Promising Anticancer Prodrugs Based on Pt(IV) Complexes with Bis-organosilane Ligands in Axial Positions.

We report two novel prodrug Pt(IV) complexes with bis-organosilane ligands in axial positions: cis-dichloro(diamine)-trans-[3-(triethoxysilyl)propylcarbamate]platinum(IV) (Pt(IV)-biSi-1) and cis-dichloro(diisopropylamine)-trans-[3-(triethoxysilyl) propyl carbamate]platinum(IV) (Pt(IV)-biSi-2). Pt(IV)-biSi-2 demonstrated enhanced in vitro cytotoxicity against colon cancer cells (HCT 116 and HT-29) compared with cisplatin and Pt(IV)-biSi-1. Notably, Pt(IV)-biSi-2 exhibited higher cytotoxicity toward cancer cells and lower toxicity on nontumorigenic intestinal cells (HIEC6). In preclinical mouse models of colorectal cancer, Pt(IV)-biSi-2 outperformed cisplatin in reducing tumor growth at lower concentrations, with reduced side effects. Mechanistically, Pt(IV)-biSi-2 induced permanent DNA damage independent of p53 levels. DNA damage such as double-strand breaks marked by histone gH2Ax was permanent after treatment with Pt(IV)-biSi-2, in contrast to cisplatin's transient effects. Pt(IV)-biSi-2's faster reduction to Pt(II) species upon exposure to biological reductants supports its superior biological response. These findings unveil a novel strategy for designing Pt(IV) anticancer prodrugs with enhanced activity and specificity, offering therapeutic opportunities beyond conventional Pt drugs.

Phenotype-specific melanoma uptake of fatty acid from human adipocytes activates AXL and CAV1-dependent ß-catenin nuclear accumulation.

Phenotypic diversity of cancer cells within tumors generated through bi-directional interactions with the tumor microenvironment has emerged as a major driver of disease progression and therapy resistance. Nutrient availability plays a critical role in determining phenotype, but whether specific nutrients elicit different responses on distinct phenotypes is poorly understood. Here we show, using melanoma as a model, that only MITF Low undifferentiated cells, but not MITF High cells, are competent to drive lipolysis in human adipocytes. In contrast to MITF High melanomas, adipocyte-derived free fatty acids are taken up by undifferentiated MITF Low cells via a fatty acid transporter (FATP)-independent mechanism. Importantly, oleic acid (OA), a monounsaturated long chain fatty acid abundant in adipose tissue and lymph, reprograms MITF Low undifferentiated melanoma cells to a highly invasive state by ligand-independent activation of AXL, a receptor tyrosine kinase associated with therapy resistance in a wide range of cancers. AXL activation by OA then drives SRC-dependent formation and nuclear translocation of a ß-catenin-CAV1 complex. The results highlight how a specific nutritional input drives phenotype-specific activation of a pro-metastasis program with implications for FATP-targeted therapies.

Fuzzy logic controller for UAV with gains optimized via genetic algorithm.

A gains optimizer of a fuzzy controller system for an Unmanned Aerial Vehicle (UAV) based on a metaheuristic algorithm is developed in the present investigation. The contribution of the work is the adjustment by the Genetic Algorithm (GA) to tune the gains at the input of a fuzzy controller. First, a typical fuzzy controller was modeled, designed, and implemented in a mathematical model obtained by Newton-Euler methodology. Subsequently, the control gains were optimized using a metaheuristic algorithm. The control objective is that the UAV consumes the least amount of energy. With this basis, the Genetic Algorithm finds the necessary gains to meet the design parameters. The tests were performed using the Matlab-Simulink environment. The results indicate an improvement, reducing the error in tracking trajectories from 30% in some tasks and following trajectories that could not be completed without a tuned controller in other tasks.

Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer.

Posttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD+-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function in cancer is not well understood. Here, we reveal that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol), the active metabolite of vitamin D (VD), promotes SIRT1 activation through auto-deacetylation in human colon carcinoma cells, and identify lysine 610 as an essential driver of SIRT1 activity. Remarkably, our data show that the post-translational control of SIRT1 activity mediates the antiproliferative action of 1,25(OH)2D3. This effect is reproduced by the SIRT1 activator SRT1720, suggesting that SIRT1 activators may offer new therapeutic possibilities for colon cancer patients who are VD deficient or unresponsive. Moreover, this might be extrapolated to inflammation and other VD deficiency-associated and highly prevalent diseases in which SIRT1 plays a prominent role.

