We combine high-resolution Hubble Space Telescope/WFC3 images with multi-wavelength photometry to track the evolution of structure and activity of massive galaxies at redshifts z = 1.4-3 in two ...fields of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey. We detect compact, star-forming galaxies (cSFGs) whose number densities, masses, sizes, and star formation rates (SFRs) qualify them as likely progenitors of compact, quiescent, massive galaxies (cQGs) at z = 1.5-3. In summary, we propose two evolutionary tracks of QG formation: an early (z > or ~ 2), formation path of rapidly quenched cSFGs fading into cQGs that later enlarge within the quiescent phase, and a late-arrival (z < o ~ 2) path in which larger SFGs form extended QGs without passing through a compact state.
Antibiotic-resistant pathogens pose a significant threat to human health. Several dispersal mechanisms have been described, but transport of both microbes and antibiotic resistance genes (ARGs) via ...atmospheric particles has received little attention as a pathway for global dissemination. These atmospheric particles can return to the Earth's surface via rain or snowfall, and thus promote long-distance spread of ARGs. However, the diversity and abundance of ARGs in fresh snow has not been studied and their potential correlation with particulate air pollution is not well explored. Here, we characterized ARGs in 44 samples of fresh snow from major cities in China, three in North America, and one in Europe, spanning a gradient from pristine to heavily anthropogenically influenced ecosystems. High-throughput qPCR analysis of ARGs and mobile genetic elements (MGEs) provided strong indications that dissemination of ARGs in fresh snow could be exacerbated by air pollution, severely increasing the health risks of both air pollution and ARGs. We showed that snowfall did effectively spread ARGs from point sources over the Earth surface. Together our findings urge for better pollution control to reduce the risk of global dissemination of antibiotic resistance genes.
Background Few studies have investigated the use of postoperative extracorporeal membrane oxygenation (ECMO) in acute type A aortic dissection (aTAAD). We identified aTAAD surgical patients at risk ...of ECMO implantation postoperatively and analyzed the prognosis of these patients. Methods We retrospectively reviewed 162 consecutive aTAAD patients undergoing operations from January 2008 to December 2015. Patient data were analyzed for risk factors leading to an ECMO requirement. Short-term and long-term outcomes in patients who did and did not require ECMO were compared. Results Postoperative ECMO was required in 20 patients (12.3%), and in-hospital mortality was higher in the ECMO group (65.0% vs 8.5%, p < 0.001). Factors predicting postoperative ECMO were preoperative hemodynamic instability ( p = 0.049), aortic cross-clamp time ( p = 0.036), and postoperative peak creatinine kinase-MB ( p = 0.002). ECMO survivors presented at a younger age ( p = 0.036) and had a less postoperative blood transfusion ( p = 0.034) than ECMO nonsurvivors. The postdischarge survival rate was equivalent in patients with or without ECMO support. Conclusions Although postoperative ECMO is an important predictor of in-hospital death, this pilot study showed that aTAAD patients supported with postoperative ECMO who survive to hospital discharge have a long-term survival comparable to patients who did not receive ECMO.
The activity and stability of supported metal catalysts, which exhibit high efficiency and activity, are significantly influenced by the interactions between the metal and the support, that is, ...metal-support interactions (MSIs). Here, we report an investigation of the MSIs between supported rhenium (Re) and oxide supports such as TiO
2
, SiO
2
, Al
2
O
3
, MgO, V
2
O
5
, and ZrO
2
using experimental and computational approaches. The reducibility of the Re species was found to strongly depend on the oxide support. Experimental studies including temperature-programmed reduction by H
2
as well as Re L
3
- and L
1
-edge X-ray absorption near edge structure (XANES) analysis revealed that the valency of the Re species started to decrease upon H
2
reduction in the 200-400 °C range, except for Re on MgO, where the shift occurred at temperatures above 500 °C. The dependence of the Re L
3
- and L
1
-edge XANES spectra of the oxide-supported Re catalysts on the size of Re was also examined.
The dependence of the Re L
3
- and L
1
-edge XANES spectra on the Re size was investigated, which revealed that the L
3
-edge was more sensitive than the L
1
-edge to the size of the Re clusters.
