Brief report: quality of life is impaired in pediatric burn survivors with posttraumatic stress disorder

OBJECTIVE: This study assessed health-related quality of life (HRQOL) and posttraumatic stress disorder (PTSD) in pediatric burn survivors and examined associations between PTSD and HRQOL. METHODS: Forty-three burn survivors, ages 7-16 years, were interviewed at an average of 4.4 years after their accident using the Clinician-Administered PTSD Scale for Children and Adolescents and the TNO-AZL Child Quality of Life Questionnaire. RESULTS: Eight children (18.6%) met DSM-IV criteria for current PTSD. While most dimensions of HRQOL were within normal limits, social functioning was impaired. Severity of PTSD was significantly associated with physical, cognitive, and emotional dimensions of HRQOL. Children with PTSD reported an impaired overall HRQOL and limited physical (e.g., more bodily complaints) and emotional functioning (e.g., more feelings of sadness). CONCLUSIONS: This study provides tentative evidence for a considerably high prevalence of PTSD in pediatric burn survivors and for a negative association between PTSD and HRQO

Electrostatic interactions contribute to the control of intramolecular thiol-disulfide isomerization in a protein

The roles of structural factors and of electrostatic interactions with the environment on the outcome of thiol–disulfide exchange reactions were investigated in a mutated immunoglobulin domain (I27*) under mechanical stress. An extensive ensemble of molecular dynamics trajectories was generated by means of QM/MM simulations for a total sampling of 5.7 μs. A significant number of thiol–disulfide exchanges were observed, and the Cys32 thiolate preferred to attack Cys55 over Cys24, in agreement with previous experimental and computational studies. The structural features as well as electronic structures of the thiol–disulfide system along the reaction were analyzed, as were the electrostatic interactions with the environment. The previous findings of better accessibility of Cys55 were confirmed. Additionally, the reaction was found to be directed by the electrostatic interactions of the involved sulfur atoms with the molecular environment. The relationships of atomic charges, which stem from the electrostatic interactions, lead to the kinetic preference of the attack on Cys55. Further, QM/MM metadynamics simulations of thiol–disulfide exchange in a small model system with varied artificial external electric potentials revealed changes in reaction kinetics of the same magnitude as in I27*. Therefore, the electrostatic interactions are confirmed to play a role in the regioselectivity of the thiol–disulfide exchange reactions in the protein

Sygdomme og velfærd

Siden anden verdenskrig er der sket store ændringer i fjerkræproduktionen. Indførslen af nye produktionssystemer, robuste og højtydende dyr, forbedret management og indførslen af biosecurity har medført en stor produktionsfremgang med lav mortalitet. I de senere år har forbrugerønsker medført at udvikling af udendørs produktionssystemer, hvor de klassiske fjerkræsygdomme nu er på fremmarch med en forhøjet mortalitet til følge. Forfatterne diskuterer, om de udendørs produktionssystemer reelt har betydet en forbedret velfærd for hønerne

Magneto-optic transmittance modulation observed in a hybrid graphene-split ring resonator terahertz metasurface

By placing a material in close vicinity of a resonant optical element, its intrinsic optical response can be tuned, possibly to a wide extent. Here, we show that a graphene monolayer, spaced a few tenths of nanometers from a split ring resonator metasurface, exhibits a magneto-optical response which is strongly influenced by the presence of the metasurface itself. This hybrid system holds promises in view of thin optical modulators, polarization rotators, and nonreciprocal devices, in the technologically relevant terahertz spectral range. Moreover, it could be chosen as the playground for investigating the cavity electrodynamics of Dirac fermions in the quantum regime.The work was supported in part by the European Union Graphene Flagship under grant agreement n° 604391.This is the author accepted manuscript. The final version is available from AIP via http://dx.doi.org/10.1063/1.493170

Position of eukaryotic translation initiation factor eIF1A on the 40S ribosomal subunit mapped by directed hydroxyl radical probing

