Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study.

BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.

Editing of SlWRKY29 by CRISPR-activation promotes somatic embryogenesis in Solanum lycopersicum cv. Micro-Tom.

At present, the development of plants with improved traits like superior quality, high yield, or stress resistance, are highly desirable in agriculture. Accelerated crop improvement, however, must capitalize on revolutionary new plant breeding technologies, like genetically modified and gene-edited crops, to heighten food crop traits. Genome editing still faces ineffective methods for the transformation and regeneration of different plant species and must surpass the genotype dependency of the transformation process. Tomato is considered an alternative plant model system to rice and Arabidopsis, and a model organism for fleshy-fruited plants. Furthermore, tomato cultivars like Micro-Tom are excellent models for tomato research due to its short life cycle, small size, and capacity to grow at high density. Therefore, we developed an indirect somatic embryo protocol from cotyledonary tomato explants and used this to generate epigenetically edited tomato plants for the SlWRKY29 gene via CRISPR-activation (CRISPRa). We found that epigenetic reprogramming for SlWRKY29 establishes a transcriptionally permissive chromatin state, as determined by an enrichment of the H3K4me3 mark. A whole transcriptome analysis of CRISPRa-edited pro-embryogenic masses and mature somatic embryos allowed us to characterize the mechanism driving somatic embryo induction in the edited tomato cv. Micro-Tom. Furthermore, we show that enhanced embryo induction and maturation are influenced by the transcriptional effector employed during CRISPRa, as well as by the medium composition and in vitro environmental conditions such as osmotic components, plant growth regulators, and light intensity.

Pharyngeal mucosal closure in total laryngectomy: comparison between vertical and T-shaped closure.

Objective: The objective of this study was to compare the outcomes vertical and T-shaped pharyngoplasty closure techniques after total laryngectomy (TL) and to evaluate the factors associated with the development of pharyngocutaneous fistula. Materials and methods: We performed a retrospective study that included patients with a histopathological diagnosis of laryngeal cancer that underwent TL between 2009 and 2021. Results: Fifty-seven patients were included in the study. A total of 14 patients underwent a vertical closure of the neopharynx (24.6%), while 43 patients underwent a T-shaped closure (74.4%). Pharyngocutaneous fistula was the most common complication, observed in 40.4% of cases (n = 23). No difference in the rate of complications was observed between groups, with the exception of tracheal dehiscence which was reduced in patients with T-shaped closure (n = 2, 4.7% vs. n = 5, 35.7%, p = 0.002). Diabetes mellitus was more frequently observed in patients withthe development of pharyngocutaneous fistula (n = 7, 30.4% vs. n = 3, 8.8%, p = 0.03). Conclusions: Although complicationswere lower in the T-shaped closure group, we could not establish the superiority of either technique.

Objetivo: Evaluar los desenlaces de la técnica vertical en comparación con la técnica en T para el cierre de faringoplastia posterior a una laringectomía total, y evaluar los factores asociados con el desarrollo de fístula faringocutánea. Método: Estudio retrospectivo de pacientes con diagnóstico de cancer de laringe a quienes se realizó laringectomía total como tratamiento, de 2009 a 2021. Resultados: Se incluyeron 57 pacientes. A 14 (24.6%) se les realizó una faringoplastia con cierre en T y a 43 (74.4%) un cierre vertical. La fístula faringocutánea fue la complicación más frecuente, presente en el 40.4% de los casos (n = 23). No se observaron diferencias en el desarrollo de complicaciones entre grupos, con excepción de la dehiscencia traqueal, la cual fue menos frecuente en el grupo de cierre en T (n = 2, 4.7% vs. n = 5, 35.7%; p = 0.002). La diabetes mellitus se asoció con el desarrollo de fístula faringocutánea (n = 7, 30.4% vs. n = 3, 8.8%; p = 0.03). Conclusiones: Aunque se observó una tendencia a una disminución de las complicaciones en el grupo de cierre en T, no se encontró superioridad de una técnica sobre otra.

Ribosome Profiling Methods Adapted to the Study of RNA-Dependent Translation Regulation in Staphylococcus aureus.

