Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell ...transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.
Own‐rooted Shiraz, spaced 1.5 m apart in 2.75 m wide rows, were compared under five different training systems in the Barossa Valley, South Australia over five seasons starting 1995–96. Our objective ...was to determine how training affected fruit composition and crop yield in a context of efficient vineyard management. Training systems were: (i) low single wire (LSW), in which vines were trained to bi‐lateral cordons, 1.0 m above the ground, non‐shoot‐positioned; (ii) high single wire (HSW), a higher cordon (1.8 m) version of LSW; (iii) vertically shoot positioned (VSP); (iv) Scott Henry, where canopies of alternate vines were cordon‐trained and shoot‐positioned upwards (SHU) or downwards (SHD); and (v) minimally pruned (MIN), the same as LSW, except vines were not annually spur‐pruned. Crop yields (kg/m of row), over four seasons, averaged 4.9 (MIN), 2.9 (combined Scott Henry), 3.2 (VSP), 2.6 (HSW) and 2.9 (LSW). The greatest year‐to‐year variation in yield occurred with MIN and Scott Henry training. Crop weight of SHD vines was inferior to that of SHU vines in two seasons due to fewer shoots and bunches per vine, and to fewer bunches per shoot. Individual berry weights (g) were consistently least with MIN (0.89), and greatest with VSP (1.17). Fruit from all training systems exhibited similar rates of sugar accumulation during two seasons in which repeated measures of fruit maturation were made. Excepting the relatively light yields observed in 1999–2000, sugar accumulation was delayed in MIN vines, relative to other training systems, even when MIN harvest was delayed up to two weeks. The delay is most readily explained by the greater crops of MIN vines. Berry total anthocyanins and total phenolics concentrations (mg/g berry fresh wt.) at harvest were not greatly affected by training system. Berry anthocyanins and total phenolics exhibited a negative relationship with crop/m of canopy and a slight positive relationship with bunch exposure when evaluated across all training systems. Experimental plot soil depth and water availability affected cane pruning weights, yield per vine, berry weight, and canopy characteristics. LSW, HSW and MIN training systems all provided good yields of high quality fruit, although MIN did have a tendency to produce excessive crops in some years. VSP and Scott Henry training were less attractive due to their inherently greater canopy management requirements.
The evolution of human diets led to preferences toward polyunsaturated fatty acid (PUFA) content with 'Western' diets enriched in ω-6 PUFAs. Mounting evidence points to ω-6 PUFA excess limiting ...metabolic and cognitive processes that define longevity in humans. When chosen during pregnancy, ω-6 PUFA-enriched 'Western' diets can reprogram maternal bodily metabolism with maternal nutrient supply precipitating the body-wide imprinting of molecular and cellular adaptations at the level of long-range intercellular signaling networks in the unborn fetus. Even though unfavorable neurological outcomes are amongst the most common complications of intrauterine ω-6 PUFA excess, cellular underpinnings of life-long modifications to brain architecture remain unknown. Here, we show that nutritional ω-6 PUFA-derived endocannabinoids desensitize CB
cannabinoid receptors, thus inducing epigenetic repression of transcriptional regulatory networks controlling neuronal differentiation. We found that cortical neurons lose their positional identity and axonal selectivity when mouse fetuses are exposed to excess ω-6 PUFAs in utero. Conversion of ω-6 PUFAs into endocannabinoids disrupted the temporal precision of signaling at neuronal CB
cannabinoid receptors, chiefly deregulating Stat3-dependent transcriptional cascades otherwise required to execute neuronal differentiation programs. Global proteomics identified the immunoglobulin family of cell adhesion molecules (IgCAMs) as direct substrates, with DNA methylation and chromatin accessibility profiling uncovering epigenetic reprogramming at >1400 sites in neurons after prolonged cannabinoid exposure. We found anxiety and depression-like behavioral traits to manifest in adult offspring, which is consistent with genetic models of reduced IgCAM expression, to suggest causality for cortical wiring defects. Overall, our data uncover a regulatory mechanism whose disruption by maternal food choices could limit an offspring's brain function for life.
Ordovician faunas of Burgess Shale type Botting, Joseph P; Orr, Patrick J; Lefebvre, Bertrand ...
