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Abstract Dynamic models of sugar kelp (Saccharina latissima) growth are used to estimate the production potential of seaweed aquaculture in many regions around the world. These models do not currently account for the existence of S. latissima ecotypes that are adapted to regional environmental conditions, particularly temperature. We tested the hypothesis that recalibrating the temperature parameters of a dynamic energy budget model using literature data for S. latissima from regions with a similar climate to the region of interest would result in more accurate predictions than using a general species‐wide temperature response curve. Calibrating the model using data from warm regions significantly improved model accuracy for kelp cultivation at the southern end of the species range (Rhode Island, USA) in cases where the original parameters underestimated growth but resulted in drastic overestimates when heavy frond erosion occurred. In Trømso, Norway, a cold parameterization produced extremely accurate predictions: the model predicted a final frond length of 88.2 cm, compared with the observed length of 87.5 (±4.70) cm. Our results demonstrate that recalibrating temperature response curves allows one model to be applied to kelp aquaculture in different regions, an important step toward the prediction of S. latissima productivity over large areas.

More effective approaches are needed in the treatment of blood cancers, in particular acute myeloid leukemia (AML), that are able to eliminate resistant leukemia stem cells (LSCs) at the bone marrow (BM), after a chemotherapy session, and then enhance hematopoietic stem cell (HSC) engraftment for the re-establishment of the HSC compartment. Here, we investigate whether light-activatable nanoparticles (NPs) encapsulating all-trans-retinoic acid (RA+NPs) could solve both problems. Our in vitro results show that mouse AML cells transfected with RA+NPs differentiate towards antitumoral M1 macrophages through RIG.1 and OASL gene expression. Our in vivo results further show that mouse AML cells transfected with RA+NPs home at the BM after transplantation in an AML mouse model. The photo-disassembly of the NPs within the grafted cells by a blue laser enables their differentiation towards a macrophage lineage. This macrophage activation seems to have systemic anti-leukemic effect within the BM, with a significant reduction of leukemic cells in all BM compartments, of animals treated with RA+NPs, when compared with animals treated with empty NPs. In a separate group of experiments, we show for the first time that normal HSCs transfected with RA+NPs show superior engraftment at the BM niche than cells without treatment or treated with empty NPs. This is the first time that the activity of RA is tested in terms of long-term hematopoietic reconstitution after transplant using an in situ activation approach without any exogenous priming or genetic conditioning of the transplanted cells. Overall, the approach documented here has the potential to improve consolidation therapy in AML since it allows a dual intervention in the BM niche: to tackle resistant leukemia and improve HSC engraftment at the same time.

Over the last fifteen years, ferroelectric (FE) and antiferroelectric (AFE) ultra-thin films based on fluorite-structured materials have drawn significant attention for a wide variety of applications requiring high integration density. AFE ZrO2, in particular, holds significant promise for nanosupercapacitors, owing to its potential for high energy storage density (ESD) and high efficiency (η). This work assesses the potential of high-performance Hf1−xZrxO2 thin films encapsulated by TiN electrodes that show linear dielectric (LD), FE, and AFE behavior. A wake-up effect is observed for AFE ZrO2, a phenomenon barely reported for pure zirconium oxide and AFE materials in general, correlated with the disappearance of the pinched hysteresis loop commonly observed for Zr-doped HfO2 thin films. ESD and η are compared for FE, AFE, and LD samples at the same electrical field (3.5 MV/cm). As expected, ESD is higher for the FE sample (95 J/cm3), but η is ridiculously small (≈55%) because of the opening of the FE hysteresis curve, inducing high loss. Conversely, LD samples exhibit the highest efficiency (nearly 100%), at the expense of a lower ESD. AFE ZrO2 thin film strikes a balance between FE and LD behavior, showing reduced losses compared to the FE sample but an ESD as high as 52 J/cm3 at 3.5 MV/cm. This value can be further increased up to 84 J/cm3 at a higher electrical field (4.0 MV/cm), with an η of 75%, among the highest values reported for fluorite-structured materials, offering promising perspectives for future optimization.

Background Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration, homing and chemoresistance of ALL cells. Methods NALM-6 and Reh cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for adhesion assay and migration assay in vitro. In in vivo experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10μg/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry. Results Both anaesthetics reduced in vivo migration and in vivo homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy. Conclusion Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.

Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, have demonstrated that: (i) more than 50% of all antibodies failed in one or more applications, (ii) yet, ~50–75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and (iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.

