1,721,109 research outputs found
Identification, analysis and inference of point mutations associated to drug resistance in bacteria: a lesson learnt from the resistance of Streptococcus pneumoniae to quinolones
Full text linkAntibiotic resistance is one of the biggest public health challenges of our time. Bacterial chemoresistance is the phenomenon whereby bacteria develop the ability to survive and multiply in the presence of an antibacterial drug; the expression of a resistant phenotype may be due to three fundamental mechanisms, including the expression of enzymes that inactivate the antibacterial drug, changes in the membrane permeability to antibiotics and the onset of point mutations causing the physical-chemical alteration of the antimicrobial targets. In recent decades, new antibiotic resistance mechanisms have emerged and are spreading globally, threatening human health and the ability to fight the most common infectious diseases.
Quinolones, a novel class of antibiotics that bind bacterial topoisomerases and inhibit cell replication, have been important in limiting the spread of penicillin- and macrolides-resistant Streptococcus pneumoniae. However, alarmingly, resistance to quinolones is spreading recently. Resistance is caused by the appearance of point mutations in the bacterial topoisomerase and gyrase. Some mutations are well known, but some are not and the information about known molecular mechanisms causing resistance is sparse and not systematically collected and organised. This means that it cannot be used to infer new mutations in newly sequenced bacterial genes and study how they may affect the drug binding. The lack of structured, organized, and reusable information about point mutations associated with antibiotic resistance represents a critical issue and is a common pattern in the field.
Here, we present a structural analysis of point mutations involved in the resistance to quinolones affecting the gyrase and topoisomerase genes in Streptococcus pneumoniae. Results, extended to other bacterial species, have
been collected in a database, Quinores3D db, and can now be used – through a web server, Quinores3D finder - to analyze both known and yet unknown mutations occurring in bacterial topoisomerases and gyrases. The development, testing and deployment of Quinores3D db and Quinores3D finder are further results of this PhD thesis.
Furthermore, structural data about point mutations associated with antibiotic resistance were used to train, test and validate a machine learning algorithm for the inference of still unknown mutations potentially involved in bacterial resistance to quinolone. As the performance of the algorithm, measured in terms of accuracy, sensitivity and specificity, is very promising, we plan to incorporate it in the web server to allow users to predict new mutations associated with bacterial resistance to quinolones
The telomeric protein AKTIP/Ft1 intercepts lamin metabolism and is important in mouse development
No full textAging is defined as the time-dependent functional decline that affects most living organisms. Impairments of telomeres maintenance, defects in DNA structure and metabolism, loss of nuclear structure integrity may accelerate events that will lead to premature aging [].
We have recently identified a novel telomeric protein named AKTIP/Ft1. It interacts with telomeric DNA and with both TRF1 and TRF2. Its depletion causes in vitro multiple telomeric signals, which are hallmarks of telomere replication defects [Burla et al., Plos genetics, 2015].
AKTIP is manly localized at the nuclear rim []. According to its localization we found that it interacts with component of the nuclear lamina, such as Lamin A/C and Lamin B1. In cell that express mutated version of Lamin A its binding with telomeric DNA is impaired, its cellular signal is mislocalized and reduced. AKTIP depleted cells show premature aging traits such as loss of chromatin organization. These data suggest an interplay between AKTIP and lamins [Burla et al., submitted].
Indeed AKTIP in vitro is involved in mechanisms which perturbation lead to aging.
Given the important role of AKTIP in vitro we wanted to investigated on the role of AKTIP (Ft1) in vivo, through the production and characterization of a knockout-first (KOF) mouse model, in which the transgenic cassette inhibits AKTIP (Ft1) expression, indeed KOF/KOF animals systematically exhibiting substantial reduction of mRNA (≤30% of WT). The analysis of these mice showed that AKTIP (Ft1) is critically important particularly during the early phases of mouse development. Indeed, 20.5% of homozygous KOF mice die at postnatal day 12-13, display gross defects in the skeleton and in the skin, in addition to a strong reduction in body weight.
The rest 79.5% of KOF/KOF animals show reduced survival respect of their wild type counterparts. They show growth defect exacerbated during mice lifespan.
Intriguingly, male KOF/KOF mice are sterile.
We reported a tissue specific phenotype for AKTIP (Ft1) depleted mice, affecting organs with high proliferative rate such as testicles, skin and bone.
Our hypothesis is that AKTIP depletion affects the proliferative status of progenitor cells leading to the exhaustion of stem cell compartment and arising a premature aging phenotype
Contryphan-Vn: A novel peptide from the venom of the Mediterranean snail Conus ventricosus
No full textThe isolation, purification, and biochemical characterization of the novel peptide Contryphan-Vn, extracted from the venom of the Mediterranean marine snail Conus ventricosus, is reported. Contryphan-Vn is the first Conus peptide described from a vermivorous species and the first purified from the venom of the single Mediterranean Conus species. The amino acid sequence of Contryphan-Vn is Gly-Asp-Cys-Pro-D-Trp-Lys-Pro-Trp-Cys-NH2. As with other contryphans, Contryphan-Vn contains a D-tryptophan residue, is amidated at the C-terminus, and maintains the five-residue intercystine loop size. However, Contryphan-Vn differs from the known contryphans by the insertion of the Asp residue at position 2, by the lack of hydroxylation of Pro(4), and, remarkably, by the presence of the basic residue Lys(6) within the intercystine loop. Although the biological function(s) of contryphans is still unknown, these characteristics suggest distinct molecular target(s) and/or function(s) for Contryphan-Vn. (C) 2001 Academic Press
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
Amino acid sequence of chicken Cu, Zn-containing superoxide dismutase and identification of glutathionyl adducts at exposed cysteine residues
No full textThe copper,zinc-containing superoxide dismutase electromorphs from chicken erythrocytes have been isolated, their complete amino acid sequence determined and the identity of the protein moieties established. All electromorphs are constituted by a polypeptide chain made of 153 amino acid residues, corresponding to a molecular mass of 15598 Da. Accurate molecular mass determination by electrospray mass spectrometry of the separated electromorphs unequivocally proved that, in the chicken superoxide dismutase, either one or two cysteine residues/subunit are involved in a mixed disulfide with glutathione. The same post-translational modification has been proven to occur in human superoxide dismutase. A different rate of S-thiolation by endogenous glutathione was also demonstrated to be responsible for charge heterogeneity in cells. Effect of this modification on the catalytic and molecular properties of superoxide dismutases, and possible mechanisms for the S-thiolation process, were also investigated and 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
SIMULATION OF SUPEROXIDE SUPEROXIDE-DISMUTASE ASSOCIATION RATE FOR 6 NATURAL VARIANTS - COMPARISON WITH THE EXPERIMENTAL CATALYTIC RATE RID F-8515-2010 RID B-8461-2008 RID A-4573-2009
No full textA Brownian dynamics simulation method has been implemented to study the superoxide-superoxide dismutase association reaction. Electrostatic potential and forces are calculated solving the linearized finite difference Poisson-Boltzmann equation. The accuracy of the algorithm has been tested carrying out simulations at different ionic strength values on bovine Cu,Zn superoxide dismutase (SOD), whose three-dimensional structure is known at 2 Angstrom resolution, and comparing the calculated association rates with the experimentally determined catalytic rates. Application of the algorithm to six Cu,Zn SOD variants shows that simulations well reproduce the experimental catalytic rate and demonstrates that the diffusion of the superoxide anion to the active site copper is the rate-Limiting step in the catalytic process of Cu,Zn superoxide dismutase
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
