1,765 research outputs found
Determinants of translation efficiency and accuracy
A given protein sequence can be encoded by an astronomical number of alternative nucleotide sequences. Recent research has revealed that this flexibility provides evolution with multiple ways to tune the efficiency and fidelity of protein translation and folding
Impact of Dreissena fouling on the physiological condition of native and invasive bivalves : interspecific and temporal variations
The impact of Dreissena fouling on unionids
has hardly been studied in Europe, despite the fact
that in some ecosystems (e.g. Lake Balaton, Hungary)
infestations of several hundreds to a thousand individuals
per unionid have been observed. At present,
the zebra mussel Dreissena polymorpha is a dominant
species in Lake Balaton and in the last decade three
other invasive bivalves were introduced, potentially
increasing the pressure on native unionid survival. We
examined whether the fouling of dreissenids (zebra
and quagga (D. rostriformis bugensis) mussels) has a
negative impact on native (Anodonta anatina, Unio
pictorum and U. tumidus) and invasive (Corbicula
fluminea and Sinanodonta woodiana) bivalves and
whether there are any interspecific and temporal
variations in fouling intensity and physiological
condition measured by standard condition index and
glycogen content. A significant negative impact was detected on native unionids only in July and September
(no impact was detected in May), when the fouling
rate was high. For invasive species, a significant
negative impact was detected on S. woodiana with a
high level of dressenid infestation; whereas no significant
impact was detected on C. fluminea. Overall, this
study confirms that Dreissena may threaten unionid
species including the invasive S. woodiana, although
high interspecific and temporal variations were
observed. This situation should be taken into account
in future ecological and conservational assessments
because species respond differently to Dreissena
fouling and effects seem to be more pronounced in
late summer/early autumn. In addition, this study
provides the first evidence that the invasive C.
fluminea appear to be less vulnerable to dressenid
fouling.The study was supported by the Hungarian Scientific Fund (KTIA-OTKA) under the contract No. CNK80140
The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer
Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al
The CAG repeat at the Huntington disease gene in the Portuguese population : insights into its dynamics and to the origin of the mutation
Huntington disease (HD) is caused by an
expansion of a CAG repeat. This repeat is a dynamic
mutation that tends to undergo intergenerational instability.
We report the analysis of the CAG repeat in a large
population sample (2,000 chromosomes) covering all regions
of Portugal, and a haplotype study of (CAG)n and
(CCG)n repeats in 140 HD Portuguese families. Intermediate
class 2 alleles represented 3.0% of the population;
and two expanded alleles (36 and 40 repeats, 0.11%) were
found. There was no evidence for geographical clustering
of the intermediate or expanded alleles. The Portuguese
families showed three different HD founder haplotypes
associated with 7-, 9- or 10-CCG repeats, suggesting the
possibility of different origins for theHDmutation among
this population. The haplotype carrying the 7-CCG repeat
was the most frequent, both in normal and in expanded
alleles. In general, we propose that three mechanisms,
occurring at different times,may lead to the evolution from
normal CAGs to full expansion: first, a mutation bias towards
larger alleles; then, a stepwise process that could
explain the CAGdistributions observed in themore recent
haplotypes; and, finally, a pool of intermediate (class 2)
alleles more prone to give rise to expanded HD alleles.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/9759/
2003.Instituto de Genética Médica Jacinto Magalhães
Discovering patterns in drug-protein interactions based on their fingerprints
<p>Abstract</p> <p>Background</p> <p>The discovering of interesting patterns in drug-protein interaction data at molecular level can reveal hidden relationship among drugs and proteins and can therefore be of paramount importance for such application as drug design. To discover such patterns, we propose here a computational approach to analyze the molecular data of drugs and proteins that are known to have interactions with each other. Specifically, we propose to use a data mining technique called <it>Drug-Protein Interaction Analysis </it>(<it>D-PIA</it>) to determine if there are any commonalities in the fingerprints of the substructures of interacting drug and protein molecules and if so, whether or not any patterns can be generalized from them.</p> <p>Method</p> <p>Given a database of drug-protein interactions, <it>D-PIA </it>performs its tasks in several steps. First, for each drug in the database, the fingerprints of its molecular substructures are first obtained. Second, for each protein in the database, the fingerprints of its protein domains are obtained. Third, based on known interactions between drugs and proteins, an interdependency measure between the fingerprint of each drug substructure and protein domain is then computed. Fourth, based on the interdependency measure, drug substructures and protein domains that are significantly interdependent are identified. Fifth, the existence of interaction relationship between a previously unknown drug-protein pairs is then predicted based on their constituent substructures that are significantly interdependent.