[Castellón Field Hospital: comprehensive analysis of its use during the SARS-CoV-2 pandemic.] / Hospital de Campaña de Castellón: análisis integral de su uso durante la pandemia por SARS-CoV-2.

OBJECTIVE: Field hospitals, also known as alternative care sites, have been an important healthcare reinforcement during the SARS-CoV-2 pandemic worldwide. In the Valencian Community, three of these hospitals were opened, one for each province. Our study aimed to make a comprehensive analysis of this resource in Castellon. METHODS: A retrospective observational study was carried out with an analytical and statistical component of 3 aspects: infrastructure, satisfaction and clinical data from COVID-positive hospitalized patients. The sources of information were primary, institutional for the infrastructure and personal for the satisfaction surveys and clinical data. RESULTS: A set of 6x3 metres polyvalent tents was chosen, which joined formed a single-floor area of about 3.500 m2. Although hospital opened for approximately a year and a half with multiple uses, most in relation to the COVID pandemic (vaccination center, emergency room observation, hospital assistance, warehouse...), reception of positive patients for the virus began during the third wave of the pandemic, remaining active for eleven days. A total of thirty-one patients with a mean age of 56 years were admitted. 41.9% did not have any comorbidity and 54.8% needed treatment with oxygen therapy. Furthermore, the length of stay was three days, finding a significant relationship between this one, the oxygen flow required during admission and the age. Satisfaction was measured by a survey of seventeen questions where an average satisfaction of 8.33/10. CONCLUSIONS: This is one of the few studies in the literature in which a field hospital is analyzed from such different points of view. After this analysis, it is concluded that it is an extraordinary and temporary resource whose use is useful without reflecting an increase of morbidity/mortality among our patients and with a very favorable subjective assessment.

OBJETIVO: Los hospitales de campaña, también conocidos como alternative care sites, han supuesto un refuerzo sanitario importante durante la pandemia por SARS-CoV-2 a nivel mundial. En la Comunidad Valenciana se abrieron tres de estos hospitales, uno por cada provincia. Nuestro estudio pretendió hacer un análisis integral de dicho recurso en la provincia de Castellón. METODOS: Se realizó un estudio observacional retrospectivo con un componente analítico y estadístico de tres aspectos: la infraestructura, la satisfacción de los pacientes atendidos y los datos o características clínicas de los pacientes ingresados positivos por COVID. Las fuentes de información fueron primarias, institucionales para el apartado de la infraestructura y personales para las encuestas de satisfacción y los datos clínicos. RESULTADOS: El tipo de infraestructura que se eligió fue un conjunto de tiendas modulares polivalentes de 6x3 metros que unidas formaban una superficie de una sola planta de unos 3.500 m2. Aunque el hospital permaneció abierto durante aproximadamente año y medio con diversas funciones, la mayoría en relación con la pandemia por COVID (centro de vacunación, observación de Urgencias, asistencia hospitalaria, almacén…), inició su acogida de pacientes positivos debido al virus durante la tercera ola de la pandemia, ejerciendo este papel durante once días. En el hospital ingresaron un total de 31 pacientes con una edad media de 57 años, de los que un 41,9% no tenían ninguna comorbilidad y un 54,8% necesitaron oxigenoterapia. La estancia media hospitalaria fue de tres días, encontrándose una relación estadísticamente significativa entre ésta, el flujo de oxígeno requerido durante el ingreso y la edad. La satisfacción se midió mediante una encuesta de diecisiete preguntas donde se obtuvo una media de 8,33/10. CONCLUSIONES: Este es uno de los pocos estudios de la literatura en los que se abarca, desde puntos tan distintos, cómo funciona un hospital de campaña. Tras el análisis se concluye que se trata de un recurso extraordinario y temporal cuyo empleo es útil sin reflejar un aumento de la morbi/mortalidad de nuestros pacientes y con una valoración subjetiva del mismo muy favorable.

