Modeling habitat suitability for Yunnan Snub-nosed monkeys in Laojun Mountain National Park

We provide new information on Yunnan snub-nosed monkey (Rhinopithecus bieti) behavioral ecology, contributing to future conservation efforts within the Laojun Mountain National Park. Habitat evaluation procedures are used to quantify the value of land as a habitat for a species. We analyzed environmental variables hypothesized to influence habitat suitability for Yunnan snub-nosed monkeys, and mapped the distribution of suitable habitats across the study area and adjacent areas. Spatial analysis with GPS data was conducted to investigate home-range change of these monkeys. Predictor variables were generated using ArcMap and R programming language. We prepared 34 environmental variables at 30-m spatial resolution. Maxent was used to analyze environmental variables that contributed to suitability. Using satellite remote sensing and GIS, we modeled the distribution of suitable habitat for Yunnan snub-nosed monkeys in the Jinsichang area of the Laojun Mountains in China. This study did not describe the frequency or intensity of habitat use. Habitat suitability was affected by several variables, the most influential, as determined by permutation importance, being mean diurnal temperature range (31.6%), precipitation during the wettest quarter of the year (30.4%), average annual precipitation (17%), normalized difference vegetation index (5%), wetness (4.6%), and aspect (4.5%). This habitat suitability model provides information about the current distribution of Yunnan snub-nosed monkeys, which is important for appropriate implementation of conservation actions

Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene

Fox-1 is a regulator of tissue-specific splicing, via binding to the element (U)GCAUG in mRNA precursors, in muscles and neuronal cells. Fox-1 can regulate splicing positively or negatively, most likely depending on where it binds relative to the regulated exon. In cases where the (U)GCAUG element lies in an intron upstream of the alternative exon, Fox-1 protein functions as a splicing repressor to induce exon skipping. Here we report the mechanism of exon skipping regulated by Fox-1, using the hF1γ gene as a model system. We found that Fox-1 induces exon 9 skipping by repressing splicing of the downstream intron 9 via binding to the GCAUG repressor elements located in the upstream intron 8. In vitro splicing analyses showed that Fox-1 prevents formation of the pre-spliceosomal early (E) complex on intron 9. In addition, we located a region of the Fox-1 protein that is required for inducing exon skipping. Taken together, our data show a novel mechanism of how RNA-binding proteins regulate alternative splicing

Vortex Lattice Structures of a Bose-Einstein Condensate in a Rotating Lattice Potential

We study vortex lattice structures of a trapped Bose-Einstein condensate in a rotating lattice potential by numerically solving the time-dependent Gross-Pitaevskii equation. By rotating the lattice potential, we observe the transition from the Abrikosov vortex lattice to the pinned lattice. We investigate the transition of the vortex lattice structure by changing conditions such as angular velocity, intensity, and lattice constant of the rotating lattice potential.Comment: 6 pages, 8 figures, submitted to Quantum Fluids and Solids Conference (QFS 2006

Multi-Junction Switching in Bi2_2Sr1.6_{1.6}La0.4_{0.4}CuO6+δ_{6+\delta} Intrinsic Josephson Junctions

We study the dynamics of multi-junction switching (MJS): several intrinsic Josephson junctions (IJJs) in an array switch to the finite voltage state simultaneously. The number of multi-switching junctions ($N$) was successfully tuned by changing the load resistance serially connected to an Bi$_2$Sr$_{1.6}$La$_{0.4}$CuO$_{6+\delta}$ IJJ array. The independence of the escape rates of $N$ in the macroscopic quantum tunneling regime indicates that MJS is a $successive$ switching process rather than a $collective$ process. The origin of MJS is explained by the gradient of a load curve and the relative magnitudes of the switching currents of quasiparticle branches in the current-voltage plane

CO_2, water, and sunlight to hydrocarbon fuels: a sustained sunlight to fuel (Joule-to-Joule) photoconversion efficiency of 1%

