Evaluation of functional warm ischemia time during controlled donation after circulatory determination of death using normothermic regional perfusion (ECMO-TT): A prospective multicenter cohort study.

BACKGROUND: Controlled donation after circulatory determination of death (cDCD) seems an effective way to mitigate the critical shortage of available organs for transplant worldwide. As a recently developed procedure for organ retrieval, some questions remain unsolved such as the uncertainty regarding the effect of functional warm ischemia time (FWIT) on organs´ viability. METHODS: We developed a multicenter prospective cohort study collecting all data from evaluated organs during cDCD from 2017 to 2020. All the procedures related to cDCD were performed with normothermic regional perfusion. The analysis included organ retrieval as endpoint and FWIT as exposure of interest. The effect of FWIT on the likelihood for organ retrieval was evaluated with Relative distribution analysis. RESULTS: A total amount of 507 organs´ related information was analyzed from 95 organ donors. Median donor age was 62 years, and 63% of donors were male. Stroke was the most common diagnosis before withdrawal of life-sustaining therapy (61%), followed by anoxic encephalopathy (21%). This analysis showed that length of FWIT was inversely associated with organ retrieval rates for liver, kidneys, and pancreas. No statistically significant association was found for lungs. CONCLUSIONS: Results showed an inverse association between functional warm ischemia time (FWIT) and retrieval rate. We also have postulated optimal FWIT's thresholds for organ retrieval. FWIT for liver retrieval remained between 6 and less than 11 min and in case of kidneys and pancreas, the optimal FWIT for retrieval was 6 to 12 min. These results could be valuable to improve organ utilization and for future analysis.

A set of accessible enhancers enables the initial response of breast cancer cells to physiological progestin concentrations.

Here, we report that in T47D breast cancer cells 50 pM progestin is sufficient to activate cell cycle entry and the progesterone gene expression program. At this concentration, equivalent to the progesterone blood levels found around the menopause, progesterone receptor (PR) binds only to 2800 genomic sites, which are accessible to ATAC cleavage prior to hormone exposure. These highly accessible sites (HAs) are surrounded by well-organized nucleosomes and exhibit breast enhancer features, including estrogen receptor alpha (ERα), higher FOXA1 and BRD4 (bromodomain containing 4) occupancy. Although HAs are enriched in RAD21 and CTCF, PR binding is the driving force for the most robust interactions with hormone-regulated genes. HAs show higher frequency of 3D contacts among themselves than with other PR binding sites, indicating colocalization in similar compartments. Gene regulation via HAs is independent of classical coregulators and ATP-activated remodelers, relying mainly on MAP kinase activation that enables PR nuclear engagement. HAs are also preferentially occupied by PR and ERα in breast cancer xenografts derived from MCF-7 cells as well as from patients, indicating their potential usefulness as targets for therapeutic intervention.

Evolution of cold tolerance and thermal plasticity in life history, behaviour and physiology during a poleward range expansion.

Many species that are moving polewards encounter novel thermal regimes to which they have to adapt. Therefore, rapid evolution of thermal tolerance and of thermal plasticity in fitness-related traits in edge populations can be crucial for the success and speed of range expansions. We tested for adaptation in cold tolerance and in life history, behavioural and physiological traits and their thermal plasticity during a poleward range expansion. We reconstructed the thermal performance curves of life history (survival, growth and development rates), behaviour (food intake) and cold tolerance (chill coma recovery time) in the aquatic larval stage of the damselfly Ischnura elegans that is currently showing a poleward range expansion in northern Europe. We studied larvae from three edge and three core populations using a common-garden experiment. Consistent with the colder annual temperatures, larvae at the expansion front evolved an improved cold tolerance. The edge populations showed no overall (across temperatures) evolution of a faster life history that would improve their range-shifting ability. Moreover, consistent with damselfly edge populations from colder latitudes, edge populations evolved at the highest rearing temperature (28°C) a faster development rate, likely to better exploit the rare periods with higher temperatures. This was associated with a higher food intake and a lower metabolic rate. In conclusion, our results suggest that the edge populations rapidly evolved adaptive changes in trait means and thermal plasticity to the novel thermal conditions at the edge front. Our results highlight the importance of considering besides trait plasticity and the evolution of trait means, also the evolution of trait plasticity to improve forecasts of responses to climate change.

