Oaks (Quercus, Fagaceae) are the dominant tree genus of North America in species number and biomass, and Mexico is a global center of oak diversity. Understanding the origins of oak diversity is key ...to understanding biodiversity of northern temperate forests.
A phylogenetic study of biogeography, niche evolution and diversification patterns in Quercus was performed using 300 samples, 146 species. Next-generation sequencing data were generated using the restriction-site associated DNA (RAD-seq) method. A time-calibrated maximum likelihood phylogeny was inferred and analyzed with bioclimatic, soils, and leaf habit data to reconstruct the biogeographic and evolutionary history of the American oaks.
Our highly resolved phylogeny demonstrates sympatric parallel diversification in climatic niche, leaf habit, and diversification rates. The two major American oak clades arose in what is now the boreal zone and radiated, in parallel, from eastern North America into Mexico and Central America.
Oaks adapted rapidly to niche transitions. The Mexican oaks are particularly numerous, not because Mexico is a center of origin, but because of high rates of lineage diversification associated with high rates of evolution along moisture gradients and between the evergreen and deciduous leaf habits. Sympatric parallel diversification in the oaks has shaped the diversity of North American forests.
This study provides 2-year data from the PARTNER trial, in which patients with aortic stenosis received transcatheter aortic-valve replacement (TAVR) or surgical replacement. Overall mortality was ...similar, but paravalvular leak increased mortality in the TAVR group.
Aortic stenosis is associated with high mortality after the appearance of cardiac symptoms.
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Nevertheless, many patients do not undergo surgical aortic-valve replacement owing to real or perceived increased risks associated with surgery.
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Transcatheter aortic-valve replacement (TAVR) has emerged as an alternative therapy in high-risk patients with aortic stenosis.
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Observational registries from various countries have reported 1-month and 1-year outcomes after TAVR,
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but there are limited long-term follow-up data.
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The Placement of Aortic Transcatheter Valves (PARTNER) trial was a randomized trial comparing TAVR with standard-of-care therapies in high-risk patients with aortic stenosis. One-year mortality outcomes from PARTNER showed . . .
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•A robust phylogeny of Quercus section Cyclobalanopsis was reconstructed.•Two lineages including six subclades were resolved in the section.•Section Cyclobalanopsis originated in ...Sino-Himalaya in the early Oligocene.•Fast geomorphological changes in Asia during Neogene induced its early diversification.•Enforced East Asia monsoon and Mid-Miocene Climatic Optimum enabled the eastward colonization.
The evolutionary history of Quercus section Cyclobalanopsis, a dominant lineage in East Asian evergreen broadleaved forests (EBLFs), has not been comprehensively studied using molecular tools. In this study, we reconstruct the first comprehensive phylogeny of this lineage using a genomic approach (restriction-site associated DNA sequencing, RAD-seq), sampling 35 of the ca. 90 species currently recognized, representing all main morphological groups of section Cyclobalanopsis. In addition, 10 other species of Quercus and two outgroups were also sampled. Divergence times were estimated using a relaxed clock model and two fossil calibrations. Ancestral areas and dispersal routes were inferred using statistical dispersal-vicariance analysis and the dispersal-extinction-cladogenesis (DEC) model. The phylogeny of Quercus section Cyclobalanopsis demonstrates the section to be monophyletic, comprising two main lineages and six subclades that are well supported by anatomical traits. Biogeographical reconstructions indicate that the wide northern hemisphere distribution of Quercus was disrupted in the Late Eocene, leading to the main extant groups at about 33 Ma. The earliest divergences in section Cyclobalanopsis correspond to the phased uplift of the Himalayas and lateral extrusion of Indochina at the transition of the Oligocene and Miocene, where the highest rate of diversification occurred in the late Miocene. Dispersal from Sino-Himalaya and the Palaeotropics to Sino-Japan in the Miocene was facilitated by the increased intensity of East Asian summer monsoons and by the Middle Miocene Climatic Optimum. Our results highlight the importance of climatic changes and Indo-Eurasian collision-induced tectonic activities from the Neogene onward to the spatial-temporal diversification patterns of Asian EBLF lineages.
Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current ...National Institute of Child Health and Human Development (NICHD)/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes.
