Edge Detection in Landing Budgerigars (Melopsittacus undulatus)

Background: While considerable scientific effort has been devoted to studying how birds navigate over long distances, relatively little is known about how targets are detected, obstacles are avoided and smooth landings are orchestrated. Here we examine how visual features in the environment, such as contrasting edges, determine where a bird will land. Methodology/Principal Findings: Landing in budgerigars (Melopsittacus undulatus) was investigated by training them to fly from a perch to a feeder, and video-filming their landings. The feeder was placed on a grey disc that produced a contrasting edge against a uniformly blue background. We found that the birds tended to land primarily at the edge of the disc and walk to the feeder, even though the feeder was in the middle of the disc. This suggests that the birds were using the visual contrast at the boundary of the disc to target their landings. When the grey level of the disc was varied systematically, whilst keeping the blue background constant, there was one intermediate grey level at which the budgerigar's preference for the disc boundary disappeared. The budgerigars then landed randomly all over the test surface. Even though this disc is (for humans) clearly distinguishable from the blue background, it offers very little contrast against the background, in the red and green regions of the spectrum. Conclusions: We conclude that budgerigars use visual edges to target and guide landings. Calculations of photoreceptor excitation reveal that edge detection in landing budgerigars is performed by a color-blind luminance channel that sums the signals from the red and green photoreceptors, or, alternatively, receives input from the red double-cones. This finding has close parallels to vision in honeybees and primates, where edge detection and motion perception are also largely color-blind

Normative values for the Foot Posture Index

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Adjuvant TACE inhibitor treatment improves the outcome of TLR2(-/- )mice with experimental pneumococcal meningitis

BACKGROUND: Streptococcus (S.) pneumoniae meningitis has a high lethality despite antibiotic treatment. Inflammation is a major pathogenetic factor, which is unresponsive to antibiotics. Therefore adjunctive therapies with antiinflammatory compounds have been developed. TNF484 is a TNF-alpha converting enzyme (TACE) inhibitor and has been found efficacious in experimental meningitis. Toll-like receptor 2 (TLR2) contributes to host response in pneumococcal meningitis by enhancing bacterial clearing and downmodulating inflammation. In this study, TNF484 was applied in mice, which lacked TLR2 and exhibited a strong meningeal inflammation. METHODS: 10(3 )CFU S. pneumoniae serotype 3 was inoculated subarachnoidally into C57BL/6 wild type (wt) mice or TLR2(-/-), CD14(-/- )and CD14(-/-)/TLR2(-/- )mice. Severity of disease and survival was followed over 9 days. Response to antibiotics (80 mg/kg ceftriaxone i.p. for 5 days) and/or TACE inhibitor treatment (1 mg/kg s.c. twice daily for 4 days) was evaluated. Animals were sacrificed after 12, 24, and 48 h for analysis of bacterial load in cerebrospinal fluid (CSF) and brain and for TNF and leukocyte measurements in CSF. RESULTS: TLR2(-/- )mice were significantly sicker than the other mouse strains 24 h after infection. All knockout mice showed higher disease severity after 48 h and died earlier than wt mice. TNF release into CSF was significantly more elevated in TLR2(-/- )than in the other strains after 24 h. Brain bacterial numbers were significantly higher in all knockout than wt mice after 24 h. Modulation of outcome by antibiotic and TACE inhibitor treatment was evaluated. With antibiotic therapy all wt, CD14(-/- )and TLR2(-/-)/CD14(-/- )mice, but only 79% of TLR2(-/- )mice, were rescued. TACE inhibitor treatment alone did not rescue, but prolonged survival in wt mice, and in TLR2(-/- )and CD14(-/- )mice to the values observed in untreated wt mice. By combined antibiotic and TACE inhibitor treatment 95% of TLR2(-/- )mice were rescued. CONCLUSION: During pneumococcal meningitis strong inflammation in TLR2-deficiency was associated with incomplete responsiveness to antibiotics and complete response to combined antibiotic and TACE inhibitor treatment. TACE inhibitor treatment offers a promising adjuvant therapeutic strategy in pneumococcal meningitis

