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Surface melting on the Antarctic Ice Sheet has been monitored by satellite microwave radiometry for over 40 years. Despite this long perspective, our understanding of the microwave emission from wet snow is still limited, preventing the full exploitation of these observations to study supraglacial hydrology. Using the Snow Microwave Radiative Transfer (SMRT) model, this study investigates the sensitivity of microwave brightness temperature to snow liquid water content at frequencies from 1.4 to 37 GHz. We first determine the snowpack properties for eight selected coastal sites by retrieving profiles of density, grain size and ice layers from microwave observations when the snowpack is dry during wintertime. Second, a series of brightness temperature simulations is run with added water. The results show that (i) a small quantity of liquid water (≈0.5 kg m−2) can be detected, but the actual quantity cannot be retrieved out of the full range of possible water quantities; (ii) the detection of a buried wet layer is possible up to a maximum depth of 1 to 6 m depending on the frequency (6–37 GHz) and on the snow properties (grain size, density) at each site; (iii) surface ponds and water-saturated areas may prevent melt detection, but the current coverage of these waterbodies in the large satellite field of view is presently too small in Antarctica to have noticeable effects; and (iv) at 1.4 GHz, while the simulations are less reliable, we found a weaker sensitivity to liquid water and the maximal depth of detection is relatively shallow ( m) compared to the typical radiation penetration depth in dry firn (≈1000 m) at this low frequency. These numerical results pave the way for the development of improved multi-frequency algorithms to detect melt intensity and the depth of liquid water below the surface in the Antarctic snowpack.

Supplemental Figure Legends from Overexpression of Smad7 Blocks Primary Tumor Growth and Lung Metastasis Development in Osteosarcoma

This supplementary figure demonstrates that Smad7 and SD-208 inhibit the Smad3 signaling pathway in SAOS2 cells and that Smad7 does not inhibit the MAPK pathway in response to TGF-β.

Purpose: Osteosarcoma is the main malignant primary bone tumor in children and adolescents for whom the prognosis remains poor, especially when metastasis is present at diagnosis. Because transforming growth factor-β (TGFβ) has been shown to promote metastasis in many solid tumors, we investigated the effect of the natural TGFβ/Smad signaling inhibitor Smad7 and the TβRI inhibitor SD-208 on osteosarcoma behavior.Experimental Design: By using a mouse model of osteosarcoma induced by paratibial injection of cells, we assessed the impact of Smad7 overexpression or SD-208 on tumor growth, tumor microenvironment, bone remodeling, and metastasis development.Results: First, we demonstrated that TGFβ levels are higher in serum samples from patients with osteosarcoma compared with healthy volunteers and that TGFβ/Smad3 signaling pathway is activated in clinical samples. Second, we showed that Smad7 slows the growth of the primary tumor and increases mice survival. We furthermore demonstrated that Smad7 expression does not affect in vitro osteosarcoma cell proliferation but affects the microarchitectural parameters of bone. In addition, Smad7-osteosarcoma bone tumors expressed lower levels of osteolytic factors such as RANKL, suggesting that Smad7 overexpression affects the “vicious cycle” established between tumor cells and bone cells by its ability to decrease osteoclast activity. Finally, we showed that Smad7 overexpression in osteosarcoma cells and the treatment of mice with SD208 inhibit the development of lung metastasis.Conclusion: Taken together, these results demonstrate that the inhibition of the TGFβ/Smad signaling pathway may be a promising therapeutic strategy against tumor progression of osteosarcoma, specifically against the development of lung metastasis. Clin Cancer Res; 20(19); 5097–112. ©2014 AACR.

An airborne microwave wide-band radiometer (500–2000 MHz) was operated for the first time in Antarctica to better understand the emission properties of sea ice, outlet glaciers and the interior ice sheet from Terra Nova Bay to Dome C. The different glaciological regimes were revealed to exhibit unique spectral signatures in this portion of the microwave spectrum. Generally, the brightness temperatures over a vertically homogeneous ice sheet are warmest at the lowest frequencies, consistent with models that predict that those channels sensed the deeper, warmer parts of the ice sheet. Vertical heterogeneities in the ice property profiles can alter this basic interpretation of the signal. Spectra along the lengths of outlet glaciers were modulated by the deposition and erosion of snow, driven by strong katabatic winds. Similar to previous experiments in Greenland, the brightness temperatures across the frequency band were low in crevasse areas. Variations in brightness temperature were consistent with spatial changes in sea ice type identified in satellite imagery and in situ ground-penetrating radar data. The results contribute to a better understanding of the utility of microwave wide-band radiometry for cryospheric studies and also advance knowledge of the important physics underlying existing L-band radiometers operating in space.