We hypothesized that magnetic resonance imaging (MRI) of structural parenchymal abnormalities will correlate with NICHD-defined BPD disease severity and predict short-term respiratory outcomes.
A total of 42 neonates (20 severe BPD, 6 moderate, 7 mild, 9 non-BPD control subjects; 40 ± 3-wk postmenstrual age) underwent quiet-breathing structural pulmonary MRI (ultrashort echo time and gradient echo) in a neonatal ICU-sited, neonatal-sized 1.5 T scanner, without sedation or respiratory support unless already clinically prescribed. Disease severity was scored independently by two radiologists. Mean scores were compared with clinical severity and short-term respiratory outcomes. Outcomes were predicted using univariate and multivariable models, including clinical data and scores.
MRI scores significantly correlated with severities and predicted respiratory support at neonatal ICU discharge (P < 0.0001). In multivariable models, MRI scores were by far the strongest predictor of respiratory support duration over clinical data, including birth weight and gestational age. Notably, NICHD severity level was not predictive of discharge support.
Quiet-breathing neonatal pulmonary MRI can independently assess structural abnormalities of BPD, describe disease severity, and predict short-term outcomes more accurately than any individual standard clinical measure. Importantly, this nonionizing technique can be implemented to phenotype disease, and has potential to serially assess efficacy of individualized therapies.
• The tree of life is highly reticulate, with the history of population divergence emerging from populations of gene phylogenies that reflect histories of introgression, lineage sorting and ...divergence. In this study, we investigate global patterns of oak diversity and test the hypothesis that there are regions of the oak genome that are broadly informative about phylogeny.
• We utilize fossil data and restriction-site associated DNA sequencing (RAD-seq) for 632 individuals representing nearly 250 Quercus species to infer a time-calibrated phylogeny of the world’s oaks. We use a reversible-jump Markov chain Monte Carlo method to reconstruct shifts in lineage diversification rates, accounting for among-clade sampling biases. We then map the > 20 000 RAD-seq loci back to an annotated oak genome and investigate genomic distribution of introgression and phylogenetic support across the phylogeny.
• Oak lineages have diversified among geographic regions, followed by ecological divergence within regions, in the Americas and Eurasia. Roughly 60% of oak diversity traces back to four clades that experienced increases in net diversification, probably in response to climatic transitions or ecological opportunity.
• The strong support for the phylogeny contrasts with high genomic heterogeneity in phylogenetic signal and introgression. Oaks are phylogenomic mosaics, and their diversity may in fact depend on the gene flow that shapes the oak genome.
RAP GTPases, important regulators of cellular adhesion, are abundant signaling molecules in the platelet/megakaryocytic lineage. However, mice lacking the predominant isoform, RAP1B, display a ...partial platelet integrin activation defect and have a normal platelet count, suggesting the existence of a RAP1-independent pathway to integrin activation in platelets and a negligible role for RAP GTPases in megakaryocyte biology. To determine the importance of individual RAP isoforms on platelet production and on platelet activation at sites of mechanical injury or vascular leakage, we generated mice with megakaryocyte-specific deletion (mKO) of Rap1a and/or Rap1b. Interestingly, Rap1a/b-mKO mice displayed a marked macrothrombocytopenia due to impaired proplatelet formation by megakaryocytes. In platelets, RAP isoforms had redundant and isoform-specific functions. Deletion of RAP1B, but not RAP1A, significantly reduced α-granule secretion and activation of the cytoskeleton regulator RAC1. Both isoforms significantly contributed to thromboxane A2 generation and the inside-out activation of platelet integrins. Combined deficiency of RAP1A and RAP1B markedly impaired platelet aggregation, spreading, and clot retraction. Consistently, thrombus formation in physiological flow conditions was abolished in Rap1a/b-mKO, but not Rap1a-mKO or Rap1b-mKO, platelets. Rap1a/b-mKO mice were strongly protected from experimental thrombosis and exhibited a severe defect in hemostasis after mechanical injury. Surprisingly, Rap1a/b-mKO platelets were indistinguishable from controls in their ability to prevent blood–lymphatic mixing during development and hemorrhage at sites of inflammation. In summary, our studies demonstrate an essential role for RAP1 signaling in platelet integrin activation and a critical role in platelet production. Although important for hemostatic/thrombotic plug formation, platelet RAP1 signaling is dispensable for vascular integrity during development and inflammation.
