A Template for Preregistration of Quantitative Research in Psychology: Report of the Joint Psychological Societies Preregistration Task Force

Recent years have seen dramatic changes in research practices in psychological science. In particular, preregistration of study plans before conducting a study has been identified as an important tool to help increase the transparency of science and to improve the robustness of psychological research findings. This article presents the Psychological Research Preregistration-Quantitative (PRP-QUANT) Template produced by a Joint Psychological Societies Preregistration Task Force consisting of the American Psychological Association (APA), the British Psychological Society (BPS), and the German Psychological Society (DGPs), supported by the Center for Open Science (COS) and the Leibniz Institute for Psychology (ZPID). The goal of the Task Force was to provide the psychological community with a consensus template for the preregistration of quantitative research in psychology, one with wide coverage and the ability, if necessary, to adapt to specific journals, disciplines, and researcher needs. This article covers the structure and use of the PRP-QUANT template, while outlining and discussing the benefits of its use for researchers, authors, funders, and other relevant stakeholders. We hope that by introducing this template and by demonstrating the support of preregistration by major academic psychological societies, we will facilitate an increase in preregistration practices and also the further advancement of transparency and knowledge-sharing in the psychological sciences

Dopaminergic modulation of appetitive trace conditioning: the role of D1 receptors in medial prefrontal cortex

Rationale: Trace conditioning may provide a behavioural model suitable to examine the maintenance of ‘on line’ information and its underlying neural substrates. Objectives: Experiment la was run to establish trace conditioning in a shortened procedure which would be suitable to test the effects of dopamine (DA) D1 receptor agents administered by microinjection directly into the brain. Experiment lb examined the effects of the DA D1 agonist SKF81297 and the DA D1 antagonist SCH23390 following systemic administration in pre-trained animals. Experiment 2 went on to test the effects of systemically administered SKF81297 on the acquisition of trace conditioning. In experiment 3, SKF81297 was administered directly in prelimbic (PL) and infralimbic (IL) sub-regions of medial prefrontal cortex (mPFC) to compare the role of different mPFC sub-regions. Results: Whilst treatment with SCH23390 impaired motor responding and/or motivation, SKF81297 had relatively little effect in the pre-trained animals tested in experiment 1b. However, systemic SKF81297 depressed the acquisition function at the 2-s trace interval in experiment 2. Similarly, in experiment 3, SKF81297 (0.1 μg in 1.0 μl) microinjected into either PL or IL mPFC impaired appetitive conditioning at the 2-s trace interval. Conclusions: Impaired trace conditioning under SKF81297 is likely to be mediated in part (but not exclusively) within the IL and PL mPFC sub-regions. The finding that trace conditioning was impaired rather than enhanced under SKF81297 provides further evidence for the inverse U-function which has been suggested to be characteristic of mPFC DA function

Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription Factor CSL

Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.Here, we utilized protein-binding microarrays (PBMs) to compare the binding site preferences of isolated CSL with the preferred binding sites of CSL when bound to the CSL-binding domains of all four different human Notch receptors. Measurements were taken both in the absence and in the presence of Mastermind-like-1 (MAML1). Our data show no detectable difference in the DNA binding site preferences of CSL before and after loading of Notch and MAML1 proteins.These findings support the conclusion that accrual of Notch and MAML1 promote transcriptional activation without dramatically altering the preferred sites of DNA binding, and illustrate the potential of PBMs to analyze the binding site preferences of multiprotein-DNA complexes

Dynamics of Molecular Evolution and Phylogeography of Barley yellow dwarf virus-PAV

Barley yellow dwarf virus (BYDV) species PAV occurs frequently in irrigated wheat fields worldwide and can be efficiently transmitted by aphids. Isolates of BYDV-PAV from different countries show great divergence both in genomic sequences and pathogenicity. Despite its economical importance, the genetic structure of natural BYDV-PAV populations, as well as of the mechanisms maintaining its high diversity, remain poorly explored. In this study, we investigate the dynamics of BYDV-PAV genome evolution utilizing time-structured data sets of complete genomic sequences from 58 isolates from different hosts obtained worldwide. First, we observed that BYDV-PAV exhibits a high frequency of homologous recombination. Second, our analysis revealed that BYDV-PAV genome evolves under purifying selection and at a substitution rate similar to other RNA viruses (3.158×10−4 nucleotide substitutions/site/year). Phylogeography analyses show that the diversification of BYDV-PAV can be explained by local geographic adaptation as well as by host-driven adaptation. These results increase our understanding of the diversity, molecular evolutionary characteristics and epidemiological properties of an economically important plant RNA virus