Durante su expansión hacia los polos, las especies encuentran nuevos regímenes de temperatura a los que tienen que adaptarse. Por esto, una rápida evolución de la tolerancia térmica y de la plasticidad térmica de rasgos fisiológicos clave en las poblaciones del borde del área de distribución es crucial para el éxito y la velocidad de las expansiones de rango. En este estudio testamos la adaptación de la tolerancia la frío y la plasticidad térmica de rasgos de historia de vida, comportamiento y fisiológicos durante una expansión de rango hacia el norte. Reconstruimos las curvas de rendimiento térmico de rasgos de historia de vida (supervivencia, tasa de crecimiento y tasa de desarrollo) y comportamiento (ingestión de alimento), así como la tolerancia al frío (tiempo de recuperación del coma por frío) en la larva acuática de la especie de caballito del diablo Ischnura elegans, especie que muestra un rango de expansión actual en el norte de Europa. Estudiamos larvas de tres poblaciones de la región de expansión norte y tres poblaciones de la región central usando experimentos en laboratorio. En concordancia con las temperaturas más bajas, las larvas del área de expansión mostraron mayor tolerancia al frío. Sin embargo, estas larvas no mostraron en general (a lo largo de las temperaturas estudiadas) evolución hacia una historia de vida más rápida, que aumentaría su habilidad para expandirse. Además, en consistencia con la menor temperatura de la región de expansión, las larvas presentaron mayor tasa de desarrollo a la temperatura experimental más alta (28°C), probablemente para explotar mejor los infrecuentes períodos con altas temperaturas en dicha región. Esto estuvo asociado con una mayor ingestión de alimento y una menor tasa metabólica. En conclusión, nuestros resultados sugieren que los valores medios y la plasticidad de los rasgos estudiados de las poblaciones del frente de expansión evolucionaron rápidamente para adaptarse a las nuevas condiciones térmicas en dicha región. Asimismo, nuestros resultados destacan la importancia de considerar, además de la media y plasticidad de los rasgos, la evolución de esta plasticidad, con el fin de mejorar las predicciones de las respuestas de las especies al cambio climático.

"Falls prevention among older people and care providers: protocol for an integrative review".

AIM: To review the evidence about the role of care providers in fall prevention in older adults aged ≥ 65 years, this includes their views, strategies, and approaches on falls prevention and effectiveness of nursing interventions. BACKGROUND: Some fall prevention programmes are successfully implemented and led by nurses and it is acknowledged the vital role they play in developing plans for fall prevention. Nevertheless, there has not been a systematic review of the literature that describes this role and care providers' views on fall's prevention initiatives. DESIGN: A convergent synthesis of qualitative, quantitative, and mixed methods studies. The eligibility criteria will be based on participants, interventions/exposure, comparisons, and outcomes for quantitative studies and on population, the phenomena of interest and the context, for qualitative studies. To extract data and assess study qualities members of the research team will work in pairs according to their expertise. The review will follow the guidelines for integrative reviews and the proposed methods will adhere to the PRISMA statement checklist complemented by the ENTREQ framework. As qualitative synthesis are emergent, all procedures and changes in procedure will be documented. DISCUSSION: The review has a constructivist drive as studies that combine methods ought to be paradigmatic driven. Review questions are broad to allow issues emerge and have purposefully left the design flexible to allow for adjustments as the review progresses. The review seeks to highlight the roles that care providers play in fall prevention and their views on fall's prevention initiatives.