Surface melt is one of the primary drivers of ice shelf collapse in Antarctica. Surface melting is expected to increase in the future as the global climate continues to warm, because there is a statistically significant positive relationship between air temperature and melt. Enhanced surface melt will negatively impact the mass balance of the Antarctic Ice Sheet (AIS) and, through dynamic feedbacks, induce changes in global mean sea level (GMSL). However, current understanding of surface melt in Antarctica remains limited in past, present or future contexts. Continental-scale spaceborne observations of surface melt are limited to the satellite era (1979–present), meaning that current estimates of Antarctic surface melt are typically derived from surface energy balance (SEB) or positive degree-day (PDD) models. SEB models require diverse and detailed input data that are not always available and require considerable computational resources. The PDD model, by comparison, has fewer input and computational requirements and is therefor suited for exploring surface melt scenarios in the past and future. The use of PDD schemes for Antarctic melt has been less extensively explored than their application to surface melting of the Greenland Ice Sheet, particularly in terms of a spatially-varying parameterization. Here, we construct a PDD model, force it only with 2-m air temperature reanalysis data, and parameterize it by minimizing the error with respect to satellite observations and SEB model outputs over the period 1979 to 2022. We compare the spatial and temporal variability of surface melt from our PDD model over the last 43 years with that of satellite observations and SEB simulations. We find that the PDD model can generally capture the same spatial and temporal surface melt patterns. Although there were at most four years over/under- estimation on ice shelf regions in the epoch, these discrepancies reduce when considering the whole AIS. With the limitations discussed, we suggest that an appropriately parameterized PDD model can be a valuable tool for exploring Antarctic surface melt beyond the satellite era.

Immunogenic cell death (ICD) is a modality of cellular demise that when it is induced by certain anticancer treatments can ignite an adaptive anticancer immune response. ICD is characterized by the emission of a specific set of danger-associated molecular patterns (DAMPs) including calreticulin exposure at the plasma membrane, ATP liberation, HMGB1 exodus and type-I IFN release. The apical signaling triggering the appearance of these hallmarks involves the phosphorylation on serine 51 of the α-subunit of eukaryotic initiation factor 2 (EIF2), a key protein in the orchestration of endoplasmic reticulum (ER) stress responses. EIF2α can be phosphorylated by a family of four EIF2A kinases: EIF2AK1-4 (best known as heme regulated inhibitor, HRI, protein kinase R, PKR, protein kinase R-like endoplasmic reticulum kinase, PERK, and general control non-derepressible 2, GCN2), that each respond to a specific type of cellular stress. Here, we describe different techniques to investigate the biochemical pathways leading to eIF2α phosphorylation in the context of ICD.

The European Space Agency SnowSAR instrument is a side-looking, dual-polarised (VV/VH), X/Ku band synthetic aperture radar (SAR), operable from various sizes of aircraft. Between 2010 and 2013, the instrument was deployed at several sites in Northern Finland, Austrian Alps and northern Canada. The purpose of the airborne campaigns was to measure the backscattering properties of snow-covered terrain to support the development of snow water equivalent retrieval techniques using SAR. SnowSAR was deployed in Sodankylä, Northern Finland, for a single flight mission in March 2011 and 12 missions at two sites (tundra and boreal forest) in the winter of 2011–2012. Over the Austrian Alps, three flight missions were performed between November 2012 and February 2013 over three sites located in different elevation zones representing a montane valley, Alpine tundra and a glacier environment. In Canada, a total of two missions were flown in March and April 2013 over sites in the Trail Valley Creek watershed, Northwest Territories, representative of the tundra snow regime. This paper introduces the airborne SAR data and coincident in situ information on land cover, vegetation and snow properties. To facilitate easy access to the data record, the datasets described here are deposited in a permanent data repository (https://doi.org/10.1594/PANGAEA.933255, Lemmetyinen et al., 2021).

The European Space Agency SnowSAR instrument is a side looking, dual polarized (VV/VH), X/Ku band synthetic aperture radar (SAR), operable from a small aircraft. Between 2010 and 2013, the instrument was deployed at several sites in Northern Finland, Austrian Alps, and northern Canada. The purpose of the airborne campaigns was to measure the backscattering properties of snow-covered terrain to support the development of snow water equivalent retrieval techniques using SAR. SnowSAR was deployed in Sodankylä, Northern Finland for a single flight mission in March 2011 and twelve missions at two sites (tundra and boreal forest) in the winter of 2011–2012. Over the Austrian Alps, three flight missions were performed between November 2012 and February 2013 over three sites located in different elevation zones, representing a montane valley, Alpine tundra, and a glacier environment. In Canada, a total of two missions were flown in March and April 2013, over sites in the Trail Valley Creek watershed, Northwest Territories, representative of the tundra snow regime. This paper introduces the airborne SAR data, as well as coincident in situ information on land cover, vegetation and snow properties. To facilitate easy access to the data record the datasets described here are deposited in a permanent data repository (https://doi.pangaea.de/10.1594/PANGAEA.933255; Lemmetyinen et al., 2021). A temporary link to access the data without login information is provided for reviewers of this manuscript: https://www.pangaea.de/tok/e8c562c3c8a15ac34daa83d00c76fcb347330884.

