Geminiviruses are single-stranded DNA plant viruses with circular genomes packaged within geminate particles. Among the
family,
and
comprise the two best characterized genera. Curtovirus and Old ...World begomovirus possess similar genome structures with six to seven open-reading frames (ORF). Among them, begomovirus and curtovirus V2 ORFs share the same location in the viral genome, encode proteins of similar size, but show extremely poor sequence homology between the genera. V2 from
(BCTV), the model species for the
genus, as it begomoviral counterpart, suppresses post-transcriptional gene silencing (PTGS) by impairing the RDR6/SGS3 pathway and localizes in the nucleus spanning from the perinuclear region to the cell periphery. By aminoacid sequence comparison we have identified that curtoviral and begomoviral V2 proteins shared two hydrophobic domains and a putative phosphorylation motif. These three domains are essential for BCTV V2 silencing suppression activity, for the proper nuclear localization of the protein and for systemic infection. The lack of suppression activity in the mutated versions of V2 is complemented by the impaired function of RDR6 in
but the ability of the viral mutants to produce a systemic infection is not recovered in gene silencing mutant backgrounds. We have also demonstrated that, as its begomoviral homolog, V2 from BCTV is able to induce systemic symptoms and necrosis associated with a hypersensitive response-like (HR-like) when expressed from Potato virus X vector in
, and that this pathogenicity activity does not dependent of its ability to supress PTGS.
The suppression of gene silencing is a key mechanism for the success of viral infection in plants. DNA viruses from the Geminiviridae family encode several proteins that suppress transcriptional and ...post-transcriptional gene silencing (TGS/PTGS). In Begomovirus, the most abundant genus of this family, three out of six genome-encoded proteins, namely C2, C4 and V2, have been shown to suppress PTGS, with V2 being the strongest PTGS suppressor in transient assays. Beet curly top virus (BCTV), the model species for the Curtovirus genus, is able to infect the widest range of plants among geminiviruses. In this genus, only one protein, C2/L2, has been described as inhibiting PTGS. We show here that, despite the lack of sequence homology with its begomoviral counterpart, BCTV V2 acts as a potent PTGS suppressor, possibly by impairing the RDR6 (RNA-dependent RNA polymerase 6)/suppressor of gene silencing 3 (SGS3) pathway.
We study the Laplacian spectrum of token graphs, also called symmetric powers of graphs. The k-token graph Fk(G) of a graph G is the graph whose vertices are the k-subsets of vertices from G, two of ...which being adjacent whenever their symmetric difference is a pair of adjacent vertices in G. In this paper, we give a relationship between the Laplacian spectra of any two token graphs of a given graph. In particular, we show that, for any integers h and k such that 1≤h≤k≤n2, the Laplacian spectrum of Fh(G) is contained in the Laplacian spectrum of Fk(G). We also show that the doubled odd graphs and doubled Johnson graphs can be obtained as token graphs of the complete graph Kn and the star Sn=K1,n−1, respectively. Besides, we obtain a relationship between the spectra of the k-token graph of G and the k-token graph of its complement G‾. This generalizes to tokens graphs a well-known property stating that the Laplacian eigenvalues of G are closely related to the Laplacian eigenvalues of G‾. Finally, the doubled odd graphs and doubled Johnson graphs provide two infinite families, together with some others, in which the algebraic connectivities of the original graph and its token graph coincide. Moreover, we conjecture that this is the case for any graph G and its token graph.
The methodology termed scanning transmission electron microscopy in scanning electron microscopy (STEM-in-SEM) has been used in this work to study the uptake of citrate stabilized gold nanoparticles ...(AuNPs) (average particle sizes of 23.5 ± 4.0 nm) into tissue samples upon in vitro exposure of the dissected gills of the Ruditapes philippinarum marine bivalve to the nanoparticle suspensions. The STEM-in-SEM methodology has been optimized for achieving optimum resolution under SEM low voltage operating conditions (20-30 kV). Based on scanning microscope assessments and resolution testing (SMART), resolutions well below 10 nm were appropriately achieved by working at magnifications over 100k×, with experimental sample thickness between 300 and 200 nm. These relatively thick slices appear to be stable under the beam and help avoid NP displacement during cutting. We herein show that both localizing of the internalized nanoparticles and imaging of ultrastructural disturbances in gill tissues are strongly accessible due to the improved resolution, even at sample thicknesses higher than those normally employed in standard TEM techniques at higher voltages. Ultrastructural imaging of bio-nano features in bioaccumulation experiments have been demonstrated in this study.
Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and ...changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain.
Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC.
The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, ...and HIV-1. In sharp contrast, the compound had no effect on the infection of nonenveloped viruses. In vitro and in vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited viral entry at a step after virus binding but before virus-cell fusion. LJ001 pretreatment also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure-activity relationship analyses of LJ001, a rhodanine derivative, implicated both the polar and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically inhibited virus-cell but not cell-cell fusion, and further studies with lipid biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes with reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals effective against enveloped viruses that target the viral lipid membrane and compromises its ability to mediate virus-cell fusion.