Summary: We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants’ level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person’s health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine.

Transcranial direct current stimulation (tDCS) can influence performance on behavioral tasks and improve symptoms of brain conditions. Yet, it remains unclear precisely how tDCS affects brain function and connectivity. Here, we measured changes in functional connectivity (FC) metrics in blood-oxygenation-level-dependent (BOLD) fMRI data acquired during MR-compatible tDCS in a whole-brain analysis with corrections for false discovery rate. Volunteers (n = 64) received active tDCS, sham tDCS, and rest (no stimulation), using one of three previously established electrode tDCS montages targeting left dorsolateral prefrontal cortex (DLPFC, n = 37), lateral temporoparietal area (LTA, n = 16), or superior temporal cortex (STC, n = 11). In brain networks where simulated E field was highest in each montage, connectivity with remote nodes decreased during active tDCS. During active DLPFC-tDCS, connectivity decreased between a fronto-parietal network and subgenual ACC, while during LTA-tDCS connectivity decreased between an auditory-somatomotor network and frontal operculum. Active DLPFC-tDCS was also associated with increased connectivity within an orbitofrontal network overlapping subgenual ACC. Irrespective of montage, FC metrics increased in sensorimotor and attention regions during both active and sham tDCS, which may reflect the cognitive-perceptual demands of tDCS. Taken together, these results indicate that tDCS may have both intended and unintended effects on ongoing brain activity, stressing the importance of including sham, stimulation-absent, and active comparators in basic science and clinical trials of tDCS.

Background Evidence suggests that subjective (perceived) social status (SSS) may predict health outcomes more strongly than objective social status, but little is known about the relationship between SSS and cardiovascular health (CVH). This study focuses on this relationship among diverse Hispanic/Latino adults because while poor CVH profiles are prevalent in this population, immigration complicates attempts to measure their social status. Methods and Results We analyzed baseline HCHS/SOL (Hispanic Community Health Study/Study of Latinos) data on 15 374 Hispanic/Latino adults aged 18 to 74 years in 2008 to 2011. SSS was assessed using the McArthur Scale, a 10‐rung “social ladder.” CVH was based on levels of 7 metrics defined by the American Heart Association. Linear and logistic regressions were used to examine cross‐sectional associations of SSS with CVH (overall and single metrics) after adjusting for objective social status, demographic, and health factors. Less than half of the population (46%) had Ideal scores in ≥4 metrics of CVH. In multivariable‐adjusted models, an increase in SSS was associated with a higher overall CVH score (β=0.04; 95% CI, 0.01–0.06) and greater likelihood of Ideal levels of body mass index, physical activity, and fasting blood glucose levels. Nativity and time in the United States modified the association between SSS and Ideal smoking. Conclusions Subjective measures of social status can enhance an understanding of CVH among Hispanic/Latino people. Future studies should explore the stability of SSS over time in comparison with objective social status and the mechanisms through which SSS may influence CVH.

In-plane compressively strained α-Sn films have been theoretically predicted and experimentally proven to possess non-trivial electronic states of a 3D topological Dirac semimetal. The robustness of these states typically strongly depends on purity, homogeneity, and stability of the grown material itself. By developing a reliable fabrication process, we were able to grow pure strained α-Sn films on InSb(100), without heating the substrate during growth nor using any dopants. The α-Sn films were grown by molecular beam epitaxy, followed by experimental verification of the achieved chemical purity and structural properties of the film’s surface. Local insight into the surface morphology was provided by scanning tunneling microscopy. We detected the existence of compressive strain using Mössbauer spectroscopy, and we observed a remarkable robustness of the grown samples against ambient conditions. The topological character of the samples was confirmed by angle-resolved photoemission spectroscopy, revealing the Dirac cone of the topological surface state. Scanning tunneling spectroscopy, moreover, allowed us to obtain an improved insight into the electronic structure of the 3D topological Dirac semimetal α-Sn above the Fermi level.

A theoretical framework to describe and assess the advancement of innovation ecosystems in the contemporary European Union is more than necessary in order to map actors and processes, and thus provide a more comprehensive and dynamic approach. For actors, the reframed innovation helix perspective is applied, while the multilevel perspective is used for processes. At each innovation progress stage, other actors should have a slightly different role, be more active and important, and also relate to each other in a different manner. The emergence and density of intermediary actors are seen as important aspects. From the process perspective, the innovation application and also its adoption at the sociotechnical landscape level are seen as crucial. Thus, collective intelligence with societal implications and consideration for the environment evolve into the key ingredients of an advanced innovation ecosystem in the European Union.

