Characterization of a large sex determination region in Salix purpurea L. (Salicaceae).

Dioecy has evolved numerous times in plants, but heteromorphic sex chromosomes are apparently rare. Sex determination has been studied in multiple Salix and Populus (Salicaceae) species, and P. trichocarpa has an XY sex determination system on chromosome 19, while S. suchowensis and S. viminalis have a ZW system on chromosome 15. Here we use whole genome sequencing coupled with quantitative trait locus mapping and a genome-wide association study to characterize the genomic composition of the non-recombining portion of the sex determination region. We demonstrate that Salix purpurea also has a ZW system on chromosome 15. The sex determination region has reduced recombination, high structural polymorphism, an abundance of transposable elements, and contains genes that are involved in sex expression in other plants. We also show that chromosome 19 contains sex-associated markers in this S. purpurea assembly, along with other autosomes. This raises the intriguing possibility of a translocation of the sex determination region within the Salicaceae lineage, suggesting a common evolutionary origin of the Populus and Salix sex determination loci

All-plastic electrochemical transistor for glucose sensing using a ferrocene mediator.

We demonstrate a glucose sensor based on an organic electrochemical transistor (OECT) in which the channel, source, drain, and gate electrodes are made from the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS). The OECT employs a ferrocene mediator to shuttle electrons between the enzyme glucose oxidase and a PEDOT:PSS gate electrode. The device can be fabricated using a one-layer patterning process and offers glucose detection down to the micromolar range, consistent with levels present in human saliva

Automation Proposal for the Intermediate Steps in the 16S FFPE Samples Analysis Pipeline

Cursos e Congresos, C-155[Abstract] In the day-to-day work of bioinformatics, the use of integrated software packages, which encompass a wide range of tools, enables the development of pipelines for omics data analysis. Within the various existing pipelines, we focus on the analysis of the 16S rRNA gene as it allows for the study of diversity and taxonomy of prokaryotic microorganisms such as Bacteria and Archaea. However, these pipelines often involve a sequence of multiple tools that require intermediate steps before further processing can proceed, as in the case between Cutadapt and DADA2. In fact, in a typical pipeline, the values for DADA2 input arguments ’trunc-len-f’ and ’trunc-len-r’ are extracted from the output of Cutadapt. The best approach for selecting optimal values (aka the trimming positions) is graphically visualizing Cutadapt output and manually selecting the most accurate trimming position length. Therefore, we propose the automation of this specific intermediate step between Cutadapt and DADA2 tools, by selecting values displayed in the graphs that meet the filtering criteria. This automation has been incorporated into a custom pipeline for the analysis of the microbiome in 16S paired-end samples from colorectal cancer patients, and could potentially serve as a standardization approach in these processesThe authors of this paper extend their sincere appreciation to the collaborative efforts and contributions of the meiGAbiome Group, aswell as the entire team of medical and anatomopathologists. Finally, we are deeply grateful to the patients whose selfless donations have made this and numerous other studies possibl

Distribución geográfica y descripción de cuatro especies de cirripedios pelágicos a lo largo de la costa chilena del Pacífico sur este - una aproximación zoogeográfica

The majority of zoogeographic studies along the Chilean Pacific coast have focused on benthic organisms and oceanographic conditions are considered the main factors influencing their distributions. Herein we examined the geographic distribution of pelagic barnacles of the family Lepadidae collected from floating macroalgae at seven sampling areas between 23 and 50° S. Four species were encountered and they are briefly described herein. The most abundant northern species was Lepas anatifera, and it diminished in abundance towards the south (33° S). Moreover, this species was not found in waters with a sea surface temperature (SST) of less than ~18 ºC. Lepas australis, primarily a circumpolar West Wind Drift species, diminished in abundance towards the north (33° S). This species was restricted to waters of < 18 ºC SST. A third species, L. pectinata, was encountered throughout almost the entire study area, but it was most abundant between 29 and 33° S. The fourth species, Dosima fascicularis, was only found at two sampling areas, namely at 27° S and 33° S, and this is the first record of this species from the central coast of Chile. The distributional pattern of the pelagic barnacles found herein corresponds to the three main zoogeographic regions as revealed by the majority of previous studies based on littoral organisms: the northern Peru-Chilean Province, the southern Magellanic Province, and the central Chilean Transition Zone where the two provinces overlap. Even though the present study only considers four species of pelagic barnacles, the results support the hypotheses on the importance of oceanographic conditions (in particular SST) in determining the zoogeographic patterns along the south east Pacific coast of Chile

Finding New Cell Wall Regulatory Genes in Populus trichocarpa Using Multiple Lines of Evidence.