We compare broad emission-line profiles and estimate line ratios for all major emission lines between Lyα and Hβ in a sample of six quasars. The sources were chosen with two criteria in mind: the ...existence of high-quality optical and ultraviolet spectra and the possibility of sampling the spectroscopic diversity in the 4D eigenvector 1 (4DE1) context. In the latter sense, each source occupies a region (bin) in the full width at half-maximum (FWHM)(Hβ) versus Fe iiopt strength plane that is significantly different from the others. High signal-to-noise ratio Hβ emission-line profiles are used as templates for modelling the other lines (Lyα, C ivλ1549, He iiλ1640, Al iiiλ1860, Si iiiλ1892 and Mg iiλ2800). We can adequately model all broad lines assuming the existence of three components distinguished by blueshifted, unshifted and redshifted centroids indicated as a blue component (BLUE), broad component (BC) and very broad component (VBC), respectively. BC (electron density ne∼ 1012 cm−3, ionization parameter U∼ 10−2 and column density Nc≳ 1023 cm−2) is present in almost all type-1 quasars and therefore corresponds most closely to the classical broad-line emitting region (the reverberating component). The bulk of Mg iiλ2800 and Fe ii emission also arises in this region. The BLUE emission (log ne∼ 10, log U∼−1 and log Nc < 23) arises in less optically thick gas; it is often thought to arise in an accretion disc wind. The least understood component involves the VBC (high ionization and large column density), which is found in no more than half (but almost all radio-loud) type-1 quasars and luminous Seyfert nuclei. It is perhaps the most distinguishing characteristic of quasars with FWHM (Hβ) ≳ 4000 km s−1 that belong to the so-called population B of our 4DE1 space. Population A quasars FWHM (Hβ) ≲ 4000 km s−1 are dominated by BC emission in Hβ and BLUE component emission in C ivλ1549 and other high ionization lines. 4DE1 appears to be the most useful current context for revealing and unifying spectral diversity in type-1 quasars.
Antiviral compounds targeting viral replicative processes have been studied as an alternative for the control of begomoviruses. Previously, we have reported that the peptide AmPep1 has strong ...affinity binding to the replication origin sequence of tomato yellow leaf curl virus (TYLCV). In this study, we describe the mechanism of action of this peptide as a novel alternative for control of plant-infecting DNA viruses. When AmPep1 was applied exogenously to tomato and Nicotiana benthamiana plants infected with TYLCV, a decrease in the synthesis of the two viral DNA strands (CS and VS) was observed, with a consequent delay in the development of disease progress in treated plants. The chemical mechanism of action of AmPep1 was deduced using Raman spectroscopy and molecular modeling showing the formation of chemical interactions such as H bonds and electrostatic interactions and the formation of π–π interactions between both biomolecules contributing to tampering with the viral replication.
EphrinB2 was recently discovered as a functional receptor for Nipah virus (NiV), a lethal emerging paramyxovirus. Ephrins constitute a class of homologous ligands for the Eph class of receptor ...tyrosine kinases and exhibit overlapping expression patterns. Thus, we examined whether other ephrins might serve as alternative receptors for NiV. Here, we show that of all known ephrins (ephrinA1-A5 and ephrinB1-B3), only the soluble Fc-fusion proteins of ephrinB3, in addition to ephrinB2, bound to soluble NiV attachment protein G (NiV-G). Soluble NiV-G bound to cell surface ephrinB3 and B2 with subnanomolar affinities (Kd = 0.58 nM and 0.06 nM for ephrinB3 and B2, respectively). Surface plasmon resonance analysis indicated that the relatively lower affinity of NiV-G for ephrinB3 was largely due to a faster off-rate (K(off) = 1.94 x 10(-3) s(-1) versus 1.06 x 10(-4) s(-1) for ephrinB3 and B2, respectively). EphrinB3 was sufficient to allow for viral entry of both pseudotype and live NiV. Soluble ephrinB2 and B3 were able to compete for NiV-envelope-mediated viral entry on both ephrinB2- and B3-expressing cells, suggesting that NiV-G interacts with both ephrinB2 and B3 via an overlapping site. Mutational analysis indicated that the Leu-Trp residues in the solvent exposed G-H loop of ephrinB2 and B3 were critical determinants of NiV binding and entry. Indeed, replacement of the Tyr-Met residues in the homologous positions in ephrinB1 with Leu-Trp conferred NiV receptor activity to ephrinB1. Thus, ephrinB3 is a bona fide alternate receptor for NiV entry, and two residues in the G-H loop of the ephrin B-class ligands are critical determinants of NiV receptor activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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