Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude
. Heavily glycosylated S trimers bind to the ...angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells
. S exhibits extensive conformational flexibility: it modulates exposure of its receptor-binding site and subsequently undergoes complete structural rearrangement to drive fusion of viral and cellular membranes
. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy
, but the structure and distribution of S on the virion surface remain unknown. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Visceral organs, such as the lungs, stomach and liver, are derived from the fetal foregut through a series of inductive interactions between the definitive endoderm (DE) and the surrounding ...splanchnic mesoderm (SM). While DE patterning is fairly well studied, the paracrine signaling controlling SM regionalization and how this is coordinated with epithelial identity is obscure. Here, we use single cell transcriptomics to generate a high-resolution cell state map of the embryonic mouse foregut. This identifies a diversity of SM cell types that develop in close register with the organ-specific epithelium. We infer a spatiotemporal signaling network of endoderm-mesoderm interactions that orchestrate foregut organogenesis. We validate key predictions with mouse genetics, showing the importance of endoderm-derived signals in mesoderm patterning. Finally, leveraging these signaling interactions, we generate different SM subtypes from human pluripotent stem cells (hPSCs), which previously have been elusive. The single cell data can be explored at: https://research.cchmc.org/ZornLab-singlecell.The fetal murine foregut develops into visceral organs via interactions between the mesoderm and endoderm, but how is unclear. Here, the authors use single cell RNAseq to show a diversity in organ specific splanchnic mesoderm cell-types, infer a signalling network governing organogenesis and use this to differentiate human pluripotent stem cells.
Future climate changes could alter hydrometeorological patterns and change the nature of droughts at global to regional scales. However, there are considerable uncertainties in future drought ...projections. Here, we focus on agricultural drought by analyzing surface soil moisture outputs from CMIP5 multi-model ensembles (MMEs) under RCP2.6, RCP4.5, RCP6.0, and RCP8.5 scenarios. First, the annual mean soil moisture by the end of the 21st century shows statistically significant large-scale drying and limited areas of wetting for all scenarios, with stronger drying as the strength of radiative forcing increases. Second, the MME mean spatial extent of severe drought is projected to increase for all regions and all future RCP scenarios, and most notably in Central America (CAM), Europe and Mediterranean (EUM), Tropical South America (TSA), and South Africa (SAF). Third, the model uncertainty presents the largest source of uncertainty (over 80%) across the entire 21st century among the three sources of uncertainty: internal variability, model uncertainty, and scenario uncertainty. Finally, we find that the spatial pattern and magnitude of annual and seasonal signal to noise (S/N) in soil moisture anomalies do not change significantly by lead time, indicating that the spreads of uncertainties become larger as the signals become stronger.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The gastrointestinal tract harbors a complex and diverse microbiota that has an important role in host metabolism. Microbial diversity is influenced by a combination of environmental and host genetic ...factors and is associated with several polygenic diseases. In this study we combined next-generation sequencing, genetic mapping, and a set of physiological traits of the BXD mouse population to explore genetic factors that explain differences in gut microbiota and its impact on metabolic traits. Molecular profiling of the gut microbiota revealed important quantitative differences in microbial composition among BXD strains. These differences in gut microbial composition are influenced by host-genetics, which is complex and involves many loci. Linkage analysis defined Quantitative Trait Loci (QTLs) restricted to a particular taxon, branch or that influenced the variation of taxa across phyla. Gene expression within the gastrointestinal tract and sequence analysis of the parental genomes in the QTL regions uncovered candidate genes with potential to alter gut immunological profiles and impact the balance between gut microbial communities. A QTL region on Chr 4 that overlaps several interferon genes modulates the population of Bacteroides, and potentially Bacteroidetes and Firmicutes-the predominant BXD gut phyla. Irak4, a signaling molecule in the Toll-like receptor pathways is a candidate for the QTL on Chr15 that modulates Rikenellaceae, whereas Tgfb3, a cytokine modulating the barrier function of the intestine and tolerance to commensal bacteria, overlaps a QTL on Chr 12 that influence