Hospital de Campaña de Castellón: análisis integral de su uso durante la pandemia por SARS-CoV-2 / Castellón Field Hospital: comprehensive analysis of its use during the SARS-CoV-2 pandemic

Fundamentos: Los hospitales de campaña, también conocidos comoalternative care sites, han supuesto un refuerzo sanitarioimportante durante la pandemia por SARS-CoV-2 a nivel mundial. En la Comunidad Valenciana se abrieron tres de estos hospitales,uno por cada provincia. Nuestro estudio pretendió hacer un análisis integral de dicho recurso en la provincia de Castellón.Métodos: Se realizó un estudio observacional retrospectivo con un componente analítico y estadístico de tres aspectos: lainfraestructura, la satisfacción de los pacientes atendidos y los datos o características clínicas de los pacientes ingresados positivospor COVID. Las fuentes de información fueron primarias, institucionales para el apartado de la infraestructura y personales para lasencuestas de satisfacción y los datos clínicos.Resultados: El tipo de infraestructura que se eligió fue un conjunto de tiendas modulares polivalentes de 6x3 metros que unidasformaban una superficie de una sola planta de unos 3.500 m 2. Aunque el hospital permaneció abierto durante aproximadamente añoy medio con diversas funciones, la mayoría en relación con la pandemia por COVID (centro de vacunación, observación de Urgencias,asistencia hospitalaria, almacén...), inició su acogida de pacientes positivos debido al virus durante la tercera ola de la pandemia,ejerciendo este papel durante once días. En el hospital ingresaron un total de 31 pacientes con una edad media de 57 años, de losque un 41,9% no tenían ninguna comorbilidad y un 54,8% necesitaron oxigenoterapia. La estancia media hospitalaria fue de tres días,encontrándose una relación estadísticamente significativa entre ésta, el flujo de oxígeno requerido durante el ingreso y la edad. Lasatisfacción se midió mediante una encuesta de diecisiete preguntas donde se obtuvo una media de 8,33/10.Conclusiones: Este es uno de los pocos estudios de la literatura en los que se abarca, desde puntos tan distintos, cómo funciona...(AU)

Background: Field hospitals, also known asalternative care sites, have been an important healthcare reinforcement during theSARS-CoV-2 pandemic worldwide. In the Valencian Community, three of these hospitals were opened, one for each province. Our studyaimed to make a comprehensive analysis of this resource in Castellon.Methods: A retrospective observational study was carried out with an analytical and statistical component of 3 aspects: infrastruc-ture, satisfaction and clinical data from COVID-positive hospitalized patients. The sources of information were primary, institutional for theinfrastructure and personal for the satisfaction surveys and clinical data.Results: A set of 6x3 metres polyvalent tents was chosen, which joined formed a single-floor area of about 3.500 m2. Althoughhospital opened for approximately a year and a half with multiple uses, most in relation to the COVID pandemic (vaccination center,emergency room observation, hospital assistance, warehouse...), reception of positive patients for the virus began during the thirdwave of the pandemic, remaining active for eleven days. A total of thirty-one patients with a mean age of 56 years were admitted.41.9% did not have any comorbidity and 54.8% needed treatment with oxygen therapy. Furthermore, the length of stay was threedays, finding a significant relationship between this one, the oxygen flow required during admission and the age. Satisfaction wasmeasured by a survey of seventeen questions where an average satisfaction of 8.33/10.Conclusions: This is one of the few studies in the literature in which a field hospital is analyzed from such different points ofview. After this analysis, it is concluded that it is an extraordinary and temporary resource whose use is useful without reflecting anincrease of morbidity/mortality among our patients and with a very favorable subjective assessment.(AU)

Enhanced gene regulation by cooperation between mRNA decay and gene transcription.

It has become increasingly clear in the last few years that gene expression in eukaryotes is not a linear process from mRNA synthesis in the nucleus to translation and degradation in the cytoplasm, but works as a circular one where the mRNA level is controlled by crosstalk between nuclear transcription and cytoplasmic decay pathways. One of the consequences of this crosstalk is the approximately constant level of mRNA. This is called mRNA buffering and happens when transcription and mRNA degradation act at compensatory rates. However, if transcription and mRNA degradation act additively, enhanced gene expression regulation occurs. In this work, we analyzed new and previously published genomic datasets obtained for several yeast mutants related to either transcription or mRNA decay that are not known to play any role in the other process. We show that some, which were presumed only transcription factors (Sfp1) or only decay factors (Puf3, Upf2/3), may represent examples of RNA-binding proteins (RBPs) that make specific crosstalk to enhance the control of the mRNA levels of their target genes by combining additive effects on transcription and mRNA stability. These results were mathematically modeled to see the effects of RBPs when they have positive or negative effects on mRNA synthesis and decay rates. We found that RBPs can be an efficient way to buffer or enhance gene expression responses depending on their respective effects on transcription and mRNA stability.

RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway.

mRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the 5' to 3' exonuclease Xrn1. Here we show that nucleocytoplasmic shuttling of several yeast mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNA-controlled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1, location of one of which is conserved from yeast to human. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Preventing Xrn1 import, either by deleting KAP120 or mutating the two Xrn1 NLSs, compromises transcription and, unexpectedly, also cytoplasmic decay, uncovering a cytoplasmic decay pathway that initiates in the nucleus. Most mRNAs are degraded by both pathways - the ratio between them represents a full spectrum. Importantly, Xrn1 shuttling is required for proper responses to environmental changes, e.g., fluctuating temperatures, involving proper changes in mRNA abundance and in cell proliferation rate.

A feedback mechanism controls rDNA copy number evolution in yeast independently of natural selection.

Ribosomal DNA (rDNA) is the genetic loci that encodes rRNA in eukaryotes. It is typically arranged as tandem repeats that vary in copy number within the same species. We have recently shown that rDNA repeats copy number in the yeast Saccharomyces cerevisiae is controlled by cell volume via a feedback circuit that senses cell volume by means of the concentration of the free upstream activator factor (UAF). The UAF strongly binds the rDNA gene promoter, but is also able to repress SIR2 deacetylase gene transcription that, in turn, represses rDNA amplification. In this way, the cells with a smaller DNA copy number than what is optimal evolve to increase that copy number until they reach a number that sequestrates free UAF and provokes SIR2 derepression that, in turn, blocks rDNA amplification. Here we propose a mathematical model to show that this evolutionary process can amplify rDNA repeats independently of the selective advantage of yeast cells having bigger or smaller rDNA copy numbers. We test several variants of this process and show that it can explain the observed experimental results independently of natural selection. These results predict that an autoregulated feedback circuit may, in some instances, drive to non Darwinian deterministic evolution for a limited time period.

Changes in mRNA stability play an important role in the adaptation of yeast cells to iron deprivation.

Eukaryotic cells rely on iron as an indispensable cofactor for multiple biological functions including mitochondrial respiration and protein synthesis. The budding yeast Saccharomyces cerevisiae utilizes both transcriptional and posttranscriptional mechanisms to couple mRNA levels to the requirements of iron deprivation. Thus, in response to iron deficiency, transcription factors Aft1 and Aft2 activate the expression of genes implicated in iron acquisition and mobilization, whereas two mRNA-binding proteins, Cth1 and Cth2, posttranscriptionally control iron metabolism. By using a genome-wide approach, we describe here a global stabilization of mRNAs, including transcripts encoding ribosomal proteins (RPs), when iron bioavailability diminishes. mRNA decay assays indicate that the mRNA-binding protein Pub1 contributes to RP transcript stabilization during adaptation to iron limitation. In fact, Pub1 becomes critical for growth and translational repression in low-iron conditions. Remarkably, we observe that pub1Δ cells also exhibit an increase in the transcription of RP genes that evidences the crosstalk between transcription and degradation mechanisms to maintain the appropriate mRNA balance under iron deficiency conditions.

Seroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Target.

Colorectal cancer (CRC) and diabetes are two of the most prevalent chronic diseases worldwide with dysregulated receptor tyrosine kinase signaling and strong co-occurrence correlation. Plasma autoantibodies represent a promising early diagnostic marker for both diseases before symptoms appear. In this study, we explore the value of autoantibodies against receptor-type tyrosine-protein phosphatase-like N (PTPRN; full-length or selected domains) as diagnostic markers using a cohort of individuals with type 2 diabetes (T2D), CRC, or both diseases or healthy individuals. We show that PTPRN autoantibody levels in plasma discriminated between patients with T2D with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of patients with CRC. Mechanistically, PTPRN depletion significantly reduced invasiveness of CRC cells in vitro and liver homing and metastasis in vivo by means of a dysregulation of the epithelial-mesenchymal transition and a decrease of the insulin receptor signaling pathway. Therefore, PTPRN autoantibodies may represent a particularly helpful marker for the stratification of patients with T2D at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidence that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in patients with CRC.

