Genetic maps are key tools in genetic research as they constitute the framework for many applications, such as quantitative trait locus analysis, and support the assembly of genome sequences. The ...resequencing of the two parents of a cross between Eucalyptus urophylla and Eucalyptus grandis was used to design a single nucleotide polymorphism (SNP) array of 6000 markers evenly distributed along the E. grandis genome. The genotyping of 1025 offspring enabled the construction of two high‐resolution genetic maps containing 1832 and 1773 markers with an average marker interval of 0.45 and 0.5 cM for E. grandis and E. urophylla, respectively. The comparison between genetic maps and the reference genome highlighted 85% of collinear regions. A total of 43 noncollinear regions and 13 nonsynthetic regions were detected and corrected in the new genome assembly. This improved version contains 4943 scaffolds totalling 691.3 Mb of which 88.6% were captured by the 11 chromosomes. The mapping data were also used to investigate the effect of population size and number of markers on linkage mapping accuracy. This study provides the most reliable linkage maps for Eucalyptus and version 2.0 of the E. grandis genome.
Stimuli‐responsive polymers are the subject of intense research because they are able to show responses to various environmental changes. Among those stimuli, light has attracted much attention since ...it can be localized in time and space and it can also be triggered from outside of the system. In this paper, we review light‐responsive block copolymers (LRBCs) that combine characteristic features of block copolymers, e.g., self‐assembly behavior, and light‐responsive systems. The different photo‐responsive moieties that have been incorporated so far in block copolymers as well as the proposed applications are discussed.
Light‐responsive block copolymers are reviewed. The different photo‐responsive moieties that have been incorporated so far in block copolymers as well as the proposed applications are discussed both in solution and in bulk.
The lack of information on the ways seasonal drought modifies the CO₂ exchange between Neotropical rainforest ecosystems and the atmosphere and the resulting carbon balance hinders our ability to ...precisely predict how these ecosystems will respond as global environmental changes force them to face increasingly contrasting conditions in the future. To address this issue, seasonal variations in daily net ecosystem productivity (NEPd) and two main components of this productivity, daily total ecosystem respiration (REd) and daily gross ecosystem productivity (GEPd), were estimated over 2 years at a flux tower site in French Guiana, South America (5 °16'54"N, 52 °54'44"W). We compared seasonal variations between wet and dry periods and between dry periods of contrasting levels of intensity (i.e. mild vs. severe) during equivalent 93-day periods. During the wet periods, the ecosystem was almost in balance with the atmosphere (storage of 9.0 g C m⁻²). Seasonal dry periods, regardless of their severity, are associated with higher incident radiation and lower REd combined with reduced soil respiration associated with low soil water availability. During the mild dry period, as is normally the case in this region, the amount of carbon stored in the ecosystem was 32.7 g C m⁻². Severe drought conditions resulted in even lower REd, whereas the photosynthetic activity was only moderately reduced and no change in canopy structure was observed. Thus, the severe dry period was characterized by greater carbon storage (64.6 g C m⁻²), emphasizing that environmental conditions, such as during a severe drought, modify the CO₂ exchange between Neotropical rainforest ecosystems and the atmosphere and potentially the resulting carbon balance.
A P300-based speller can be used to control a home automation system via brain activity. Evaluation of the visual stimuli used in a P300-based speller is a common topic in the field of brain-computer ...interfaces (BCIs). The aim of the present work is to compare, using the usability approach, two types of stimuli that have provided high performance in previous studies. Twelve participants controlled a BCI under two conditions, which varied in terms of the type of stimulus employed: a red famous face surrounded by a white rectangle (RFW) and a range of neutral pictures (NPs). The usability approach included variables related to effectiveness (accuracy and information transfer rate), efficiency (stress and fatigue), and satisfaction (pleasantness and System Usability Scale and Affect Grid questionnaires). The results indicated that there were no significant differences in effectiveness, but the system that used NPs was reported as significantly more pleasant. Hence, since satisfaction variables should also be considered in systems that potential users are likely to employ regularly, the use of different NPs may be a more suitable option than the use of a single RFW for the development of a home automation system based on a visual P300-based speller.
Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is ...available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing.
Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A) were identified as significantly mutated in mBC (false discovery rate FDR < 0.1). Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN) were more frequently mutated in mBC as compared to eBC (FDR < 0.01). ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI 9-155, p = 1.2e-12) and also presented with focal amplification (n = 9) for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+) and HER2 negative (HER2-) mBCs (19%). HR+/HER2- mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR) pathway (TSC1 and TSC2) as compared to HR+/HER2- eBC (respectively 6% and 0.7%, p = 0.0004). Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8), NOTCH3 (n = 7), and ALK (n = 7). Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2- metastatic tumors as compared to primary TCGA samples (p < 2e-16). The main limitations of this study include the absence of bone metastases and the size of the cohort, which might not have allowed the identification of rare mutations and their effect on survival.
This work reports the results of the analysis of the first large-scale study on mutation profiles of mBC. This study revealed genomic alterations and mutational signatures involved in the resistance to therapies, including actionable mutations.
Sickle cell disease is characterized by chronic anemia and vaso-occlusive crises, which eventually lead to multi-organ damage and premature death. Hematopoietic stem cell transplantation is the only ...curative treatment but it is limited by toxicity and poor availability of HLA-compatible donors. A gene therapy approach based on the autologous transplantation of lentiviral-corrected hematopoietic stem and progenitor cells was shown to be efficacious in one patient. However, alterations of the bone marrow environment and properties of the red blood cells hamper the harvesting and immunoselection of patients' stem cells from bone marrow. The use of Filgrastim to mobilize large numbers of hematopoietic stem and progenitor cells into the circulation has been associated with severe adverse events in sickle cell patients. Thus, broader application of the gene therapy approach requires the development of alternative mobilization methods. We set up a phase I/II clinical trial whose primary objective was to assess the safety of a single injection of Plerixafor in sickle cell patients undergoing red blood cell exchange to decrease the hemoglobin S level to below 30%. The secondary objective was to measure the efficiency of mobilization and isolation of hematopoietic stem and progenitor cells. No adverse events were observed. Large numbers of CD34
cells were mobilized extremely quickly. Importantly, the mobilized cells contained high numbers of hematopoietic stem cells, expressed high levels of stemness genes, and engrafted very efficiently in immunodeficient mice. Thus, Plerixafor can be safely used to mobilize hematopoietic stem cells in sickle cell patients; this finding opens up new avenues for treatment approaches based on gene addition and genome editing.
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Background
Tissue oximetry using near‐infrared spectroscopy (NIRS) is a noninvasive monitor of cerebral oxygenation. This new technology has been used during cardiac arrest (CA) because of its ...ability to give measures in low‐blood‐flow situations. The aim of this study was to assess the evidence regarding the association between the types of NIRS measurements (mean, initial, and highest values) and resuscitation outcomes (return of spontaneous circulation ROSC, survival to discharge, and good neurologic outcome) in patients undergoing cardiopulmonary resuscitation.
Methods
This review was registered (Prospero CRD42015017380) and is reported as per the PRISMA guidelines. Medline, Embase, and CENTRAL were searched. All studies, except case reports and case series of fewer than five patients, reporting on adults that had NIRS monitoring during CA were eligible for inclusion. Two reviewers assessed the quality of the included articles and extracted the data. The outcome effect was standardized using standardized mean difference (SMD).
Results
Twenty nonrandomized observational studies (15 articles and five conference s) were included in this review, for a total of 2,436 patients. We found a stronger association between ROSC and mean NIRS values (SMD = 1.33; 95% confidence interval CI = 0.92 to 1.74) than between ROSC and initial NIRS measurements (SMD = 0.51; 95% CI = 0.23 to 0.78). There was too much heterogeneity among the highest NIRS measurements group to perform meta‐analysis. Only two of the 75 patients who experienced ROSC had a mean NIRS saturation under 30%. Patients who survived to discharge and who had good neurologic outcome displayed superior combined initial and mean NIRS values than their counterparts (SMD = 1.63; 95% CI = 1.34 to 1.92; and SMD = 2.12; 95% CI = 1.14 to 3.10).
Conclusions
Patients with good resuscitation outcomes have significantly higher NIRS saturations during resuscitation than their counterparts. The types of NIRS measurements during resuscitation influenced the association between ROSC and NIRS saturation. Prolonged failure to obtain a NIRS saturation higher than 30% may be included in a multimodal approach to the decision of terminating resuscitation efforts (Class IIb, Level of Evidence C‐Limited Data).