Communication styles are the three communication patterns that result from merging the verbal elements of communication, the non-verbal elements and the paraverbal elements. The objective of this study was to test what effect different communication styles have on attention performance in primary school children. We administered the assertive behavior scale for children (CABS), the symbol digit modalities test (SDMT) and the d2 attention test to a sample of 77 participants of primary school. A statistically significant and proportional correlation was found between the assertive communication style and the total number of correct answers of the SDMT. We also found positive correlations between the assertive communication style and d2 attention test performance. Children with an assertive communication style have better attention performance than children with passive or aggressive communication styles.

Timely identification of COVID-19 patients at high risk of mortality can significantly improve patient management and resource allocation within hospitals. This study seeks to develop and validate a data-driven personalized mortality risk calculator for hospitalized COVID-19 patients. De-identified data was obtained for 3,927 COVID-19 positive patients from six independent centers, comprising 33 different hospitals. Demographic, clinical, and laboratory variables were collected at hospital admission. The COVID-19 Mortality Risk (CMR) tool was developed using the XGBoost algorithm to predict mortality. Its discrimination performance was subsequently evaluated on three validation cohorts. The derivation cohort of 3,062 patients has an observed mortality rate of 26.84%. Increased age, decreased oxygen saturation (≤ 93%), elevated levels of C-reactive protein (≥ 130 mg/L), blood urea nitrogen (≥ 18 mg/dL), and blood creatinine (≥ 1.2 mg/dL) were identified as primary risk factors, validating clinical findings. The model obtains out-of-sample AUCs of 0.90 (95% CI, 0.87-0.94) on the derivation cohort. In the validation cohorts, the model obtains AUCs of 0.92 (95% CI, 0.88-0.95) on Seville patients, 0.87 (95% CI, 0.84-0.91) on Hellenic COVID-19 Study Group patients, and 0.81 (95% CI, 0.76-0.85) on Hartford Hospital patients. The CMR tool is available as an online application at covidanalytics.io/mortality_calculator and is currently in clinical use. The CMR model leverages machine learning to generate accurate mortality predictions using commonly available clinical features. This is the first risk score trained and validated on a cohort of COVID-19 patients from Europe and the United States.

Sorption of oxyanions by soils and mineral surfaces is of interest due to their role as nutrients or pollutants. Volcanic soils are variable charge soils, rich in active forms of aluminum and iron, and capable of sorbing anions. Sorption and desorption of vanadate, arsenate, and chromate by two African andosols was studied in laboratory experiments. Sorption isotherms were determined by equilibrating at 293 K soil samples with oxyanion solutions of concentrations between 0 and 100 mg L−1 V, As, or Cr, equivalent to 0−2.0 mmol V L−1, 0−1.3 mmol As L−1, and 0−1.9 mmol Cr L−1, in NaNO3; V, As, or Cr were determined by ICP-mass spectrometry in the equilibrium solution. After sorption, the soil samples were equilibrated with 0.02 M NaNO3 to study desorption. The isotherms were adjusted to mathematical models. After desorption with NaNO3, desorption experiments were carried out with a 1 mM phosphate. The sorption of vanadate and arsenate was greater than 90% of the amount added, while the chromate sorption was much lower (19–97%). The sorption by the Silandic Andosol is attributed to non-crystalline Fe and Al, while in the Vitric Andosol, crystalline iron species play a relevant role. The V and Cr sorption isotherms fitted to the Freundlich model, while the As sorption isotherms conformed to the Temkin model. For the highest concentrations of oxyanions in the equilibrating solution, the sorbed concentrations were 37–38 mmol V kg−1, 25 mmol As kg−1, and 7.2–8.8 mmol Cr kg−1. The desorption was low for V and As and high for Cr. The comparison of the sorption and desorption isotherms reveals a pronounced hysteresis for V in both andosols and for Cr in the Silandic Andosol. Phosphate induced almost no V desorption, moderate As desorption, and considerable Cr desorption.

