The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as ...several 2c CoVs have been described from various species in the family
Here, we describe a MERS-like CoV identified from a
bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.
Global surveillance efforts for undiscovered viruses are an important component of pandemic prevention initiatives. These surveys can be useful for finding novel viruses and for gaining insights into the ecological and evolutionary factors driving viral diversity; however, finding a viral sequence is not sufficient to determine whether it can infect people (i.e., poses a zoonotic threat). Here, we investigated the specific zoonotic risk of a MERS-like coronavirus (PREDICT/PDF-2180) identified in a bat from Uganda and showed that, despite being closely related to MERS-CoV, it is unlikely to pose a threat to humans. We suggest that this approach constitutes an appropriate strategy for beginning to determine the zoonotic potential of wildlife viruses. By showing that PREDICT/PDF-2180 does not infect cells that express the functional receptor for MERS-CoV, we further show that recombination was likely to be the critical step that allowed MERS to emerge in humans.
Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic ...and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of “Oncofertility Around the Globe” to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.
Previous efforts to report estimates of cancer incidence and mortality in India and its different parts include the National Cancer Registry Programme Reports, Sample Registration System cause of ...death findings, Cancer Incidence in Five Continents Series, and GLOBOCAN. We present a comprehensive picture of the patterns and time trends of the burden of total cancer and specific cancer types in each state of India estimated as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 because such a systematic compilation is not readily available.
We used all accessible data from multiple sources, including 42 population-based cancer registries and the nationwide Sample Registration System of India, to estimate the incidence of 28 types of cancer in every state of India from 1990 to 2016 and the deaths and disability-adjusted life-years (DALYs) caused by them, as part of GBD 2016. We present incidence, DALYs, and death rates for all cancers together, and the trends of all types of cancers, highlighting the heterogeneity in the burden of specific types of cancers across the states of India. We also present the contribution of major risk factors to cancer DALYs in India.
8·3% (95% uncertainty interval UI 7·9–8·6) of the total deaths and 5·0% (4·6–5·5) of the total DALYs in India in 2016 were due to cancer, which was double the contribution of cancer in 1990. However, the age-standardised incidence rate of cancer did not change substantially during this period. The age-standardised cancer DALY rate had a 2·6 times variation across the states of India in 2016. The ten cancers responsible for the highest proportion of cancer DALYs in India in 2016 were stomach (9·0% of the total cancer DALYs), breast (8·2%), lung (7·5%), lip and oral cavity (7·2%), pharynx other than nasopharynx (6·8%), colon and rectum (5·8%), leukaemia (5·2%), cervical (5·2%), oesophageal (4·3%), and brain and nervous system (3·5%) cancer. Among these cancers, the age-standardised incidence rate of breast cancer increased significantly by 40·7% (95% UI 7·0–85·6) from 1990 to 2016, whereas it decreased for stomach (39·7%; 34·3–44·0), lip and oral cavity (6·4%; 0·4–18·6), cervical (39·7%; 26·5–57·3), and oesophageal cancer (31·2%; 27·9–34·9), and leukaemia (16·1%; 4·3–24·2). We found substantial inter-state heterogeneity in the age-standardised incidence rate of the different types of cancers in 2016, with a 3·3 times to 11·6 times variation for the four most frequent cancers (lip and oral, breast, lung, and stomach). Tobacco use was the leading risk factor for cancers in India to which the highest proportion (10·9%) of cancer DALYs could be attributed in 2016.
The substantial heterogeneity in the state-level incidence rate and health loss trends of the different types of cancer in India over this 26-year period should be taken into account to strengthen infrastructure and human resources for cancer prevention and control at both the national and state levels. These efforts should focus on the ten cancers contributing the highest DALYs in India, including cancers of the stomach, lung, pharynx other than nasopharynx, colon and rectum, leukaemia, oesophageal, and brain and nervous system, in addition to breast, lip and oral cavity, and cervical cancer, which are currently the focus of screening and early detection programmes.
Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.
Highlights • Adult rat CNS endothelial cells express functional TLR4. • The opioid receptor-inactive morphine metabolite M3G activates TLR4-dependent inflammatory signaling in endothelial cells. • ...Nalmefene is a mu opioid receptor antagonist without TLR4 activity, whereas CTAP is an antagonist at both receptors. • Stimulation of endothelial cells by M3G induces in vivo responses of decreased mechanical thresholds and vasodilation. • The putative glial inhibitors AV1013 and propentofylline also inhibit the inflammatory response of endothelial cells.
This phase III randomized study compared concurrent cisplatin–radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 ...patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m2 weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval CI = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio HR = 0.71 95% CI = 0.5 to 1.0). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 95% CI = 0.59 to 1.4), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 95% CI = 0.3 to 0.88), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.