Involvement of a citrus meiotic recombination TTC-repeat motif in the formation of gross deletions generated by ionizing radiation and MULE activation.

BACKGROUND: Transposable-element mediated chromosomal rearrangements require the involvement of two transposons and two double-strand breaks (DSB) located in close proximity. In radiobiology, DSB proximity is also a major factor contributing to rearrangements. However, the whole issue of DSB proximity remains virtually unexplored. RESULTS: Based on DNA sequencing analysis we show that the genomes of 2 derived mutations, Arrufatina (sport) and Nero (irradiation), share a similar 2 Mb deletion of chromosome 3. A 7 kb Mutator-like element found in Clemenules was present in Arrufatina in inverted orientation flanking the 5' end of the deletion. The Arrufatina Mule displayed "dissimilar" 9-bp target site duplications separated by 2 Mb. Fine-scale single nucleotide variant analyses of the deleted fragments identified a TTC-repeat sequence motif located in the center of the deletion responsible of a meiotic crossover detected in the citrus reference genome. CONCLUSIONS: Taken together, this information is compatible with the proposal that in both mutants, the TTC-repeat motif formed a triplex DNA structure generating a loop that brought in close proximity the originally distinct reactive ends. In Arrufatina, the loop brought the Mule ends nearby the 2 distinct insertion target sites and the inverted insertion of the transposable element between these target sites provoked the release of the in-between fragment. This proposal requires the involvement of a unique transposon and sheds light on the unresolved question of how two distinct sites become located in close proximity. These observations confer a crucial role to the TTC-repeats in fundamental plant processes as meiotic recombination and chromosomal rearrangements.

Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance.

INTRODUCTION: The stress index (SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). METHODS: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. RESULTS: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg(-1), P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat- and SI-groups respectively, without differences in overinflated lung areas at end- inspiration in both groups. Cytokines and histopathology showed no differences. CONCLUSIONS: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.

Inferring the functional effect of gene expression changes in signaling pathways.

Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few methods aimed to identify the signaling circuits, within a pathway, associated to the biological problem studied exist and none of them provide a convenient graphical web interface. We present PATHiWAYS, a web-based signaling pathway visualization system that infers changes in signaling that affect cell functionality from the measurements of gene expression values in typical expression microarray case-control experiments. A simple probabilistic model of the pathway is used to estimate the probabilities for signal transmission from any receptor to any final effector molecule (taking into account the pathway topology) using for this the individual probabilities of gene product presence/absence inferred from gene expression values. Significant changes in these probabilities allow linking different cell functionalities triggered by the pathway to the biological problem studied. PATHiWAYS is available at: http://pathiways.babelomics.org/.

Accuracy of an autocalibrated pulse contour analysis in cardiac surgery patients: a bi-center clinical trial.

BACKGROUND: Less-invasive and easy to install monitoring systems for continuous estimation of cardiac index (CI) have gained increasing interest, especially in cardiac surgery patients who often exhibit abrupt haemodynamic changes. The aim of the present study was to compare the accuracy of CI by a new semi-invasive monitoring system with transpulmonary thermodilution before and after cardiopulmonary bypass (CPB). METHODS: Sixty-five patients (41 Germany, 24 Spain) scheduled for elective coronary surgery were studied before and after CPB, respectively. Measurements included CI obtained by transpulmonary thermodilution (CITPTD) and autocalibrated semi-invasive pulse contour analysis (CIPFX). Percentage changes of CI were also calculated. RESULTS: There was only a poor correlation between CITPTD and CIPFX both before (r (2) = 0.34, p < 0.0001) and after (r (2) = 0.31, p < 0.0001) CPB, with a percentage error (PE) of 62 and 49 %, respectively. Four quadrant plots revealed a concordance rate over 90 % indicating an acceptable correlation of trends between CITPTD and CIPFX before (concordance: 93 %) and after (concordance: 94 %) CPB. In contrast, polar plot analysis showed poor trending before and an acceptable trending ability of changes in CI after CPB. CONCLUSIONS: Semi-invasive CI by autocalibrated pulse contour analysis showed a poor ability to estimate CI compared with transpulmonary thermodilution. Furthermore, the new semi-invasive device revealed an acceptable trending ability for haemodynamic changes only after CPB. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02312505 Date: 12.03.2012.

Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration.

BACKGROUND: Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT. PATIENTS AND METHODS: We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. Blood and ultradiafiltrate samples were collected on Day 3 (during steady-state) before, and at regular intervals after, the infusion had started. Anidulafungin concentrations were determined with HPLC. RESULTS: On Day 3, peak plasma concentrations with the 100 mg dose were 6.2 ±â€Š1.7 mg/L and 7.1 ±â€Š1.9 mg/L in the arterial and venous samples, respectively. The mean, pre-filter trough concentration was 3.0 ±â€Š0.6 mg/L. The mean AUC0-24 values for plasma anidulafungin were 93.9 ±â€Š19.4 and 104.1 ±â€Š20.3mg·h/L in the arterial and venous samples, respectively. There was no adsorption to synthetic surfaces, and the anidulafungin concentration in the ultradiafiltrate was below the limit of detection. CONCLUSION: The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT.

Looking for biological factors to predict the risk of active cytomegalovirus infection in non-immunosuppressed critically ill patients.

The identification of non-immunosuppressed critically ill patients most at risk for developing cytomegalovirus (CMV) reactivation is potentially of great clinical relevance. The current study was aimed at determining (i) whether single nucleotide polymorphisms in the genes coding for chemokine receptor 5 (CCR5), interleukin-10 IL-10), and monocyte chemoattractant protein-1 (MCP-1) have an impact on the incidence rate of active CMV infection, (ii) whether serum levels of CMV-specific IgGs are associated with the risk of CMV reactivation, and (iii) whether detection of CMV DNA in saliva precedes that in the lower respiratory tract or the blood compartment. A total of 36 out of 78 patients (46%) developed an episode of active CMV infection. The incidence rate of active CMV infection was not significantly associated with any single nucleotide polymorphisms. A trend towards a lower incidence of active CMV infection (P = 0.06) was noted in patients harboring the IL10 C/C genotype. Patients carrying the CCR5 A/A genotype had high CMV DNA loads in tracheal aspirates. The serum levels of CMV IgGs did not differ significantly between patients with a subsequent episode of active CMV infection (median, 217 IU/mL) or without one (median, 494 IU/mL). Detection of CMV DNA in saliva did not usually precede that in plasma and/or tracheal aspirates. In summary, the analysis of single nucleotide polymorphisms in the IL10 and CCR5 genes might help to determine the risk of active CMV infection or the level of CMV replication within episodes, respectively, in non-immunosuppressed critically ill patients.

Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation.

BACKGROUND: We investigated whether individualized positive end-expiratory pressure (PEEP) improves oxygenation, ventilation, and lung mechanics during one-lung ventilation compared with standardized PEEP. METHODS: Thirty patients undergoing thoracic surgery were randomly allocated to the study or control group. Both groups received an alveolar recruitment maneuver at the beginning and end of one-lung ventilation. After the alveolar recruitment maneuver, the control group had their lungs ventilated with a 5 cm·H2O PEEP, while the study group had their lungs ventilated with an individualized PEEP level determined by a PEEP decrement trial. Arterial blood samples, lung mechanics, and volumetric capnography were recorded at multiple timepoints throughout the procedure. RESULTS: The individualized PEEP values in study group were higher than the standardized PEEP values (10 ± 2 vs 5 cm·H2O; P < 0.001). In both groups, arterial oxygenation decreased when bilateral-lung ventilation was switched to one-lung ventilation and increased after the alveolar recruitment maneuver. During one-lung ventilation, oxygenation was maintained in the study group but decreased in the control group. After one-lung ventilation, arterial oxygenation was significantly higher in the study group (306 vs 231 mm·Hg, P = 0.007). Static compliance decreased in both groups when bilateral-lung ventilation was switched to one-lung ventilation. Static compliance increased significantly only in the study group (P < 0.001) after the alveolar recruitment maneuver and optimal PEEP adjustment. The alveolar recruitment maneuver did not decrease cardiac index in any patient. CONCLUSIONS: During one-lung ventilation, the improvements in oxygenation and lung mechanics after an alveolar recruitment maneuver were better preserved by ventilation by using individualized PEEP with a PEEP decrement trial than with a standardized 5 cm·H2O of PEEP.

