Satb1 overexpression drives tumor-promoting activities in cancer-associated dendritic cells

Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating major histocompatibility complex class II (MHC II) expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46(+) inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression.Fil: Tesone, Amelia J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Rutkowski, Melanie R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Brencicova, Eva. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Svoronos, Nikolaos. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Perales Puchal, Alfredo. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Stephen, Tom L.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Allegrezza, Michael J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Payne, Kyle K.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Nguyen, Jenny M.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Wickramasinghe, Jayamanna. The Wistar Institute. Center for Systems and Computational Biology; Estados UnidosFil: Tchou, Julia. University of Pennsylvania; Estados UnidosFil: Borowsky, Mark E.. Christiana Care Health System. Helen F. Graham Cancer Center; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kossenkov, Andrew V.. The Wistar Institute. Center for Systems and Computational Biology; Estados UnidosFil: Conejo Garcia, José R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unido

Kepler Eclipsing Binary Stars. VI. Identification of Eclipsing Binaries in the K2 Campaign 0 Data-set

The original {\it Kepler} mission observed and characterized over 2400 eclipsing binaries in addition to its prolific exoplanet detections. Despite the mechanical malfunction and subsequent non-recovery of two reaction wheels used to stabilize the instrument, the {\it Kepler} satellite continues collecting data in its repurposed {\it K2} mission surveying a series of fields along the ecliptic plane. Here we present an analysis of the first full baseline {\it K2} data release: the Campaign 0 data-set. In the 7761 light curves, we have identified a total of 207 eclipsing binaries. Of these, 97 are new discoveries that were not previously identified. Our pixel-level analysis of these objects has also resulted in identification of several false positives (observed targets contaminated by neighboring eclipsing binaries), as well as the serendipitous discovery of two short period exoplanet candidates. We provide catalog cross-matched source identifications, orbital periods, morphologies and ephemerides for these eclipsing systems. We also describe the incorporation of the K2 sample into the Kepler Eclipsing Binary Catalog\footnote{\url{keplerebs.villanova.edu/k2}}, present spectroscopic follow-up observations for a limited selection of nine systems, and discuss prospects for upcoming {\it K2} campaigns.Comment: Accepted for publication in MNRAS. 51 pages [20 figures, 8 tables]. Results available online in the Kepler Eclipsing Binary Star Catalog http://keplerebs.villanova.edu/k

Knowing the unknowns: uncertainties in simple estimators of galactic dynamical masses

The observed stellar kinematics of dispersion-supported galaxies are often used to measure dynamical masses. Recently, several analytical relationships between the stellar line-of-sight velocity dispersion, the projected (2D) or deprojected (3D) half-light radius and the total mass enclosed within the half-light radius, relying on the spherical Jeans equation, have been proposed. Here, we use the APOSTLE cosmological hydrodynamical simulations of the Local Group to test the validity and accuracy of such mass estimators for both dispersion and rotation-supported galaxies, for field and satellite galaxies, and for galaxies of varying masses, shapes and velocity dispersion anisotropies. We find that the mass estimators of Walker et al. and Wolf et al. are able to recover the masses of dispersion-dominated systems with little systematic bias, but with a 1σ scatter of 25 and 23 per cent, respectively. The error on the estimated mass is dominated by the impact of the 3D shape of the stellar mass distribution, which is difficult to constrain observationally. This intrinsic scatter becomes the dominant source of uncertainty in the masses estimated for galaxies like the dwarf spheroidal (dSph) satellites of the Milky Way, where the observational errors in their sizes and velocity dispersions are small. Such scatter may also affect the inner density slopes of dSphs derived from multiple stellar populations, relaxing the significance with which Navarro–Frenk–White profiles may be excluded, depending on the degree to which the relevant properties of the different stellar populations are correlated. Finally, we derive a new optimal mass estimator that removes the residual biases and achieves a statistically significant reduction in the scatter to 20 per cent overall for dispersion-dominated galaxies, allowing more precise and accurate mass estimates

Using Unoccupied Aerial Vehicles to Map and Monitor Changes in Emergent Kelp Canopy after an Ecological Regime Shift