When combined with infrared observations with the Spitzer telescope (3 to 160 μm), the Herschel
Space Observatory now fully samples the thermal dust emission up to 500 μm and enables us to better ...estimate the total infrared-submm energy budget (L
TIR) of nearby galaxies. We present new empirical calibrations to estimate resolved and integrated total infrared luminosities from Spitzer and Herschel bands used as monochromatic or combined tracers. We base our calibrations on resolved elements of nearby galaxies (3 to 30 Mpc) observed with Herschel. We perform a resolved spectral energy distribution (SED) modelling of these objects using the Draine & Li dust models and investigate the influence of the addition of Spectral and Photometric Imaging Receiver (SPIRE) measurements in the estimation of L
TIR. We find that using data up to 250 μm leads to local L
TIR values consistent with those obtained with a complete coverage (up to 500 μm) within ±10 per cent for most of our resolved elements. We then study the distribution of energy in the resolved SEDs of our galaxies. The bulk of energy (30-50 per cent) is contained in the 70-160 μm band. The 24-70 μm fraction decreases with increasing metallicity. The 160-1100 μmsubmillimetre band can account for up to 25 per cent of the L
TIR in metal-rich galaxies. We investigate the correlation between the total infrared (TIR) surface brightnesses/luminosities and monochromatic Spitzer and Herschel surface brightnesses/luminosities. The three Photodetector Array Camera and Spectrometer (PACS) bands can be used as reliable monochromatic estimators of the L
TIR, the 100 μm band being the most reliable monochromatic tracer. There is also a strong correlation between the SPIRE 250 μm and L
TIR, although with more scatter than for the PACS relations. We also study the ability of our monochromatic relations to reproduce integrated L
TIR of nearby galaxies as well as L
TIR of z ∼ 1-3 sources. Finally, we provide calibration coefficients that can be used to derive TIR surface brightnesses/luminosities from a combination of Spitzer and Herschel surface brightnesses/fluxes and analyse the associated uncertainties.
Abstract
In cuprate superconductors, the doping of carriers into the parent Mott insulator induces superconductivity and various other phases whose characteristic temperatures are typically plotted ...versus the doping level
p
. In most materials,
p
cannot be determined from the chemical composition, but it is derived from the superconducting transition temperature,
T
c
, using the assumption that the
T
c
dependence on doping is universal. Here, we present angle-resolved photoemission studies of Bi
2
Sr
2
CaCu
2
O
8+
δ
, cleaved and annealed in vacuum or in ozone to reduce or increase the doping from the initial value corresponding to
T
c
= 91 K. We show that
p
can be determined from the underlying Fermi surfaces and that in-situ annealing allows mapping of a wide doping regime, covering the superconducting dome and the non-superconducting phase on the overdoped side. Our results show a surprisingly smooth dependence of the inferred Fermi surface with doping. In the highly overdoped regime, the superconducting gap approaches the value of 2Δ
0
= (4 ± 1)
k
B
T
c
A pronounced, widespread and persistent regime shift among marine ecosystems is observable on temperate rocky reefs as a result of sea urchin overgrazing. Here, we empirically define regime-shift ...dynamics for this grazing system which transitions between productive macroalgal beds and impoverished urchin barrens. Catastrophic in nature, urchin overgrazing in a well-studied Australian system demonstrates a discontinuous regime shift, which is of particular management concern as recovery of desirable macroalgal beds requires reducing grazers to well below the initial threshold of overgrazing. Generality of this regime-shift dynamic is explored across 13 rocky reef systems (spanning 11 different regions from both hemispheres) by compiling available survey data (totalling 10 901 quadrats surveyed in situ) plus experimental regime-shift responses (observed during a total of 57 in situ manipulations). The emergent and globally coherent pattern shows urchin grazing to cause a discontinuous 'catastrophic' regime shift, with hysteresis effect of approximately one order of magnitude in urchin biomass between critical thresholds of overgrazing and recovery. Different life-history traits appear to create asymmetry in the pace of overgrazing versus recovery. Once shifted, strong feedback mechanisms provide resilience for each alternative state thus defining the catastrophic nature of this regime shift. Importantly, human-derived stressors can act to erode resilience of desirable macroalgal beds while strengthening resilience of urchin barrens, thus exacerbating the risk, spatial extent and irreversibility of an unwanted regime shift for marine ecosystems.
ABSTRACT
The use of acoustic Doppler current profilers (ADCP) for discharge measurements and three‐dimensional flow mapping has increased rapidly in recent years and has been primarily driven by ...advances in acoustic technology and signal processing. Recent research has developed a variety of methods for processing data obtained from a range of ADCP deployments and this paper builds on this progress by describing new software for processing and visualizing ADCP data collected along transects in rivers or other bodies of water. The new utility, the Velocity Mapping Toolbox (VMT), allows rapid processing (vector rotation, projection, averaging and smoothing), visualization (planform and cross‐section vector and contouring), and analysis of a range of ADCP‐derived datasets. The paper documents the data processing routines in the toolbox and presents a set of diverse examples that demonstrate its capabilities. The toolbox is applicable to the analysis of ADCP data collected in a wide range of aquatic environments and is made available as open‐source code along with this publication. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
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