Effects of different flow patterns and end-inspiratory pause on oxygenation and ventilation in newborn piglets: an experimental study.

BACKGROUND: Historically, the elective ventilatory flow pattern for neonates has been decelerating flow (DF). Decelerating flow waveform has been suggested to improve gas exchange in the neonate when compared with square flow (SF) waveform by improving the ventilation perfusion. However, the superiority of DF compared with SF has not yet been demonstrated during ventilation in small infants. The aim of this study was to compare SF vs. DF, with or without end-inspiratory pause (EIP), in terms of oxygenation and ventilation in an experimental model of newborn piglets. METHODS: The lungs of 12 newborn Landrace/LargeWhite crossbred piglets were ventilated with SF, DF, SF-EIP and DF-EIP. Tidal volume (VT), inspiratory to expiratory ratio (I/E), respiratory rate (RR), and FiO2 were keep constant during the study. In order to assure an open lung during the study while preventing alveolar collapse, a positive end-expiratory pressure (PEEP) of 6 cmH2O was applied after a single recruitment maneuver. Gas exchange, lung mechanics and hemodynamics were measured. RESULTS: The inspiratory flow waveform had no effect on arterial oxygenation pressure (PaO2) (276 vs. 278 mmHg, p = 0.77), alveolar dead space to alveolar tidal volume (VDalv/VTalv) (0.21 vs. 0.19 ml, p = 0.33), mean airway pressure (Pawm) (13.1 vs. 14.0 cmH2O, p = 0.69) and compliance (Crs) (3.5 vs. 3.5 ml cmH2O(-1), p = 0.73) when comparing SF and DF. A short EIP (10%) did not produce changes in the results. CONCLUSION: The present study showed that there are no differences between SF, DF, SF-EIP and DF-EIP in oxygenation, ventilation, lung mechanics, or hemodynamics in this experimental model of newborn piglets with healthy lungs.

Plasticity and associated epigenetic mechanisms play a role in thermal evolution during range expansion.

Due to global change, many species are shifting their distribution and are thereby confronted with novel thermal conditions at the moving range edges. Especially during the initial phases of exposure to a new environment, it has been hypothesized that plasticity and associated epigenetic mechanisms enable species to cope with environmental change. We tested this idea by capitalizing on the well-documented southward range expansion of the damselfly Ischnura elegans from France into Spain where the species invaded warmer regions in the 1950s in eastern Spain (old edge region) and in the 2010s in central Spain (new edge region). Using a common garden experiment at rearing temperatures matching the ancestral and invaded thermal regimes, we tested for evolutionary changes in (thermal plasticity in) larval life history and heat tolerance in these expansion zones. Through the use of de- and hypermethylating agents, we tested whether epigenetic mechanisms play a role in enabling heat tolerance during expansion. We used the phenotype of the native sister species in Spain, I. graellsii, as proxy for the locally adapted phenotype. New edge populations converged toward the phenotype of the native species through plastic thermal responses in life history and heat tolerance while old edge populations (partly) constitutively evolved a faster life history and higher heat tolerance than the core populations, thereby matching the native species. Only the heat tolerance of new edge populations increased significantly when exposed to the hypermethylating agent. This suggests that the DNA methylation machinery is more amenable to perturbation at the new edge and shows it is able to play a role in achieving a higher heat tolerance. Our results show that both (evolved) plasticity as well as associated epigenetic mechanisms are initially important when facing new thermal regimes but that their importance diminishes with time.

