Glycogen Synthase Kinase 3 is Required for Optimal AKT Activation

The phosphatidylinositol 3-kinase (PI3K) pathway, through its major effector node AKT, is critical for the promotion of cell growth, division, motility and apoptosis evasion. This signaling axis is therefore commonly targeted in the form of mutations and amplifications in a myriad of malignancies. Glycogen synthase kinase 3 (GSK3) was first discovered as the kinase responsible for phosphorylating and inhibiting the activity of glycogen synthase, ultimately antagonizing the storage of glucose as glycogen. Its activity counteracts the effects of insulin in glucose metabolism and AKT has long been recognized as one of the key molecules capable of phosphorylating GSK3 and inhibiting its activity. However, here we demonstrate that GSK3 is required for optimal phosphorylation and activation of AKT in different malignant cell lines, and that this effect is independent of the type of growth factor stimulation and can happen even in basal states. Both GSK3 alpha and GSK3 beta isoforms are necessary for AKT to become fully active, displaying a redundant role in the setting. We also demonstrate that this effect of GSK3 on AKT phosphorylation and full activation is dependent on its kinase activity, since highly specific inhibitors targeting GSK3 catalytic activity also promote a reduction in phosphorylated AKT. Analysis of reverse phase protein array screening of MDA-MB-231 breast cancer cells treated with RNA interference targeting GSK3 unexpectedly revealed an increase in levels of phosphorylated MAPK14 (p38). Treatment with the selective p38 inhibitor SB 202190 rescued AKT activation in that cell line, corroborating the importance of unbiased proteomic analysis in exposing cross-talks between signaling networks and demonstrating a critical role for p38 in the regulation of AKT phosphorylation

Pembrolizumab-Induced Immune-Mediated Colitis in a Patient with Concurrent Clostridium Difficile Infection

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies. Immune-mediated colitis is a known but uncommon adverse effect of pembrolizumab. Symptoms of immune-mediated colitis can be similar to those of many other gastrointestinal illnesses, including Clostridium difficile infection (CDI). If not recognized and treated in a timely fashion, immune-mediated colitis can lead to significant morbidity in cancer patients. We report the case of a 56-year-old woman on pembrolizumab for metastatic non-small cell lung cancer (NSCLC) who presented with severe colitis symptoms and initially tested positive for CDI. Her colitis symptoms worsened despite appropriate treatment for CDI but later improved rapidly after systemic corticosteroid was started for suspected immune-mediated colitis. To our knowledge, this is the first reported case of concurrent pembrolizumab-induced colitis and CDI. Immune-mediated colitis should be considered in the differential diagnoses in patients on pembrolizumab or other immune checkpoint inhibitors who present with colitis symptoms, even when a concurrent infectious etiology is suspected

Hierarchical Classification of Financial Transactions Through Context-Fusion of Transformer-based Embeddings and Taxonomy-aware Attention Layer

This work proposes the Two-headed DragoNet, a Transformer-based model for hierarchical multi-label classification of financial transactions. Our model is based on a stack of Transformers encoder layers that generate contextual embeddings from two short textual descriptors (merchant name and business activity), followed by a Context Fusion layer and two output heads that classify transactions according to a hierarchical two-level taxonomy (macro and micro categories). Finally, our proposed Taxonomy-aware Attention Layer corrects predictions that break categorical hierarchy rules defined in the given taxonomy. Our proposal outperforms classical machine learning methods in experiments of macro-category classification by achieving an F1-score of 93\% on a card dataset and 95% on a current account dataset

A 3D Printing Scaffold Using Alginate/Hydroxyapatite for Application in Bone Regeneration