PatternLab for proteomics: a tool for differential shotgun proteomics

<p>Abstract</p> <p>Background</p> <p>A goal of proteomics is to distinguish between states of a biological system by identifying protein expression differences. Liu <it>et al</it>. demonstrated a method to perform semi-relative protein quantitation in shotgun proteomics data by correlating the number of tandem mass spectra obtained for each protein, or "spectral count", with its abundance in a mixture; however, two issues have remained open: how to normalize spectral counting data and how to efficiently pinpoint differences between profiles. Moreover, Chen <it>et al</it>. recently showed how to increase the number of identified proteins in shotgun proteomics by analyzing samples with different MS-compatible detergents while performing proteolytic digestion. The latter introduced new challenges as seen from the data analysis perspective, since replicate readings are not acquired.</p> <p>Results</p> <p>To address the open issues above, we present a program termed PatternLab for proteomics. This program implements existing strategies and adds two new methods to pinpoint differences in protein profiles. The first method, ACFold, addresses experiments with less than three replicates from each state or having assays acquired by different protocols as described by Chen <it>et al</it>. ACFold uses a combined criterion based on expression fold changes, the AC test, and the false-discovery rate, and can supply a "bird's-eye view" of differentially expressed proteins. The other method addresses experimental designs having multiple readings from each state and is referred to as nSVM (natural support vector machine) because of its roots in evolutionary computing and in statistical learning theory. Our observations suggest that nSVM's niche comprises projects that select a minimum set of proteins for classification purposes; for example, the development of an early detection kit for a given pathology. We demonstrate the effectiveness of each method on experimental data and confront them with existing strategies.</p> <p>Conclusion</p> <p>PatternLab offers an easy and unified access to a variety of feature selection and normalization strategies, each having its own niche. Additionally, graphing tools are available to aid in the analysis of high throughput experimental data. PatternLab is available at <url>http://pcarvalho.com/patternlab</url>.</p

A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal

Polyfunctional Hiv-Specific Antibody Responses Are Associated with Spontaneous Hiv Control

Elite controllers (ECs) represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC) that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune–recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

AYUMS: an algorithm for completely automatic quantitation based on LC-MS/MS proteome data and its application to the analysis of signal transduction

BACKGROUND: Comprehensive description of the behavior of cellular components in a quantitative manner is essential for systematic understanding of biological events. Recent LC-MS/MS (tandem mass spectrometry coupled with liquid chromatography) technology, in combination with the SILAC (Stable Isotope Labeling by Amino acids in Cell culture) method, has enabled us to make relative quantitation at the proteome level. The recent report by Blagoev et al. (Nat. Biotechnol., 22, 1139–1145, 2004) indicated that this method was also applicable for the time-course analysis of cellular signaling events. Relative quatitation can easily be performed by calculating the ratio of peak intensities corresponding to differentially labeled peptides in the MS spectrum. As currently available software requires some GUI applications and is time-consuming, it is not suitable for processing large-scale proteome data. RESULTS: To resolve this difficulty, we developed an algorithm that automatically detects the peaks in each spectrum. Using this algorithm, we developed a software tool named AYUMS that automatically identifies the peaks corresponding to differentially labeled peptides, compares these peaks, calculates each of the peak ratios in mixed samples, and integrates them into one data sheet. This software has enabled us to dramatically save time for generation of the final report. CONCLUSION: AYUMS is a useful software tool for comprehensive quantitation of the proteome data generated by LC-MS/MS analysis. This software was developed using Java and runs on Linux, Windows, and Mac OS X. Please contact [email protected] if you are interested in the application. The project web page is

Selected static foot assessments do not predict medial longitudinal arch motion during running

Background: Static assessments of the foot are commonly advocated within the running community to classify the foot with a view to recommending the appropriate type of running shoe. The aim of this work was to determine whether selected static foot assessment could predict medial longitudinal arch (MLA) motion during running. Methods: Fifteen physically active males (27 ± 5 years, 1.77 ± 0.04m, 80 ± 10kg) participated in the study. Foot Posture Index (FPI-6), MLA angle and rearfoot angle were measured in a relaxed standing position. MLA motion was calculated using the position of retro-reflective markers tracked by a VICON motion analysis system, while participants ran barefoot on a treadmill at a self-selected pace (2.8 ± 0.5m.s-1). Bivariate linear regression was used to determine whether the static measures predicted MLA deformation and MLA angles at initial contact, midsupport and toe off. Results: All three foot classification measures were significant predictors of MLA angle at initial contact, midsupport and toe off (p < .05) explaining 41-90% of the variance. None of the static foot classification measures were significant predictors of MLA deformation during the stance phase of running. Conclusion: Selected static foot measures did not predict dynamic MLA deformation during running. Given that MLA deformation has theoretically been linked to running injuries, the clinical relevance of predicting MLA angle at discrete time points during the stance phase of running is questioned. These findings also question the validity of the selected static foot classification measures when looking to characterise the foot during running. This indicates that alternative means of assessing the foot to inform footwear selection are required