The Course of Posterior Antebrachial Cutaneous Nerve: Anatomical and Sonographic Study with a Clinical Implication.

The course of the posterior antebrachial cutaneous nerve (PACN) was studied via ultrasound (US) and dissection. The aim of this study was to reveal the anatomical relationships of PACN with the surrounding structures along its pathway to identify possible critical points of compression. Nineteen cryopreserved cadaver body donor upper extremities were explored via US and further dissected. During US exploration, two reference points, in relation with the compression of the nerve, were marked using dye injection: (1) the point where the RN pierces the lateral intermuscular septum (LIMS) and (2) the point where the PACN pierces the deep fascia. Anatomical measurements referred to the lateral epicondyle (LE) were taken at these two points. Dissection confirmed the correct site of US-guided dye injection at 100% of points where the RN crossed the LIMS (10.5 cm from the LE) and was correctly injected at 74% of points where the PACN pierce the deep fascia (7.4 cm from the LE). There were variations in the course of the PACN, but it always divided from the RN as an only branch. Either ran close and parallel to the LIMS until the RN crossed the LIMS (84%) or clearly separated from the RN, 1 cm before it crossed the LIMS (16%). In 21% of cases, the PACN crossed the LIMS with the RN, while in the rest of the cases it always followed in the posterior compartment. A close relationship between PACN and LIMS, as well as triceps brachii muscle and deep fascia was observed. The US and anatomical study showed that the course of PACN maintains a close relationship with the LIMS and other connective tissues (such as the fascia and subcutaneous tissue) to be present in its pathology and treatment.

The total mRNA concentration buffering system in yeast is global rather than gene-specific.

Gene expression in eukaryotes does not follow a linear process from transcription to translation and mRNA degradation. Instead it follows a circular process in which cytoplasmic mRNA decay crosstalks with nuclear transcription. In many instances, this crosstalk contributes to buffer mRNA at a roughly constant concentration. Whether the mRNA buffering concept operates on the total mRNA concentration or at the gene-specific level, and if the mechanism to do so is a global or a specific one, remain unknown. Here we assessed changes in mRNA concentrations and their synthesis rates along the transcriptome of aneuploid strains of the yeast Saccharomyces cerevisiae We also assessed mRNA concentrations and their synthesis rates in nonsense-mediated decay (NMD) targets in euploid strains. We found that the altered synthesis rates in the genes from the aneuploid chromosome and the changes in their mRNA stabilities were not counterbalanced. In addition, the stability of NMD targets was not specifically compensated by the changes in synthesis rate. We conclude that there is no genetic compensation of NMD mRNA targets in yeast, and total mRNA buffering uses mostly a global system rather than a gene-specific one.

Metabolic and hormonal remodeling of colorectal cancer cell signalling by diabetes.

The existence of molecular links that facilitate colorectal cancer (CRC) development in the population with type 2 diabetes (T2D) is supported by substantial epidemiological evidence. This review summarizes how the systemic, metabolic and hormonal imbalances from T2D alter CRC cell metabolism, signalling and gene expression as well as their reciprocal meshing, with an overview of CRC molecular subtypes and animal models to study the diabetes-CRC cancer links. Metabolic and growth factor checkpoints ensure a physiological cell proliferation rate compatible with limited nutrient supply. Hyperinsulinaemia and hyperleptinaemia in prediabetes and excess circulating glucose and lipids in T2D overcome formidable barriers for tumour development. Increased nutrient availability favours metabolic reprogramming, alters signalling and generates mutations and epigenetic modifications through increased reactive oxygen species and oncometabolites. The reciprocal control between metabolism and hormone signalling is lost in diabetes. Excess adipose tissue at the origin of T2D unbalances adipokine (leptin/adiponectin) secretion ratios and function and disrupts the insulin/IGF axes. Leptin/adiponectin imbalances in T2D are believed to promote proliferation and invasion of CRC cancer cells and contribute to inflammation, an important component of CRC tumourigenesis. Disruption of the insulin/IGF axes in T2D targets systemic and CRC cell metabolic reprogramming, survival and proliferation. Future research to clarify the molecular diabetes-CRC links will help to prevent CRC and reduce its incidence in the diabetic population and must guide therapeutic decisions.

Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast.

The adjustment of transcription and translation rates to the changing needs of cells is of utmost importance for their fitness and survival. We have previously shown that the global transcription rate for RNA polymerase II in budding yeast Saccharomyces cerevisiae is regulated in relation to cell volume. Total mRNA concentration is constant with cell volume since global RNApol II-dependent nascent transcription rate (nTR) also keeps constant but mRNA stability increases with cell size. In this paper, we focus on the case of rRNA and RNA polymerase I. Contrarily to that found for RNA pol II, we detected that RNA polymerase I nTR increases proportionally to genome copies and cell size in polyploid cells. In haploid mutant cells with larger cell sizes, the rDNA repeat copy number rises. By combining mathematical modeling and experimental work with the large-size cln3 strain, we observed that the increasing repeat copy number is based on a feedback mechanism in which Sir2 histone deacetylase homeostatically controls the amplification of rDNA repeats in a volume-dependent manner. This amplification is paralleled with an increase in rRNA nTR, which indicates a control of the RNA pol I synthesis rate by cell volume.

Remodelling of colorectal cancer cell signalling by microbiota and immunity in diabetes.

Obesity is the strongest known risk factor to develop type 2 diabetes (T2D) and both share a state of chronic, diffuse and low-grade inflammation, impaired immune responses and alterations in the composition and function of the microbiome. Notably, these hallmarks are shared with colorectal cancer (CRC), which is epidemiologically associated to obesity and T2D. Gut barrier damages in T2D destabilize the microbiome that metabolizes the diet and modulates the host immune response triggering inflammatory and proliferative pathways. In this review, we discuss the pathways altered by defects in the immune response and microbiota that may link T2D to CRC development. Stressed adipocytes, metabolic incongruity in blood and gut barrier failure with dysbiosis cooperate to establish imbalances between immune innate and adaptive cells and cytokines such as interleukin 6 (IL6) or TNFA that define low-grade diffuse inflammation in T2D. Inflammation drives tissue repair through proliferation and migration (critical mechanisms for tumourigenesis) and under physiological conditions feeds anti-inflammatory cytokine production to resolve the process. The disproportion in pro- vs anti-inflammatory cells and cytokines imposed by T2D will impact the tumour micro- and macro-environment, favouring tumour proliferation, angiogenesis and decreased immune responses. Complex bidirectional relationships between the metabolic environment of T2D, gut microbiota, and immune dysfunctions may favour tumour cell demands and will define the outcome. Animal models developed to study the relationships between T2D and CRC in the context of microbiota and immune system are discussed.

Validation of the Activities' Scale in Higher Education Students' Personal Learning Environments.

BACKGROUND: Personal learning environments are the networks of tools, activities, and connections that each person uses for their learning. Although there have been increasing numbers of studies, measurement instruments in this regard are still limited. The aim of this study is to construct and validate a scale to assess the activities that make up Personal Learning Environments. METHOD: The sample comprised 1,187 students in their final year of undergraduate degrees. 64% were women and 36% men, with a mean age of 24 and a standard deviation of 4.21 years. RESULTS: The scale consists of 27 Likert-type items responding to three factors according to the theoretical construct reviewed, and produced high coefficients in internal consistency tests. CONCLUSIONS: The analyses demonstrate a valid instrument with solid psychometric properties. More specifically, the results indicate suitable content validity. Exploratory and confirmatory factor analyses indicate appropriate construct validation, with consistency between the theoretical and factorial model.

A Trans-Omics Comparison Reveals Common Gene Expression Strategies in Four Model Organisms and Exposes Similarities and Differences between Them.