The universally conserved eukaryotic initiation factor (eIF), eIF1A, plays multiple roles throughout initiation: it stimulates eIF2/GTP/Met-tRNAiMet attachment to 40S ribosomal subunits, scanning, start codon selection and subunit joining. Its bacterial ortholog IF1 consists of an oligonucleotide/oligosaccharide-binding (OB) domain, whereas eIF1A additionally contains a helical subdomain, N-terminal tail (NTT) and C-terminal tail (CTT). The NTT and CTT both enhance ribosomal recruitment of eIF2/GTP/Met-tRNAiMet, but have opposite effects on the stringency of start codon selection: the CTT increases, whereas the NTT decreases it. Here, we determined the position of eIF1A on the 40S subunit by directed hydroxyl radical cleavage. eIF1A's OB domain binds in the A site, similar to IF1, whereas the helical subdomain contacts the head, forming a bridge over the mRNA channel. The NTT and CTT both thread under Met-tRNAiMet reaching into the P-site. The NTT threads closer to the mRNA channel. In the proposed model, the NTT does not clash with either mRNA or Met-tRNAiMet, consistent with its suggested role in promoting the ‘closed’ conformation of ribosomal complexes upon start codon recognition. In contrast, eIF1A-CTT appears to interfere with the P-site tRNA-head interaction in the ‘closed’ complex and is likely ejected from the P-site upon start codon recognition

Position of eukaryotic translation initiation factor eIF1A on the 40S ribosomal subunit mapped by directed hydroxyl radical probing

The universally conserved eukaryotic initiation factor (eIF), eIF1A, plays multiple roles throughout initiation: it stimulates eIF2/GTP/Met-tRNAiMet attachment to 40S ribosomal subunits, scanning, start codon selection and subunit joining. Its bacterial ortholog IF1 consists of an oligonucleotide/oligosaccharide-binding (OB) domain, whereas eIF1A additionally contains a helical subdomain, N-terminal tail (NTT) and C-terminal tail (CTT). The NTT and CTT both enhance ribosomal recruitment of eIF2/GTP/Met-tRNAiMet, but have opposite effects on the stringency of start codon selection: the CTT increases, whereas the NTT decreases it. Here, we determined the position of eIF1A on the 40S subunit by directed hydroxyl radical cleavage. eIF1A's OB domain binds in the A site, similar to IF1, whereas the helical subdomain contacts the head, forming a bridge over the mRNA channel. The NTT and CTT both thread under Met-tRNAiMet reaching into the P-site. The NTT threads closer to the mRNA channel. In the proposed model, the NTT does not clash with either mRNA or Met-tRNAiMet, consistent with its suggested role in promoting the ‘closed’ conformation of ribosomal complexes upon start codon recognition. In contrast, eIF1A-CTT appears to interfere with the P-site tRNA-head interaction in the ‘closed’ complex and is likely ejected from the P-site upon start codon recognition

Structure-function of anticoagulant TIX-5, the inhibitor of factor Xa-mediated FV activation

Background The prothrombinase complex consists of factors Xa (FXa) and Va (FVa) on an anionic phospholipid surface and converts prothrombin into thrombin. Both coagulation factors require activation before complex assembly. We recently identified TIX-5, a unique anticoagulant tick protein that specifically inhibits FXa-mediated activation of FV. Because TIX-5 inhibited thrombin generation in blood plasma, it was concluded that FV activation by FXa contributes importantly to coagulation.Objective We aimed to unravel the structure-function relationships of TIX-5.Method We used a structure model generated based on homology with the allergen Der F7.Results Tick inhibitor of factor Xa toward FV was predicted to consist of a single rod formed by several beta sheets wrapped around a central C-terminal alpha helix. By mutagenesis we could show that two hydrophobic loops at one end of the rod mediate the phospholipid binding of TIX-5. On the other end of the rod an FV interaction region was identified on one side, whereas on the other side an EGK sequence was identified that could potentially form a pseudosubstrate of FXa. All three interaction sites were important for the anticoagulant properties of TIX-5 in a tissue factor-initiated thrombin generation assay as well as in the inhibition of FV activation by FXa in a purified system.Conclusion The structure-function properties of TIX-5 are in perfect agreement with a protein that inhibits the FXa-mediated activation on a phospholipid surface. The present elucidation of the mechanism of action of TIX-5 will aid in deciphering the processes involved in the initiation phase of blood coagulation.Thrombosis and Hemostasi