Autoxidation Products of the Methanolic Extract of the Leaves of Combretum micranthum Exert Antiviral Activity against Tomato Brown Rugose Fruit Virus (ToBRFV)

open7noTomato brown rugose fruit virus (ToBRFV) is a new damaging plant virus of great interest from both an economical and research point of view. ToBRFV is transmitted by contact, remains infective for months, and to-date, no resistant cultivars have been developed. Due to the relevance of this virus, new effective, sustainable, and operator-safe antiviral agents are needed. Thus, 4- hydroxybenzoic acid was identified as the main product of the alkaline autoxidation at high temperature of the methanolic extract of the leaves of C. micranthum, known for antiviral activity. The autoxidized extract and 4-hydroxybenzoic acid were assayed in in vitro experiments, in combination with a mechanical inoculation test of tomato plants. Catechinic acid, a common product of rearrangement of catechins in hot alkaline solution, was also tested. Degradation of the viral particles, evidenced by the absence of detectable ToBRFV RNA and the loss of virus infectivity, as a possible consequence of disassembly of the virus coat protein (CP), were shown. Homology modeling was then applied to prepare the protein model of ToBRFV CP, and its structure was optimized. Molecular docking simulation showed the interactions of the two compounds, with the amino acid residues responsible for CP-CP interactions. Catechinic acid showed the best binding energy value in comparison with ribavirin, an anti-tobamovirus agent.openValeria Iobbi, Anna Paola Lanteri, Andrea Minuto, Valentina Santoro, Giuseppe Ferrea, Paola Fossa, Angela BisioIobbi, Valeria; Paola Lanteri, Anna; Minuto, Andrea; Santoro, Valentina; Ferrea, Giuseppe; Fossa, Paola; Bisio, Angel

Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.

Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104-106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1->8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and pathology after vaginal ZIKV transmission compared to a mosquito transmitted ZIKV

Obstructive Sleep Apnea With or Without Excessive Daytime Sleepiness: Clinical and Experimental Data-Driven Phenotyping

Introduction: Obstructive sleep apnea (OSA) is a serious and prevalent medical condition with major consequences for health and safety. Excessive daytime sleepiness (EDS) is a common\u2014but not universal\u2014accompanying symptom. The purpose of this literature analysis is to understand whether the presence/absence of EDS is associated with different physiopathologic, prognostic, and therapeutic outcomes in OSA patients. Methods: Articles in English published in PubMed, Medline, and EMBASE between January 2000 and June 2017, focusing on no-EDS OSA patients, were critically reviewed. Results: A relevant percentage of OSA patients do not complain of EDS. EDS is a significant and independent predictor of incident cardiovascular disease (CVD) and is associated with all-cause mortality and an increased risk of metabolic syndrome and diabetes. Male gender, younger age, high body mass index, are predictors of EDS. The positive effects of nasal continuous positive airway pressure (CPAP) therapy on blood pressure, insulin resistance, fatal and non-fatal CVD, and endothelial dysfunction risk factors have been demonstrated in EDS-OSA patients, but results are inconsistent in no-EDS patients. The most sustainable cause of EDS is nocturnal hypoxemia and alterations of sleep architecture, including sleep fragmentation. These changes are less evident in no-EDS patients that seem less susceptible to the cortical effects of apneas. Conclusions: There is no consensus if we should consider OSA as a single disease with different phenotypes with or without EDS, or if there are different diseases with different genetic/epigenetic determinants, pathogenic mechanisms, prognosis, and treatment.The small number of studies focused on this issue indicates the need for further research in this area. Clinicians must carefully assess the presence or absence of EDS and decide accordingly the treatment. This approach could improve combination therapy targeted to a patient\u2019s specific pathology to enhance both efficacy and long-term adherence to OSA treatment and significantly reduce the social, economic, and health negative impact of OSA

Single Primer Enrichment Technology (SPET) for High-Throughput Genotyping in Tomato and Eggplant Germplasm