The ultimate goal of gene expression regulation is on the protein level. However, because the amounts of mRNAs and proteins are controlled by their synthesis and degradation rates, the cellular amount of a given protein can be attained by following different strategies. By studying omics data for six expression variables (mRNA and protein amounts, plus their synthesis and decay rates), we previously demonstrated the existence of common expression strategies (CESs) for functionally related genes in the yeast Saccharomyces cerevisiae. Here we extend that study to two other eukaryotes: the yeast Schizosaccharomyces pombe and cultured human HeLa cells. We also use genomic data from the model prokaryote Escherichia coli as an external reference. We show that six-variable profiles (6VPs) can be constructed for every gene and that these 6VPs are similar for genes with similar functions in all the studied organisms. The differences in 6VPs between organisms can be used to establish their phylogenetic relationships. The analysis of the correlations among the six variables supports the hypothesis that most gene expression control occurs in actively growing organisms at the transcription rate level, and that translation plays a minor role. We propose that living organisms use CESs for the genes acting on the same physiological pathways, especially for those belonging to stable macromolecular complexes, but CESs have been modeled by evolution to adapt to the specific life circumstances of each organism.

Recruitment of Xrn1 to stress-induced genes allows efficient transcription by controlling RNA polymerase II backtracking.

A new paradigm has emerged proposing that the crosstalk between nuclear transcription and cytoplasmic mRNA stability keeps robust mRNA levels in cells under steady-state conditions. A key piece in this crosstalk is the highly conserved 5'-3' RNA exonuclease Xrn1, which degrades most cytoplasmic mRNAs but also associates with nuclear chromatin to activate transcription by not well-understood mechanisms. Here, we investigated the role of Xrn1 in the transcriptional response of Saccharomyces cerevisiae cells to osmotic stress. We show that a lack of Xrn1 results in much lower transcriptional induction of the upregulated genes but in similar high levels of their transcripts because of parallel mRNA stabilization. Unexpectedly, lower transcription in xrn1 occurs with a higher accumulation of RNA polymerase II (RNAPII) at stress-inducible genes, suggesting that this polymerase remains inactive backtracked. Xrn1 seems to be directly implicated in the formation of a competent elongation complex because Xrn1 is recruited to the osmotic stress-upregulated genes in parallel with the RNAPII complex, and both are dependent on the mitogen-activated protein kinase Hog1. Our findings extend the role of Xrn1 in preventing the accumulation of inactive RNAPII at highly induced genes to other situations of rapid and strong transcriptional upregulation.

Validation of the Activities’ Scale in Higher Education Students’ Personal Learning Environments / Validación de la Escala de Actividades en los Entornos Personales de Aprendizaje de Estudiantes de Educación Superior

Background: Personal learning environments are the networks of tools, activities, and connections that each person uses for their learning. Although there have been increasing numbers of studies, measurement instruments in this regard are still limited. The aim of this study is to construct and validate a scale to assess the activities that make up Personal Learning Environments. Method: The sample comprised 1,187 students in their final year of undergraduate degrees. 64% were women and 36% men, with a mean age of 24 and a standard deviation of 4.21 years. Results: the scale consists of 27 Likert-type items responding to three factors according to the theoretical construct reviewed, and produced high coefficients in internal consistency tests. Conclusions: the analyses demonstrate a valid instrument with solid psychometric properties. More specifically, the results indicate suitable content validity. Exploratory and confirmatory factor analyses indicate appropriate construct validation, with consistency between the theoretical and factorial model. (AU)

Antecedentes: los entornos personales de aprendizaje se definen como el entramado de herramientas, actividades y conexiones que cada persona utiliza para su aprendizaje. Los estudios sobre el tema han ido en aumento, sin embargo, son todavía escasos los instrumentos de medición al respecto. El objetivo de este trabajo es construir y validar una escala para evaluar las actividades que integran los Entornos Personales de Aprendizaje. Método: la muestra estaba formada por 1.187 estudiantes universitarios de último año de carrera. Un 64% eran mujeres y un 36% hombres, con una edad media de 24 años y una desviación típica de 4.21. Resultados: la escala queda formada por 27 ítems tipo Likert respondiendo a tres factores de acuerdo con el constructo teórico revisado, obteniendo coeficientes elevados en las pruebas de consistencia interna. Conclusiones: los análisis realizados muestran un instrumento válido y con propiedades psicométricas sólidas. Concretamente, los resultados arrojan una adecuada validez de contenido. Los análisis factoriales exploratorio y confirmatorio indican una pertinente validación de constructo, existiendo coherencia entre el modelo teórico y factorial. (AU)