Nature (London),
05/2010, Volume:
465, Issue:
7295
Journal Article
Peer reviewed
Open access
The renowned soft-bodied faunas of the Cambrian period, which include the Burgess Shale, disappear from the fossil record in the late Middle Cambrian, after which the Palaeozoic fauna dominates. The ...disappearance of faunas of Burgess Shale type curtails the stratigraphic record of a number of iconic Cambrian taxa. One possible explanation for this loss is a major extinction, but more probably it reflects the absence of preservation of similar soft-bodied faunas in later periods. Here we report the discovery of numerous diverse soft-bodied assemblages in the Lower and Upper Fezouata Formations (Lower Ordovician) of Morocco, which include a range of remarkable stem-group morphologies normally considered characteristic of the Cambrian. It is clear that biotas of Burgess Shale type persisted after the Cambrian and are preserved where suitable facies occur. The Fezouata biota provides a link between the Burgess Shale communities and the early stages of the Great Ordovician Biodiversification Event.
Worldwide, testing capacity for SARS-CoV-2 is limited and bottlenecks in the scale up of polymerase chain reaction (PCR-based testing exist. Our aim was to develop and evaluate a machine learning ...algorithm to diagnose COVID-19 in the inpatient setting. The algorithm was based on basic demographic and laboratory features to serve as a screening tool at hospitals where testing is scarce or unavailable. We used retrospectively collected data from the UCLA Health System in Los Angeles, California. We included all emergency room or inpatient cases receiving SARS-CoV-2 PCR testing who also had a set of ancillary laboratory features (n = 1,455) between 1 March 2020 and 24 May 2020. We tested seven machine learning models and used a combination of those models for the final diagnostic classification. In the test set (n = 392), our combined model had an area under the receiver operator curve of 0.91 (95% confidence interval 0.87-0.96). The model achieved a sensitivity of 0.93 (95% CI 0.85-0.98), specificity of 0.64 (95% CI 0.58-0.69). We found that our machine learning algorithm had excellent diagnostic metrics compared to SARS-CoV-2 PCR. This ensemble machine learning algorithm to diagnose COVID-19 has the potential to be used as a screening tool in hospital settings where PCR testing is scarce or unavailable.
We sought to determine the extent of SARS-CoV-2 seroprevalence and the factors associated with seroprevalence across a diverse cohort of healthcare workers.
Observational cohort study of healthcare ...workers, including SARS-CoV-2 serology testing and participant questionnaires.
A multisite healthcare delivery system located in Los Angeles County.
A diverse and unselected population of adults (n=6062) employed in a multisite healthcare delivery system located in Los Angeles County, including individuals with direct patient contact and others with non-patient-oriented work functions.
Using Bayesian and multivariate analyses, we estimated seroprevalence and factors associated with seropositivity and antibody levels, including pre-existing demographic and clinical characteristics; potential COVID-19 illness-related exposures; and symptoms consistent with COVID-19 infection.
We observed a seroprevalence rate of 4.1%, with anosmia as the most prominently associated self-reported symptom (OR 11.04, p<0.001) in addition to fever (OR 2.02, p=0.002) and myalgias (OR 1.65, p=0.035). After adjusting for potential confounders, seroprevalence was also associated with Hispanic ethnicity (OR 1.98, p=0.001) and African-American race (OR 2.02, p=0.027) as well as contact with a COVID-19-diagnosed individual in the household (OR 5.73, p<0.001) or clinical work setting (OR 1.76, p=0.002). Importantly, African-American race and Hispanic ethnicity were associated with antibody positivity even after adjusting for personal COVID-19 diagnosis status, suggesting the contribution of unmeasured structural or societal factors.
The demographic factors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace. The size and diversity of our study population, combined with robust survey and modelling techniques, provide a vibrant picture of the demographic factors, exposures and symptoms that can identify individuals with susceptibility as well as potential to mount an immune response to COVID-19.
Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to ...vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19–2.51) and dose 2 (1.76, 1.28–2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.
•Female sex was associated with a >70% increased odds of substantial symptoms following each vaccine dose.•Prior SARS-CoV-2 infection was associated with a doubling of the odds of symptoms following dose 1.•Younger age and a history of hypertension were also associated with increased odds of substantial symptoms following dose 2.
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