[EN] Single primer enrichment technology (SPET) is a new, robust, and customizable solution for targeted genotyping. Unlike genotyping by sequencing (GBS), and like DNA chips, SPET is a targeted genotyping technology, relying on the sequencing of a region flanking a primer. Its reliance on single primers, rather than on primer pairs, greatly simplifies panel design, and allows higher levels of multiplexing than PCR-based genotyping. Thanks to the sequencing of the regions surrounding the target SNP, SPET allows the discovery of thousands of closely linked, novel SNPs. In order to assess the potential of SPET for high-throughput genotyping in plants, a panel comprising 5k target SNPs, designed both on coding regions and introns/UTRs, was developed for tomato and eggplant. Genotyping of two panels composed of 400 tomato and 422 eggplant accessions, comprising both domesticated material and wild relatives, generated a total of 12,002 and 30,731 high confidence SNPs, respectively, which comprised both target and novel SNPs in an approximate ratio of 1:1.6, and 1:5.5 in tomato and eggplant, respectively. The vast majority of the markers was transferrable to related species that diverged up to 3.4 million years ago (Solanum pennellii for tomato and S. macrocarpon for eggplant). Maximum Likelihood phylogenetic trees and PCA outputs obtained from the whole dataset highlighted genetic relationships among accessions and species which were congruent with what was previously reported in literature. Better discrimination among domesticated accessions was achieved by using the target SNPs, while better discrimination among wild species was achieved using the whole SNP dataset. Our results reveal that SPET genotyping is a robust, high-throughput technology for genetic fingerprinting, with a high degree of cross-transferability between crops and their cultivated and wild relatives, and allows identification of duplicates and mislabeled accessions in genebanks.This work has been funded by the European Union's Horizon 2020 Research and Innovation Programme under the grant agreement number 677379 (G2P-SOL project: Linking genetic resources, genomes, and phenotypes of solanaceous crops).Barchi, L.; Acquadro, A.; Alonso-Martín, D.; Aprea, G.; Bassolino, L.; Demurtas, O.; Ferrante, P.... (2019). Single Primer Enrichment Technology (SPET) for High-Throughput Genotyping in Tomato and Eggplant Germplasm. Frontiers in Plant Science. 10:1-17. https://doi.org/10.3389/fpls.2019.01005S11710Acquadro, A., Barchi, L., Gramazio, P., Portis, E., Vilanova, S., Comino, C., … Lanteri, S. (2017). 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Does observance of Ramadan affect sleep in athletes and physically active individuals? A systematic review and meta-analysis

This article presents a systematic review and meta-analysis is to provide an accurate description of the effect of Ramadan observance on sleep duration, sleep quality, daily nap duration, and daytime sleepiness in athletes and physically active individuals

Distal motor neuropathy associated with novel EMILIN1 mutation

Abstract Elastin microfibril interface-located proteins (EMILINs) are extracellular matrix glycoproteins implicated in elastogenesis and cell proliferation. Recently, a missense mutation in the EMILIN1 gene has been associated with autosomal dominant connective tissue disorder and motor-sensory neuropathy in a single family. We identified by whole exome sequencing a novel heterozygous EMILIN1 mutation c.748C>T [p.R250C] located in the coiled coil forming region of the protein, in four affected members of an autosomal dominant family presenting a distal motor neuropathy phenotype. In affected patient a sensory nerve biopsy showed slight and unspecific changes in the number and morphology of myelinated fibers. Immunofluorescence study of a motor nerve within a muscle biopsy documented the presence of EMILIN-1 in nerve structures. Skin section and skin derived fibroblasts displayed a reduced extracellular deposition of EMILIN-1 protein with a disorganized network of poorly ramified fibers in comparison with controls. Downregulation of emilin1a in zebrafish displayed developmental delay, locomotion defects, and abnormal axonal arborization from spinal cord motor neurons. The phenotype was complemented by wild-type zebrafish emilin1a, and partially the human wild-type EMILIN1 cRNA, but not by the cRNA harboring the novel c.748C>T [p.R250C]. These data suggest a role of EMILIN-1 in the pathogenesis of diseases affecting the peripheral nervous system

Digitatio and Scientific Exploitation of the Italian and Vatican Astronomical Plate Archives

There is a widespread interest to digitize the precious information contained in the astronomical plate archives, both for the preservation of their content and for its fast distribution to all interested researchers in order to achieve their better scientific exploitation. This paper presents the first results of our large-scale project to digitize the archive of plates of the Italian Astronomical Observatories and of the Specola Vaticana. Similar systems, composed by commercial flat-bed retro-illuminated scanners plus dedicated personal computers and acquisition and analysis software, have been installed in all participating Institutes. Ad-hoc codes have been developed to acquire the data, to test the suitability of the machines to our scientific needs, and to reduce the digital data in order to extract the astrometric, photometric and spectroscopic content. Two more elements complete the overall project: the provision of high quality BVRI CCD sequences in selected fields with the Campo Imperatore telescopes, and the distribution of the digitized information to all interested researchers via the Web. The methods we have derived in the course of this project have been already applied successfully to plates taken by other Observatories, for instance at Byurakan and at Hamburg.Comment: To appear in Experimental Astronom