Understanding the regulatory network controlling cell wall biosynthesis is of great interest in Populus trichocarpa, both because of its status as a model woody perennial and its importance for lignocellulosic products. We searched for genes with putatively unknown roles in regulating cell wall biosynthesis using an extended network-based Lines of Evidence (LOE) pipeline to combine multiple omics data sets in P. trichocarpa, including gene coexpression, gene comethylation, population level pairwise SNP correlations, and two distinct SNP-metabolite Genome Wide Association Study (GWAS) layers. By incorporating validation, ranking, and filtering approaches we produced a list of nine high priority gene candidates for involvement in the regulation of cell wall biosynthesis. We subsequently performed a detailed investigation of candidate gene GROWTH-REGULATING FACTOR 9 (PtGRF9). To investigate the role of PtGRF9 in regulating cell wall biosynthesis, we assessed the genome-wide connections of PtGRF9 and a paralog across data layers with functional enrichment analyses, predictive transcription factor binding site analysis, and an independent comparison to eQTN data. Our findings indicate that PtGRF9 likely affects the cell wall by directly repressing genes involved in cell wall biosynthesis, such as PtCCoAOMT and PtMYB.41, and indirectly by regulating homeobox genes. Furthermore, evidence suggests that PtGRF9 paralogs may act as transcriptional co-regulators that direct the global energy usage of the plant. Using our extended pipeline, we show multiple lines of evidence implicating the involvement of these genes in cell wall regulatory functions and demonstrate the value of this method for prioritizing candidate genes for experimental validation

Distortion of the QRS in elderly patients with myocardial infarction

Background: Distortion of the terminal portion of the QRS in the initial electrocardiogram (ECG) is a strong predictor of adverse outcome in myocardial infarction. Our purpose is to assess the relationship of distortion of QRS and other ECG characteristics with older age. Methods and results: We analysed 634 consecutive patients (age 62.6 &#177; 13.7, 77% male) admitted in the first 12 hours of ST-elevation myocardial infarction. Two groups of age were defined: < 75 years-old and &#8805; 75 years-old. Additionally, we defined two ECG groups according to the presence of ST segment elevation with distortion of the terminal portion of the QRS in two or more adjacent leads (QRS+) or the absence of this pattern (QRS&#8211;). Older people had more often QRS+ (30% vs. 20%, p = 0.023). The older group with QRS+ had an in-hospital mortality of 18%, vs. 7% with QRS&#8211; (p = 0.04), and an incidence of major adverse events of 40% vs. 14% (p = 0.002). In the multivariate analysis, age &#8805; 75 years was an independent predictor of distortion of the QRS (odds ratio 2.1, 1.2&#8211;4.9, p = 0.016). Conclusions: The distortion of the terminal portion of the QRS in myocardial infarction is more frequent in elderly people, and is significantly related to adverse prognosis. This ECG finding can be helpful to promptly stratify the risk in elderly patient

The TOSCA Registry for Tuberous Sclerosis-Lessons Learnt for Future Registry Development in Rare and Complex Diseases.

