Children's working understanding of the knowledge gained from seeing and feeling

In three Experiments, (N = 48 3- to 4-year olds; 100 3- to 5-year olds; 54 4-yearolds), children who could see or feel a target toy, recognized when they had sufficient information to answer “Which one is it?” and when they needed additional access. They were weaker at taking the informative modality of access when the choice was between seeing more of a partially visible toy and feeling it; at doing so when the target was completely hidden; and at reporting seeing or feeling as their source of knowledge of the target’s identity having experienced both. Working understanding of the knowledge gained from seeing and feeling (identifying the target efficiently) was not necessarily in advance of explicit understanding (reporting the informative source)

Humanized hemato-lymphoid system mice

Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment

Seasonal Rainfall and Runoff Promote Coral Disease on an Inshore Reef

Background: Declining water quality coupled with the effects of climate change are rapidly increasing coral diseases on reefs worldwide, although links between coral diseases and environmental parameters remain poorly understood. This is the first study to document a correlation between coral disease and water quality on an inshore reef.\ud \ud Methodology/Principal Findings: The temporal dynamics of the coral disease atramentous necrosis (AN) was investigated over two years within inshore populations of Montipora aequituberculata in the central Great Barrier Reef, in relation to rainfall, salinity, temperature, water column chlorophyll a, suspended solids, sedimentation, dissolved organic carbon, and particulate nitrogen, phosphorus and organic carbon. Overall, mean AN prevalence was 10-fold greater during summer wet seasons than winter dry seasons. A 2.5-fold greater mean disease abundance was detected during the summer of 2009 (44 ± SE 6.7 diseased colonies per 25 m2), when rainfall was 1.6-fold greater than in the summer of 2008. Two water quality parameters explained 67% of the variance in monthly disease prevalence in a Partial Least Squares regression analysis; disease abundance was negatively correlated with salinity (R2 = −0.6) but positively correlated with water column particulate organic carbon concentration (R2 = 0.32). Seasonal temperature patterns were also positively correlated with disease abundance, but explained only a small portion of the variance.\ud \ud Conclusions/Significance: The results suggest that rainfall and associated runoff may facilitate seasonal disease outbreaks, potentially by reducing host fitness or by increasing pathogen virulence due to higher availability of nutrients and organic matter. In the future, rainfall and seawater temperatures are likely to increase due to climate change which may lead to decreased health of inshore reefs

TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway

The biological response to tumor necrosis factor (TNF) involves activation of MAP kinases. Here we report a mechanism of MAP kinase activation by TNF that is mediated by the Rho GTPase family members Rac/Cdc42. This signaling pathway requires Src-dependent activation of the guanosine nucleotide exchange factor Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site (CRIB motif) on mixed-lineage protein kinases (MLKs). We show that this pathway is essential for full MAP kinase activation during the response to TNF. Moreover, this MLK pathway contributes to inflammation in vivo

Transport of Proteins into Mitochondria

The mitochondrial ADP/ATP carrier is an integral transmembrane protein of the inner membrane. It is synthesized on cytoplasmic ribosomes. Kinetic data suggested that this protein is transferred into mitochondria in a posttranslational manner. The following results provide further evidence for such a mechanism and provide information on its details. 1. In homologous and heterologous translation systems the newly synthesized ADP/ATP carrier protein is present in the postribosomal supernatant. 2. Analysis by density gradient centrifugation and gel filtration shows, that the ADP/ATP carrier molecules in the postribosomal fraction are present as soluble complexes with apparent molecular weights of about 120000 and 500000 or larger. The carrier binds detergents such as Triton X-100 and deoxycholate forming mixed micelles with molecular weights of about 200000–400000. 3. Incubation of a postribosomal supernatant of a reticulocyte lysate containing newly synthesized ADP/ATP carrier with mitochondria isolated from Neurospora spheroplasts results in efficient transfer of the carrier into mitochondria. About 20–30% of the transferred carrier are resistant to proteinase in whole mitochondria. The authentic mature protein is also largely resistant to proteinase in whole mitochondria and sensitive after lysis of mitochondria with detergent. Integrity of mitochondria is a prerequisite for translocation into proteinase resistant position. 4. The transfer in vitro into a proteinase-resistant form is inhibited by the uncoupler carbonyl-cyanide m-chlorophenylhydrazone but not the proteinase-sensitive binding. These observations suggest that the posttranslational transfer of ADP/ATP carrier occurs via the cytosolic space through a soluble oligomeric precursor form. This precursor is taken up by intact mitochondria into an integral position in the membrane. These findings are considered to be of general importance for the intracellular transfer of insoluble membrane proteins. They support the view that such proteins can exist in a water-soluble form its precursors and upon integration into the membrane undergo a conformational change. Uptake into the membrane may involve the cleavage of an additional sequence in some proteins, but this appears not to be a prerequisite as demonstrated by the ADP/ATP carrier protein

Genome-wide association mapping in winter barley for grain yield and culm cell wall polymer content using the high-throughput CoMPP technique

<div><p>A collection of 112 winter barley varieties (<i>Hordeum vulgare</i> L.) was grown in the field for two years (2008/09 and 2009/10) in northern Italy and grain and straw yields recorded. In the first year of the trial, a severe attack of barley yellow mosaic virus (BaYMV) strongly influenced final performances with an average reduction of ~ 50% for grain and straw harvested in comparison to the second year. The genetic determination (GD) for grain yield was 0.49 and 0.70, for the two years respectively, and for straw yield GD was low in 2009 (0.09) and higher in 2010 (0.29). Cell wall polymers in culms were quantified by means of the monoclonal antibodies LM6, LM11, JIM13 and BS-400-3 and the carbohydrate-binding module CBM3a using the high-throughput CoMPP technique. Of these, LM6, which detects arabinan components, showed a relatively high GD in both years and a significantly negative correlation with grain yield (GYLD). Overall, heritability (<i>H</i>^<i>2</i>) was calculated for GYLD, LM6 and JIM and resulted to be 0.42, 0.32 and 0.20, respectively. A total of 4,976 SNPs from the 9K iSelect array were used in the study for the analysis of population structure, linkage disequilibrium (LD) and genome-wide association study (GWAS). Marker-trait associations (MTA) were analyzed for grain yield and cell wall determination by LM6 and JIM13 as these were the traits showing significant correlations between the years. A single QTL for GYLD containing three MTAs was found on chromosome 3H located close to the Hv-eIF4E gene, which is known to regulate resistance to BaYMV. Subsequently the QTL was shown to be tightly linked to rym4, a locus for resistance to the virus. GWAs on arabinans quantified by LM6 resulted in the identification of major QTLs closely located on 3H and hypotheses regarding putative candidate genes were formulated through the study of gene expression levels based on bioinformatics tools.</p></div

Low prevalence of Epstein–Barr virus in incident gastric adenocarcinomas from the United Kingdom

Epstein–Barr virus has been associated with a proportion of typical gastric adenocarcinomas. Here we report that the prevalence of Epstein–Barr virus in gastric adenocarcinomas from the United Kingdom is one of the lowest in the World. Gastric adenocarcinoma is another tumour whose association with Epstein–Barr virus varies with the population studied