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Dendrimers Functionalized with Membrane-Interacting Peptides for Viral Inhibition
No full textThis contribution reports the synthesis of a poly(amide)-based dendrimer functionalized at the termini with a membrane-interacting peptide derived from the Herpes Simplex virus (HSV) type 1 glycoprotein H, namely gH625-644. This peptide has been shown to interact with model membranes and to inhibit viral infectivity. The peptidodendrimer inhibits both HSV-1 and HSV-2 at a very early stage of the entry process, most likely through an interaction with the viral envelope glycoproteins; thus preventing the virus from coming into close contact with cellular membranes, a prerequisite of viral internalization. The 50% inhibitory concentration was 100 nM and 300 nM against HSV-1 and HSV-2 respectively, with no evidence of cell toxicity at these concentrations. Our results show that the functionalization of a dendrimer with the peptide sequence derived from a HSV glycoprotein shows promising inhibitory activity towards viruses of the herpesviridae family
Functionalization of a Dendrimer with a Membrane-Interacting Domain of Herpes Simplex Virus Type 1: Applications toward Intracellular Delivery
No full textFunctionalization of a Dendrimer with a Membrane-Interacting Domain of Herpes Simplex Virus Type 1: Applications toward Intracellular Deliver
Microbe-host interactions: structure and role of Gram-negative bacterial porins.
No full textGram negative bacteria have evolved many mechanisms of attaching to and invading host epithelial and immune
cells. In particular, many outer membrane proteins (OMPs) are involved in this initial interaction between the
pathogen and their host. The outer membrane (OM) of Gram-negative bacteria performs the crucial role of providing an
extra layer of protection to the organism without compromising the exchange of material required for sustaining life. The
OM, therefore, represents a sophisticated macromolecular assembly, whose complexity has yet to be fully elucidated. This
review will summarize the structural information available for porins, a class of OMP, and highlight their role in bacterial
pathogenesis and their potential as therapeutic targets.
The functional role of porins in microbe-host interactions during various bacterial infections has emerged only during the
last few decades, and their interaction with a variety of host tissues for adhesion to and invasion of the cell and for evasion
of host-defense mechanisms have placed bacterial porins at the forefront of research in bacterial pathogenesis. This review
will discuss the role that porins play in activating immunological responses, in inducing signaling pathways and their influence
on antibiotic resistance mechanisms that involve modifications of the properties of the OM lipid barrier
Review of a viral peptide nanosystem for intracellular delivery
No full textThe internalization of bioactive molecules is one of the most critical problems to
overcome in theranostics. In order to improve pharmacokinetic and pharmacodynamic properties,
synthetic transporters are widely investigated. A new nanotechnological transporter, gH625,
is based on a viral peptide sequence derived from the herpes simplex virus type 1 glycoprotein
H (gH) that has proved to be a useful delivery vehicle, due to its intrinsic properties of inducing
membrane perturbation. The peptide functionalization with several kinds of nanoparticles like
quantum dots, dendrimers, and liposomes could be of particular interest in biomedical applications
to improve drug release within cells, to increase site-specific action, and eventually to
reduce related cytotoxicity
Septic shock by gram-negative infections: role of outer membrane proteins
Get PDFThe magnitude of septic shock as a clinical problem is often understated. Despite advances
in our ability to diagnose and treat infectious diseases, severe sepsis leading to shock due to
gram-negative infections remains one of the leading causes of mortality worldwide. Septic
shock develops because of a disregulation in the host response, and the mechanisms initially
recruited to fight infection produce life-threatening tissue damage and death. Recent
research has witnessed a significant increase in our understanding of host-pathogen
interactions, particularly in the area of innate immunity and the molecular recognition of
gram-positive and gram-negative bacteria. Important new mediators of sepsis and novel
mechanisms of host-cell toxicity have been identified and, together with clinical trials
targeting pathways considered central to sepsis pathogenesis, provide new insight into the
molecular and cellular basis of sepsis for the formulation of new strategies of intervention.
Research on septic shock pathogenesis by gram-negative bacteria is mainly focused on the
understanding of the molecular and cellular role played by lipopolysaccharide (LPS). Strong
experimental evidence and clinical observations suggest that the release of proinflammatory
cytokine mediators by LPS-responsive cells (mainly macrophages, endothelial cells and
neutrophils) in response to toxic products sets in motion the genetic and physiologic
program that manifests as shock. The best characterized of these toxic components is LPS,
which is considered as a paradigm for other less well-characterized toxic microbial
molecules. The immune protection stimulated by highly purified LPS in animals does not
resolve the symptomatology of septic shock, while LPS mixed to outer membrane proteins
shows a better protective activity. Several studies evidence the major role played by outer
membrane proteins in the molecular interaction between the host cell and the gram-negative
bacteria. Endotoxin-associated proteins consist of a complex of several major proteins that
are intimately associated with the LPS. Very little is known about release of non-LPS gramnegative
outer membrane components such as OMPs in sepsis. Among the OMPs, porins
have been shown to play an important role in pathogenesis of bacterial infections. Porins
were pyrogenic in rabbits and elicited a localized reaction when used as the sensiting and
eliciting agent. Porins were also shown to kill D-galactosamine sensitized LPS-responsive
and LPS-unresponsive mice. Treatment of Human Umbilical Vein Endothelial Cells:
(HUVEC) with porins increased the transmigration of different leukocyte populations, inparticular of neutrophils. Porins by several gram-negative bacteria induce cytokine release
by human leukocytes as well as enhancement of cytokine gene expression. Also, other
components of the bacterial envelope are important in the induction and pathogenesis of
septic shock such as bacterial lipoproteins (LP). As anti-LPS therapies does not seem to
improve by the addition of proteins from the outer membrane or small fragments of these
proteins, a great alternative to existing strategies will involve the blockage of signal
transduction pathways, cytokine and inflammatory mechanisms
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Generation effect of Newkome dendrimers on cellular uptake
No full textPoly(amide)-based dendrimers can be used as delivery scaffolds in conjunction with the cell-penetrating peptide gH625 derived from the glycoprotein of the Herpes Simplex virus type 1. In this contribution, we aim to isolate the optimal dendrimer generation for cellular uptake for Newkome type dendrimers conjugated with gH625. For this study, we synthesized generations zero to three of the Newkome dendrimer-gH625 bioconjugate. Fluorescent microscopy experiments showed that the second and third generations are the most efficient for cellular uptake with the second generation having the synthetic advantage. The optimal second generation can be used as an improved material for a dendrimer based delivery scaffold for peptide therapeutics
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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