Qualimap: evaluating next-generation sequencing alignment data.

MOTIVATION: The sequence alignment/map (SAM) and the binary alignment/map (BAM) formats have become the standard method of representation of nucleotide sequence alignments for next-generation sequencing data. SAM/BAM files usually contain information from tens to hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted biases in these data. The systematic detection of such biases is a non-trivial task that is crucial to drive appropriate downstream analyses. RESULTS: We have developed Qualimap, a Java application that supports user-friendly quality control of mapping data, by considering sequence features and their genomic properties. Qualimap takes sequence alignment data and provides graphical and statistical analyses for the evaluation of data. Such quality-control data are vital for highlighting problems in the sequencing and/or mapping processes, which must be addressed prior to further analyses. AVAILABILITY: Qualimap is freely available from http://www.qualimap.org.

Evaluation of cytomegalovirus (CMV)-specific T-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients.

The current study was designed to assess the predictive value of the evaluation of cytomegalovirus (CMV)-specific T-cell immunity early following admission to the intensive care unit for inferring the risk of active CMV infection in non-immunosuppressed surgical and trauma patients. A total of 31 CMV-seropositive patients were included. Patients were screened for the presence of CMV DNA in plasma and in tracheal aspirates by real-time PCR. Enumeration of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T cells was performed by flow cytometry for intracellular cytokine staining. Virological and immunological monitoring was conducted once or twice a week. Active CMV infection occurred in 17 out of 31 patients. Undetectable levels of pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell subsets cells were observed in 10 patients who developed active CMV infection and in one who did not (at a median of 2 days following ICU admission). Peak CMV DNA loads in both tracheal aspirates and plasma were substantially higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN-γ T-cell responses than in patients with detectable responses. The expansion of both CMV-specific T-cell subsets following detection of active CMV infection was demonstrated in 9 out of 14 patients with active CMV infection. In conclusion, the evaluation of CMV pp65 and IE-1-specific IFN-γ-producing CD8(+) and CD4(+) T cells early following ICU admission may allow the identification of patients most at risk of either having or developing an episode of active CMV infection, particularly those associated with high-level virus replication.

Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing.

Phylemon 2.0 is a new release of the suite of web tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing. It has been designed as a response to the increasing demand of molecular sequence analyses for experts and non-expert users. Phylemon 2.0 has several unique features that differentiates it from other similar web resources: (i) it offers an integrated environment that enables evolutionary analyses, format conversion, file storage and edition of results; (ii) it suggests further analyses, thereby guiding the users through the web server; and (iii) it allows users to design and save phylogenetic pipelines to be used over multiple genes (phylogenomics). Altogether, Phylemon 2.0 integrates a suite of 30 tools covering sequence alignment reconstruction and trimming; tree reconstruction, visualization and manipulation; and evolutionary hypotheses testing.

Serial Expression Analysis: a web tool for the analysis of serial gene expression data.

Serial transcriptomics experiments investigate the dynamics of gene expression changes associated with a quantitative variable such as time or dosage. The statistical analysis of these data implies the study of global and gene-specific expression trends, the identification of significant serial changes, the comparison of expression profiles and the assessment of transcriptional changes in terms of cellular processes. We have created the SEA (Serial Expression Analysis) suite to provide a complete web-based resource for the analysis of serial transcriptomics data. SEA offers five different algorithms based on univariate, multivariate and functional profiling strategies framed within a user-friendly interface and a project-oriented architecture to facilitate the analysis of serial gene expression data sets from different perspectives. SEA is available at sea.bioinfo.cipf.es.