Noncoding RNAs, including regulatory RNAs (sRNAs), are instrumental in regulating gene expression in pathogenic bacteria, allowing them to adapt to various stresses encountered in their host environments. Staphylococcus aureus is a well-studied model for RNA-mediated regulation of virulence and pathogenicity, with sRNAs playing significant roles in shaping S. aureus interactions with human and animal hosts. By modulating the translation and/or stability of target mRNAs, sRNAs regulate the synthesis of virulence factors and regulatory proteins required for pathogenesis. Moreover, perturbation of the levels of RNA modifications in two other classes of noncoding RNAs, rRNAs, and tRNAs, has been proposed to contribute to stress adaptation. However, the study of how these various factors affect translation regulation has often been restricted to specific genes, using in vivo reporters and/or in vitro translation systems. Genome-wide sequencing approaches offer novel perspectives for studying RNA-dependent regulation. In particular, ribosome profiling methods provide a powerful resource for characterizing the overall landscape of translational regulation, contributing to a better understanding of S. aureus physiopathology. Here, we describe protocols that we have adapted to perform ribosome profiling in S. aureus.

RlmQ: a newly discovered rRNA modification enzyme bridging RNA modification and virulence traits in Staphylococcus aureus.

rRNA modifications play crucial roles in fine-tuning the delicate balance between translation speed and accuracy, yet the underlying mechanisms remain elusive. Comparative analyses of the rRNA modifications in taxonomically distant bacteria could help define their general, as well as species-specific, roles. In this study, we identified a new methyltransferase, RlmQ, in Staphylococcus aureus responsible for the Gram-positive specific m7G2601, which is not modified in Escherichia coli (G2574). We also demonstrate the absence of methylation on C1989, equivalent to E. coli C1962, which is methylated at position 5 by the Gram-negative specific RlmI methyltransferase, a paralog of RlmQ. Both modifications (S. aureus m7G2601 and E. coli m5C1962) are situated within the same tRNA accommodation corridor, hinting at a potential shared function in translation. Inactivation of S. aureus rlmQ causes the loss of methylation at G2601 and significantly impacts growth, cytotoxicity, and biofilm formation. These findings unravel the intricate connections between rRNA modifications, translation, and virulence in pathogenic Gram-positive bacteria.

The Cytokinins BAP and 2-iP Modulate Different Molecular Mechanisms on Shoot Proliferation and Root Development in Lemongrass (Cymbopogon citratus).

The known activities of cytokinins (CKs) are promoting shoot multiplication, root growth inhibition, and delaying senescence. 6-Benzylaminopurine (BAP) has been the most effective CK to induce shoot proliferation in cereal and grasses. Previously, we reported that in lemongrass (Cymbopogon citratus) micropropagation, BAP 10 µM induces high shoot proliferation, while the natural CK 6-(γ,γ-Dimethylallylamino)purine (2-iP) 10 µM shows less pronounced effects and developed rooting. To understand the molecular mechanisms involved, we perform a protein-protein interaction (PPI) network based on the genes of Brachypodium distachyon involved in shoot proliferation/repression, cell cycle, stem cell maintenance, auxin response factors, and CK signaling to analyze the molecular mechanisms in BAP versus 2-iP plants. A different pattern of gene expression was observed between BAP- versus 2-iP-treated plants. In shoots derived from BAP, we found upregulated genes that have already been demonstrated to be involved in de novo shoot proliferation development in several plant species; CK receptors (AHK3, ARR1), stem cell maintenance (STM, REV and CLV3), cell cycle regulation (CDKA-CYCD3 complex), as well as the auxin response factor (ARF5) and CK metabolism (CKX1). In contrast, in the 2-iP culture medium, there was an upregulation of genes involved in shoot repression (BRC1, MAX3), ARR4, a type A-response regulator (RR), and auxin metabolism (SHY2).

Exploring the Potential Role of Ribosomal Proteins to Enhance Potato Resilience in the Face of Changing Climatic Conditions.

Potatoes have emerged as a key non-grain crop for food security worldwide. However, the looming threat of climate change poses significant risks to this vital food source, particularly through the projected reduction in crop yields under warmer temperatures. To mitigate potential crises, the development of potato varieties through genome editing holds great promise. In this study, we performed a comprehensive transcriptomic analysis to investigate microtuber development and identified several differentially expressed genes, with a particular focus on ribosomal proteins-RPL11, RPL29, RPL40 and RPL17. Our results reveal, by protein-protein interaction (PPI) network analyses, performed with the highest confidence in the STRING database platform (v11.5), the critical involvement of these ribosomal proteins in microtuber development, and highlighted their interaction with PEBP family members as potential microtuber activators. The elucidation of the molecular biological mechanisms governing ribosomal proteins will help improve the resilience of potato crops in the face of today's changing climatic conditions.