Inflammation is a prominent feature of ischemia-reperfusion injury (IRI), which is characterized by leukocyte infiltration and renal tubular injury. However, signals that initiate these events remain ...poorly understood. We examined the role of the nuclear alarmin IL-33 in tissue injury and innate immune response triggered by experimental kidney ischemia-reperfusion. In wild-type mice, we found that IL-33 was constitutively expressed throughout the kidney in peritubular and periglomerular spaces, mainly by microvascular endothelial cells, from which it was released immediately during IRI. Compared with wild-type mice, mice lacking IL-33 (IL-33
) exhibited reductions in early tubular cell injury and subsequent renal infiltration of IFN-
/IL-17A-producing neutrophils, with preservation of renal functions. This protection associated with decreased renal recruitment of myeloid dendritic cells, natural killer (NK) cells, and invariant natural killer T (iNKT) cells, the latter of which were reported as deleterious in IRI. Increases in the level of circulating IL-12, a key IL-33 cofactor, and the expression of ST2, an IL-33-specific receptor, on the surface of iNKT cells preceded the IL-33- and iNKT cell-dependent phase of neutrophil infiltration. Furthermore, IL-33 directly targeted iNKT cells
, inducing IFN-
and IL-17A production. We propose that endogenous IL-33 is released as an alarmin and contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. Our findings show a novel molecular mediator contributing to innate immune cell recruitment induced by renal ischemia-reperfusion and may provide therapeutic insights into AKI associated with renal transplantation.
One of the major current ecological challenges is to understand how to reconcile human activities with biodiversity conservation concerns. This issue is particularly relevant in freshwater ecosystems ...where biodiversity is globally under severe threat. Artificial waterbodies, such as ditch networks, are part of the few remaining wetlands in agricultural landscapes and hence play a crucial role in maintaining aquatic biodiversity in these landscapes.
We investigated the responses of adult Odonata assemblages at different spatial scales in a marshland crossed by ditches to two factors expected to be pivotal influences on assemblages. At the local scale, this was mainly the water regime in ditches and, at a broader scale, the composition of the landscape. Both taxonomic alpha and beta diversity, and functional trait composition were considered as response variables.
Significant differences were found between the responses of the two Odonata suborders. We showed that Zygoptera species richness decreased and species turnover increased with the duration of drying episodes in ditches. Geographical distances between local assemblages as well as landscape characteristics, notably woodland cover, meadow cover and ditch network length, also significantly shaped the distribution of Zygoptera. For Anisoptera, species richness was not explained by environmental variables and beta diversity was associated only with local conditions; it increased with increasing dissimilarity in water quality and riparian vegetation. We also found evidence of functional trait syndromes (combinations of correlated traits) in Odonata assemblages, but without clear relationships to environmental gradients.
This study reveals the structuring role of water regime for Odonata in ditch networks and demonstrates the need to jointly consider environmental variables at different spatial scales to properly understand the distribution of Odonata.
Our findings have important conservation implications as the water regime is heavily managed in such ecosystems. Even though the relationship between functional composition and environmental gradients was found to be of limited extent in this study, we discuss how it might provide new insights for Odonata assemblage structure and be useful, locally, for stakeholders and managers. Lastly, we call for further multiscale investigations considering both the taxonomic and functional responses of Odonata assemblages (functional analyses with multiple traits and several species being scarce in this taxonomic group) in other anthropogenic freshwater ecosystems to gather more lessons for their conservation.
To compare epirubicin, cisplatin, and capecitabine (ECX) with fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatments in patients with advanced gastric or esophagogastric junction ...(EGJ) adenocarcinoma.
This open, randomized, phase III study was carried out in 71 centers. Patients with locally advanced or metastatic gastric or EGJ cancer were randomly assigned to receive either ECX as first-line treatment (ECX arm) or FOLFIRI (FOLFIRI arm). Second-line treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). The primary criterion was time-to-treatment failure (TTF) of the first-line therapy. Secondary criteria were progression-free survival (PFS), overall survival (OS), toxicity, and quality of life.
In all, 416 patients were included (median age, 61.4 years; 74% male). After a median follow-up of 31 months, median TTF was significantly longer with FOLFIRI than with ECX (5.1 v 4.2 months; P = .008). There was no significant difference between the two groups in median PFS (5.3 v 5.8 months; P = .96), median OS (9.5 v 9.7 months; P = .95), or response rate (39.2% v 37.8%). First-line FOLFIRI was better tolerated (overall rate of grade 3 to 4 toxicity, 69% v 84%; P < .001; hematologic adverse events AEs, 38% v 64.5%; P < .001; nonhematologic AEs: 53% v 53.5%; P = .81).
FOLFIRI as first-line treatment for advanced gastric and EGJ cancer demonstrated significantly better TTF than did ECX. Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents.
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