Bursts and Isolated Spikes Code for Opposite Movement Directions in Midbrain Electrosensory Neurons

Directional selectivity, in which neurons respond strongly to an object moving in a given direction but weakly or not at all to the same object moving in the opposite direction, is a crucial computation that is thought to provide a neural correlate of motion perception. However, directional selectivity has been traditionally quantified by using the full spike train, which does not take into account particular action potential patterns. We investigated how different action potential patterns, namely bursts (i.e. packets of action potentials followed by quiescence) and isolated spikes, contribute to movement direction coding in a mathematical model of midbrain electrosensory neurons. We found that bursts and isolated spikes could be selectively elicited when the same object moved in opposite directions. In particular, it was possible to find parameter values for which our model neuron did not display directional selectivity when the full spike train was considered but displayed strong directional selectivity when bursts or isolated spikes were instead considered. Further analysis of our model revealed that an intrinsic burst mechanism based on subthreshold T-type calcium channels was not required to observe parameter regimes for which bursts and isolated spikes code for opposite movement directions. However, this burst mechanism enhanced the range of parameter values for which such regimes were observed. Experimental recordings from midbrain neurons confirmed our modeling prediction that bursts and isolated spikes can indeed code for opposite movement directions. Finally, we quantified the performance of a plausible neural circuit and found that it could respond more or less selectively to isolated spikes for a wide range of parameter values when compared with an interspike interval threshold. Our results thus show for the first time that different action potential patterns can differentially encode movement and that traditional measures of directional selectivity need to be revised in such cases

An Incomplete TCA Cycle Increases Survival of Salmonella Typhimurium during Infection of Resting and Activated Murine Macrophages

In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice.We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence.Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous

The Transcription Factor SOX18 Regulates the Expression of Matrix Metalloproteinase 7 and Guidance Molecules in Human Endothelial Cells

Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one, MMP7, in detail.SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene, MMP7, was chosen for further analysis, including detailed promoter studies using reporter gene assays, electrophoretic mobility shift analysis and chromatin-immunoprecipitation, revealing that it responds directly to SOX18. Immunohistochemical analysis demonstrated the co-expression of SOX18 and MMP7 in blood vessels of human skin.The identification of MMP7 as a direct SOX18 target gene as well as other potential candidates including guidance molecules provides a molecular basis for the proposed function of this transcription factor in the regulation of vessel formation

Investigating the Antiproliferative Activity of High Affinity DNA Aptamer on Cancer Cells

10.1371/journal.pone.0050964PLoS ONE81

Management of hydrocele in adolescent patients

Hydrocele is defined as an abnormal collection of serous fluid in the potential space between the parietal and visceral layers of the tunica vaginalis. In the majority of affected adolescents, hydrocele is acquired and is idiopathic in origin. The pathogenesis of idiopathic hydrocele is thought to be an imbalance in the normal process of fluid production and reabsorption. The diagnosis is usually clinical. Taking a thorough history is essential to rule out any fluctuation in size, which is an indication of a patent processus vaginalis. Scrotal ultrasonography is mandatory in nonpalpable testicles to rule out a subtending testicular solid mass requiring inguinal exploration. Otherwise, open hydrocelectomy via a scrotal incision is the standard treatment of idiopathic hydroceles. The second most common cause of hydrocele in adolescents is varicocelectomy. The risk of hydrocele formation is higher with non-artery-sparing procedures or those performed without microsurgical aid, and in surgery requiring cord dissection. If hydrocele occurs after varicocelectomy, initial management should include observation with or without hydrocele aspiration. Large persistent hydroceles are best served by open hydrocelectomy