Integrating Fossil Flowers into the Angiosperm Phylogeny Using Molecular and Morphological Evidence.

Fossils are essential to infer past evolutionary processes. The assignment of fossils to extant clades has traditionally relied on morphological similarity and on apomorphies shared with extant taxa. The use of explicit phylogenetic analyses to establish fossil affinities has so far remained limited. In this study, we built a comprehensive framework to investigate the phylogenetic placement of 24 exceptionally preserved fossil flowers. For this, we assembled a new species-level data set of 30 floral traits for 1201 extant species that were sampled to capture the stem and crown nodes of all angiosperm families. We explored multiple analytical approaches to integrate the fossils into the phylogeny, including different phylogenetic estimation methods, topological-constrained analyses, and combining molecular and morphological data of extant and fossil species. Our results were widely consistent across approaches and showed minor differences in the support of fossils at different phylogenetic positions. The placement of some fossils agrees with previously suggested relationships, but for others, a new placement is inferred. We also identified fossils that are well supported within particular extant families, whereas others showed high phylogenetic uncertainty. Finally, we present recommendations for future analyses combining molecular and morphological evidence, regarding the selection of fossils and appropriate methodologies, and provide some perspectives on how to integrate fossils into the investigation of divergence times and the temporal evolution of morphological traits. [Angiosperms; fossil flowers; phylogenetic uncertainty; RoguePlots.].

Synthesis, Optical Characterization in Solution and Solid-State, and DFT Calculations of 3-Acetyl and 3-(1'-(2'-Phenylhydrazono)ethyl)-coumarin-(7)-substituted Derivatives.

Intramolecular charge transfer (ICT) effects are responsible for the photoluminescent properties of coumarins. Hence, optical properties with different applications can be obtained by ICT modulation. Herein, four 3-acetyl-2H-chromen-2-ones (1a-d) and their corresponding fluorescent hybrids 3- (phenylhydrazone)-chromen-2-ones (2a-d) were synthesized in 74-65% yields. The UV-Vis data were in the 295-428 nm range. The emission depends on the substituent in position C-7 bearing electron-donating groups. Compounds 1b-d showed good optical properties due to the D-π-A structural arrangement. In compounds 2a-d, there is a quenching effect of fluorescence in solution. However, in the solid, an increase is shown due to an aggregation-induced emission (AIE) effect given by the rotational restraints and stacking in the crystal. Computational calculations of the HOMO-LUMO orbitals indicate high absorbance and emission values of the molecules, and gap values represent the bathochromic effect and the electronic efficiency of the compounds. Compounds 1a-d and 2a-d are good candidates for optical applications, such as OLEDs, organic solar cells, or fluorescence markers.

Regulation of Metabolic Reprogramming by Long Non-Coding RNAs in Cancer.

Metabolic reprogramming is a well described hallmark of cancer. Oncogenic stimuli and the microenvironment shape the metabolic phenotype of cancer cells, causing pathological modifications of carbohydrate, amino acid and lipid metabolism that support the uncontrolled growth and proliferation of cancer cells. Conversely, metabolic alterations in cancer can drive changes in genetic programs affecting cell proliferation and differentiation. In recent years, the role of non-coding RNAs in metabolic reprogramming in cancer has been extensively studied. Here, we review this topic, with a focus on glucose, glutamine, and lipid metabolism and point to some evidence that metabolic alterations occurring in cancer can drive changes in non-coding RNA expression, thus adding an additional level of complexity in the relationship between metabolism and genetic programs in cancer cells.

Genotoxic Treatment Enhances Immune Response in a Genetic Model of Lung Cancer.

Recent advances in immunotherapy have reshaped the clinical management of lung cancer, and immune checkpoint inhibitors (ICIs) are now first-line treatment for advanced lung cancer. However, the majority of patients do not respond to ICIs as single agents, and many develop resistance after initial responses. Therefore, there is urgent need to improve the current ICI strategies. Murine models currently available for pre-clinical studies have serious limitations for evaluating novel immunotherapies. GEMMs are reliable and predictable models driven by oncogenic mutations mirroring those found in cancer patients. However, they lack the mutational burden of human cancers and thus do not elicit proper immune surveillance. Carcinogen-induced models are characterized by mutational burden that more closely resembles human cancer, but they often require extremely long experimental times with inconsistent results. Here, we present a hybrid model in which genetically engineered mice are exposed to the carcinogen N-Methyl-N-Nitrosourea (MNU) to increase tumor mutational burden (TMB), induce early-stage immune responses, and enhance susceptibility to ICIs. We anticipate that this model will be useful for pre-clinical evaluation of novel immunotherapies.

