1,721,007 research outputs found
Transformation of elite white poplar (Populus alba L.) with a stilbene synthase-encoding gene using Agrobacterium tumefaciens
No full textModelling of Ca2+-promoted structural effects in wild type and post-translationally modified Connexin26
No full textDiscriminating between competing models for the allosteric regulation of oncogenic phosphatase SHP2 by characterizing its active state
Full text linkThe Src-homology 2 domain containing phosphatase 2 (SHP2) plays a critical role in crucial signaling pathways and is involved in oncogenesis and in developmental disorders. Its structure includes two SH2 domains (N-SH2 and C-SH2), and a protein tyrosine phosphatase (PTP) domain. Under basal conditions, SHP2 is auto-inhibited, with the N-SH2 domain blocking the PTP active site. Activation involves a rearrangement of the domains that makes the catalytic site accessible, coupled to the association between the SH2 domains and cognate proteins containing phosphotyrosines. Several aspects of this transition are debated and competing mechanistic models have been proposed. A crystallographic structure of SHP2 in an active state has been reported (PDB code 6crf), but several lines of evidence suggests that it is not fully representative of the conformations populated in solution. To clarify the structural rearrangements involved in SHP2 activation, enhanced sampling simulations of the autoinhibited and active states have been performed, for wild type SHP2 and its pathogenic E76K variant. Our results demonstrate that the crystallographic conformation of the active state is unstable in solution, and multiple interdomain arrangements are populated, thus allowing association to bisphosphorylated sequences. Contrary to a recent proposal, activation is coupled to the conformational changes of the N-SH2 binding site, which is significantly more accessible in the active sate, rather than to the structure of the central β-sheet of the domain. In this coupling, a previously undescribed role for the N-SH2 BG loop emerged
Nano-bio interactions: a neutrophil-centric view
Full text linkNeutrophils are key components of the innate arm of the immune system and represent the frontline of host defense against intruding pathogens. However, neutrophils can also cause damage to the host. Nanomaterials are being developed for a multitude of different purposes and these minute materials may find their way into the body through deliberate or inadvertent exposure; understanding nanomaterial interactions with the immune system is therefore of critical importance. However, whereas numerous studies have focused on macrophages, less attention is devoted to nanomaterial interactions with neutrophils, the most abundant leukocytes in the blood. We discuss the impact of engineered nanomaterials on neutrophils and how neutrophils, in turn, may digest certain carbon-based materials such as carbon nanotubes and graphene oxide. We also discuss the role of the corona of proteins adsorbed onto the surface of nanomaterials and whether nanomaterials are sensed as pathogens by cells of the immune system
STORIA DI UNA FRATELLANZA CULTURALE SORTA DALLE MACERIE DEL TERREMOTO DI MESSINA
No full textAll'alba del 28 dicembre del 1908 una violenta scossa tellurica in soli trenta secondi squassò la zona dello Stretto e distrusse completamente Messina. Il tremendo terremoto di Messina, le storie di solidarietà e coraggio, di fronte alla violenza del moto sismico (decimo grado della scala Mercalli) si aggiunse quella del maremoto che circa dieci minuti dopo la scossa riversò diverse ondate sulla città. Tutto ciò avvenne in un ora in cui non era molto facile trovare scampo ed in un luogo ove la gente viveva ammassata in costruzioni che non poggiavano su solide basi. La stima approssimativa fu di 60.000 vittime
Design, synthesis, antibacterial potential, and structural characterization of N-acylated derivatives of the human autophagy 16 polypeptide
No full textA synthetic antimicrobial peptide library based on the human autophagy 16 polypeptide has been developed. Designed acetylated peptides bearing lipids of different chain lengths resulted in peptides with enhanced potency compared to the parent Atg16. A 21-residue fragment of Atg16 conjugated to 4-methylhexanoic acid (K30) emerged as the most potent antibacterial, with negligible hemolysis. Several studies, including microscopy, dye leakage, and ITC, were conducted to gain insight into the antibacterial mechanism of action of the peptide. Visual inspection using both SEM and TEM revealed the membranolytic effect of the peptide on bacterial cells. The selectivity of the peptide against bacterial cell membranes was also proven using dye leakage assays. ITC analysis revealed the exothermic nature of the binding interaction of the peptide to D8PG micelles. The three-dimensional solution NMR structure of K30 in complex with dioctanoylphosphatidylglycerol (D8PG) micelles revealed that the peptide adopts a helix-loop-helix structure in the presence of anionic membrane lipids mimicking bacterial membranes. Intermolecular NOEs between the peptide and lipid deciphered the location of the peptide in the bound state, which was subsequently supported by the paramagnetic relaxation enhancement (PRE) NMR experiment. Collectively, these results describe the structure-function relationship of the peptide in the bacterial membrane
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
Genetic transformation of white poplar (Populus alba L.) with a Vitreoscilla hemoglobin (vhB) - encoding gene and evaluation of growth rate and biomass production.
No full textMultiple scale dynamics in proteins probed at multiple time scales through fluctuations of NMR chemical shifts
No full textInternational audience: Fluctuations of NMR resonance frequency shifts and their relation with protein exchanging conformations are usually analysed in terms of simple two-site jump processes. However, this description is unable to account for the presence of multiple time scale dynamics. In this work, we present an alternative model for the interpretation of the stochastic processes underlying these fluctuations of resonance frequencies. Time correlation functions of (15)N amide chemical shifts computed from molecular dynamics simulations (MD) were analysed in terms of a transiently fractional diffusion process. The analysis of MD trajectories spanning dramatically different time scales (~200 ns and 1ms [Shaw, D. E. et al. Science, 2010, 330, 341-346]) allowed us to show that our model could capture the multiple scale structure of chemical shift fluctuations. Moreover, the predicted exchange contribution Rex to the NMR transverse relaxation rate is in qualitative agreement with experimental results. These observations suggest that the proposed fractional diffusion model may provide significative improvement to the analysis of NMR dispersion experiments
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