Many types of viruses directly or indirectly target the vascular endothelial growth factor (VEGF) system, which is a central regulator of vasculogenesis and angiogenesis in physiological homeostasis, causing diverse pathologies. Other viruses have been developed into effective therapeutic tools for VEGF modulation in conditions such as cancer and eye diseases. Some viruses may alter the levels of VEGF in the pathogenesis of respiratory syndromes, or they may encode VEGF-like factors, promoting vascular disruption and angiogenesis to enable viruses' systemic spread.
View Article and Find Full Text PDFThe problems that arise with coexistence between schoolchildren are a challenge when it comes to carrying out the teaching-learning process. In recent years, the presence of bullying has increased in schools. The aim of this study is to identify the perceptions of teachers regarding the problems of coexistence among schoolchildren, more specifically concerning bullying, as well as to identify their position regarding the prevention of bullying.
View Article and Find Full Text PDFInformation and Communication Technologies are now a common feature in classroom activities. The aim of this study was to present praxis developed for the tablet for use by primary education students (aged 6-12) studying the natural sciences and mathematics. This research is qualitative and follows the narrative-ethnographic approach.
View Article and Find Full Text PDFParvoviruses are promising anticancer and gene therapy agents, but a deep knowledge of the entry process is crucial to exploit their therapeutic potential. We addressed this issue while attempting to retarget the oncolytic parvovirus minute virus of mice (MVMp) to the tumor vasculature. Residues at three functional domains of the icosahedral capsid were substituted by rational design with peptides competing with the vascular endothelial growth factor.
View Article and Find Full Text PDFInt J Environ Res Public Health
January 2022
Environmental education, at least in northwest Spain, is often overlooked in the education system from infant schooling onwards and interventions are needed to raise the profile of this subject. The aim of this study was to examine the impact of a learning program designed for primary school students to broaden their ecological awareness and improve digital literacy using gamification tools. The research was developed using a qualitative approach, with data obtained from 156 subjects, including teachers, students and families.
View Article and Find Full Text PDFAs many tumor cells synthetize vascular endothelial growth factors (VEGF) that promote neo-vascularization and metastasis, frontline cancer therapies often administer anti-VEGF (α-VEGF) antibodies. To target the oncolytic parvovirus minute virus of mice (MVM) to the tumor vasculature, we studied the functional tolerance, evasion of neutralization, and induction of α-VEGF antibodies of chimeric viruses in which the footprint of a neutralizing monoclonal antibody within the 3-fold capsid spike was replaced by VEGF-blocking peptides: P6L (PQPRPL) and A7R (ATWLPPR). Both peptides allowed viral genome replication and nuclear translocation of chimeric capsid subunits.
View Article and Find Full Text PDFThe unordered N-termini of parvovirus capsid proteins (Nt) are translocated through a channel at the icosahedral five-fold axis to serve for virus traffick. Heterologous peptides were genetically inserted at the Nt of MVM to study their functional tolerance to manipulations. Insertion of a 5T4-single-chain antibody at VP2-Nt (2Nt) yielded chimeric capsid subunits failing to enter the nucleus.
View Article and Find Full Text PDFMetastatic melanoma cells are highly adaptable to their in vivo microenvironment and can switch between protease-dependent mesenchymal and protease-independent amoeboid invasion to facilitate metastasis. Such adaptability can be visualized in vitro, when cells are cultured in conditions that recapitulate three-dimensional microenvironments. Using thick collagen layers in cell culture and in vivo extravasation assays, we found that pigment epithelium-derived factor (PEDF) suppressed lung extravasation of aggressive melanoma by coordinated regulation of cell shape and proteolysis.
View Article and Find Full Text PDFPigment epithelium-derived factor (PEDF) is a broad-spectrum angiogenesis inhibitor that displays potent antimetastatic activity in multiple tumor types. We have previously shown that PEDF prevents primary tumor growth and metastatic spread of human melanoma in mouse experimental models. Consistent with these observations, PEDF expression is lost at the late stages of melanoma progression, allowing melanoma cells to become angiogenic, migratory, and invasive.
View Article and Find Full Text PDFExtracellular factors control the angiogenic switch in endothelial cells (ECs) via competing survival and apoptotic pathways. Previously, we showed that proangiogenic and antiangiogenic factors target the same signaling molecules, which thereby become pivots of angiogenic balance. Here we show that in remodeling endothelium (ECs and EC precursors) natural angiogenic inhibitors enhance nuclear factor-kappaB (NF-kappaB) DNA binding, which is critical for antiangiogenesis, and that blocking the NF-kappaB pathway abolishes multiple antiangiogenic events in vitro and in vivo.
View Article and Find Full Text PDFTwo phosphofructokinase (PFK) chimeras were constructed by exchanging the N- and C-terminal halves of the mammalian M- and C-type isozymes, to investigate the contribution of each terminus to the catalytic site and the fructose-2,6-P(2)/fructose-1,6-P(2) allosteric site. The homogeneously-purified chimeric enzymes organized into tetramers, and exhibited kinetic properties for fructose-6-P and MgATP similar to those of the native enzyme that furnished the N-terminal domain in each case, whereas their fructose-2,6-P(2) activatory characteristics coincided with those of the isozyme that provided the C-terminal half. This reflected the role of each domain in the formation of the corresponding binding site.
View Article and Find Full Text PDFIn the spherical virion of the parvovirus minute virus of mice, several amino acid side chains of the capsid were previously found to be involved in interactions with the viral single-stranded DNA molecule. We have individually truncated by mutation to alanine many (ten) of these side chains and analyzed the effects on capsid assembly, stability and conformation, viral DNA encapsidation, and virion infectivity. Mutation of residues Tyr-270, Asp-273, or Asp-474 led to a drastic reduction in infectivity.
View Article and Find Full Text PDFSystematic deletions and point mutations in the C-terminal extension of mammalian PFK (phosphofructokinase) led us to identify Leu-767 and Glu-768 of the M-type isoform (PFK-M) as the motifs responsible for the role of this region in inhibition by MgATP. These amino acids are the only residues of the C-terminus that are conserved in all mammalian isoforms, and were found to have a similar function in the C-type isoenzyme. Both residues in PFK-C and Leu-767 in PFK-M were also observed to be critical for inhibition by citrate, which is synergistic with that by MgATP.
View Article and Find Full Text PDFCandida albicans is able to respond to environmental changes by inducing a distinct morphological program, which is related to the ability to infect mammalian hosts. Although some of the signal transduction pathways involved in this response are known, it is not clear how the environmental signals are sensed and transmitted to these transduction cascades. In this work, we have studied the function of GPA2, a new gene from C.
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