Consecutive reactions to construct tricarbonyl compounds and synthetic applications thereof.

Lithium anions derived from O-carbonate-protected cyanohydrins undergo conjugate addition to cycloalkenones with the concomitant transfer of the alkoxycarbonyl group to produce tricarbonyl compounds. These products offer numerous possibilities for further elaboration. The synthetic potential of the cascade products was demonstrated by forming bicyclic and tricyclic systems through intramolecular condensation reactions.

Metabolic Regulation of Epigenetic Modifications and Cell Differentiation in Cancer.

Metabolic reprogramming is a hallmark of cancer, with consistent rewiring of glucose, glutamine, and mitochondrial metabolism. While these metabolic alterations are adequate to meet the metabolic needs of cell growth and proliferation, the changes in critical metabolites have also consequences for the regulation of the cell differentiation state. Cancer evolution is characterized by progression towards a poorly differentiated, stem-like phenotype, and epigenetic modulation of the chromatin structure is an important prerequisite for the maintenance of an undifferentiated state by repression of lineage-specific genes. Epigenetic modifiers depend on intermediates of cellular metabolism both as substrates and as co-factors. Therefore, the metabolic reprogramming that occurs in cancer likely plays an important role in the process of the de-differentiation characteristic of the neoplastic process. Here, we review the epigenetic consequences of metabolic reprogramming in cancer, with particular focus on the role of mitochondrial intermediates and hypoxia in the regulation of cellular de-differentiation. We also discuss therapeutic implications.

Heterogeneity of Glucose Transport in Lung Cancer.

Increased glucose uptake is a known hallmark of cancer. Cancer cells need glucose for energy production via glycolysis and the tricarboxylic acid cycle, and also to fuel the pentose phosphate pathway, the serine biosynthetic pathway, lipogenesis, and the hexosamine pathway. For this reason, glucose transport inhibition is an emerging new treatment for different malignancies, including lung cancer. However, studies both in animal models and in humans have shown high levels of heterogeneity in the utilization of glucose and other metabolites in cancer, unveiling a complexity that is difficult to target therapeutically. Here, we present an overview of different levels of heterogeneity in glucose uptake and utilization in lung cancer, with diagnostic and therapeutic implications.

Tetraspanin 33 (TSPAN33) regulates endocytosis and migration of human B lymphocytes by affecting the tension of the plasma membrane.

B lymphocytes are a leukocyte subset capable of developing several functions apart from differentiating into antibody-secreting cells. These processes are triggered by external activation signals that induce changes in the plasma membrane properties, regulated by the formation of different lipid-bilayer subdomains that are associated with the underlying cytoskeleton through different linker molecules, thus allowing the functional specialization of regions within the membrane. Among these, there are tetraspanin-enriched domains. Tetraspanins constitute a superfamily of transmembrane proteins that establish lateral associations with other molecules, determining its activity and localization. In this study, we identified TSPAN33 as an active player during B-lymphocyte cytoskeleton and plasma membrane-related phenomena, including protrusion formation, adhesion, phagocytosis, and cell motility. By using an overexpression model of TSPAN33 in human Raji cells, we detected a specific distribution of this protein that includes membrane microvilli, the Golgi apparatus, and extracellular vesicles. Additionally, we identified diminished phagocytic ability and altered cell adhesion properties due to the aberrant expression of integrins. Accordingly, these cells presented an enhanced migratory phenotype, as shown by its augmented chemotaxis and invasion rates. When we evaluated the mechanic response of cells during fibronectin-induced spreading, we found that TSPAN33 expression inhibited changes in roughness and membrane tension. Contrariwise, TSPAN33 knockdown cells displayed opposite phenotypes to those observed in the overexpression model. Altogether, our data indicate that TSPAN33 represents a regulatory element of the adhesion and migration of B lymphocytes, suggesting a novel implication of this tetraspanin in the control of the mechanical properties of their plasma membrane.

Medicinal plants from the genus Alchornea (Euphorbiaceae): a review of their ethnopharmacology uses and phytochemistry / Plantas Medicinales del género Alchornea (Euphorbiaceae): Review de los usos etnofarmacológicos y fitoquímicos

The genus Alchornea compromises 55 accepted and other two unresolved species (Alchornea acerifera Croizat and Alchornea oblonga Müll. Arg.) which well various ecosystems over all the continents, with a special pantropical distribution. Numerous reports of ethnopharmacological uses of species belonging this genus exist mainly in Africa and Brazil, to treat different inflammatory and infectious diseases: arthritis, dysentery, infectious diseases, inflammation, intestinal disorders, fractures, leprosy, malaria, management of ringworm affections, muscle pain, rheumatism and ulcer. The genus Alchornea, contains different secondary metabolites and they have been reported such as: Alkaloids, terpenes and steroids, phenolic acid, saponins, principaly. The aim of the present review is to provide gathered and organized information with pharmacological, toxicological, traditional and phytochemical traits of plants from the Alchornea genus in order to define the biological potential of the genus and to define a state-of-art-platform stating the perspectives for further pharmacological/chemotaxonomical studies.

El género Alchornea comprende 55 especies aceptadas y otras dos especies por confirmar (Alchornea acerifera Croizat y Alchornea oblonga Müll. Arg.) qué habitan en diversos ecosistemas en todos los continentes, con una distribución pantropical especial. Existen numerosos reportes de usos ethnofarmacologicos de especies que pertenecen a este género en Africa y Brasil, en el tratamiento de diferentes enfermedades inflamatorias e infecciosas: la artritis, la disentería, los desórdenes intestinales, las fracturas, la lepra, la malaria, dolor del músculo, reumatismo y úlcera. En el género Alchornea, se han reportado diversos tipos de metabolitos secundarios tales como: alcaloides, terpenos y esteroides, ácidos fenolicos, saponinas, principalmente. El objetivo de esta revisión fue de compendiar y organizar la información farmacológica, toxicológica, de usos tradicionales y de fitocompuestos de plantas del género de Alchornea en el orden de definir el potencial biológico del género y establecer la plataforma del estado-de-arte con las perspectivas de los futuros estudios farmacológico/quimiotaxonómicos que se podrían realizar.

Apigenin glycoside: an antioxidant isolated from Alchornea coelophylla pax & k. Hoffm. (euphorbiaceae) leaf extract / Glicósido de apigenina: un antioxidante aislado del extracto de hoja de Alchornea coelophylla Pax & K. Hoflm. (Euphorbiaceae) / Glicosídeo de apigenina: um antioxidante do extrato das folhas de Alchornea coelophylla Pax & K. Hoflm. (Euphorbiaceae)

Abstract An antioxidant flavonoid has been isolated from methanolic leaf extract of Alchornea coelophylla Pax & K. Hoffm. by means of different column chromatography steps with DIAION HP-20 resin and silica gel in combination with analytical highperformance liquid chromatography (HPLC). It was identified as Apigenin-8-C- (α-L-rhamnopyranosyl-(1-›2)-β-D-glucopyranoside) on the basis of spectroscopic analysis and by comparison with related values reported in the literature. This compound exhibited high in vitro antioxidant activity through DPPH. and ABTS • + colorimetric assays with IC50 values of 7.528 and 379.7 µg. mL-1, respectively.

Resumen Se aisló un flavonoide antioxidante del extracto metanólico de hojas de Alchornea coelophylla Pax & K. Hoffm. El compuesto se obtuvo por medio de sucesivas cromatografías en columna (con la resina DIAION HP-20 y sílica gel), seguidas de cromatografía líquida de alta eficiencia (HPLC). Con base en el análisis espectroscópico y por comparación con valores relacionados reportados en la literatura, el flavonoide se identificó como Apigenin-8-C-(α-L-rhamnopiranosil-(1-›2)-β-D-glucopiranósido). Este compuesto presentó una alta actividad antioxidante in vitro: ensayos colorimétricos utilizando DPPH. y ABTS • + mostraron valores de IC50 de 7.528 y 379.7 µg mL-1, respectivamente.

