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The most comprehensive exhibition catalog dedicated to the work of Brazilian artist Tarsila do Amaral (1886-1973), a pioneering figure in Latin American modernism. The focus of the exhibition is the popular, or the vernacular, a notion as complex in Brazil as it is contested, and which Tarsila explored in different ways throughout her career. The popular is associated with debates on national art or identity and the invention or construction of brasilidade, Brazilianness. In Tarsila, the popular is manifested in landscapes of the countryside or the suburbs, the farm or the favela, populated by people of indigenous or African descent, characters from Brazilian folklore, full of animals and plants, both real and fantastic. But Tarsila's palette (which served as inspiration for the colors of the exhibition design) is also popular: \"pure blue, violaceous rose, bright yellow, singing green.\" Much of the art criticism on Tarsila to this day in Brazil has emphasized her French affiliations and genealogies, possibly in search of the artist's international legitimization, but thus marginalizing the themes, characters, and popular narratives that she constructed. Today, after successful shows in the United States and Europe, we can look at Tarsila in other ways. In this sense, the essays and commentaries on her works included in the exhibition and in the catalog are central elements of this project. It is not by chance that the controversial painting A Negra [The Negress] has received special attention from the authors and is a central work in the exhibition. Tarsila do Amaral: Cannibalizing Modernism does not seek to exhaust all these discussions, which take into account questions of race, class and colonialism. But the project does point to the need to study this artist, so fundamental in our art history, from new perspectives and approaches. This exhibition is part of a series that MASP has organized reassessing the notion of the popular in Brazil: from A mنao do povo brasileiro, 1969/2016 [The Hand of the Brazilian People, 1969/2016] and Portinari popular [Popular Portinari] in 2016 to Agostinho Batista de Freitas in 2017 and Maria Auxiliadora in 2018. Tarsila do Amaral: Cannibalizing Modernism is contextualized in a full year dedicated to women artists at the museum in 2019 under the heading Women's Histories, Feminist Histories. The exhibition dialogues with two others dedicated to artists who explored the notion of the popular through different approaches: Djanira: Picturing Brazil, on view through May 19th, and Lina Bo Bardi: Habitat, on view through July 28th.

Glioblastoma (GBM), the most aggressive form of brain cancer, has witnessed very little clinical progress over the last decades, in part, due to the absence of effective drug delivery strategies. Intravenous injection is the least invasive drug delivery route to the brain, but has been severely limited by the blood-brain barrier (BBB). Inspired by the capacity of natural proteins and viral particulates to cross the BBB, we engineered a synthetic protein nanoparticle (SPNP) based on polymerized human serum albumin (HSA) equipped with the cell-penetrating peptide iRGD. SPNPs containing siRNA against Signal Transducer and Activation of Transcription 3 factor (STAT3 i ) result in in vitro and in vivo downregulation of STAT3, a central hub associated with GBM progression. When combined with the standard of care, ionized radiation, STAT3 i SPNPs result in tumor regression and long-term survival in 87.5% of GBM-bearing mice and prime the immune system to develop anti-GBM immunological memory. The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM.

Understanding processes controlling stream nutrient dynamics over time is crucial for implementing effective management strategies to prevent water quality degradation. In this respect, the study of the nutrient concentration–discharge (C–Q) relationship during individual runoff events can be a valuable tool for extrapolating the hydrochemical processes controlling nutrient fluxes in streams. This study investigated nitrogen concentration dynamics during events by analyzing and interpreting the nitrogen C–Q relationship in a small Atlantic (NW Iberian Peninsula) rural catchment. To this end, nitrate (NO3-N) and total Kjeldahl nitrogen (TKN) concentrations were monitored at a high temporal resolution during 102 runoff events over a 6-year period. For each of the selected runoff events, C–Q response was examined visually for the presence and direction of hysteresis loops and classified into three types of responses, namely clockwise, counterclockwise, and no hysteresis. Changes in concentration (ΔC) and the hysteresis direction (ΔR) were used to quantify nitrogen (NO3- and TKN) patterns during the runoff events. The transport mechanisms varied between compounds. The most frequent hysteretic response for NO3- was counterclockwise with enrichment. On the contrary, the main TKN dynamic was enrichment with clockwise hysteresis. Event characteristics, such as rainfall amount, peak discharge (i.e., maximum discharge of the runoff event), and event magnitude relative to the initial baseflow (i.e., the difference between the maximum discharge of the runoff event and the initial baseflow divided by initial baseflow) provided a better explanation for hysteresis direction and magnitude for TKN than antecedent conditions (antecedent precipitation and baseflow at the beginning of the event). For NO3- hysteresis, the role of hydrometeorological conditions was more complex. The NO3- hysteresis magnitude was related to the magnitude of the event relative to the initial baseflow and the time elapsed since a preceding runoff event. These findings could be used as a reference for the development of N mitigation strategy in the region.