•Deletion of both Rap1a and Rap1b impairs platelet production and abolishes platelet adhesion at sites of mechanical trauma.•Platelet RAP1 signaling is dispensable for vascular integrity during development and at sites of inflammation.
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Purpose
To demonstrate that ultrashort echo time (UTE) magnetic resonance imaging (MRI) can achieve computed tomography (CT)‐like quantification of lung parenchyma in free‐breathing, non‐sedated ...neonates. Because infant CTs are used sparingly, parenchymal disease evaluation via UTE MRI has potential for translational impact.
Materials and Methods
Two neonatal control cohorts without suspected pulmonary morbidities underwent either a research UTE MRI (n = 5; 1.5T) or a clinically‐ordered CT (n = 9). Whole‐lung means and anterior–posterior gradients of UTE‐measured image intensity (arbitrary units, au, normalized to muscle) and CT‐measured density (g/cm3) were compared (Mann–Whitney U‐test). Separately, a diseased neonatal cohort (n = 5) with various pulmonary morbidities underwent both UTE MRI and CT. UTE intensity and CT density were compared with Spearman correlations within ∼33 anatomically matched regions of interest (ROIs) in each diseased subject, spanning low‐ to high‐density tissues. Radiological classifications were evaluated in all ROIs, with mean UTE intensities and CT densities compared in each classification.
Results
In control subjects, whole‐lung UTE intensities (0.51 ± 0.04 au) were similar to CT densities (0.44 ± 0.09 g/cm3) (P = 0.062), as were UTE (0.021 ± 0.020 au/cm) and CT (0.034 ± 0.024 g/cm3/cm) anterior–posterior gradients (P = 0.351). In diseased subjects' ROIs, significant correlations were observed between UTE and CT (P ≤0.007 in each case). Relative differences between UTE and CT were small in all classifications (4–25%).
Conclusion
These results demonstrate a strong association between UTE image intensity and CT density, both between whole‐lung tissue in control patients and regional radiological pathologies in diseased patients. This indicates the potential for UTE MRI to longitudinally evaluate neonatal pulmonary disease and to provide visualization of pathologies similar to CT, without sedation/anesthesia or ionizing radiation.
Level of Evidence: 3
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2017;46:992–1000.
Children raised in economically disadvantaged households face increased risks of poor health in adulthood, suggesting that inequalities in health have early origins. From the child’s perspective, ...exposure to economic hardship may begin as early as conception, potentially via maternal neuroendocrine–immune responses to prenatal stressors, which adversely impact neurodevelopment. Here we investigate whether socioeconomic disadvantage is associated with gestational immune activity and whether such activity is associated with abnormalities among offspring during infancy. We analyzed concentrations of five immune markers (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in maternal serum from 1,494 participants in the New England Family Study in relation to the level of maternal socioeconomic disadvantage and their involvement in offspring neurologic abnormalities at 4 mo and 1 y of age. Median concentrations of IL-8 were lower in the most disadvantaged pregnancies −1.53 log(pg/mL); 95% CI: −1.81, −1.25. Offspring of these pregnancies had significantly higher risk of neurologic abnormalities at 4 mo odds ratio (OR) = 4.61; CI = 2.84, 7.48 and 1 y (OR = 2.05; CI = 1.08, 3.90). This higher risk was accounted for in part by fetal exposure to lower maternal IL-8, which also predicted higher risks of neurologic abnormalities at 4 mo (OR = 7.67; CI = 4.05, 14.49) and 1 y (OR = 2.92; CI = 1.46, 5.87). Findings support the role of maternal immune activity in fetal neurodevelopment, exacerbated in part by socioeconomic disadvantage. This finding reveals a potential pathophysiologic pathway involved in the intergenerational transmission of socioeconomic inequalities in health.
Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational ...characteristics of T-MN (n = 129) and primary myelodysplastic syndrome (P-MDS, n = 108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5 vs. 7%), while spliceosomal complex mutations were more common in P-MDS (56.5 vs. 25.6%). In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with "Very low" or "Low" Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetics, disease-modifying therapy, and NRAS mutation. Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification.
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