Volcanic soils cover 1% of the Earth’s surface but support 10% of the world’s population. They are among the most fertile soils in the world, due to their excellent physical properties and richness in available nutrients. The major limiting factor for plant growth in volcanic soils is phosphate fixation, which is mainly attributable to active species of aluminium and iron. The sorption and desorption of phosphate is studied on the surface horizons of two African agricultural soils, a silandic Andosol (Rwanda) and a vitric Andosol (São Tomé and Principe). Both soils are slightly acid. The silandic Andosol is rich in active aluminium forms, while the vitric Andosol has high amounts of crystalline iron and aluminium oxides. Sorption isotherms were determined by equilibrating at 293K soil samples with phosphate solutions of concentrations between 0 and 100 mg P L−1 in NaNO3; phosphate was determined by visible spectrophotometry in the equilibrium solution. To study desorption, the soil samples from the sorption experiment were equilibrated with 0.02 M NaNO3. The isotherms were adjusted to mathematical models. In almost all the concentration range, the adsorption of phosphate by the silandic Andosol was greater than 90% of the amount added, being lower in the vitric Andosol but always higher than 65%. The high sorption by the silandic Andosol is attributed to its richness in non-crystalline Fe and Al, while in the vitric Andosol crystalline iron species seem to play a relevant role in the adsorption. The sorption isotherms of both soils fitted to the Temkin model, the adjustment to the Langmuir or Freundlich models being unsatisfactory; throughout the range studied, the sorption increases with increasing phosphorus concentration, a maximum sorption is not predictable (as occurs when the sorption is adjusted to the Langmuir model). For an added P concentration of 100 mg L−1 (3.2 mmol L−1), the sorption is 47.7 µmol P g−1 in the silandic Andosol and 41.6 µmol P g−1 in the vitric Andosol. The desorption is low and the comparison of the sorption and desorption isotherms reveals a pronounced hysteresis, that is, the irreversibility of the sorption. The high phosphate sorption and its irreversibility are comparable to those published for other volcanic soils with high contents of allophane, active aluminium and free iron. The strong phosphate adsorption is a serious limiting factor for plant growth, which requires a careful management of phosphorus fertilization.

Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, have demonstrated that: (i) more than 50% of all antibodies failed in one or more applications, (ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and (iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.

The present case study looked into the feasibility of using brain−computer interface (BCI) technology combined with computer-supported cooperative work (CSCW) in a wireless network. We had two objectives; first, to test the wireless BCI-based configuration and the practical use of this idea we assessed workload perception in participants located several kilometers apart taking part in the same drawing task. Second, we studied the cortical activation patterns of participants performing the drawing task with and without the BCI technology. Results showed higher mental workload perception and broader cortical activation (frontal-temporal-occipital) under BCI experimental conditions. This idea shows a possible application of BCI research in the social field, where two or more users could engage in a computer networking task using BCI technology over the internet. New research avenues for CSCW are discussed and possibilities for future research are given.

The potential of Brain Computer Interfaces (BCIs) to translate brain activity into commands to control external devices during mechanical ventilation (MV) remains largely unexplored. This is surprising since the amount of patients that might benefit from such assistance is considerably larger than the number of patients requiring BCI for motor control. Given the transient nature of MV (i.e., used mainly over night or during acute clinical conditions), precluding the use of invasive methods, and inspired by current research on BCIs, we argue that scalp recorded EEG (electroencephalography) signals can provide a non-invasive direct communication pathway between the brain and the ventilator. In this paper we propose a Patient Ventilator Interface (PVI) to control a ventilator during variable conscious states (i.e., wake, sleep, etc.). After a brief introduction on the neural control of breathing and the clinical conditions requiring the use of MV we discuss the conventional techniques used during MV. The schema of the PVI is presented followed by a description of the neural signals that can be used for the on-line control. To illustrate the full approach, we present data from a healthy subject, where the inspiration and expiration periods during voluntary breathing were discriminated with a 92% accuracy (10-fold cross-validation) from the scalp EEG data. The paper ends with a discussion on the advantages and obstacles that can be forecasted in this novel application of the concept of BCI.

About 10% of patients with a genetic disease carry a nonsense mutation causing their pathology. A strategy for correcting nonsense mutations is premature termination codon (PTC) readthrough, i.e. incorporation of an amino acid at the PTC position during translation. PTC-readthrough-activating molecules appear as promising therapeutic tools for these patients. Unfortunately, the molecules shown to induce PTC readthrough show low efficacy, probably because the mRNAs carrying a nonsense mutation are scarce, as they are also substrates of the quality control mechanism called nonsense-mediated mRNA decay (NMD). The screening systems previously developed to identify readthrough-promoting molecules used cDNA constructs encoding mRNAs immune to NMD. As the molecules identified were not selected for the ability to correct nonsense mutations on NMD-prone PTC-mRNAs, they could be unsuitable for the context of nonsense-mutation-linked human pathologies. Here, a screening system based on an NMD-prone mRNA is described. It should be suitable for identifying molecules capable of efficiently rescuing the expression of human genes harboring a nonsense mutation. This system should favor the discovery of candidate drugs for treating genetic diseases caused by nonsense mutations. One hit selected with this screening system is presented and validated on cells from three cystic fibrosis patients.