The Multifarious Functions of Leukotrienes in Bone Metabolism.

Leukotrienes (LTs) are derived from arachidonic acid metabolism by the 5-lipoxygenase (5-LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5-LO knockout (KO) mouse model. Results from micro-computed tomography (µCT) analysis of femur from 8-week-old 5-LO-deficient mice showed increased cortical bone and medullary region in females and males and decreased trabecular bone in females. In the vertebra, we observed increased marrow area in both females and males 5-LO KO and decreased trabecular bone only in females 5-LO KO. Immunohistochemistry (IHC) analysis showed higher levels of osteogenic markers tissue-nonspecific alkaline phosphatase (TNAP) and osteopontin (OPN) and lower expression of osteoclastogenic marker tartrate-resistant acid phosphatase (TRAP) in the femurs of 5-LO KO mice versus wild-type (WT). Alkaline phosphatase activity and mineralization assay results showed that the 5-LO absence enhances osteoblasts differentiation and mineralization but decreases the proliferation. Alkaline phosphatase (ALP), Bglap, and Sp7 gene expression were higher in 5-LO KO osteoblasts compared to WT cells. Eicosanoids production was higher in 5-LO KO osteoblasts except for thromboxane 2, which was lower in 5-LO-deficient mice. Proteomic analysis identified the downregulation of proteins related to adenosine triphosphate (ATP) metabolism in 5-LO KO osteoblasts, and the upregulation of transcription factors such as the adaptor-related protein complex 1 (AP-1 complex) in long bones from 5-LO KO mice leading to an increased bone formation pattern in 5-LO-deficient mice. We observed enormous differences in the morphology and function of osteoclasts with reduced bone resorption markers and impaired osteoclasts in 5-LO KO compared to WT osteoclasts. Altogether, these results demonstrate that the absence of 5-LO is related to the greater osteogenic profile. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Variable Intrinsic Expression of Immunoregulatory Biomarkers in Breast Cancer Cell Lines, Mammospheres, and Co-Cultures.

Advances in immunotherapy have increased interest in knowing the role of the immune system in breast cancer (BC) pathogenesis. Therefore, immune checkpoints (IC) and other pathways related to immune regulation, such as JAK2 and FoXO1, have emerged as potential targets for BC treatment. However, their intrinsic gene expression in vitro has not been extensively studied in this neoplasia. Thus, we evaluated the mRNA expression of tumor-cell-intrinsic CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FoXO1 in different BC cell lines, derived mammospheres, and co-cultures with peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (qRT-PCR). Our results showed that intrinsic CTLA-4, CD274 (PD-L1), and PDCD1LG2 (PD-L2) were highly expressed in triple-negative cell lines, while CD276 was predominantly overexpressed in luminal cell lines. In contrast, JAK2 and FoXO1 were under-expressed. Moreover, high levels of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and JAK2 were found after mammosphere formation. Finally, the interaction between BC cell lines and peripheral blood mononuclear cells (PBMCs) stimulates the intrinsic expression of CTLA-4, PCDC1 (PD1), CD274 (PD-L1), and PDCD1LG2 (PD-L2). In conclusion, the intrinsic expression of immunoregulatory genes seems very dynamic, depending on BC phenotype, culture conditions, and tumor-immune cell interactions.

CRISPRa-mediated transcriptional activation of the SlPR-1 gene in edited tomato plants.

With the continuous deterioration of arable land due to an ever-growing population, improvement of crops and crop protection have a fundamental role in maintaining and increasing crop productivity. Alternatives to the use of pesticides encompass the use of biological control agents, generation of new resistant crop cultivars, the application of plant activator agrochemicals to enhance plant defenses, and the use of gene editing techniques, like the CRISPR-Cas system. Here, we test the hypothesis that epigenome editing, via CRISPR activation (CRISPRa), activate tomato plant defense genes to confer resistance against pathogen attack. We provide evidence that edited tomato plants for the PATHOGENESIS-RELATED GENE 1 gene (SlPR-1) show enhanced disease resistance to Clavibacter michiganensis subsp. michiganensis infection. Resistance was assessed by evaluating disease progression and symptom appearance, pathogen accumulation, and changes in SlPR-1 gene expression at different time points. We determined that CRISPRa-edited plants develop enhanced disease-resistant to the pathogen without altering their agronomic characteristics and, above all, preventing the advancement of disease symptoms, stem canker, and plant death.

Solution X-ray scattering highlights discrepancies in Plasmodium multi-aminoacyl-tRNA synthetase complexes.

tRip is a tRNA import protein specific to Plasmodium, the causative agent of malaria. In addition to its membrane localization and tRNA trafficking properties, tRip has the capacity to associate with three aminoacyl-tRNA synthetases (aaRS), the glutamyl- (ERS), glutaminyl- (QRS), and methionyl- (MRS) tRNA synthetases. In eukaryotes, such multi-aaRSs complexes (MSC) regulate the moonlighting activities of aaRSs. In Plasmodium, tRip and the three aaRSs all contain an N-terminal GST-like domain involved in the assembly of two independent complexes: the Q-complex (tRip:ERS:QRS) and the M-complex (tRip:ERS:MRS) with a 2:2:2 stoichiometry and in which the association of the GST-like domains of tRip and ERS (tRip-N:ERS-N) is central. In this study, the crystal structure of the N-terminal GST-like domain of ERS was solved and made possible further investigation of the solution architecture of the Q- and M-complexes by small-angle x-ray scattering (SAXS). This strategy relied on the engineering of a tRip-N-ERS-N chimeric protein to study the structural scaffold of both Plasmodium MSCs and confirm the unique homodimerization pattern of tRip in solution. The biological impact of these structural arrangements is discussed.

Role of early extraction of odontogenic focus in deep neck infections

Background: Odontogenic deep neck infections remain a common condition that presents a challenging issue due to the complex involvement of the neck and adjacent structures and its potential life-threatening risk. Periapical infection of the second or third molar with spread to the submandibular and parapharyngeal spaces is the most commonly observed scenario. However, the time of dental extraction of the infection focus remains controversial. The aim of this study is to provide an overview of the epidemiology, clinical and radiological features, and management in patients diagnosed with ODNI and to identify the role of early dental extraction on patient outcomes and recovery. Material and methods: This retrospective study included patients over 18 years old with a diagnosis of ODNI who were admitted to the University Hospital "Dr Jose Eleuterio Gonzalez" from January 2017 to January 2022. ODNI diagnosis was based on clinical and radiological evidence of the disease supplemented by dental and maxillofacial evaluation for an odontogenic aetiology. Results: A total of 68 patients were included in the study. The patients' mean age was 40.96 ± 14.9. Diabetes mellitus was the most common comorbidity. The submandibular space was the most common deep neck space involved (n=59, 86.8%). Mediastinitis, marginal nerve injury and orocervical fistula were observed in 7.5% of patients, with no fatality in this series. A delay of >3 days for dental extraction of the involved tooth was associated with an increased rate of mediastinitis (n=3, 100%, p= 0.022), number of surgical interventions (1.45 ± 0.61, p= 0.006), ICU stay (n=8, 40%, p= 0.019), and ICU length of stay (0.85 ± 0.8, p= 0.001). Conclusions: Expedited management with surgical drainage and intravenous antibiotic treatment, along with early extraction of the involved tooth, is mandatory. (AU)

Plasmodium, the Apicomplexa Outlier When It Comes to Protein Synthesis.

Plasmodium is an obligate intracellular parasite that has numerous interactions with different hosts during its elaborate life cycle. This is also the case for the other parasites belonging to the same phylum Apicomplexa. In this study, we bioinformatically identified the components of the multi-synthetase complexes (MSCs) of several Apicomplexa parasites and modelled their assembly using AlphaFold2. It appears that none of these MSCs resemble the two MSCs that we have identified and characterized in Plasmodium. Indeed, tRip, the central protein involved in the association of the two Plasmodium MSCs is different from its homologues, suggesting also that the tRip-dependent import of exogenous tRNAs is not conserved in other apicomplexan parasites. Based on this observation, we searched for obvious differences that could explain the singularity of Plasmodium protein synthesis by comparing tRNA genes and amino acid usage in the different genomes. We noted a contradiction between the large number of asparagine residues used in Plasmodium proteomes and the single gene encoding the tRNA that inserts them into proteins. This observation remains true for all the Plasmodia strains studied, even those that do not contain long asparagine homorepeats.

