Efforts in biodiversity conservation have long embraced the task of reducing the impactsof the stressors imposed by anthropogenic and environmental changes. In the past, moststressors have been either on-going but gradual or incremental, such as pollution ordeforestation, or one-time catastrophic events, such as large oil spills, or a severe drought. Theprevailing conservation principle has been to plan for a static protected area or series of protectedareas, with the goal of preserving important specific habitat types, or biodiversity assemblages.The assumption has been that if properly protected, these ecosystems would remain stable(Hansen et al., 2009). Climate change has created new challenges in biodiversity conservation.While it is already changing ecosystems across the globe, it will continue to do so for decadesand perhaps centuries to come, and at a faster pace than originally anticipated (Hansen et al.,2009). The current pace of change is unprecedented in evolutionary history (Barnosky et al.,2003).Climate change is reshaping how we think about conservation. Even if fully protectedfrom the ongoing threats imposed by human activities, the ecosystems and biota we have beenprotecting will not remain the same. Conservation planners must change the way decisions aremade because aspects of the environment we have always considered to be relatively constant,including weather patterns, water supply, temperature extremes, even biotic communities, will bechanging. This is a difficult endeavor because, not only can we not predict exactly how thingswill change, but we don’t know when they will achieve a new stable state. We can no longerplan for stasis.With these ideas in mind, the African Wildlife Foundation and the International GorillaConservation Programme have partnered with EcoAdapt to initiate the development of anadaptation framework to address climate change in planning in the continuing efforts to conservemountain gorillas (Gorilla beringei beringei) in East Africa. With a grant by the John D. andCatherine T. MacArthur Foundation, a series of Climate Camp workshops in the region wereheld and expert research commissioned to produce this initial White Paper. The work focuses onbuilding understanding and assessing the scope for reducing the vulnerability of mountaingorillas to regional and global changes expected to occur as a result of climate change. The goalis to reduce the vulnerability of mountain gorillas to the negative effects of climate change byunderstanding and accommodating its effects on their habitat, food supply, and access to waterresources. The specific task of the White Paper preparation process was to carry out initialmulti-stakeholder assessment of the implications of global climate change for mountain gorillaconservation in the Albertine Rift, and identify key elements of an adaptation framework,including priority adaptation strategies and actions.

Background

Understanding the intricate signaling network involved in triple-negative breast cancer (TNBC) represents a challenge for developing novel therapeutic approaches. Here, we aim to provide novel mechanistic insights on the function of the S100A8/A9-RAGE system in TNBC.

Methods

TNM plot analyzer, Kaplan-Meier plotter, Meta-analysis, GEPIA2 and GOBO publicly available datasets were used to evaluate the clinical significance of S100A8/A9 and expression levels of S100A8/A9, RAGE and Filamin family members in breast cancer (BC) subtypes. METABRIC database and Cox proportional hazard model defined the clinical impact of high RAGE expression in BC patients. Multiple bioinformatics programs identified the main enriched pathways within high RAGE expression BC cohorts. By lentiviral system, TNBC cells were engineered to overexpress RAGE. Western blotting, immunofluorescence, nucleus/cytoplasm fractionation, qRT-PCR, gene silencing and luciferase experiments were performed to identify signal transduction mediators engaged by RAGE upon stimulation with S100A8/A9 in TNBC cells. Proliferation, colony formation and transwell migration assays were carried out to evaluate the growth and migratory capacity of TNBC cells. Statistical analysis was performed by ANOVA and independent t-tests.

Results

We found a remarkable high expression of S100A8 and S100A9 in BC, particularly in HER2-positive and TNBC, with the latter associated to worst clinical outcomes. In addition, high RAGE expression correlated with a poor overall survival in BC. Next, we determined that the S100A8/A9-RAGE system triggers FAK activation by engaging a cytoskeleton mechanosensing complex in TNBC cells. Through bioinformatics analysis, we identified the Hippo pathway as the most enriched in BC patients expressing high RAGE levels. In accordance with these data, we demonstrated the involvement of S100A8/A9-RAGE-FAK signaling in the control of Hippo/YAP activities, and we established the crucial contribution of RAGE-FAK-YAP circuitry in the growth and migratory effects initiated by S100A8/A9 in TNBC cells.

Conclusions

The present study provides novel mechanistic insights on RAGE actions in TNBC. Moreover, our findings suggest that RAGE-FAK-YAP transduction pathway could be exploited as a druggable system halting the aggressive TNBC subtype.

We analyze spatially resolved and co-added SDSS-IV MaNGA spectra with signal-to-noise ratio �1/4100 from 2200 passive central galaxies (z ∼0.05) to understand how central galaxy assembly depends on stellar mass (M ∗) and halo mass (M h ). We control for systematic errors in M h by employing a new group catalog from Tinker and the widely used Yang et al. catalog. At fixed M ∗, the strengths of several stellar absorption features vary systematically with M h . Completely model-free, this is one of the first indications that the stellar populations of centrals with identical M ∗ are affected by the properties of their host halos. To interpret these variations, we applied full spectral fitting with the code alf. At fixed M ∗, centrals in more massive halos are older, show lower [Fe/H], and have higher [Mg/Fe] with 3.5σ confidence. We conclude that halos not only dictate how much M ∗ galaxies assemble but also modulate their chemical enrichment histories. Turning to our analysis at fixed M h , high-M ∗ centrals are older, show lower [Fe/H], and have higher [Mg/Fe] for M h > 1012 h -1 M ⊙ with confidence >4σ. While massive passive galaxies are thought to form early and rapidly, our results are among the first to distinguish these trends at fixed M h . They suggest that high-M ∗ centrals experienced unique early formation histories, either through enhanced collapse and gas fueling or because their halos were early forming and highly concentrated, a possible signal of galaxy assembly bias.

The MaNGA Survey (Mapping Nearby Galaxies at Apache Point Observatory) is one of three core programs in the Sloan Digital Sky Survey IV. It is obtaining integral field spectroscopy for 10,000 nearby galaxies at a spectral resolution of R ∼ 2000 from 3622 to 10354 Å. The design of the survey is driven by a set of science requirements on the precision of estimates of the following properties: star formation rate surface density, gas metallicity, stellar population age, metallicity, and abundance ratio, and their gradients; stellar and gas kinematics; and enclosed gravitational mass as a function of radius. We describe how these science requirements set the depth of the observations and dictate sample selection. The majority of targeted galaxies are selected to ensure uniform spatial coverage in units of effective radius (R e) while maximizing spatial resolution. About two-thirds of the sample is covered out to 1.5R e (Primary sample), and one-third of the sample is covered to 2.5R e (Secondary sample). We describe the survey execution with details that would be useful in the design of similar future surveys. We also present statistics on the achieved data quality, specifically the point-spread function, sampling uniformity, spectral resolution, sky subtraction, and flux calibration. For our Primary sample, the median r-band signal-to-noise ratio is ∼70 per 1.4 Å pixel for spectra stacked between 1R e and 1.5R e. Measurements of various galaxy properties from the first-year data show that we are meeting or exceeding the defined requirements for the majority of our science goals.

This catalog summarizes 117 high-confidence ≥0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions. © 2013. The American Astronomical Society. All rights reserved..