A costimulatory molecule-related signature in regard to evaluation of prognosis and immune features for clear cell renal cell carcinoma

Costimulatory molecules have been proven to enhance antitumor immune responses, but their roles in clear cell renal cell carcinoma (ccRCC) remain unexplored. In this study, we aimed to explore the gene expression profiles of costimulatory molecule genes in ccRCC and construct a prognostic signature to improve treatment decision-making and clinical outcomes. We performed the first comprehensive analysis of costimulatory molecules in patients with ccRCC and identified 13 costimulatory molecule genes with prognostic values and diagnostic values. Consensus clustering analysis based on these 13 costimulatory molecular genes showed different distribution patterns and prognostic differences for the two clusters identified. Then, a costimulatory molecule-related signature was constructed based on these 13 costimulatory molecular genes, and validated in an external dataset, showing good performance for predicting a patient’s prognosis. The signature was an independent risk factor for ccRCC patients and was significantly correlated with patients’ clinical factors, which could be used as a complement for clinical factors. In addition, the signature was associated with the tumor immune microenvironment and the response to immunotherapy. Patients identified as high-risk based on our signature exhibited a high mutation frequency, a high level of immune cell infiltration, and an immunosuppressive microenvironment. High-risk patients tended to have high cytolytic activity scores and immunophenoscore of CTLA4 and PD1/PD-L1/PD-L2 blocker than low-risk patients, suggesting these patients may be more suitable for immunotherapy. Therefore, our signature could provide clinicians with prognosis predictions and help guide treatment for ccRCC patients.

Christia Vespertilionis Extract Induced Antiproliferation and Apoptosis in Breast Cancer (MCF7) Cells

Background: C. vespertiliomis extracts were evaluated for antiproliferative and apoptosis effect on breast cancer (MCF7) cells. Methods and Results: The leaves extracts were analysed for its antiproliferative effect on breast cancer (MCF7) cells and normal epithelial breast (MCF 10A) cells using Sulforhodamine B (SRB) assay. The selective extract was evaluated for its ability to induce apoptosis using Annexin V-FITC apoptosis staining and the expression of molecular genes using qualitative reverse transcription-polymerase chain reaction (RT-PCR) against MCF7 cells. Gas chromatography–mass spectrometry (GC–MS) was used to identify the compounds from the selective extract. The findings showed that dichloromethane fraction (CV-Dcm) extract had high antiproliferative effect against MCF7 cells (IC50 = 24 µg/mL, selective index (SI) = 8.17). The percentages of apoptosis cells in CV-Dcm-treated MCF7 cells was 58.8%. The CV-Dcm extract induced downregulation of PCNA level. The apoptotic genes were also triggered in both extrinsic and intrinsic signaling pathways, affecting a 1.5-fold increase in BAX, 1.4-fold increase in cytochrome c, 1.3-fold increase in caspase-8, 1.7-fold increase in caspase-3 and 0.5-fold-decrease in BCL-2. Treated MCF7 cells also activated P53-dependent apoptotic death pathway. Conclusions: The present work strongly suggests that high efficacy of CV-Dcm extract was attributed to its antiproliferative and apoptosis-inducing activation in MCF7 cells, most likely due to its favourable compounds.

Phylogeny of drepanosiphine aphids sensu lato (Hemiptera, Aphidoidea) inferred from molecular and morphological data

As the second largest and most diverse group in the superfamily Aphidoidea, the phylogeny of drepanosiphine aphids sensu lato (s.l.) is critical for discussing the evolution of aphids. However, the taxa composition and phylogenetic relationships of drepanosiphine aphids s.l. have not been fully elucidated to date. In this study, based on total-evidence analyses combining 4 molecular genes (3 mitochondrial, COI, tRNA-Leu/COII, and CytB; 1 nuclear, EF-1ɑ) and 64 morphological and biological characteristics, the phylogeny of this group was reconstructed for the first time at the subfamily level using different datasets, parsimonies and model-based methods. All of our phylogenetic inferences clearly indicated that the drepanosiphine aphids s.l. was not a monophyletic group and seemed to support the division of the drepanosiphine aphids s.l. into different groups classified at the subfamily level. Calaphidinae was also not a monophyletic group, and Saltusaphidinae was nested within this subfamily. Drepanosiphinae was not clustered with Chaitophorinae, which was inconsistent with the previous hypothesis of a close relationship between them, illustrating that their phylogeny remains controversial. Overall, some groups of drepanosiphine aphids s.l., including Phyllaphidinae, Macropodaphidinae, Pterastheniinae, Lizeriinae, Drepanosiphinae, Spicaphidinae, Saltusaphidinae, and Calaphidinae, clustered together and might constitute the actual drepanosiphine aphids s.l. To a certain extent, our results clarified the phylogenetic relationships among drepanosiphine aphids s.l. and confirmed their taxonomic status as subfamilies.

Plasticity and Multiplicity of Trophic Modes in the Dinoflagellate Karlodinium and Their Pertinence to Population Maintenance and Bloom Dynamics

As the number of mixotrophic protists has been increasingly documented, “mixoplankton”, a third category separated from the traditional categorization of plankton into “phytoplankton” and “zooplankton”, has become a new paradigm and research hotspot in aquatic plankton ecology. While species of dinoflagellates are a dominant group among all recorded members of mixoplankton, the trophic modes of Karlodinium, a genus constituted of cosmopolitan toxic species, were reviewed due to their representative features as mixoplankton and harmful algal blooms (HABs)-causing dinoflagellates. Among at least 15 reported species in the genus, three have been intensively studied for their trophic modes, and all found to be phagotrophic. Their phagotrophy exhibits multiple characteristics: (1) omnivority, i.e., they can ingest a variety of preys in many forms; (2) flexibility in phagotrophic mechanisms, i.e., they can ingest small preys by direct engulfment and much bigger preys by myzocytosis using a peduncle; (3) cannibalism, i.e., species including at least K. veneficum can ingest the dead cells of their own species. However, for some recently described and barely studied species, their tropical modes still need to be investigated further regarding all of the above-mentioned aspects. Mixotrophy of Karlodinium plays a significant role in the population dynamics and the formation of HABs in many ways, which thus deserves further investigation in the aspects of physiological ecology, environmental triggers (e.g., levels of inorganic nutrients and/or presence of preys), energetics, molecular (genes and gene expression regulations) and biochemical (e.g., relevant enzymes and signal molecules) bases, origins, and evaluation of the advantages of being a phagotroph.

