Although the balance of recent evidence supports the efficacy of antiretroviral (ARV)-based pre-exposure prophylaxis (PrEP) against HIV-1 infection, recent negative trial results are perplexing. Of ...seven trials with available HIV endpoints, three different products have been tested: tenofovir 1% vaginal gel, oral tenofovir disoproxil fumarate (TDF) tablets, and TDF/emtricitabine tablets. Six of these trials were conducted exclusively in sub-Saharan Africa; all found the products to be well tolerated, and four demonstrated effectiveness. Furthermore, the HIV Prevention Trial Network (HPTN) 052 trial recently confirmed that antiretroviral treatment leads to 96% reduction in transmission to HIV-negative partners in HIV-serodiscordant couples. These results, along with human and animal data, provide substantial evidence for the efficacy of antiretroviral-based HIV prevention. Yet assessment of oral TDF/emtricitabine in the FEM-PrEP study and of oral and vaginal tenofovir in the Microbicide Trial Network (MTN)-003 trial (VOICE) was stopped for futility. How do we make sense of these discrepant results? We believe that adherence is a key factor, although it cannot be the only factor. Expanding upon a recent editorial in the Lancet, we discuss the impact of suboptimal product adherence on PrEP efficacy in the context of variable drug concentration at the exposure site, integrity of the vaginal epithelium, and the role of acute infection.
In this interim phase 1–2a trial of an adenovirus-based vaccine (Ad26.COV2.S), participants were divided into two age groups and received one or two injections of either a low-dose or high-dose ...vaccine or placebo. The vaccine elicited a local injection response in most patients and high titers of neutralizing antibodies in all vaccinated groups. In addition, T-cell responses were noted.
ABSTRACT
EBLM J0113+31 is a moderately bright (V = 10.1), metal-poor (Fe/H ≈−0.3) G0V star with a much fainter M dwarf companion on a wide, eccentric orbit (= 14.3 d). We have used near-infrared ...spectroscopy obtained with the SPIRou spectrograph to measure the semi-amplitude of the M dwarf’s spectroscopic orbit, and high-precision photometry of the eclipse and transit from the CHEOPS and TESS space missions to measure the geometry of this binary system. From the combined analysis of these data together with previously published observations, we obtain the following model-independent masses and radii: M1 = 1.029 ± 0.025 M⊙, M2 = 0.197 ± 0.003 M⊙, R1 = 1.417 ± 0.014 R⊙, R2 = 0.215 ± 0.002 R⊙. Using R1 and the parallax from Gaia EDR3 we find that this star’s angular diameter is θ = 0.0745 ± 0.0007 mas. The apparent bolometric flux of the G0V star corrected for both extinction and the contribution from the M dwarf (<0.2 per cent) is ${\mathcal {F}}_{\oplus ,0} = (2.62\pm 0.05)\times 10^{-9}$ erg cm−2 s−1. Hence, this G0V star has an effective temperature $T_{\rm eff,1} = 6124{\rm \, K} \pm 40{\rm \, K\, (rnd.)} \pm 10 {\rm \, K\, (sys.)}$. EBLM J0113+31 is an ideal benchmark star that can be used for ‘end-to-end’ tests of the stellar parameters measured by large-scale spectroscopic surveys, or stellar parameters derived from asteroseismology with PLATO. The techniques developed here can be applied to many other eclipsing binaries in order to create a network of such benchmark stars.
The family of EUL-related lectins groups all proteins with an Euonymus lectin (EUL) domain, a protein motif which is highly conserved throughout the plant kingdom and occurs as part of many chimeric ...proteins with different domain architectures. The S3 type EUL lectin from Arabidopsis thaliana (ArathEULS3) has become the model protein within this EUL family. Based on sequence homology to an ABA/NaCl inducible gene from rice and some publicly available high-throughput micro-array data, it was hypothesized that ArathEULS3 is transcriptionally regulated by osmotic stress responses. Here we present a detailed expression analysis of the ArathEULS3 lectin gene. Under normal growth conditions, ArathEULS3 is stably expressed throughout plant development. After ABA, NaCl and methyl jasmonate (MeJA) treatments transcription is upregulated. Furthermore, in silico promoter and co-expression analyses suggested the A. thaliana Homeobox 7 (ATHB-7) as a candidate transcription factor that may regulate ArathEULS3 expression. Taken together, our data confirm that the ArathEULS3 lectin gene indeed shows a stress-inducible expression pattern. We speculate on a role for ArathEULS3 in the plant stress response.
Decreased cancer specific survival in older colorectal patients is mainly due to mortality in the first year, emphasizing the importance of the first postoperative year. This study aims to gain an ...overview and time trends of short-term mortality in octogenarians (≥80 years) with colorectal cancer across four North European countries.
Patients of 80 years or older, operated for colorectal cancer (stage I-III) between 2005 and 2014, were included. Population-based cohorts from Belgium, Denmark, the Netherlands, and Sweden were collected. Separately for colon- and rectal cancer, 30-day, 90-day, one-year, and excess one-year mortality were calculated. Also, short-term mortality over three time periods (2005–2008, 2009–2011, 2012–2014) was analyzed.
In total, 35,158 colon cancer patients and 10,144 rectal cancer patients were included. For colon cancer, 90-day mortality rate was highest in Denmark (15%) and lowest in Sweden (8%). For rectal cancer, 90-day mortality rate was highest in Belgium (11%) and lowest in Sweden (7%). One-year excess mortality rate of colon cancer patients decreased from 2005 to 2008 to 2012–2014 for all countries (Belgium: 17%–11%, Denmark: 21%–15%, the Netherlands: 18%–10%, and Sweden: 10%–8%). For rectal cancer, from 2005 to 2008 to 2012–2014 one-year excess mortality rate decreased in the Netherlands from 16% to 7% and Sweden: 8%–2%).