</p> <p>Results</p> <p>To evaluate the effectiveness of <it>D-PIA</it>, we have tested it with real drug-protein interaction data. <it>D-PIA </it>has been tested with real drug-protein interaction data including enzymes, ion channels, and protein-coupled receptors. Experimental results show that there are indeed patterns that one can discover in the interdependency relationship between drug substructures and protein domains of interacting drugs and proteins. Based on these relationships, a testing set of drug-protein data are used to see if <it>D-PIA </it>can correctly predict the existence of interaction between drug-protein pairs. The results show that the prediction accuracy can be very high. An AUC score of a ROC plot could reach as high as 75% which shows the effectiveness of this classifier.</p> <p>Conclusions</p> <p><it>D-PIA </it>has the advantage that it is able to perform its tasks effectively based on the fingerprints of drug and protein molecules without requiring any 3D information about their structures and <it>D-PIA </it>is therefore very fast to compute. <it>D-PIA </it>has been tested with real drug-protein interaction data and experimental results show that it can be very useful for predicting previously unknown drug-protein as well as protein-ligand interactions. It can also be used to tackle problems such as ligand specificity which is related directly and indirectly to drug design and discovery.</p
Population Structure of a Hybrid Clonal Group of Methicillin-Resistant Staphylococcus aureus, ST239-MRSA-III
The methicillin-resistant Staphylococcus aureus (MRSA) clonal group known as ST239-MRSA-III is notable for its hybrid origin and for causing sustained hospital epidemics worldwide since the late 1970s. We studied the population structure of this MRSA clonal group using a sample of 111 isolates that were collected over 34 years from 29 countries. Genetic variation was assessed using typing methods and novel ascertainment methods, resulting in approximately 15 kb of sequence from 32 loci for all isolates. A single most parsimonious tree, free of homoplasy, partitioned 28 haplotypes into geographically-associated clades, including prominent European, Asian, and South American clades. The rate of evolution was estimated to be approximately 100× faster than standard estimates for bacteria, and dated the most recent common ancestor of these isolates to the mid-20th century. Associations were discovered between the ST239 phylogeny and the ccrB and dru loci of the methicillin resistance genetic element, SCCmec type III, but not with the accessory components of the element that are targeted by multiplex PCR subtyping tools. In summary, the evolutionary history of ST239 can be characterized by rapid clonal diversification that has left strong evidence of geographic and temporal population structure. SCCmec type III has remained linked to the ST239 chromosome during clonal diversification, but it has undergone homoplasious losses of accessory components. These results provide a population genetics framework for the precise identification of emerging ST239 variants, and invite a re-evaluation of the markers used for subtyping SCCmec
Molecular Analysis of Repeated Methicillin-Resistant Staphylococcus aureus Infections in Children
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen that causes severe morbidity and mortality in hospitalized patients. It is unclear whether repeated MRSA infections in pediatric patients are caused by relapse of previous infecting strains or by acquiring new strains from extrinsic sources. The study aimed to define the genetic relatedness of MRSA isolates from children with repeated infections. METHODOLOGY/PRINCIPAL FINDINGS: Children with multiple MRSA infections during 2004-2006 were identified in a teaching hospital. Repeated infections were confirmed by chart review and the responsible isolates were genotyped and screened for Panton-Valentine leukocidin (PVL) genes. Two consecutive episodes comprised an infection pair, and strain relatedness was defined for each pair as indistinguishable, highly related, or distinct if the isolates were of the same subtype, the same genotype, or different genotype, respectively. A total of 114 episodes comprising 66 infection pairs were identified in 48 children. The interval of infection pairs ranged from 15 days to 346 days, with a median duration of 57.5 days. Genotypings classified all isolates into 7 genotypes and 31 subtypes. Of 66 pairs, 46 (69.7%), 13 (19.7%) and 7 (10.6%) pairs were caused by indistinguishable, highly related and distinct strains, respectively. Subsequent infections caused by indistinguishable strains were more common for PVL-positive strains (17/18, 94.4%) than for PVL-negative strains (29/48, 60.4%, P = 0.007). The strain relatedness was not affected by the durations of interval between infections. CONCLUSIONS/SIGNIFICANCE: Most repeated MRSA infections in children are caused by indistinguishable strains even after a long period of interval, suggesting that persistent carriage and relapse of initial infecting strains were responsible for the majority of recurrent MRSA infections
Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines
A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us
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