This work aimed to manufacture scaffolds from a hydrogel composed of a sodium alginate matrix with hydroxyapatite reinforcements using a 3D bioprinter, aiming at application in bone tissue regeneration. The alginate solution was prepared by dissolving sodium alginate at a concentration of 10% (w/v). Hydroxyapatite (HAp) was added to the solution at 2.5% and 5.0% (w/v) concentrations, followed by placing the samples in a container with a 1.0% (w/v) calcium chloride solution. The scaffolds were analyzed for HAp concentration and morphological characteristics, physicochemical properties, and biological response. The scaffolds show reproducibility and spectroscopic analyses confirm hydrogel formation and hydroxyapatite incorporation in the alginate matrix. The hydrophilic properties are compatible with scaffolds obtained through 3D printing made from polysaccharides, and the thermal analysis showed the expected behavior of these same materials. Preliminary findings indicated that scaffolds containing 2.5% (w/v) hydroxyapatite are inside cytotoxicity limit (66.4 ± 7.0%) towards canine E20 lineage cells. In contrast, scaffolds with 0% and 5.0% (w/v) hydroxyapatite were non-cytotoxic. Notably, the latter scaffold demonstrated enhanced cell proliferation, as anticipated, owing to the hydrophilic properties of alginate that enable easy and swift cell seeding, facilitating nutrient transport and cellular growth within the scaffold

Practical Science and Environmental Education Workshop in Manaus, Brazil

It is an unequivocal fact that Amazonian tropical forest is the largest remaining primary forest in the world. The ecosystem in the region is e tremely comple with high biodiversity (Peres et al. 2010). Conservation and protection of the dynamic forest and river regions is e tremely important not only for the natural environments, but also for the economy and social dependence of benefits from such abundant natural environments. Important natural parameters that affect status of the natural environments include light (natural sunlight), soil, and water, which abundantly e ist in the Amazon region. Solar energy is the primary energy source for the majority of living organisms in both terrestrial and aquatic ecosystems, and drives the diurnal and seasonal cycles of biogeochemical processes (Monteith & Unsworth 2013). In particular, in situ light data remains one of the most underappreciated data measurements although having a significant impact on the physical, chemical and biological processes in the ecosystem (Johnsen 2012). Soil provides the fundamental basis for all terrestrial living organisms including the Amazonian forests as well as life-sustaining infrastructure for human society. Water is the most essential single entity to constitute all organisms from a single cell to the earth. Understanding of importance and roles of each factor and interaction of such comple dynamics in the natural environments can serve as fundamental platform for natural scientists, particularly for young scientists such as university students. The objective of this workshop was to provide hand- on scientific and environmental education for university students in Manaus, Amazonas, Brazil through practical field measurements using the three most important parameters in the natural ecosystem composed of natural sunlight, soil, and water. The workshop was divided into a series of lectures, in situ field sampling, and data processing, analysis and interpretation with the ultimate goal of empowering the undergraduate students with research-centered environmental education and e perience of developing international collaboration.departmental bulletin pape