Oleate, the most abundantly occurring cis-unsaturated fatty acid, has the particularity to induce the accumulation of MAP1LC3B/LC3 (microtubule associated protein 1 light chain 3 beta) at the trans-Golgi apparatus. A genome-wide RNA interference screen designed to identify the mechanisms of this LC3 redistribution led to the identification of a BECN1-PIK3C3-independent pathway that, however, requires the ATG12–ATG5 and ATG7-dependent conjugation system, and several genes/proteins involved in endoplasmic reticulum (ER)-to-Golgi anterograde protein transport, as well as the unfolded protein response, including the integrated stress response that results in the phosphorylation of EIF2A/eIF2α (eukaryotic translation initiation factor 2A). Functional experiments revealed that oleate blocks conventional protein secretion, stalling the process at the level of the trans-Golgi network. Oleate-induced blockade of protein secretion occurred even after depletion of ATG5, suggesting that it does not rely on the recruitment of LC3 to the Golgi apparatus (which does require ATG5). Rather, it appears that oleate and other pharmacological inhibitors of protein secretion with a similar mode of action provoke a perturbation of the trans-Golgi compartment that secondarily results in the local enrichment of LC3.

BackgroundHigh activity of poly(ADP-ribose) polymerase-1 (PARP1) in non-small cell lung cancer (NSCLC) cells leads to an increase in immunohistochemically detectable PAR, correlating with poor prognosis in patients with NSCLC, as well as reduced tumor infiltration by cytotoxic T lymphocytes (CTLs). Intrigued by this observation, we decided to determine whether PARP1 activity in NSCLC cells may cause an alteration of anticancer immunosurveillance.MethodsContinuous culture of mouse NSCLC cells in the presence of cisplatin led to the generation of cisplatin-resistant PARhigh clones. As compared with their parental controls, such PARhigh cells formed tumors that were less infiltrated by CTLs when they were injected into immunocompetent mice, suggesting a causative link between high PARP1 activity and compromised immunosurveillance. To confirm this cause-and-effect relationship, we used CRISPR/Cas9 technology to knock out PARP1 in two PARhigh NSCLC mouse cell lines (Lewis lung cancer [LLC] and tissue culture number one [TC1]), showing that the removal of PARP1 indeed restored cisplatin-induced cell death responses.ResultsPARP1 knockout (PARP1KO) cells became largely resistant to the PARP inhibitor niraparib, meaning that they exhibited less cell death induction, reduced DNA damage response, attenuated metabolic shifts and no induction of PD-L1 and MHC class-I molecules that may affect their immunogenicity. PARhigh tumors implanted in mice responded to niraparib irrespective of the presence or absence of T lymphocytes, suggesting that cancer cell-autonomous effects of niraparib dominate over its possible immunomodulatory action. While PARhigh NSCLC mouse cell lines proliferated similarly in immunocompetent and T cell-deficient mice, PARP1KO cells were strongly affected by the presence of T cells. PARP1KO LLC tumors grew more quickly in immunodeficient than in immunocompetent mice, and PARP1KO TC1 cells could only form tumors in T cell-deficient mice, not in immunocompetent controls. Importantly, as compared with PARhigh controls, the PARP1KO LLC tumors exhibited signs of T cell activation in the immune infiltrate such as higher inducible costimulator (ICOS) expression and lower PD-1 expression on CTLs.ConclusionsThese results prove at the genetic level that PARP1 activity within malignant cells modulates the tumor microenvironment.

An airborne microwave wide-band radiometer (500–2000 MHz) was operated for the first time in Antarctica to better understand the emission properties of sea ice, outlet glaciers and the interior ice sheet from Terra Nova Bay to Dome C. The different glaciological regimes were revealed to exhibit unique spectral signatures in this portion of the microwave spectrum. Generally, the brightness temperatures over the inland ice sheet were warmest at the lowest frequencies consistent with models that predict that those channels sensed the deeper, warmer parts of the ice sheet. Spectra along the lengths of outlet glaciers were modulated by the deposition and erosion of snow, driven by strong katabatic winds. Similar to previous experiments in Greenland, the brightness temperatures across the frequency band were low in crevasse areas. Variations in brightness temperature were consistent with spatial changes in sea ice type identified in satellite imagery and in situ ground penetrating radar data. The results contribute to a better understanding of the utility of microwave wide-band radiometry for cryospheric studies and also advance knowledge of the important physics underlying existing L-band radiometers operating in space.

Robotized high throughput screening allows for the assessment of autophagy in a large number of samples. Here, we describe a drug discovery platform for the phenotypic identification of novel autophagy inducers by means of automated cell biology workflows employing robotized cell culture, sample preparation and data acquisition. In this setting, fluorescent biosensor cells that express microtubule-associated proteins 1A/1B light chain 3B (best known as LC3) conjugated to green fluorescent protein (GFP), are utilized together with automated high content microscopy for the image-based assessment of autophagy. In sum, we detail a drug discovery screening workflow from high throughput sample preparation and processing to data acquisition and analysis.

International audience; A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFN gamma-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.