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A Spectroscopic Study of the Aggregation State of the Human Antimicrobial Peptide LL-37 in Bacterial versus Host Cell Model Membranes
No full textThe LL-37 antimicrobial peptide is the only cathelicidin peptide found in
humans that has antimicrobial and immunomodulatory properties. Because it exerts also
chemotactic and angiogenetic activity, LL-37 is involved in promoting wound healing,
reducing inflammation, and strengthening the host immune response. The key to the
effectiveness of antimicrobial peptides (AMPs) lies in the different compositions of bacterial
versus host cell membranes. In this context, antimicrobial peptide LL-37 and two variants
were studied in the presence of model membranes with different lipid compositions and
charges. The investigation was performed using an experimental strategy that combines the
site-directed spin labeling−electron paramagnetic resonance technique with circular
dichroism and fluorescence emission spectroscopies. LL-37 interacts with negatively charged
membranes forming a stable aggregate, which can likely produce toroidal pores until the
amount of bound peptide exceeds a critical concentration. At the same time, we have clearly detected an aggregate with a higher
oligomeric degree for interaction of LL-37 with neutral membranes. These data confirm the absence of cell selectivity of the
peptide and a more complex role in stimulating host cells
Anti-oxidant and anti-inflammatory activity of ketogenic diet. New perspectives for neuroprotection in alzheimer’s disease
Full text linkThe ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD+/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins. Furthermore, the ketogenic diet performs anti-inflammatory activity by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome as well as inhibiting histone deacetylases (HDACs), improving memory encoding. The underlying mechanisms and the perspectives for the treatment of Alzheimer’s disease are discussed
Human neutrophil peptide 1 variants bearing arginine modified cationic side chains: Effects on membrane partitioning
Full text linkα-Defensins (e.g. human neutrophil peptides, HNPs) have a broad spectrum bactericidal activity contributing to human innate immunity. The positive charge of amino acid side chains is responsible for the first interaction of cationic antimicrobial peptides with negatively charged bacterial membranes. α-Defensins contain a high content of Arg residues compared to Lys. In this paper, different peptide analogs including substitution of Arg-14 respectively with NG-NG′-asymmetric dimethyl-l-arginine (ADMA), NG-NG′-symmetric dimethyl-l-arginine (SDMA) and Lys (R14K and R15KR14KR15K) variants have been studied to test the role of Arg guanidino group and the localized cationic charge of Lys for interaction with lipid membranes. Our findings show that all the variants have a decreased disruptive activity against the bilayer. The methylated analogs show a reduction in membrane partitioning due to the lack of their ability to form hydrogen bonds. Comparison with the native HNP-1 peptide has been discussed. © 2014 Elsevier B.V. All rights reserved
Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach
Full text linkThe X-chromosome-linked inhibitor of apoptosis protein (XIAP) is a multidomain protein whose main function is to block apoptosis by caspase inhibition. XIAP is also involved in other signalling pathways, including NF-κB activation and copper homeostasis. XIAP is overexpressed in tumours, potentiating cell survival and resistance to chemotherapeutics, and has therefore become an important target for the treatment of malignancy. Despite the fact that the structure of each single domain is known, the conformation of the full-length protein has never been determined. Here, the first structural model of the full-length XIAP dimer, determined by an integrated approach using nuclear magnetic resonance, small-angle X-ray scattering and electron paramagnetic resonance data, is presented. It is shown that XIAP adopts a compact and relatively rigid conformation, implying that the spatial arrangement of its domains must be taken into account when studying the interactions with its physiological partners and in developing effective inhibitors
The defensin–lipid interaction: Insights on the binding states of the human antimicrobial peptide HNP-1 to model bacterial membranes
Full text linkAntimicrobial peptides are an important component of innate immunity and have generated considerable interest as a new potential class of natural antibiotics. The biological activity of antimicrobial peptides is strongly influenced by peptide-membrane interactions. Human Neutrophil Peptide 1 (HNP-1) is a 30 aminoacid peptide, belonging to the class of α-defensins. Many biophysical studies have been performed on this peptide to define its mechanism of action. Combining spectroscopic and thermodynamic analysis, insights on the interaction of the α-defensin with POPE:POPG:CL negative charged bilayers are given. The binding states of the peptide below and above the threshold concentration have been analyzed showing that the interaction with lipid bilayers is dependent by peptide concentration. These novel results that indicate how affinity and biological activities of natural antibiotics are depending by their concentration, might open new way of investigation of the antimicrobial mode of action
Intimate Female Partner Homicide Suicide. Demographic and psychopathology aspects of perpetrators and a potential not yet classified diagnostic entityAnalyses of data taken from newspapers in Italy from 2009 to 2019
Full text linkIntroduction. The homicide of the female partner followed by suicide of the perpetrator (Intimate Female Partner Homicide Suicide -IFPHS) has been a growing phenomenon over last years, but its psychosocial and psychopathological aspects have not been analyzed in-depth yet. Purpose. The aim of this study was to investigate common psychopathological elements in different IFPHS and a specific risk profile for both the couple and the male partner, with the possibility to define a new serial mental condition not classified to date. Methods. A series of 50 cases of greater media coverage was reconstructed from the Italian newspapers in the period from 2009 to 2019 and information was collected through a pre-defined form. The characteristics of the perpetrators and the modalities through which the events occurred have been considered. Results. No definite mental disorder is present in the history of almost all cases. A more common psychological profile is found for the homicide/suicide male partner, mainly characterized by jealousy, possessiveness, mood reactivity, rage, and impulsiveness. Conclusions. It can be hypothesized that such a severe act may express a form of mental disorder not yet classified, with main features of an acute state of mixed depressive mood, emotional discontrol and aggressive impulsiveness, on a personality basis of jealousy and possessiveness, possibly reinforced by previous dependent traits of the female partner. But the methodological limitations of gathering information from the press make it neces-sary the study in depth, based on more direct and objective methodologies, of such a highly dramatic and heterogeneous phenomenon
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“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
Full text linkWe 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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