Solanum tuberosum Microtuber Development under Darkness Unveiled through RNAseq Transcriptomic Analysis.

Potato microtuber (MT) development through in vitro techniques are ideal propagules for producing high quality potato plants. MT formation is influenced by several factors, i.e., photoperiod, sucrose, hormones, and osmotic stress. We have previously developed a protocol of MT induction in medium with sucrose (8% w/v), gelrite (6g/L), and 2iP as cytokinin under darkness. To understand the molecular mechanisms involved, we performed a transcriptome-wide analysis. Here we show that 1715 up- and 1624 down-regulated genes were involved in this biological process. Through the protein-protein interaction (PPI) network analyses performed in the STRING database (v11.5), we found 299 genes tightly associated in 14 clusters. Two major clusters of up-regulated proteins fundamental for life growth and development were found: 29 ribosomal proteins (RPs) interacting with 6 PEBP family members and 117 cell cycle (CC) proteins. The PPI network of up-regulated transcription factors (TFs) revealed that at least six TFs-MYB43, TSF, bZIP27, bZIP43, HAT4 and WOX9-may be involved during MTs development. The PPI network of down-regulated genes revealed a cluster of 83 proteins involved in light and photosynthesis, 110 in response to hormone, 74 in hormone mediate signaling pathway and 22 related to aging.

17-ß Estradiol up-regulates energy metabolic pathways, cellular proliferation and tumor invasiveness in ER+ breast cancer spheroids.

Several biological processes related to cancer malignancy are regulated by 17-ß estradiol (E2) in ER+-breast cancer. To establish the role of E2 on the atypical cancer energy metabolism, a systematic study analyzing transcription factors, proteins, and fluxes associated with energy metabolism was undertaken in multicellular tumor spheroids (MCTS) from human ER+ MCF-7 breast cancer cells. At E2 physiological concentrations (10 and 100 nM for 24 h), both ERα and ERß receptors, and their protein target pS2, increased by 0.6-3.5 times vs. non-treated MCTS, revealing an activated E2/ER axis. E2 also increased by 30-470% the content of several transcription factors associated to mitochondrial biogenesis and oxidative phosphorylation (OxPhos) (p53, PGC1-α) and glycolytic pathways (HIF1-α, c-MYC). Several OxPhos and glycolytic proteins (36-257%) as well as pathway fluxes (48-156%) significantly increased being OxPhos the principal ATP cellular supplier (>75%). As result of energy metabolism stimulation by E2, cancer cell migration and invasion processes and related proteins (SNAIL, FN, MM-9) contents augmented by 24-189% vs. non-treated MCTS. Celecoxib at 10 nM blocked OxPhos (60%) as well as MCTS growth, cell migration and invasiveness (>40%); whereas the glycolytic inhibitor iodoacetate (0.5 µM) and doxorubicin (70 nM) were innocuous. Our results show for the first time using a more physiological tridimensional cancer model, resembling the initial stages of solid tumors, that anti-mitochondrial therapy may be useful to deter hormone-dependent breast carcinomas.

Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health.

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in seeds, grains, tea, coffee, wine, chocolate, cocoa, vegetables and, mainly, in citrus fruits. Neohesperidin, hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory and antioxidant potential. Neohesperidin, in the form of neohesperidin dihydrochalcone (NHDC), also has dietary properties as a sweetener. In general, these flavanones have been investigated as a strategy to control bone diseases, such as osteoporosis and osteoarthritis. In this literature review, we compiled studies that investigated the effects of neohesperidin, hesperidin and its aglycone, hesperetin, on bone health. In vitro studies showed that these flavanones exerted an antiosteoclastic and anti- inflammatory effects, inhibiting the expression of osteoclastic markers and reducing the levels of reactive oxygen species, proinflammatory cytokines and matrix metalloproteinase levels. Similarly, such studies favored the osteogenic potential of preosteoblastic cells and induced the overexpression of osteogenic markers. In vivo, these flavanones favored the regeneration of bone defects and minimized inflammation in arthritis- and periodontitis-induced models. Additionally, they exerted a significant anticatabolic effect in ovariectomy models, reducing trabecular bone loss and increasing bone mineral density. Although research should advance to the clinical field, these flavanones may have therapeutic potential for controlling the progression of metabolic, autoimmune or inflammatory bone diseases.