Data standardization of plant-pollinator interactions

Background: Animal pollination is an important ecosystem function and service, ensuring both the integrity of natural systems and human well-being. Although many knowledge shortfalls remain, some high-quality data sets on biological interactions are now available. The development and adoption of standards for biodiversity data and metadata has promoted great advances in biological data sharing and aggregation, supporting large-scale studies and science-based public policies. However, these standards are currently not suitable to fully support interaction data sharing. Results: Here we present a vocabulary of terms and a data model for sharing plant–pollinator interactions data based on the Darwin Core standard. The vocabulary introduces 48 new terms targeting several aspects of plant–pollinator interactions and can be used to capture information from different approaches and scales. Additionally, we provide solutions for data serialization using RDF, XML, and DwC-Archives and recommendations of existing controlled vocabularies for some of the terms. Our contribution supports open access to standardized data on plant–pollinator interactions. Conclusions: The adoption of the vocabulary would facilitate data sharing to support studies ranging from the spatial and temporal distribution of interactions to the taxonomic, phenological, functional, and phylogenetic aspects of plant–pollinator interactions. We expect to fill data and knowledge gaps, thus further enabling scientific research on the ecology and evolution of plant–pollinator communities, biodiversity conservation, ecosystem services, and the development of public policies. The proposed data model is flexible and can be adapted for sharing other types of interactions data by developing discipline-specific vocabularies of terms.Fil: Salim, José A. Universidade de Sao Paulo; BrasilFil: Saraiva, Antonio M.. Universidade de Sao Paulo; BrasilFil: Zermoglio, Paula Florencia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Recursos Naturales, Agroecologia y Desarrollo Rural. - Universidad Nacional de Rio Negro. Instituto de Investigaciones En Recursos Naturales, Agroecologia y Desarrollo Rural.; ArgentinaFil: Agostini, Kayna. Universidade Federal do São Carlos; BrasilFil: Wolowski, Marina. Universidade Federal de Alfenas; BrasilFil: Drucker, Debora P.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Soares, Filipi M.. Universidade de Sao Paulo; BrasilFil: Bergamo, Pedro J.. Jardim Botânico do Rio de Janeiro; BrasilFil: Varassin, Isabela G.. Universidade Federal do Paraná; BrasilFil: Freitas, Leandro. Jardim Botânico do Rio de Janeiro; BrasilFil: Maués, Márcia M.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Rech, Andre R.. Universidade Federal dos Vales do Jequitinhonha e Mucuri; BrasilFil: Veiga, Allan K.. Universidade de Sao Paulo; BrasilFil: Acosta, Andre L.. Instituto Tecnológico Vale; BrasilFil: Araujo, Andréa C. Universidade Federal do Mato Grosso do Sul; BrasilFil: Nogueira, Anselmo. Universidad Federal do Abc; BrasilFil: Blochtein, Betina. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Freitas, Breno M.. Universidade Estadual do Ceará; BrasilFil: Albertini, Bruno C.. Universidade de Sao Paulo; BrasilFil: Maia Silva, Camila. Universidade Federal Rural Do Semi Arido; BrasilFil: Nunes, Carlos E. P.. University of Stirling; BrasilFil: Pires, Carmen S. S.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Dos Santos, Charles F.. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Queiroz, Elisa P.. Universidade de Sao Paulo; BrasilFil: Cartolano, Etienne A.. Universidade de Sao Paulo; BrasilFil: de Oliveira, Favízia F. Universidade Federal da Bahia; BrasilFil: Amorim, Felipe W.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Fontúrbel, Francisco E.. Pontificia Universidad Católica de Valparaíso; ChileFil: da Silva, Gleycon V.. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Consolaro, Hélder. Universidade Federal de Catalão; Brasi

Data standardization of plant–pollinator interactions

Background: Animal pollination is an important ecosystem function and service, ensuring both the integrity of natural systems and human well-being. Although many knowledge shortfalls remain, some high-quality data sets on biological interactions are now available. The development and adoption of standards for biodiversity data and metadata has promoted great advances in biological data sharing and aggregation, supporting large-scale studies and science-based public policies. However, these standards are currently not suitable to fully support interaction data sharing. Results: Here we present a vocabulary of terms and a data model for sharing plant–pollinator interactions data based on the Darwin Core standard. The vocabulary introduces 48 new terms targeting several aspects of plant–pollinator interactions and can be used to capture information from different approaches and scales. Additionally, we provide solutions for data serialization using RDF, XML, and DwC-Archives and recommendations of existing controlled vocabularies for some of the terms. Our contribution supports open access to standardized data on plant–pollinator interactions. Conclusions: The adoption of the vocabulary would facilitate data sharing to support studies ranging from the spatial and temporal distribution of interactions to the taxonomic, phenological, functional, and phylogenetic aspects of plant–pollinator interactions. We expect to fill data and knowledge gaps, thus further enabling scientific research on the ecology and evolution of plant–pollinator communities, biodiversity conservation, ecosystem services, and the development of public policies. The proposed data model is flexible and can be adapted for sharing other types of interactions data by developing discipline-specific vocabularies of termsinfo:eu-repo/semantics/publishedVersio

Haplotype Affinities Resolve a Major Component of Goat (Capra hircus) MtDNA D-Loop Diversity and Reveal Specific Features of the Sardinian Stock

Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using Bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity