Estimation of Bone Marrow DNA Damage Induced by Lambda cyhalothrin and Dimethoate Insecticides using Alkaline Comet Assay

Dimethoate (DM) and Lambda cyhalothrin (LCT) are commonly used insecticides. Human being and farm animals are expected to have acute toxicity. The present work aimed to explore the effect of acute exposure to DM and LCT on hematological parameters and to detect DNA damage in bone marrow of Sprague Dawley rats using the alkaline single cell gel electrophoresis assay (comet assay). Thirty animals were divided into three groups of ten rats each. LCT group administered 26 mg/kg body weight, DM group administered 103 mg/kg body weight orally for 24 and 48 hours, while the control group received the vehicle only. Blood samples were collected for hematological analysis, bone marrow was flushed from the femur bone for comet assay and spleen samples were preserved in formalin for histopathological examination.  Results showed minor changes in blood profile in all exposed groups associated with mild changes in histology of spleen tissue. Alkaline single cell gel electrophoresis assay in bone marrow cells showed that LCT and DM caused extensive and severe DNA damage after 48 h exposure expressed as significant increases in all comet parameters (% DNA in tail, tail length, tail moment and Olive tail moment). The results concluded that LCT and DM induced DNA damage in bone marrow of rats, LCT showed higher degree of DNA damage in comparison with DM

Familias divididas y cadenas globales de cuidado

Incluye BibliografíaEl estudio realiza una caracterización de la migración sudamericana a España, explora los contextos familiares previos a la migración de los distintos grupos migratorios, estima la extensión de las familias divididas como producto de la migración y establece las diferencias que establece el género. Particular atención se pone en el análisis de dos fenómenos, la maternidad a larga distancia y la conformación de cadenas globales de cuidado. Las posibilidad de que el traslado se realice en forma asociativa/familiar o de manera independiente, dando lugar a la conformación de familias divididas o transnacionales, difiere no solamente de acuerdo al sexo, los rasgos educativos y la situación documentaria, sino también y fundamentalmente con la situación familiar previa a la migración

Inserción laboral e ingresos de los migrantes de países limítrofes y peruanos en el gran Buenos Aires

Incluye BibliografíaEl objetivo de este trabajo es profundizar el conocimiento sobre la inserción laboral y los diferenciales de ingresos entre los migrantes de países limítrofes y de Perú y la población nativa en el Gran Buenos Aires, en el nuevo contexto de recuperación económica. En primer lugar se describen las formas de inserción laboral de migrantes y nativos. En segundo lugar se examinan las brechas de ingresos entre ambos grupos de trabajadores y se analiza su relación con los niveles educativos y la califi cación de la tarea que realizan. Por último, se establece la medida en que esas brechas se reducen o aumentan al considerar simultáneamente rasgos vinculados no solo al capital humano sino también a la inserción laboral de los migrantes. En el análisis se hace hincapié en la situación diferenciada de hombres y mujeres. La aplicación de técnicas multivariadas permitió realizar nuevos hallazgos y distinguir varios factores determinantes ligados a las diferencias de ingresos entre nativos y migrantes

Energy efficient target detection through waveform selection for multi-sensor RF sensing based Internet of Things

—In this paper, we explore multi-sensor Radio Frequency (RF) sensing based Internet of Things (IoT) for surveillance applications. RF sensing techniques are the next generation technologies which offer distinct advantages over traditional means of sensing. Traditionally, Energy detection (ED) has been used for surveillance applications due to its low computational complexity. However, ED is unreliable due to high false detection rates. There is a need to develop surveillance strategies which offer reliable target detection rates. In this paper, we have proposed a multi-sensor RF sensing based target detection architecture for IoT. To perform surveillance within IoT, multiple sensor nodes are required to co-exist while performing the desired tasks. Interfering waveforms from the neighbouring sensor nodes have a significant impact on the target detection reliability of IoT. n this paper, a waveform selection criterion has been proposed to optimise the target detection reliability and power consumption within IoT in the presence of interfering waveforms

ALADYN: a web server for aligning proteins by matching their large-scale motion

The ALADYN web server aligns pairs of protein structures by comparing their internal dynamics and detecting regions that sustain similar large-scale movements. The latter often accompany functional conformational changes in proteins and enzymes. The ALADYN dynamics-based alignment can therefore highlight functionally-oriented correspondences that could be more elusive to sequence- or structure-based comparisons. The ALADYN server takes the structure files of the two proteins as input. The optimal relative positioning of the molecules is found by maximizing the similarity of the pattern of structural fluctuations which are calculated via an elastic network model. The resulting alignment is presented via an interactive graphical Java applet and is accompanied by a number of quantitative indicators and downloadable data files. The ALADYN web server is freely accessible at the http://aladyn.escience-lab.org address

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society

Molecular Dynamics of Mesophilic-Like Mutants of a Cold-Adapted Enzyme: Insights into Distal Effects Induced by the Mutations

Networks and clusters of intramolecular interactions, as well as their “communication” across the three-dimensional architecture have a prominent role in determining protein stability and function. Special attention has been dedicated to their role in thermal adaptation. In the present contribution, seven previously experimentally characterized mutants of a cold-adapted α-amylase, featuring mesophilic-like behavior, have been investigated by multiple molecular dynamics simulations, essential dynamics and analyses of correlated motions and electrostatic interactions. Our data elucidate the molecular mechanisms underlying the ability of single and multiple mutations to globally modulate dynamic properties of the cold-adapted α-amylase, including both local and complex unpredictable distal effects. Our investigation also shows, in agreement with the experimental data, that the conversion of the cold-adapted enzyme in a warm-adapted variant cannot be completely achieved by the introduction of few mutations, also providing the rationale behind these effects. Moreover, pivotal residues, which are likely to mediate the effects induced by the mutations, have been identified from our analyses, as well as a group of suitable candidates for protein engineering. In fact, a subset of residues here identified (as an isoleucine, or networks of mesophilic-like salt bridges in the proximity of the catalytic site) should be considered, in experimental studies, to get a more efficient modification of the features of the cold-adapted enzyme

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients

Mechanisms of Intramolecular Communication in a Hyperthermophilic Acylaminoacyl Peptidase: A Molecular Dynamics Investigation

Protein dynamics and the underlying networks of intramolecular interactions and communicating residues within the three-dimensional (3D) structure are known to influence protein function and stability, as well as to modulate conformational changes and allostery. Acylaminoacyl peptidase (AAP) subfamily of enzymes belongs to a unique class of serine proteases, the prolyl oligopeptidase (POP) family, which has not been thoroughly investigated yet. POPs have a characteristic multidomain three-dimensional architecture with the active site at the interface of the C-terminal catalytic domain and a β-propeller domain, whose N-terminal region acts as a bridge to the hydrolase domain. In the present contribution, protein dynamics signatures of a hyperthermophilic acylaminoacyl peptidase (AAP) of the prolyl oligopeptidase (POP) family, as well as of a deletion variant and alanine mutants (I12A, V13A, V16A, L19A, I20A) are reported. In particular, we aimed at identifying crucial residues for long range communications to the catalytic site or promoting the conformational changes to switch from closed to open ApAAP conformations. Our investigation shows that the N-terminal α1-helix mediates structural intramolecular communication to the catalytic site, concurring to the maintenance of a proper functional architecture of the catalytic triad. Main determinants of the effects induced by α1-helix are a subset of hydrophobic residues (V16, L19 and I20). Moreover, a subset of residues characterized by relevant interaction networks or coupled motions have been identified, which are likely to modulate the conformational properties at the interdomain interface

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design