Discovery of two distinct aminoacyl-tRNA synthetase complexes anchored to the Plasmodium surface tRNA import protein.

Aminoacyl-tRNA synthetases (aaRSs) attach amino acids to their cognate transfer RNAs. In eukaryotes, a subset of cytosolic aaRSs is organized into a multisynthetase complex (MSC), along with specialized scaffolding proteins referred to as aaRS-interacting multifunctional proteins (AIMPs). In Plasmodium, the causative agent of malaria, the tRNA import protein (tRip), is a membrane protein that participates in tRNA trafficking; we show that tRip also functions as an AIMP. We identified three aaRSs, the glutamyl-tRNA synthetase (ERS), glutaminyl-tRNA synthetase (QRS), and methionyl-tRNA synthetase (MRS), which were specifically coimmunoprecipitated with tRip in Plasmodium berghei blood stage parasites. All four proteins contain an N-terminal glutathione-S-transferase (GST)-like domain that was demonstrated to be involved in MSC assembly. In contrast to previous studies, further dissection of GST-like interactions identified two exclusive heterotrimeric complexes: the Q-complex (tRip-ERS-QRS) and the M-complex (tRip-ERS-MRS). Gel filtration and light scattering suggest a 2:2:2 stoichiometry for both complexes but with distinct biophysical properties and mutational analysis further revealed that the GST-like domains of QRS and MRS use different strategies to bind ERS. Taken together, our results demonstrate that neither the singular homodimerization of tRip nor its localization in the parasite plasma membrane prevents the formation of MSCs in Plasmodium. Besides, the extracellular localization of the tRNA-binding module of tRip is compensated by the presence of additional tRNA-binding modules fused to MRS and QRS, providing each MSC with two spatially distinct functions: aminoacylation of intraparasitic tRNAs and binding of extracellular tRNAs. This unique host-pathogen interaction is discussed.

Evaluación de cribado de la calidad de vida en cuidadores primarios informales de pacientes oncológicos / Screening assessment of quality of life in informal primary caregivers of cancer patients

Objetivo: determinar las propiedades psicométricas de un instrumento de CV (CQoLC) y evaluar la calidad de vida (CV) de los cuidadores primarios (CPI) de pacientes con cáncer. Material y método:estudio tres fases: (1) evaluación de CV en CPI con un instrumento validado para población general y de pacientes que requieren atención médica (InCaViSa); (2) adaptación y piloteo del CQoLC y; (3) evaluación de confiabilidad, validez y normas del CQoLC. Se incluyeron 317 CPI de pacientes con diferentes diagnósticos oncológicos. Se realizaron análisis descriptivos de la CV reportada por los CPI. Para piloteo del instrumento se estimó el porcentaje de CPI que tuvieron dificultades para comprender algún reactivo. En la fase de validación se realizó un análisis factorial por ejes principales y la estructura propuesta se sometió a un análisis factorial confirmatorio (AFC). La confiabilidad se obtuvo a través del Alfa de Cronbach y el coeficiente Omega de McDonald’s. Finalmente, se estimaron los parámetros para calificación del CQoLC. Resultados: los CPI obtuvieron puntajes de “baja” a “muy baja” CV en la mayoría de las subescalas del InCaViSa. El CQoLC no mostró dificultades para su comprensión y se obtuvo una versión de nueve reactivos, distribuidos en cuatro indicadores, que explican el 45,62% de la varianza con adecuado ajuste en el AFC y adecuados índices de confiabilidad (Alfas de Cronbach de 0,496 a 0,866 y coeficiente Omega de McDonald’s = 0,868).Conclusiones:la CV de los CPI de pacientes con cáncer se encuentra afectada importantemente. El CQoLC es un instrumento especializado, que demostró ser adecuado como herramienta de cribado en las mediciones de auto-reporte (AU)