This article deals with two controversial debates that took place in Castile at the end of the fifteenth century, specifically about the nature and founding principles of nobility and about the existence of new Christians of Jewish origin. With a particular focus on the 1449 events in Toledo and their ideological consequences, the author shows how the two controversial debates were linked. The controversy around the nature of nobility therefore helped structure and fuel debates about the place that New Christians should occupy in society at the time. The situation was such that the notion of pure-blood, which first appeared in treatises about the nobility, gradually became key to distinguishing the New Christians from the Old ones.

Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.

This work intends to propose an interpretation of the Andanças e viajes, Pero Tafur’s travel book, as a chivalrous biography. Through a comparison between the topic of nobility in this text with the concerns and debates about the Castilian nobility of the 15th Century, this article attempts to show how Pero Tafur’s travel book can be read as a mythical lineage book, serving his concerns.

Most Cryptococccus neoformans genes are interrupted by introns, and alternative splicing occurs very often. In this study, we examined the influence of introns on C. neoformans gene expression. For most tested genes, elimination of introns greatly reduces mRNA accumulation. Strikingly, the number and the position of introns modulate the gene expression level in a cumulative manner. A screen for mutant strains able to express functionally an intronless allele revealed that the nuclear poly(A) binding protein Pab2 modulates intron-dependent regulation of gene expression in C. neoformans. PAB2 deletion partially restored accumulation of intronless mRNA. In addition, our results demonstrated that the essential nucleases Rrp44p and Xrn2p are implicated in the degradation of mRNA transcribed from an intronless allele in C. neoformans. Double mutant constructions and over-expression experiments suggested that Pab2p and Xrn2p could act in the same pathway whereas Rrp44p appears to act independently. Finally, deletion of the RRP6 or the CID14 gene, encoding the nuclear exosome nuclease and the TRAMP complex associated poly(A) polymerase, respectively, has no effect on intronless allele expression.

This article aims to rebuild the catalogues of the Barcelona scholastic libraries (those of the Dominicans, the Franciscans and the Discalced Carmelites) by the end of the Middle Ages. The inventories are based on the few remaining manuscripts of that time and on some research works about conventual libraries. The account of the formerly mentioned libraries is completed by a thematic presentation of their manuscripts.

Ce travail présente une analyse de l’émergence en Castille au xve siècle de biographies particulières. La confrontation des chroniques biographiques de Pero Niño, don Álvaro de Luna, don Rodrigo Ponce de León et don Alonso de Monrroy permet de mettre en évidence les diverses stratégies de légitimation de la noblesse trastamariste. En cette période de redéfinition de la noblesse, ces textes doivent être lus comme de véritables traités nobiliaires dont les héros viennent illustrer les différentes thèses défendues: primauté ou non de la noblesse issue de lignages anciens, parfois opposés à la couronne, face à une milice fonctionnarisée entièrement dévouée au service du souverain et qui en retire des bénéfices.

Background Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration, homing and chemoresistance of ALL cells. Methods NALM-6 and Reh cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for adhesion assay and migration assay in vitro. In in vivo experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10μg/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry. Results Both anaesthetics reduced in vivo migration and in vivo homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy. Conclusion Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.

Background: Acute lymphoblastic leukaemia (ALL) is the most common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of two commonly used general anaesthetics, intravenous propofol and inhalational sevoflurane, on the migration and homing of ALL cells in vitro and in vivo. Methods: NALM-6 cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for flow cytometry analysis. For in vitro migration experiments, NALM-6 cells were pre-treated with propofol and sevoflurane for six hours before being loaded onto the upper chamber of a migration chamber and cells were collected in the lower chamber after six hours of migration. For in vivo adhesion assays, NALM-6 cells were pre-treated with propofol and sevoflurane before an adhesion assay was carried out. In in vitro experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. Results: Both anaesthetics reduced in vitro migration, in vivo migration and in vivo homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to the nearest endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression. In addition, the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced by general anaesthetics. Those changes might result in the alterations in migration and homing. Conclusion: Together, our data suggest that both propofol and sevoflurane could reduce ALL migration and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms.