Negative Priming Under Rapid Serial Visual Presentation

Negative priming (NP) was examined under a new paradigm wherein a target and distractors were temporally separated using rapid serial visual presentation (RSVP). The results from the two experiments revealed that (a) NP was robust under RSVP, such that the responses to a target were slower when the target served as a distractor in a previous trial than when it did not; (b) NP was found regardless of whether the distractors appeared before or after the targets; and (c) NP was stronger when the distractor was more distinctive. These findings are generally similar to those on NP in the spatial search task. The implications for the processes causing NP under RSVP are discussed in the current paper

Inhibition of NOS- like activity in maize alters the expression of genes involved in H2O2 scavenging and glycine betaine biosynthesis

Nitric oxide synthase-like activity contributes to the production of nitric oxide in plants, which controls plant responses to stress. This study investigates if changes in ascorbate peroxidase enzymatic activity and glycine betaine content in response to inhibition of nitric oxide synthase-like activity are associated with transcriptional regulation by analyzing transcript levels of genes (betaine aldehyde dehydrogenase) involved in glycine betaine biosynthesis and those encoding antioxidant enzymes (ascorbate peroxidase and catalase) in leaves of maize seedlings treated with an inhibitor of nitric oxide synthase-like activity. In seedlings treated with a nitric oxide synthase inhibitor, transcript levels of betaine aldehyde dehydrogenase were decreased. In plants treated with the nitric oxide synthase inhibitor, the transcript levels of ascorbate peroxidase-encoding genes were down-regulated. We thus conclude that inhibition of nitric oxide synthase-like activity suppresses the expression of ascorbate peroxidase and betaine aldehyde dehydrogenase genes in maize leaves. Furthermore, catalase activity was suppressed in leaves of plants treated with nitric oxide synthase inhibitor; and this corresponded with the suppression of the expression of catalase genes. We further conclude that inhibition of nitric oxide synthase-like activity, which suppresses ascorbate peroxidase and catalase enzymatic activities, results in increased H2O2 content

T Regulatory Cells Control Susceptibility to Invasive Pneumococcal Pneumonia in Mice

Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3+Helios+ T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design

Identification of novel small molecules that inhibit STAT3-dependent transcription and function

Activation of Signal Transducer and Activator of Transcription 3 (STAT3) has been linked to several processes that are critical for oncogenic transformation, cancer progression, cancer cell proliferation, survival, drug resistance and metastasis. Inhibition of STAT3 signaling has shown a striking ability to inhibit cancer cell growth and therefore, STAT3 has become a promising target for anti-cancer drug development. The aim of this study was to identify novel inhibitors of STAT-dependent gene transcription. A cellular reporter-based system for monitoring STAT3 transcriptional activity was developed which was suitable for high-throughput screening (Z’ = 0,8). This system was used to screen a library of 28,000 compounds (the ENAMINE Drug-Like Diversity Set). Following counter-screenings and toxicity studies, we identified four hit compounds that were subjected to detailed biological characterization. Of the four hits, KI16 stood out as the most promising compound, inhibiting STAT3 phosphorylation and transcriptional activity in response to IL6 stimulation. In silico docking studies showed that KI16 had favorable interactions with the STAT3 SH2 domain, however, no inhibitory activity could be observed in the STAT3 fluorescence polarization assay. KI16 inhibited cell viability preferentially in STAT3-dependent cell lines. Taken together, using a targeted, cell-based approach, novel inhibitors of STAT-driven transcriptional activity were discovered which are interesting leads to pursue further for the development of anti-cancer therapeutic agents

The personal and contextual contributors to school belongingness among primary school students

School belongingness has gained currency among educators and school health professionals as an important determinant of adolescent health. The current cross-sectional study presents the 15 most significant personal and contextual factors that collectively explain 66.4% (two-thirds) of the variability in 12-year old students' perceptions of belongingness in primary school. The study is part of a larger longitudinal study investigating the factors associated with student adjustment in the transition from primary to secondary school. The study found that girls and students with disabilities had higher school belongingness scores than boys, and their typically developing counterparts respectively; and explained 2.5% of the variability in school belongingness. The majority (47.1% out of 66.4%) of the variability in school belongingness was explained by student personal factors, such as social acceptance, physical appearance competence, coping skills, and social affiliation motivation; followed by parental expectations (3% out of 66.4%), and school-based factors (13.9% out of 66.4%) such as, classroom involvement, task-goal structure, autonomy provision, cultural pluralism, and absence of bullying. Each of the identified contributors of primary school belongingness can be shaped through interventions, system changes, or policy reforms

The genome of the sea urchin Strongylocentrotus purpuratus

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field