Introduction: The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to provide insights into the clinical characteristics of patients with Tuberous Sclerosis Complex (TSC). The aims of this study were to identify issues that arose during the design, execution, and publication phases of TOSCA, and to reflect on lessons learnt that may guide future registries in rare and complex diseases. Methods: A questionnaire was designed to identify the strengths, weaknesses, and issues that arose at any stage of development and implementation of the TOSCA registry. The questionnaire contained 225 questions distributed in 7 sections (identification of issues during registry planning, during the operation of the registry, during data analysis, during the publication of the results, other issues, assessment of lessons learnt, and additional comments), and was sent by e-mail to 511 people involved in the registry, including 28 members of the Scientific Advisory Board (SAB), 162 principal investigators (PIs), and 321 employees of the sponsor belonging to the medical department or that were clinical research associate (CRA). Questionnaires received within the 2 months from the initial mailing were included in the analysis. Results: A total of 53 (10.4%) questionnaires were received (64.3% for SAB members, 12.3% for PIs and 4.7% for employees of the sponsor), and the overall completeness rate for closed questions was 87.6%. The most common issues identified were the limited duration of the registry (38%) and issues related to handling of missing data (32%). In addition, 25% of the respondents commented that biases might have compromised the validity of the results. More than 80% of the respondents reported that the registry improved the knowledge on the natural history and manifestations of TSC, increased disease awareness and helped to identify relevant information for clinical research in TSC. Conclusions: This analysis shows the importance of registries as a powerful tool to increase disease awareness, to produce real-world evidence, and to generate questions for future research. However, there is a need to implement strategies to ensure patient retention and long-term sustainability of patient registries, to improve data quality, and to reduce biases

Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria

<p>Abstract</p> <p>Background</p> <p>The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC.</p> <p>Methods</p> <p>Data were obtained from 26 pregnant women in the second (22 - 26 weeks) or the third (32 - 36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling.</p> <p>Results</p> <p>A simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7 - 72.3%).</p> <p>Conclusions</p> <p>In this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls.</p

Ebola virus glycoprotein stimulates IL-18 dependent natural killer cell responses

BACKGROUNDNK cells are activated by innate cytokines and viral ligands to kill virus-infected cells. These functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined.METHODSThe novel 2-dose heterologous Adenovirus type 26.ZEBOV (Ad26.ZEBOV) and modified vaccinia Ankara-BN-Filo (MVA-BN-Filo) vaccine regimen is safe and provides specific immunity against Ebola glycoprotein, and is currently in phase 2 and 3 studies. Here, we analyzed NK cell phenotype and function in response to Ad26.ZEBOV, MVA-BN-Filo vaccination regimen and in response to in vitro Ebola glycoprotein stimulation of PBMCs isolated before and after vaccination.RESULTSWe show enhanced NK cell proliferation and activation after vaccination compared with baseline. Ebola glycoprotein-induced activation of NK cells was dependent on accessory cells and TLR-4-dependent innate cytokine secretion (predominantly from CD14+ monocytes) and enriched within less differentiated NK cell subsets. Optimal NK cell responses were dependent on IL-18 and IL-12, whereas IFN-γ secretion was restricted by high concentrations of IL-10.CONCLUSIONThis study demonstrates the induction of NK cell effector functions early after Ad26.ZEBOV, MVA-BN-Filo vaccination and provides a mechanism for the activation and regulation of NK cells by Ebola glycoprotein.TRIAL REGISTRATIONClinicalTrials.gov NCT02313077.FUNDINGUnited Kingdom Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (grant 115861) and Crucell Holland (now Janssen Vaccines and Prevention B.V.), European Union's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA)

Antibody-Dependent Natural Killer Cell Activation after Ebola Vaccination

BACKGROUND:Antibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein antibodies suggest that Fc-dependent activation of effector cells, including NK cells, could play a role in vaccination against Ebola virus disease. METHODS:We analysed the effect of anti-Ebola glycoprotein antibody in the serum of U.K.-based volunteers vaccinated with the novel 2-dose heterologous Adenovirus type 26.ZEBOV, Modified Vaccinia Ankara-BN-Filo vaccine regimen, on primary human NK cell activation. RESULTS:We demonstrate primary human NK cell CD107a and IFN-γ expression, combined with downregulation of CD16, in response to recombinant Ebola virus glycoprotein and post-vaccine dose 1 and dose 2 sera. These responses varied significantly with vaccine regimen and NK cell activation was found to correlate with anti-glycoprotein antibody concentration. We also reveal an impact of NK cell differentiation phenotype on antibody-dependent NK cell activation, with highly differentiated CD56dimCD57+ NK cells being the most responsive. CONCLUSIONS:This study thus highlights the dual importance of vaccine-induced antibody concentration and NK cell differentiation status in promoting Fc-mediated activation of NK cells after vaccination, raising a potential role for antibody-mediated NK cell activation in vaccine-induced immune responses