Background The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastroesophageal reflux ...disease GERD, nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. Objective The purpose of this study was to determine whether clinical features of EoE, measured through PEESS v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. Methods We systematically recruited treated and untreated pediatric patients with EoE (aged 2-18 years) and examined parent proxy–reported symptoms using the PEESS v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by using the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biological features were analyzed with Wilcoxon rank sum and Spearman correlation. Results The PEESS v2.0 domains correlated to specific parent-reported symptoms: dysphagia ( P = .0012), GERD ( P = .0001), and nausea/vomiting ( P < .0001). Pain correlated with multiple symptoms ( P < .0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus ( P ≤ .0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = 0.37, P = .02). Eosinophil levels were more associated with pain ( r = 0.27, P = .06) than dysphagia ( r = 0.24, P = .13). The dysphagia domain correlated most with esophageal gene transcript levels, predominantly with mast cell–specific genes. Conclusion We have (1) established a validated, parent proxy–reported measure for pediatric EoE, the PEESS v2.0; (2) verified that the parent proxy effectively captures symptoms; (3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; (4) established that symptoms correlate with EPX staining; and (5) observed association between mast cells and dysphagia.
Moral emotions are experienced in daily life and are crucial for mediating appropriate social behaviors, as they prevent individuals from committing transgressions. In this study, caregivers of 377 ...children aged between 2.5 and 6.5 years old completed the Moral Emotions Questionnaire (MEQ), a parent report aimed to separately identify the presence of shame, guilt, and pride behaviors in early childhood. To validate this newly developed questionnaire, a confirmatory factor analysis and measurement invariance were conducted, and internal consistency, and concurrent validity were tested. Outcomes confirmed that the three moral emotions can be individually identified through the MEQ, even at such an early age. The MEQ scales showed acceptable internal consistencies and the associations between the three moral emotions and externalizing behaviors, internalizing behaviors, and social competence were in accordance with previous research, therefore confirming concurrent validity.
Background Patients with chronic kidney failure (CKF) experience impaired functional cardiovascular reserve with reduced oxygen consumption at peak exercise (V o2peak ). No studies have examined ...whether this is related to impaired cardiovascular compliance as a consequence of loss of adaptive structural alterations, resulting from chronic uremia or hypertension. Study Design Prospective matched-cohort study. Setting & Participants We assessed CKF in parallel with patients with essential hypertension but without cardiovascular disease. Patients with CKF were either scheduled for kidney transplantation or transplant waitlisted. 80 patients with CKF and 80 with essential hypertension matched in age, sex, and body mass index were evaluated. 61 patients with CKF (76.3%) were dialysis dependent. Predictor CKF versus essential hypertension without cardiovascular disease. Measurements & Outcomes V o2peak was measured during maximal exercise testing. 2-dimensional echocardiography and arterial applanation tonometry were performed prior to exercise testing. To evaluate for the difference in V o2peak between study groups, statistically significant predictors of V o2peak in multiple regression models were additionally assessed by fitting models comprising the interaction term of patient group with the predictor variable of interest. Results V o2peak was significantly lower in patients with CKF than those with essential hypertension (18.8 vs 24.5 mL/min·kg; P < 0.001). Independent predictors of V o2peak for CKF included left ventricular (LV) filling pressure (E/mean e′; unstandardized regression coefficient: change in V o2peak in mL/min·kg per 1-unit change of variable = −5.1) and pulse wave velocity (−4.0); in essential hypertension, these were LV mass index (0.2), LV end-diastolic volume index (0.4), peak heart rate (0.2), and pulse wave velocity (−8.8). The interaction effect of V o2peak between patient groups with LV mass index ( P < 0.001), LV end-diastolic volume index ( P < 0.001), and peak heart rate ( P < 0.01) were significantly stronger in the hypertension group, whereby higher values led to greater V o2peak. Limitations Skeletal muscle strength was not assessed. Conclusion This study suggests that maladaptive LV changes, as well as blunted chronotropic response, are important mechanistic factors resulting in reduced cardiovascular reserve in patients with CKF, beyond predominantly vascular changes associated with hypertension.
Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging ...because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.