Short-term mortality rates were high in octogenarians operated for colorectal cancer. Short-term mortality rates differ across four North European countries, but decreased over time for both colon and rectal cancer patients in all countries.
Coronaviruses are important human and animal pathogens, the relevance of which increased due to the emergence of new human coronaviruses like SARS-CoV, HKU1 and NL63. Together with toroviruses, ...arteriviruses, and roniviruses the coronaviruses belong to the order
Nidovirales. So far antivirals are hardly available to combat infections with viruses of this order. Therefore, various antiviral strategies to counter nidoviral infections are under evaluation. Lectins, which bind to N-linked oligosaccharide elements of enveloped viruses, can be considered as a conceptionally new class of virus inhibitors. These agents were recently evaluated for their antiviral activity towards a variety of enveloped viruses and were shown in most cases to inhibit virus infection at low concentrations. However, limited knowledge is available for their efficacy towards nidoviruses. In this article the application of the plant lectins
Hippeastrum hybrid agglutinin (HHA),
Galanthus nivalis agglutinin (GNA),
Cymbidium sp. agglutinin (CA) and
Urtica dioica agglutinin (UDA) as well as non-plant derived pradimicin-A (PRM-A) and cyanovirin-N (CV-N) as potential antiviral agents was evaluated. Three antiviral tests were compared based on different evaluation principles: cell viability (MTT-based colorimetric assay), number of infected cells (immunoperoxidase assay) and amount of viral protein expression (luciferase-based assay). The presence of carbohydrate-binding agents strongly inhibited coronaviruses (transmissible gastroenteritis virus, infectious bronchitis virus, feline coronaviruses serotypes I and II, mouse hepatitis virus), arteriviruses (equine arteritis virus and porcine respiratory and reproductive syndrome virus) and torovirus (equine Berne virus). Remarkably, serotype II feline coronaviruses and arteriviruses were not inhibited by PRM-A, in contrast to the other viruses tested.
•Detection and quantification of pospiviroids in Myzus persicae aphids were achieved by means of RT-qPCR with a detection limit of 1.69×106 viroid copies per aphid.•Localization of Tomato apical ...stunt viroid (TASVd) in the stylet and foregut of feeding M. persicae aphids was accomplished by fluorescence in situ hybridization and confocal laser scanning microscopy.•The incidence of viroids in M. persicae aphids after 24h of feeding on infected plants was 29%.
In this paper, the potential role of aphids in viroid transmission was explored. Apterous aphids were fed on pospiviroid-infected plants and viroid targets in the aphids were consequently quantified through RT-qPCR and localized within the aphid body using fluorescence in situ hybridization (FISH). Based on the analytical sensitivity test, the limit of detection (LOD) was estimated at 1.69×106 viroid copies per individual aphid body. To localize the viroids in the aphids, a pospiviroid-generic Cy5-labelled probe was used and the fluorescent signal was determined by confocal microscopy. Viroids were clearly observed in the aphid's stylet and stomach, but not in the embryos. Viroids were detected in 29% of the aphids after a 24h feeding period, which suggests only a partial and low concentration viroid uptake by the aphid population including viroid concentrations under the LOD. However, these results show that viroids can be ingested by aphids while feeding on infected plants, thus potentially increasing the transmission risk. The combination of FISH and RT-qPCR provides reliable and fast localization and quantitation of viroid targets in individual aphids and thus constitutes a valuable tool in future epidemiological research.
The effects of the Rhizoctonia solani lectin (RSA) on the growth, development and survival of an economically important caterpillar in agriculture and horticulture, the cotton leafworm, Spodoptera ...littoralis were studied. The high lectin concentration present in the sclerotes of the soil pathogen R. solani allowed the purification of large amounts of the pure lectin for feeding experiments with cotton leafworm. Rearing of insects on a diet containing different concentrations of RSA exerted a strong effect on the larval weight gain. This effect was visible at the lowest concentration of 0.1 % RSA at day 8 and day 11. Interestingly with 1 % RSA, there was a dramatic reduction in larval weight of 89 % at the end of L6 which was followed by a high mortality rate of 82 % in the treated larvae. Furthermore, the other developmental stages of pupation and adult formation were also affected. In addition, the data demonstrated that the combination of RSA with Bt toxin yielded synergistic effects. For instance, 0.03 % RSA+0.005 % Bt toxin caused reduced growth rate and higher mortalities. These findings suggest that RSA is an interesting tool that can be used for bioengineering insect resistance in important agronomical crops.
In the last two decades plants have emerged as valuable alternatives to mammalian cells for the production of pharmaceuticals and their potential as expression systems was shown by the commercial ...availability and acceptance of several plant made therapeuticals in clinical trials. Plants have many advantages over yeast, insect and bacterial expression systems such as the potential to properly fold the expressed proteins and the synthesis of more human-like N-glycans on the proteins. However, several constraints, such as expression yields, downstream processing and structural authenticity, currently limit the widespread use of plant expression systems. In this review, the focus is on the current limitations of plant systems for the production of pharmaceuticals and the possibilities to overcome these obstacles. A comparison is made with insect cell and yeast expression systems. Furthermore, the importance of glycosylation, in particular N-glycosylation for the biological function(s) of therapeutics in the human body will be discussed in detail and an overview of the state of art in the humanization of the N-glycosylation pathway in plants is provided.
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