If we wish to sustain our terrestrial ecosphere as we know it, then reducing the concentration of atmospheric CO_2 is of critical importance. An ideal pathway for achieving this would be the use of sunlight to recycle CO_2, in combination with water, into hydrocarbon fuels compatible with our current energy infrastructure. However, while the concept is intriguing such a technology has not been viable due to the vanishingly small CO_2-to-fuel photoconversion efficiencies achieved. Herein we report a photocatalyst, reduced blue-titania sensitized with bimetallic Cu–Pt nanoparticles that generates a substantial amount of both methane and ethane by CO_2 photoreduction under artificial sunlight (AM1.5): over a 6 h period 3.0 mmol g^(−1) methane and 0.15 mmol g^(−1) ethane are obtained (on an area normalized basis 0.244 mol m^(−2) methane and 0.012 mol m^(−2) ethane), while no H_2 nor CO is detected. This activity (6 h) translates into a sustained Joule (sunlight) to Joule (fuel) photoconversion efficiency of 1%, with an apparent quantum efficiency of φ = 86%. The time-dependent photoconversion efficiency over 0.5 h intervals yields a maximum value of 3.3% (φ = 92%). Isotopic tracer experiments confirm the hydrocarbon products originate from CO_2 and water

EGFR T790M Mutation as a Possible Target for Immunotherapy; Identification of HLA-A*0201-Restricted T Cell Epitopes Derived from the EGFR T790M Mutation

Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, has achieved high clinical response rates in patients with non–small cell lung cancers (NSCLCs). However, over time, most tumors develop acquired resistance to EGFR-TKIs, which is associated with the secondary EGFR T790M resistance mutation in about half the cases. Currently there are no effective treatment options for patients with this resistance mutation. Here we identified two novel HLA-A*0201 (A2)-restricted T cell epitopes containing the mutated methionine residue of the EGFR T790M mutation, T790M-5 (MQLMPFGCLL) and T790M-7 (LIMQLMPFGCL), as potential targets for EGFR-TKI-resistant patients. When peripheral blood cells were repeatedly stimulated in vitro with these two peptides and assessed by antigen-specific IFN-γ secretion, T cell lines responsive to T790M-5 and T790M-7 were established in 5 of 6 (83%) and 3 of 6 (50%) healthy donors, respectively. Additionally, the T790M-5- and T790M-7-specific T cell lines displayed an MHC class I-restricted reactivity against NSCLC cell lines expressing both HLA-A2 and the T790M mutation. Interestingly, the NSCLC patients with antigen-specific T cell responses to these epitopes showed a significantly less frequency of EGFR-T790M mutation than those without them [1 of 7 (14%) vs 9 of 15 (60%); chi-squared test, p = 0.0449], indicating the negative correlation between the immune responses to the EGFR-T790M-derived epitopes and the presence of EGFR-T790M mutation in NSCLC patients. This finding could possibly be explained by the hypothesis that immune responses to the mutated neo-antigens derived from T790M might prevent the emergence of tumor cell variants with the T790M resistance mutation in NSCLC patients during EGFR-TKI treatment. Together, our results suggest that the identified T cell epitopes might provide a novel immunotherapeutic approach for prevention and/or treatment of EGFR-TKI resistance with the secondary EGFR T790M resistance mutation in NSCLC patients

Post-Infection Immunodeficiency Virus Control by Neutralizing Antibodies

BACKGROUND: Unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (NAbs), primary HIV infections are not met with such potent and early antibody responses. This brings into question if or how the presence of potent antibodies can contribute to primary HIV control, but protective efficacies of antiviral antibodies in primary HIV infections have remained elusive; and, it has been speculated that even NAb induction could have only a limited suppressive effect on primary HIV replication once infection is established. Here, in an attempt to answer this question, we examined the effect of passive NAb immunization post-infection on primary viral replication in a macaque AIDS model. METHODS AND FINDINGS: The inoculums for passive immunization with simian immunodeficiency virus mac239 (SIVmac239)-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC)-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced T cell priming. CONCLUSIONS: Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for sterile HIV protection by prophylactic vaccination has been suggested, this study points out a possibility of non-sterile HIV control by prophylactic vaccine-induced, sub-sterile titers of NAbs post-infection, providing a rationale of vaccine-based NAb induction for primary HIV control

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention