1,203 research outputs found
Multifunctional protein labeling via enzymatic N-terminal tagging and elaboration by click chemistry
The Faces in Infant-Perspective Scenes Change over the First Year of Life
Mature face perception has its origins in the face experiences of infants. However, little is known about the basic statistics of faces in early visual environments. We used head cameras to capture and analyze over 72,000 infant-perspective scenes from 22 infants aged 1-11 months as they engaged in daily activities. The frequency of faces in these scenes declined markedly with age: for the youngest infants, faces were present 15 minutes in every waking hour but only 5 minutes for the oldest infants. In general, the available faces were well characterized by three properties: (1) they belonged to relatively few individuals; (2) they were close and visually large; and (3) they presented views showing both eyes. These three properties most strongly characterized the face corpora of our youngest infants and constitute environmental constraints on the early development of the visual system
Tracing the dynamic life story of a Bronze Age Female
YesAncient human mobility at the individual level is conventionally studied by the diverse application of suitable techniques (e.g. aDNA, radiogenic strontium isotopes, as well as oxygen and lead isotopes) to either hard and/or soft tissues. However, the limited preservation of coexisting hard and soft human tissues hampers the possibilities of investigating high-resolution diachronic mobility periods in the life of a single individual. Here, we present the results of a multidisciplinary study of an exceptionally well preserved circa 3.400-year old Danish Bronze Age female find, known as the Egtved Girl. We applied biomolecular, biochemical and geochemical analyses to reconstruct her mobility and diet. We demonstrate that she originated from a place outside present day Denmark (the island of Bornholm excluded), and that she travelled back and forth over large distances during the final months of her life, while consuming a terrestrial diet with intervals of reduced protein intake. We also provide evidence that all her garments were made of non-locally produced wool. Our study advocates the huge potential of combining biomolecular and biogeochemical provenance tracer analyses to hard and soft tissues of a single ancient individual for the reconstruction of high-resolution human mobility.The Danish National Research Foundation; The Carlsberg Foundation, L'Oreal Denmark-UNESCO; The ERC agreement no. 26944
Roles of AP-2 in clathrin-mediated endocytosis.
The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway
Population structure and genetic diversity in a commercial maize breeding program assessed with SSR and SNP markers
Information about the genetic diversity and population structure in elite breeding material is of fundamental importance for the improvement of crops. The objectives of our study were to (a) examine the population structure and the genetic diversity in elite maize germplasm based on simple sequence repeat (SSR) markers, (b) compare these results with those obtained from single nucleotide polymorphism (SNP) markers, and (c) compare the coancestry coefficient calculated from pedigree records with genetic distance estimates calculated from SSR and SNP markers. Our study was based on 1,537 elite maize inbred lines genotyped with 359 SSR and 8,244 SNP markers. The average number of alleles per locus, of group specific alleles, and the gene diversity (D) were higher for SSRs than for SNPs. Modified Rogerâs distance (MRD) estimates and membership probabilities of the STRUCTURE matrices were higher for SSR than for SNP markers but the germplasm organization in four heterotic pools was consistent with STRUCTURE results based on SSRs and SNPs. MRD estimates calculated for the two marker systems were highly correlated (0.87). Our results suggested that the same conclusions regarding the structure and the diversity of heterotic pools could be drawn from both markers types. Furthermore, although our results suggested that the ratio of the number of SSRs and SNPs required to obtain MRD or D estimates with similar precision is not constant across the various precision levels, we propose that between 7 and 11Â times more SNPs than SSRs should be used for analyzing population structure and genetic diversity
Endotoxin tolerance and cross-tolerance in mast cells involves TLR4, TLR2 and FcΔR1 interactions and SOCS expression: perspectives on immunomodulation in infectious and allergic diseases
<p>Abstract</p> <p>Background</p> <p>The study of the endotoxin tolerance phenomenon in light of the recently defined roles of mast cells and toll-like receptors as essential components of the innate immune response and as orchestrators of acquired immunity may reveal potentially useful mechanisms of immunomodulation of infectious and allergic inflammatory responses, such as sepsis or asthma. Here we evaluated the phenomenon of direct tolerance of endotoxins, as well as the induction of cross-tolerance and synergism by stimulation with toll-like receptor-2 (TLR2) and FcΔR1 agonists, in murine mast cells prestimulated with lipopolysaccharide (LPS). Additionally, we evaluated some stimulatory and inhibitory signaling molecules potentially involved in these phenomena.</p> <p>Methods</p> <p>MC/9 cells and primary bone marrow-derived mast cells obtained from C57BL/6 and TLR4<sup>-/- </sup>knock-out mice were sensitized to DNP-HSA (antigen) by incubation with DNP-IgE and were prestimulated with LPS for 18 hr prior to stimulation. Cultures were stimulated with LPS or Pam3Cys-Ser-(Lys)4 3HCl (P3C), a TLR2 agonist, individually or in combination with antigen. The production of IL-6 and TNFα, the phosphorylation of NFÎșB and p38 MAPK, and the expression of TLR4 and SOCS-1 and -3 were analyzed.</p> <p>Results</p> <p>We found that production of TNFα and IL-6 in murine mast cells that have been pretreated with LPS and challenged with TLR4 (LPS) or -2 (P3C) agonists was reduced, phenomena described as endotoxin tolerance (LPS) and cross-tolerance (P3C), respectively. The expression of TLR4 was not affected by LPS pretreatment. Our results show that the FcΔR1 agonist DNP-HSA (antigen) interacts synergistically with LPS or P3C to markedly enhance production of cytokines (TNFα and IL-6). This synergistic effect with LPS and P3C was also attenuated by LPS pretreatment and was mediated by TLR4. These results may be attributed to the reduction in phosphorylation of the mitogen-activated protein kinase (MAPK), p38, and the transcription factor NFÎșB, as well as to an increase in the expression of the suppressors of cytokine signaling (SOCS)-1 and -3 proteins in LPS-pretreated mast cells.</p> <p>Conclusions</p> <p>These findings can be explored with respect to the modulation of inflammatory responses associated with infectious and allergic processes in future studies.</p
Immunoregulatory gene polymorphisms in women with preeclampsia
The costimulatory molecules CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) (cytotoxic T-lymphocyte-associated antigen-4) and inducible costimulator (ICOS) are believed to have a critical modulatory role in the immune response. However, few studies have been performed on the role of these immune regulatory molecules and their polymorphisms in women with preeclampsia (PE). the aim of our study was to evaluate the CTLA4 (+49 A/G) (rs 231775), CD28 (+17 T/C) (rs 3116496) and ICOS (-1564 T/C) (rs 4675378) gene polymorphisms in Brazilian women with PE. This case-control study included 130 patients with PE and 261 control women without any obstetric or systemic disorders. Genomic DNA was extracted from peripheral blood, and the polymorphism genotyping was performed by digesting the PCR products with the restriction endonucleases BbvI (CTLA-4), Afel (CD28) and AluI (ICOS). Data were analyzed by X(2) or Fisher's exact test; a P-value of < 0.05 was considered as significant. There were significant differences in the ICOS genotype and allelic frequencies between the PE and control groups (P=0.01 and P=0.01, respectively). We found a significantly lower frequency of the ICOS (-1564) T allele in women with mild PE compared with the controls. There were no differences in the CTLA-4 (+49 A/G) and CD28 (+17 T/C) genotypes and allelic frequencies between the PE patients and controls. Our data suggest that PE is associated with ICOS, but is not associated with the CTLA-4 or CD28 gene polymorphisms. Hypertension Research (2011) 34, 384-388; doi:10.1038/hr.2010.247; published online 16 December 2010Fundacao de Amparo a PesquisaCoordenação de Aperfeiçoamento de Pessoal de NĂvel Superior (CAPES)Universidade Federal de SĂŁo Paulo, Dept Obstet, BR-01415002 SĂŁo Paulo, BrazilUniversidade Federal de SĂŁo Paulo, Dept Obstet, BR-01415002 SĂŁo Paulo, BrazilFundacao de Amparo a Pesquisa: 07/57446-0Web of Scienc
Intracellular Trafficking of Guanylate-Binding Proteins Is Regulated by Heterodimerization in a Hierarchical Manner
Guanylate-binding proteins (GBPs) belong to the dynamin family of large GTPases and represent the major IFN-Îł-induced proteins. Here we systematically investigated the mechanisms regulating the subcellular localization of GBPs. Three GBPs (GBP-1, GBP-2 and GBP-5) carry a C-terminal CaaX-prenylation signal, which is typical for small GTPases of the Ras family, and increases the membrane affinity of proteins. In this study, we demonstrated that GBP-1, GBP-2 and GBP-5 are prenylated in vivo and that prenylation is required for the membrane association of GBP-1, GBP-2 and GBP-5. Using co-immunoprecipitation, yeast-two-hybrid analysis and fluorescence complementation assays, we showed for the first time that GBPs are able to homodimerize in vivo and that the membrane association of GBPs is regulated by dimerization similarly to dynamin. Interestingly, GBPs could also heterodimerize. This resulted in hierarchical positioning effects on the intracellular localization of the proteins. Specifically, GBP-1 recruited GBP-5 and GBP-2 into its own cellular compartment and GBP-5 repositioned GBP-2. In addition, GBP-1, GBP-2 and GBP-5 were able to redirect non-prenylated GBPs to their compartment in a prenylation-dependent manner. Overall, these findings prove in vivo the ability of GBPs to dimerize, indicate that heterodimerization regulates sub-cellular localization of GBPs and underscore putative membrane-associated functions of this family of proteins
Nationwide Molecular Surveillance of Pandemic H1N1 Influenza A Virus Genomes: Canada, 2009
BACKGROUND: In April 2009, a novel triple-reassortant swine influenza A H1N1 virus ("A/H1N1pdm"; also known as SOIV) was detected and spread globally as the first influenza pandemic of the 21(st) century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior. METHODOLOGY/PRINCIPAL FINDINGS: By Sanger sequencing, we determined consensus whole-genome sequences for A/H1N1pdm viruses sampled nationwide in Canada over 33 weeks during the 2009 first and second pandemic waves. A total of 235 virus genomes sampled from unique subjects were analyzed, providing insight into the temporal and spatial trajectory of A/H1N1pdm lineages within Canada. Three clades (2, 3, and 7) were identifiable within the first two weeks of A/H1N1pdm appearance, with clades 5 and 6 appearing thereafter; further diversification was not apparent. Only two viral sites displayed evidence of adaptive evolution, located in hemagglutinin (HA) corresponding to D222 in the HA receptor-binding site, and to E374 at HA2-subunit position 47. Among the Canadian sampled viruses, we observed notable genetic diversity (1.47 x 10â»Âł amino acid substitutions per site) in the gene encoding PB1, particularly within the viral genomic RNA (vRNA)-binding domain (residues 493-757). This genome data set supports the conclusion that A/H1N1pdm is evolving but not excessively relative to other H1N1 influenza A viruses. Entropy analysis was used to investigate whether any mutated A/H1N1pdm protein residues were associated with infection severity; however no virus genotypes were observed to trend with infection severity. One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown. CONCLUSIONS/SIGNIFICANCE: These findings contribute to enhanced understanding of Influenza A/H1N1pdm viral dynamics
Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at âs = 7 TeV with the ATLAS detector
This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of âs = 7 TeV;{\rm Te}{\rm V}4.6\;{\rm f}{{{\rm b}}^{-1}}{{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}|\eta |\lt 1.9{{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
- âŠ