Morphology lies: a case-in-point with a new non-biting midge species from Oriental China (Diptera, Chironomidae)

Morphological traits are generally indicative of specific taxa, and particularly function as keys in taxonomy and species delimitation. In this study, a non-biting midge species with an Einfeldia-like superior volsella makes it hard to accurately determined based on its morphological characteristics. Molecular genes of two ribosomal genes and three protein-encoding genes were compiled to construct a related genera phylogeny and to address the taxonomic issues. Phylogenetic inference clearly supports the undetermined species as belonging to Kiefferulus. Therefore, a new species classified in the genus Kiefferulus is described and figured as an adult male from Oriental China. The species could be easily distinguished from other species in having an Einfeldia-like superior volsella and a triangular tergite IX.

Estudio molecular de genes candidatos para el color de capa de llamas (Lama glama)

La llama es el más grande de los Camélidos Sudamericanos domésticos y el más abundante en Argentina. Es una especie productora de fibra que se caracteriza por presentar una gran diversidad de colores y patrones de pigmentación. El color de la fibra tiene un impacto directo sobre su valor comercial, siendo el blanco uno de los colores más buscados. La pigmentación en los mamíferos es un proceso altamente conservado en el cual el color de capa base está dado por la relación entre eumelanina y feomelanina, controlada principalmente por los genes MC1R y ASIP. Se conoce que la producción de eumelanina en la llama está asociada a mutaciones recesivas en la región codificante de ASIP, mientas que los alelos de MC1R muestran asociación con la presencia/ausencia de pigmento. Sin embargo, aún se desconoce el mecanismo molecular que genera el fenotipo blanco. El objetivo general de esta tesis es estudiar a nivel molecular genes que intervienen en la ruta de síntesis de los pigmentos y determinar su rol en la producción del color de capa blanco en llamas. En primer lugar se realizó un estudio de los alelos de MC1R para determinar su asociación con este color. Se logró identificar el alelo dominante de la serie (alelo E) y se confirmó que MC1R*2 está asociado al blanco pero, necesariamente debe existir otro gen implicado en la producción de este fenotipo. En base a esto, se evaluaron distintas hipótesis que plantean mecanismos alternativos para la obtención del fenotipo blanco. Se estudiaron los genes KIT y MITF y los genes TYR y SLC7A11 relacionados con alteraciones en el desarrollo, la diferenciación o la migración de los melanocitos y con la dilución de melaninas o hipopigmentación, respectivamente. Para todos ellos se secuenció y se describió la región codificante y se estudiaron sus polimorfismos y su expresión en llamas con distintos fenotipos de color. No se encontraron mutaciones en ninguno de ellos que puedan ser causales del fenotipo blanco, pero se observó que todos los genes se expresaron significativamente menos en las llamas blancas respecto de las pigmentadas. Este patrón de expresión se puede explicar por la acción de ASIP. Se observó que este gen presenta una sobreexpresión en animales blancos y feomelánicos comparado con los negros. Se estudiaron las variantes transcripcionales de ASIP y se pudo determinar que la sobreexpresión es causada por un transcripto cuya región 5’UTR pertenece al gen NCOA6, sugiriendo que existe un reordenamiento de ASIP en el genoma de las llamas con los fenotipos blanco y feomelánico. Este transcripto podría corresponder al alelo de ASIP denominado Awt. Finalmente, considerando los alelos de MC1R y de ASIP se propone un modelo para la producción de los fenotipos de color de capa sólidos en la llama.

Caracterización, alcances y dificultades de las "bases biológicas" del Trastorno por Déficit de Atención e Hiperactividad (TDAH). Un enfoque desde la Filosofía de la Biología

Resumen El trastorno por déficit de atención e hiperactividad (TDAH) se encuentra entre los trastornos psiquiátricos infantiles más prevalentes en la actualidad y, desde áreas biomédicas y neurobiológicas, se considera que presenta una base biológica. En el presente trabajo se analizarán, desde una aproximación filosófica, los discursos que se despliegan desde dichas investigaciones con el objetivo de detectar y clarificar diversos aspectos fenoménicos, teóricos y ontológicos que le subyacen. En términos generales, hemos encontrado que la conceptualización del TDAH está atravesada por al menos cuatro niveles de organización diferentes: genético-molecular (genes y proteínas), tisular (partes del cerebro), órgano (cerebro como un todo) y el organísmico (individuo). Dichos niveles ocupan roles sumamente diferentes; ocupando los niveles inferiores de organización roles predominantes en lo explicativo así como presentando las entidades fundamentales en términos ontológicos. A su vez, el discurso neurocientífico presenta sesgos relacionados con la pérdida de consideración de la heterogeneidad, la omisión de los niveles superiores al organísmico y simplificaciones del ámbito genético-molecular y de la relación genotipo-fenotipo. Así, el tipo de indagación simplificante y que prepondera los niveles inferiores de la jerarquía biológica parece mostrar más dificultades que éxitos, y epistémicamente muestra grietas que no son saldadas.