Multifrequency monitoring of the blazar 0716+714 during the GASP-WEBT-AGILE campaign of 2007

Since the CGRO operation in 1991-2000, one of the primary unresolved questions about the blazar gamma-ray emission has been its possible correlation with the low-energy (in particular optical) emission. To help answer this problem, the Whole Earth Blazar Telescope (WEBT) consortium has organized the GLAST-AGILE Support Program (GASP) to provide the optical-to-radio monitoring data to be compared with the gamma-ray detections by the AGILE and GLAST satellites. This new WEBT project started in early September 2007, just before a strong gamma-ray detection of 0716+714 by AGILE. We present the GASP-WEBT optical and radio light curves of this blazar obtained in July-November 2007, about various AGILE pointings at the source. We construct NIR-to-UV spectral energy distributions (SEDs), by assembling GASP-WEBT data together with UV data from the Swift ToO observations of late October. We observe a contemporaneous optical-radio outburst, which is a rare and interesting phenomenon in blazars. The shape of the SEDs during the outburst appears peculiarly wavy because of an optical excess and a UV drop-and-rise. The optical light curve is well sampled during the AGILE pointings, showing prominent and sharp flares. A future cross-correlation analysis of the optical and AGILE data will shed light on the expected relationship between these flares and the gamma-ray events.Comment: 5 pages, 5 figures, to be published in A&A (Letters); revised to match the final version (changes in Fig. 5 and related text

Radio-to-UV monitoring of AO 0235+164 by the WEBT and Swift during the 2006--2007 outburst

The blazar AO 0235+164 was claimed to show a quasi-periodic behaviour in the radio and optical bands. Moreover, an extra emission component contributing to the UV and soft X-ray flux was detected, whose nature is not yet clear. A predicted optical outburst was observed in late 2006/early 2007. We here present the radio-to-optical WEBT light curves during the outburst, together with UV data acquired by Swift in the same period. We found the optical outburst to be as strong as the big outbursts of the past: starting from late September 2006, a brightness increase of 5 mag led to the outburst peak in February 19-21, 2007. We also observed an outburst at mm and then at cm wavelengths, with an increasing time delay going toward lower frequencies during the rising phase. Cross-correlation analysis indicates that the 1 mm and 37 GHz flux variations lagged behind the R-band ones by about 3 weeks and 2 months, respectively. These short time delays suggest that the corresponding jet emitting regions are only slightly separated and/or misaligned. In contrast, during the outburst decreasing phase the flux faded contemporaneously at all cm wavelengths. This abrupt change in the emission behaviour may suggest the presence of some shutdown mechanism of intrinsic or geometric nature. The behaviour of the UV flux closely follows the optical and near-IR one. By separating the synchrotron and extra component contributions to the UV flux, we found that they correlate, which suggests that the two emissions have a common origin.Comment: 9 pages, 7 figures, in press for Astronomy and Astrophysic

The correlated optical and radio variability of BL Lacertae. WEBT data analysis 1994-2005

Since 1997, BL Lacertae has undergone a phase of high optical activity, with the occurrence of several prominent outbursts. Starting from 1999, the Whole Earth Blazar Telescope (WEBT) consortium has organized various multifrequency campaigns on this blazar, collecting tens of thousands of data points. One of the main issues in the study of this huge dataset has been the search for correlations between the optical and radio flux variations, and for possible periodicities in the light curves. The analysis of the data assembled during the first four campaigns (comprising also archival data to cover the period 1968-2003) revealed a fair optical-radio correlation in 1994-2003, with a delay of the hard radio events of ~100 days. Moreover, various statistical methods suggested the existence of a radio periodicity of ~8 years. In 2004 the WEBT started a new campaign to extend the dataset to the most recent observing seasons, in order to possibly confirm and better understand the previous results. In this campaign we have collected and assembled about 11000 new optical observations from twenty telescopes, plus near-IR and radio data at various frequencies. Here, we perform a correlation analysis on the long-term R-band and radio light curves. In general, we confirm the ~100-day delay of the hard radio events with respect to the optical ones, even if longer (~200-300 days) time lags are also found in particular periods. The radio quasi-periodicity is confirmed too, but the "period" seems to progressively lengthen from 7.4 to 9.3 years in the last three cycles. The optical and radio behaviour in the last forty years suggests a scenario where geometric effects play a major role. In particular, the alternation of enhanced and suppressed optical activity (accompanied by hard and soft radio events, respectively) canComment: 6 pages, 4 figure