Objective: To determine the psychometric properties of a QoL instrument (CQoLC) and to assess the quality of life (QoL) of primary caregivers (PC) of cancer patients. Methods:Three-phase study: (1) assessment of QoL in PC with an instrument validated for general population and patients requiring medical care (InCaViSa); (2) adaptation and piloting of the CQoLC and (3) assessment of reliability, validity, and norms of the CQoLC. A total of 317 PCs of patients with different oncologic diagnoses were included. Descriptive analyses of the QOL reported by the PCs were performed. For piloting the instrument, the percentage of PCs who had difficulties in understanding any item was estimated. Factor analysis by main axes was performed in the validation phase, and the proposed structure was subjected to confirmatory factor analysis (CFA). Reliability was obtained through Cronbach’s Alpha and McDonald’s Omega coefficient. Finally, the parameters for CQoLC scoring were estimated. Results: The PCs obtained “low” to “deficient” QoL scores in most InCaViSa subscales. The CQoLC showed no difficulties in its comprehension, and a version of nine items was obtained, distributed in four indicators, which explain 45,62% of the variance with adequate adjustment in the AFC and adequate reliability indexes (Cronbach’s alphas from 0,496 to 0,866 and McDonald’s Omega coefficient = 0,868). Conclusions: The QoL of the CQoLC of cancer patients is significantly affected. The CQoLC is a specialized instrument, which proved to be adequate as a screening tool in self-report measurements (AU)

Tec1, a member of the TEA transcription factors family, is involved in virulence and basidiocarp development in Ustilago maydis / Tec1, un miembro de la familia de factores de transcripción TEA, está involucrado en la virulencia y el desarrollo de basidiocarpio en Ustilago maydis

The life cycle of Ustilago maydis involves alternation of a haploid saprophytic yeast-like stage and a dikaryotic hyphal virulent form. Under in vitro conditions, basidiocarps are formed. Analysis of the transcriptional network of basidiocarp formation revealed the possible involvement of a Tec transcription factor (Tec1, UMAG_02835) in the process. In some Ascomycota, Tec factors are involved in mycelial formation, pathogenesis, and interaction with other regulatory elements, but their role in Basidiomycota species is almost unknown. Accordingly, we proceeded to determine the role of this gene in U. maydis by its mutation. Tec1 was found to be a crucial factor for normal mating, basidiocarp development, and virulence, all of the functions related to the dikaryotic stage dependent of the b genes, whereas dimorphism and resistance to different stress conditions occurring in the haploid stage were not affected in tec1 mutants. The observation that mutants showed a low residual wild-type phenotype suggests the presence of a secondary mechanism that partially compensates the loss of Tec1.(AU)

¿Cuál es el conocimiento que poseen las donantes de ovocitos sobre su salud reproductiva? / What is the knowledge of oocyte donors about their reproductive health?

Los donantes de gametos constituyen un grupo especialmente involucrado en los tratamientos de re- producción asistida, así como en la salud reproductiva, pues ayudan a muchos pacientes a solucionar sus problemas reproductivos. No obstante, existen pocos estudios en España que aborden el conoci- miento que las donantes de gametos tienen acerca de su salud reproductiva. Por ello, el objetivo de este estudio ha sido conocer el grado de conocimiento que las donantes de gametos tienen sobre salud re- productiva y fertilidad. Se ha realizado un estudio prospectivo, transversal y multicéntrico que incluyó donantes de ovocitos de 10 clínicas de reproducción asistida en España. Durante 2 meses se han reclu- tado donantes entre 19 y 35 años, de las cuales, 63 han sido incluidas en el estudio, en el que se ha re- alizado un cuestionario de 41 preguntas divididas en tres partes: características sociodemográficas (11 preguntas), conocimientos sobre fertilidad (22 preguntas) y un cuestionario en escala de Likert para de- terminar la información que tenían sobre salud reproductiva, así como los riesgos acerca de su fertilidad (8 preguntas). Además de la estadística descriptiva, se ha realizado el análisis estadístico con Chi-cua- drado y p<0,05 se consideró significativo.Los resultados mostraron que las participantes evalúan el aumento de la edad de las mujeres como un factor de riesgo decisivo para la fertilidad, pero sin un conocimiento exacto, pues el 39,7 % afirmó que la disminución de la fertilidad sucedía entre los 35 y 40 años, y un 30 % afirmó que sucedía entro los 40 y los 45 años. Sólo el 47 % de las encuestadas entiende qué es la reserva ovárica. El 47,6 % de las donantes cree que las mujeres crean nuevos óvulos cada mes.Los resultados obtenidos en este estudio nos muestran que las donantes son conscientes de que existen alteraciones de la fertilidad, pero sus conocimientos sobre salud reproductiva pueden ser insuficientes. (AU)