Resumen Um flavonoide antioxidante foi isolado do extrato metanólico das folhas de Alchornea coelophylla Pax & K. Hoffm. por meio de diferentes etapas de cromatografia em coluna usando resina DIAION HP-20 e gel de sílica em combinação com Cromatografia Líquida de Alta Eficiencia (HPLC) analítica. O composto foi identificado como apigenina-8-C-(α-L-ramnopiranosil-(1-›2)-β-D-glicopiranosido) com base em análises espectroscópicas e por comparação com valores descritos na literatura. Este composto exibiu elevada atividade antioxidante in vitro por meio de ensaios colorimétricos por DPPH e ABTS • + com valores de IC50 de 7,528 e 379,7 µg. mL-1, respectivamente.

Grosor de segmento uterino inferior como predictor de resolución de embarazo vía vaginal en pacientes con cesárea previa / Thickness of the lower uterine segment as a predictor of pregnancy resolution vaginally in patients with previous cesarean

Objetivo El objetivo de esta investigación fue determinar siel grosor del segmento uterino, medido por ultrasonido, esun predictor de la resolución del embarazo por vía vaginal.Método Estudio observacional de prueba diagnóstica quese llevó a cabo en el Hospital General San Juan de Diosde la Ciudad de Guatemala, en la Unidad de Obstetricia. Elestudio incluyo a todas las pacientes que cumplieron conlos requisitos de una cesárea previa en el periodo de enerode 2011 a enero 2012. Resultados del grupo total (n 43), el81% (n=35) resolvieron parto por vía vaginal, y el 19% (n=8)por cesárea. El 58% tenían un grosor menor de 3.5 mm y el42% fue mayor o igual a ello. De 35 pacientes que tuvieronparto eutócico simple, el 48 %(n= 19) fue menor de 3.5 mm,mientras que 52 % (n=17) tenían una medición igual o mayor;de las 8 sometidas a cesárea, en 7 fue menor de 3.5 mm. Lamorbilidad se presentó solamente en el grupo cuyo segmentofue menor de 3.5 mm, 2.3% (n=1) ruptura uterina y 4.6% (n=2)dehiscencias uterinas, y representaron el 12.5 % de las 24pacientes. No hubo mortalidad materna. Conclusión Se puedeofrecer prueba de parto vaginal a pacientes con una cesàreaprevia independientemente del grosor del segmento uterinoinferior; sin embargo cuando el mismo es menor de 3.5mmse debe realizar un monitoreo materno fetal más estricto.

Objective The objective of this research was to determinewhether uterine segment thickness, measured by ultrasound,is a predictor of pregnancy resolution vaginally. MethodObservational study of diagnostic test that took place inHospital General San Juan de Dios in Guatemala City, atthe Obstetrics Unit. The study included all patients who metthe requirements of a previous cesarean in the period fromJanuary 2011 to January 2012. Results of the total group (n43), 81% (n = 35) resolved vaginal delivery, and 19% (n =8) by cesarean section. 58% had a thickness less than 3.5mm and 42% was greater than or equal to it. 35 patientswho had single vaginal delivery, 48% (n = 19) was less than3.5 mm, while 52% (n = 17) had a measurement equal to orgreater; from 8 subjected to caesarean section 7 was lessthan 3.5 mm. The morbidity was observed only in the groupwhose segment was less than 3.5 mm, 2.3% (n = 1) uterinerupture and 4.6% (n = 2) uterine dehiscence, and accountedfor 12.5% of the 24 patients. There were no maternal deaths.Conclusion We can offer trial of labor in patients with aprevious cesarean section regardless of the thickness of thelower uterine segment; however when it is less than 3.5mmstrict materno-fetal monitoring is mandatory.

Cáncer de mama asociado a embarazo / Breast cancer associated with pregnancy

Resumen: Se presenta a continuación una serie de casos, de cáncer de mama asociado a embarazo, que se documentaron en el Hospital General San Juan de Dios en un período de 22 meses. El promedio de edad de estas pacientes es de 33 años y la histología más común es el Carcinoma Ductal infiltrante. Por lo interesante de esta patología se hace una revisión exhaustiva de la literatura en cuanto al manejo y la sobrevida de estas pacientes.

Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma.

Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels.

Caracterización del tumor ovárico en la mujer centroamericana / Characterization of ovarian tumor in American women

El diagnóstico de una masa anexial es uno de los hallazgos más frecuentes en la práctica clínica de un ginecólogo. De los tumores ováricos el 80% son benignos y se presentan generalmente en mujeres menores de 45 años, el 20% son malignos y se presentan principalmente en mujeres postmenopáusicas...