Annona neoinsignis H. Rainer (Annonaceae) is a tree native to the Amazon rainforest. Its fruits are also suitable for human consumption in their natural state or are processed to make desserts. In this work, we characterized the chemical composition of the essential oil (EO) from the leaves of A. neoinsignis and evaluated its anti-liver-cancer potential via in vitro and in vivo approaches. Chemical composition analysis revealed β-elemene, (E)-caryophyllene, germacrene D, and germacrene B as the main constituents. The EO had IC50 values ranging from 12.28 to 37.50 μg/mL for B16-F10 cells and MCF-7 cells, whereas an IC50 value of >50 μg/mL was found for noncancerous MRC-5 cells. DNA fragmentation, YO-PRO-1 staining, and loss of mitochondrial transmembrane potential were detected in EO-treated HepG2 cells, indicating the induction of apoptosis. Significant in vivo growth inhibition of 53.7% was observed in mice bearing HepG2 cell xenografts treated with EO at a dosage of 40 mg/kg. These data suggest that EO from A. neoinsignis leaves is a drug source for liver cancer.

Lung cancer is one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 18%. Current treatment modalities include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Despite advances in therapeutic options, resistance to therapy remains a major obstacle to the effectiveness of long-term treatment, eventually leading to therapeutic insensitivity, poor progression-free survival, and disease relapse. Resistance mechanisms stem from genetic mutations and/or epigenetic changes, unregulated drug efflux, tumor hypoxia, alterations in the tumor microenvironment, and several other cellular and molecular alterations. A better understanding of these mechanisms is crucial for targeting factors involved in therapeutic resistance, establishing novel antitumor targets, and developing therapeutic strategies to resensitize cancer cells towards treatment. In this review, we summarize diverse mechanisms driving resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and promising strategies to help overcome this therapeutic resistance.

Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG.

Epigenetic remodeling is a molecular hallmark of gliomas, and it has been identified as a key mediator of glioma progression. Epigenetic dysregulation contributes to gliomagenesis, tumor progression, and responses to immunotherapies, as well as determining clinical features. This epigenetic remodeling includes changes in histone modifications, chromatin structure, and DNA methylation, all of which are driven by mutations in genes such as histone 3 genes (H3C1 and H3F3A), isocitrate dehydrogenase 1/2 (IDH1/2), α-thalassemia/mental retardation, X-linked (ATRX), and additional chromatin remodelers. Although much of the initial research primarily identified how the epigenetic aberrations impacted glioma progression by solely examining the glioma cells, recent studies have aimed at establishing the role of epigenetic alterations in shaping the tumor microenvironment (TME). In this review, we discuss the mechanisms by which these epigenetic phenomena in glioma remodel the TME and how current therapies targeting epigenetic dysregulation affect the glioma immune response and therapeutic outcomes. Understanding the link between epigenetic remodeling and the glioma TME provides insights into the implementation of epigenetic-targeting therapies to improve the antitumor immune response.

This work explores the self-assembly and optical properties of a novel chiral, aromatic-rich Boc-Phe-Phe dipeptide derivative functionalized with a benzothiazole bicyclic ring that forms supramolecular structures. Leveraging the well-known self-assembling capabilities of diphenylalanine dipeptides, this modified derivative introduces a heterocyclic benzothiazole unit that significantly enhances the fluorescence of the resulting nanostructures. The derivative’s rich aromatic character drives the formation of supramolecular structures through self-organization mechanisms influenced by quantum confinement. By adjusting the solvent system, the nanostructures exhibit tunable morphologies, ranging from nanospheres to nanobelts. The nonlinear optical properties of these self-assembled structures were studied and an estimated deff of ~0.9 pm/V was obtained, which is comparable to that reported for the highly aromatic triphenylalanine peptide.

Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guanylates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, administration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease. Targeting genotype-independent abnormalities may overcome therapy resistance in glioblastoma despite intratumoral genomic heterogeneity. Here, the authors show that glioblastoma radiation resistance is promoted by purine metabolism and can be overcome by inhibitors of purine synthesis.

Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected using ex vivo explants and in vivo intravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and potentially the collective invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. Col1a1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of Col1a1 eliminates oncostreams, reprograms the malignant histopathological phenotype, reduces expression of the mesenchymal associated genes, induces changes in the tumor microenvironment and prolongs animal survival. Oncostreams represent a pathological marker of potential value for diagnosis, prognosis, and treatment. It is essential to improve our understanding of the features that influence aggressiveness and invasion in high grade gliomas (HGG). Here, the authors characterize dynamic anatomical structures in HGG called oncostreams, which are associated with tumor growth and are regulated by COL1A1.