Kelp forests are complex underwater habitats that form the foundation of many nearshore marine environments and provide valuable services for coastal communities. Despite their ecological and economic importance, increasingly severe stressors have resulted in declines in kelp abundance in many regions over the past few decades, including the North Coast of California, USA. Given the significant and sustained loss of kelp in this region, management intervention is likely a necessary tool to reset the ecosystem and geospatial data on kelp dynamics are needed to strategically implement restoration projects. Because canopy-forming kelp forests are distinguishable in aerial imagery, remote sensing is an important tool for documenting changes in canopy area and abundance to meet these data needs. We used small unoccupied aerial vehicles (UAVs) to survey emergent kelp canopy in priority sites along the North Coast in 2019 and 2020 to fill a key data gap for kelp restoration practitioners working at local scales. With over 4,300 hectares surveyed between 2019 and 2020, these surveys represent the two largest marine resource-focused UAV surveys conducted in California to our knowledge. We present remote sensing methods using UAVs and a repeatable workflow for conducting consistent surveys, creating orthomosaics, georeferencing data, classifying emergent kelp and creating kelp canopy maps that can be used to assess trends in kelp canopy dynamics over space and time. We illustrate the impacts of spatial resolution on emergent kelp canopy classification between different sensors to help practitioners decide which data stream to select when asking restoration and management questions at varying spatial scales. Our results suggest that high spatial resolution data of emergent kelp canopy from UAVs have the potential to advance strategic kelp restoration and adaptive management

The effect of self-sorting and co-assembly on the mechanical properties of low molecular weight hydrogels

Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties

Potential effects of ionizing radiation on the evidentiary value of DNA, latent fingerprints, hair, and fibers: A comprehensive review and new results

An extensive literature review and new post-irradiation experimental results are presented of genotyping blood stains and hair, and physical examinations of latent fingerprints, hairs, and fibers. Results indicate that successful development of nuclear short tandem repeat (STR) and mitochondrial DNA sequence profiles from human blood and hair evidence is possible—up to a point—following exposure to gamma, neutron, beta, and alpha radiation at several levels that would most likely be present at this type of crime scene (i.e., a “dirty bomb,” etc.). Commencing at gamma radiation levels between 90 and 900 kGy, DNA analysis using conventional DNA techniques was unsuccessful. In general, irradiation negatively affected the quality of latent fingerprints. All four radiation types degraded most fingerprint samples at all doses; nevertheless, many fingerprints remained of value for potential use in comparison. Although variable from one hair to another, microscopic changes observed for all types and levels of irradiation could potentially result in false exclusions. Negligible microscopic changes were observed in papers and fibers (used as substrates for fingerprints and bloodstains) up to 90 kGy gamma, but fluorescence of fibers began to change above that dose. Paper and fibers, as well as plastic evidence enclosures, became extremely brittle leading to breakage after a gamma dose of 900 kGy

Cumulative effects of cyclones and bleaching on coral cover and species richness at Lizard Island

Funding was provided by the Australian Council Centre of Excellence for Coral Reef Studies (COE140100020) and the John Templeton Foundation (M.D., J.S.M. grant #60501 'Putting the Extended Evolutionary Synthesis to the Test’).Coral reefs are being subjected to an increase in the frequency and intensity of disturbance, such as bleaching and cyclones, and it is important to document the effects of such disturbance on reef coral assemblages. Between March 2014 and May 2017, the reefs of Lizard Island in the northern section of the Great Barrier Reef were affected by 4 consecutive disturbances: severe tropical cyclones Ita and Nathan in 2014 and 2015, and mass bleaching events in 2016 and 2017. Loss of coral cover following the cyclones was patchy and dependent on the direction of the waves generated. In contrast, loss of cover following bleaching was much more uniform. Overall, coral cover declined 5-fold from 36% pre-cyclone Ita to 7% post-bleaching in 2017, while mean species richness dropped from 10 to 4 species per transect. The spatial scale and magnitude of the loss of coral cover in the region suggests that it will be many years before these reefs recover.PostprintPeer reviewe

Open science in archaeology

No abstract available