Discrimination Reversal Learning in Capuchin Monkeys (Cebus apella)

Learning styles in capuchin monkeys were assessed with a computerized reversal- learning task called the mediationaJ paradigm. First, monkeys were trained to respond with 90% accuracy on a two-choice discrimination (A+B-). Then the authors examined differences in performance on three different types of reversal trials (A-B+, A-C+, B+C-), each of which offered differing predictions for performance, depending on whether the monkeys were using associative cues or rule-based strategies. Performance indicated that the monkeys mainly learned to avoid the B stimulus during training, as the A-C+ condition produced the best performance levels. Therefore, negative stimuli showed greater control over responding after reversal and reflected a more associative rather than rule-based form of learning

Characteristics of US public schools with reported cases of novel influenza A (H1N1)

Objective The 2009 pandemic of influenza A (H1N1) has disproportionately affected children and young adults, resulting in attention by public health officials and the news media on schools as important settings for disease transmission and spread. We aimed to characterize US schools affected by novel influenza A (H1N1) relative to other schools in the same communities. Methods A database of US school-related cases was obtained by electronic news media monitoring for early reports of novel H1N1 influenza between April 23 and June 8, 2009. We performed a matched case–control study of 32 public primary and secondary schools that had one or more confirmed cases of H1N1 influenza and 6815 control schools located in the same 23 counties as case schools. Results Compared with controls from the same county, schools with reports of confirmed cases of H1N1 influenza were less likely to have a high proportion of economically disadvantaged students (adjusted odds ratio (aOR) 0.385; 95% confidence interval (CI) 0.166–0.894) and less likely to have older students (aOR 0.792; 95% CI 0.670–0.938). Conclusions We conclude that public schools with younger, more affluent students may be considered sentinels of the epidemic and may have played a role in its initial spread.National Institute of Allergy and Infectious Diseases (U.S.) (R21AI073591-01)National Institutes of Health (U.S.)Canadian Institutes of Health Research (PAN-83152)Canadian Institutes of Health Research (CAT-86857)Google (Firm) (Research Grant

Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation

Human plasmacytoid dendritic cells (PDCs) can produce interferon (IFN)-α and/or mature and participate in the adaptive immune response. Three classes of CpG oligonucleotide ligands for Toll-like receptor (TLR)9 can be distinguished by different sequence motifs and different abilities to stimulate IFN-α production and maturation of PDCs. We show that the nature of the PDC response is determined by the higher order structure and endosomal location of the CpG oligonucleotide. Activation of TLR9 by the multimeric CpG-A occurs in transferrin receptor (TfR)-positive endosomes and leads exclusively to IFN-α production, whereas monomeric CpG-B oligonucleotides localize to lysosome-associated membrane protein (LAMP)-1–positive endosomes and promote maturation of PDCs. However, CpG-B, when complexed into microparticles, localizes in TfR-positive endosomes and induces IFN-α from PDCs, whereas monomeric forms of CpG-A localize to LAMP-1–positive endosomes accompanied by the loss of IFN-α production and a gain in PDC maturation activity. CpG-C sequences, which induce both IFN-α and maturation of PDCs, are distributed in both type of endosomes. Encapsulation of CpG-C in liposomes stable above pH 5.75 completely abrogated the IFN-α response while increasing PDC maturation. This establishes that the primary determinant of TLR9 signaling is not valency but endosomal location and demonstrates a strict compartmentalization of the biological response to TLR9 activation in PDCs

Fibroblast Growth Factor-10 Promotes Cardiomyocyte Differentiation from Embryonic and Induced Pluripotent Stem Cells

BACKGROUND: The fibroblast growth factor (FGF) family is essential to normal heart development. Yet, its contribution to cardiomyocyte differentiation from stem cells has not been systemically studied. In this study, we examined the mechanisms and characters of cardiomyocyte differentiation from FGF family protein treated embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. METHODOLOGY/PRINCIPAL FINDINGS: We used mouse ES cells stably transfected with a cardiac-specific α-myosin heavy chain (αMHC) promoter-driven enhanced green fluorescent protein (EGFP) and mouse iPS cells to investigate cardiomyocyte differentiation. During cardiomyocyte differentiation from mouse ES cells, FGF-3, -8, -10, -11, -13 and -15 showed an expression pattern similar to the mesodermal marker Brachyury and the cardiovascular progenitor marker Flk-1. Among them, FGF-10 induced cardiomyocyte differentiation in a time- and concentration-dependent manner. FGF-10 neutralizing antibody, small molecule FGF receptor antagonist PD173074 and FGF-10 and FGF receptor-2 short hairpin RNAs inhibited cardiomyocyte differentiation. FGF-10 also increased mouse iPS cell differentiation into cardiomyocyte lineage, and this effect was abolished by FGF-10 neutralizing antibody or PD173074. Following Gene Ontology analysis, microarray data indicated that genes involved in cardiac development were upregulated after FGF-10 treatment. In vivo, intramyocardial co-administration of FGF-10 and ES cells demonstrated that FGF-10 also promoted cardiomyocyte differentiation. CONCLUSION/SIGNIFICANCE: FGF-10 induced cardiomyocyte differentiation from ES cells and iPS cells, which may have potential for translation into clinical applications

Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3 and KIT driven Leukemogenesis

Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN) and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK), whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis

Using Web Search Query Data to Monitor Dengue Epidemics: A New Model for Neglected Tropical Disease Surveillance

A variety of obstacles, including bureaucracy and lack of resources, delay detection and reporting of dengue and exist in many countries where the disease is a major public health threat. Surveillance efforts have turned to modern data sources such as Internet usage data. People often seek health-related information online and it has been found that the frequency of, for example, influenza-related web searches as a whole rises as the number of people sick with influenza rises. Tools have been developed to help track influenza epidemics by finding patterns in certain web search activity. However, few have evaluated whether this approach would also be effective for other diseases, especially those that affect many people, that have severe consequences, or for which there is no vaccine. In this study, we found that aggregated, anonymized Google search query data were also capable of tracking dengue activity in Bolivia, Brazil, India, Indonesia and Singapore. Whereas traditional dengue data from official sources are often not available until after a long delay, web search query data is available for analysis within a day. Therefore, because it could potentially provide earlier warnings, these data represent a valuable complement to traditional dengue surveillance