) method to quantify fragmentation. We recommend the combination of the Crop Inventory Mapping of the Prairies and the CanVec datasets as the most suitable for monitoring grassland fragmentation. The grassland area remaining amounts to 87,570.45 km
2
in FG4 (strict grassland definition) and 183,242.042 km
2
in FG1 (broad grassland definition), out of 461,503.97 km
2
(entire Prairie Ecozone area). The very low values of
m
eff
of 14.23 km
2
in FG4 and 25.44 km
2
in FG1 indicate an extremely high level of grassland fragmentation. The
m
eff
method is supported in this study as highly suitable and recommended for long-term monitoring of grasslands in the Canadian Prairies; it can help set measurable targets and/or limits for regions to guide management efforts and as a tool for performance review of protection efforts, for increasing awareness, and for guiding efforts to minimize grassland fragmentation. This approach can also be applied in other parts of the world and to other ecosystems.
An accurate prediction of how extrinsic stimuli influence changes in gene expression has been challenging. In this issue, Nagano and colleagues successfully model genome-wide mRNA expression changes ...under variable environmental conditions in rice, raising hopes that scientists will soon be able to predict genome-wide transcriptional responses in a variety of organisms in uncontrolled real-world settings.
Habitat loss and deterioration represent the main threats to wildlife species, and are closely linked to the expansion of roads and human settlements. Unfortunately, large-scale effects of these ...structures remain generally overlooked. Here, we analyzed the European transportation infrastructure network and found that 50% of the continent is within 1.5 km of transportation infrastructure. We present a method for assessing the impacts from infrastructure on wildlife, based on functional response curves describing density reductions in birds and mammals (e.g., road-effect zones), and apply it to Spain as a case study. The imprint of infrastructure extends over most of the country (55.5% in the case of birds and 97.9% for mammals), with moderate declines predicted for birds (22.6% of individuals) and severe declines predicted for mammals (46.6%). Despite certain limitations, we suggest the approach proposed is widely applicable to the evaluation of effects of planned infrastructure developments under multiple scenarios, and propose an internationally coordinated strategy to update and improve it in the future.
We demonstrate spiral Bragg grating waveguides (BGWs) on the silicon-on-insulator (SOI) platform for the fundamental transverse magnetic (TM) mode. We also compare TM spiral waveguides to equivalent ...transverse electric (TE) spiral waveguides and show that the TM spiral waveguides have lower propagation losses. Our spiral waveguides are space-efficient, requiring only areas of 131×131 µm(2) to accommodate 4 mm long BGWs, and, thus, are less susceptible to fabrication non-uniformities. Due to the lengths and reduced susceptibility to fabrication non-uniformities, we were able to obtain narrow bandwidth, large extinction ratio (ER) devices, as narrow as 0.09 nm and as large as 52 dB, respectively. Finally, we demonstrate a 4 mm long TM chirped spiral Bragg grating waveguide with a negative, average, group delay slope of -11 ps/nm.
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