Prevotellaceae. Relationships between gut microflora, morphological and metabolic traits were uncovered, some potentially a result of common genetic sources of variation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Jiaojia Fault (JJF) in the Jiaodong area of eastern China is an important NNE-trending structure that is subsidiary to the regional Tancheng–Lujiang (Tan-Lu) Fault Zone, and hosts >1200 t of gold ...reserves contained in disseminated and stockwork ore, dominantly in the footwall of the fault. We present new zircon U–Pb, apatite fission track, and illite K–Ar data along the JJF and have delineated its tectonic history focusing on its formation and reactivation. Zircon U–Pb dating shows that the Shangzhuang granite is a composite body with ages between 132 ± 1 and 127 ± 1 Ma. Illite K–Ar ages for the fault’s gouge range from 83 ± 2 to 68 ± 2 Ma, and the measured apatite fission track ages for ores are between 55 and 21 Ma. Previous zircon U–Pb geochronology and structural studies suggest that the JJF was originally activated in the Jurassic during 160–150 Ma as a sinistral fault. The JJF was a normal fault in the Early Cretaceous due to NW–SE orientated tension and NE–SW compression, which lasted from 135 to 120 Ma. This was followed by sinistral strike–slip faulting due to NW–SE compression and NE–SW tension during 120–110 Ma, and it changed to normal displacement at ca. 110 Ma. Our apatite fission track data analysis and thermal modeling of representative samples suggest that there was a subsequent dextral reactivation of the fault at ca. 55 Ma. Previous age data of ca. 130–110 Ma for gold mineralization along the JJF coincides with the Early Cretaceous magmatism and is coeval with the transition from normal faulting to sinistral strike–slip faulting of the JJF in Early Cretaceous, which is interpreted to be due to changing direction of the subducting Pacific Plate.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
The discovery of optical transverse orbital angular momentum (OAM) has broadened our understanding of light and is expected to promote optics and other physics. However, some fundamental ...questions concerning the nature of such OAM remain, particularly whether they can survive from observed mode degradation and hold OAM values higher than 1. Here, we show that the strong degradation actually origins from inappropriate time-delayed
k
x
–
ω
modulation, instead, for transverse OAM having inherent space-time coupling, immediate modulation is necessary. Thus, using immediate
x
–
ω
modulation, we demonstrate theoretically and experimentally degradation-free spatiotemporal Bessel (STB) vortices with transverse OAM even beyond 10
2
. Remarkably, we observe a time-symmetrical evolution, verifying pure time diffraction on transverse OAM beams. More importantly, we quantify such nontrivial evolution as an intrinsic dispersion factor, opening the door towards time diffraction-free STB vortices via dispersion engineering. Our results may find analogues in other physical systems, such as surface plasmon-polaritons, superfluids, and Bose-Einstein condensates.
Primary hyperoxaluria type 1 is caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. This trial tested whether an ...oligonucleotide drug can reduce the production of hepatic oxalate.
In response to the COVID-19 pandemic, there has been a rapid growth in the use of telehealth/telemedicine that will likely be sustained in the postpandemic setting. Mobile health applications (apps) ...can be used as part of the telehealth encounter to monitor patient-reported outcomes (PROs) and enhance patient-provider communication.
A systematic review was performed of mobile health apps with symptom trackers. We searched the iOS App Store and Android Google Play using the words cancer, oncology, and symptom tracker. Apps were included if they incorporated a symptom tracking function that could allow patients with cancer to record symptoms and PROs. Apps were evaluated using the mobile apps rating scale, which includes engagement, functionality, aesthetics, information, and app subjective quality.
The initial search yielded 1189 apps, with 101 apps eligible after title and description screening. A total of 41 apps met eligibility criteria and were included in this study. The majority of apps (73%, n = 30) were general health/pain symptom trackers, and 27% (n = 11) were cancer-specific. The app quality mean scores assessed using the mobile apps rating scale ranged from 2.43 to 4.23 (out of 5.00). Only 1 app has been trialed for usability among patients with cancer.
Although various symptom tracking apps are available, cancer-specific apps remain limited. Future collaboration between oncologists, app developers, and patients to optimize PRO assessment and integration with telehealth/telemedicine encounters to increase symptom recognition and enhance patient-provider communication is urgently needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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