•Genetically heterogeneous BC progenitors demonstrate molecular convergence on PRC1- and PRC2-regulated pathways.•A model of PRC-driven reprogramming identifies novel BC combination therapies, tumor suppressor genes, and biomarkers for transformation.
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ABSTRACT
Background
25-hydroxyvitamin D can undergo C-3 epimerization to produce 3-epi-25(OH)D3. 3-epi-25(OH)D3 levels decline in chronic kidney disease (CKD), but its role in regulating the ...cardiovascular system is unknown. Herein, we examined the relationship between 3-epi-25(OH)D3, and cardiovascular functional and structural endpoints in patients with CKD.
Methods
We examined n = 165 patients with advanced CKD from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study cohort, including those who underwent kidney transplant (KTR, n = 76) and waitlisted patients who did not (NTWC, n = 89). All patients underwent cardiopulmonary exercise testing and echocardiography at baseline, 2 months and 12 months. Serum 3-epi-25(OH)D3 was analyzed by liquid chromatography-tandem mass spectrometry.
Results
Patients were stratified into quartiles of baseline 3-epi-25(OH)D3 (Q1: <0.4 ng/mL, n = 51; Q2: 0.4 ng/mL, n = 26; Q3: 0.5–0.7 ng/mL, n = 47; Q4: ≥0.8 ng/mL, n = 41). Patients in Q1 exhibited lower peak oxygen uptake VO2Peak = 18.4 (16.2–20.8) mL/min/kg compared with Q4 20.8 (18.6–23.2) mL/min/kg; P = .009. Linear mixed regression model showed that 3-epi-25(OH)D3 levels increased in KTR from 0.47 (0.30) ng/mL to 0.90 (0.45) ng/mL and declined in NTWC from 0.61 (0.32) ng/mL to 0.45 (0.29) ng/mL; P < .001. Serum 3-epi-25(OH)D3 was associated with VO2Peak longitudinally in both groups KTR: β (standard error) = 2.53 (0.56), P < .001; NTWC: 2.73 (0.70), P < .001, but was not with left ventricular mass or arterial stiffness. Non-epimeric 25(OH)D3, 24,25(OH)2D3 and the 25(OH)D3:24,25(OH)2D3 ratio were not associated with any cardiovascular outcome (all P > .05).
Conclusions
Changes in 3-epi-25(OH)D3 levels may regulate cardiovascular functional capacity in patients with advanced CKD.
Graphical Abstract
Graphical Abstract
BACKGROUND
Ovarian tissue cryopreservation is the only option for preserving fertility in prepubertal girls and cancer patients requiring immediate treatment. Following ovarian tissue ...cryopreservation, fertility can be restored after tissue transplant or in vitro follicle maturation.
METHODS
Macaque (n= 4) ovarian cortex was cryopreserved using slow-rate freezing (slow freezing) or vitrification. Tissues were fixed for histology or phosphohistone H3 (PPH3) analysis, cultured with bromodeoxyuridine (BrdU) or used for three-dimensional secondary follicle culture. Follicular diameter and steroid hormones were measured weekly.
RESULTS
Slow freezing induced frequent cryo-injuries while vitrification consistently maintained morphology of the stroma and secondary follicles. PPH3 was similar in fresh and vitrified, but sparse in slow-frozen tissues. BrdU uptake appeared diminished following both methods compared with that in fresh follicles. In vitro follicle survival and growth were greater in fresh than in cryopreserved follicles. Antrum formation appeared similar after vitrification compared with the fresh, but was reduced following slow freezing. Steroid production was delayed or diminished following both methods compared with fresh samples.
CONCLUSIONS
Secondary follicle morphology was improved after vitrification relative to slow freezing. Following vitrification, stroma was consistently more compact with intact cells typical to that of fresh tissue. BrdU uptake demonstrated follicle viability post-thaw/warming. For the first time, although not to the extent of fresh follicles, macaque follicles from cryopreserved tissue can survive, grow, form an antrum and produce steroid hormones, indicating some functional preservation. The combination of successful ovarian tissue cryopreservation with in vitro maturation of follicles will offer a major advancement to the field of fertility preservation.
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