Immunohistochemical detection of macrophage migration inhibitory factor in fetal and adult bovine epididymis: Release by the apocrine secretion mode?

Originally defined as a lymphokine inhibiting the random migration of macrophages, the macrophage migration inhibitory factor (MIF) is an important mediator of the host response to infection. Beyond its function as a classical cytokine, MIF is currently portrayed as a multifunctional protein with growth-regulating properties present in organ systems beyond immune cells. In previous studies, we detected substantial amounts of MIF in the rat epididymis and epididymal spermatozoa, where it appears to play a role during post-testicular sperm maturation and the acquisition of fertilization ability. To explore its presence in other species not yet examined in this respect, we extended the range of studies to the bull. Using a polyclonal antibody raised against MIF purified from bovine eye lenses, we detected MIF in the epithelium of the adult bovine epididymis with the basal cells representing a prominently stained cell type. A distinct accumulation of MIF at the apical cell pole of the epithelial cells and in membranous vesicles localized in the lumen of the epididynnal duct was obvious. In the fetal bovine epididymis, we also detected MIF in the epithelium, whereas MIF accumulation was evident at the apical cell surface and in apical protrusions. By immuno-electron microscopy of the adult bovine epididymis, we localized MIF in apical protrusions of the epithelial cells and in luminal membrane-bound vesicles that were found in close proximity to sperm cells. Although the precise origin of the MIF-containing vesicles remains to be delineated, our morphological observations support the hypothesis that they become detached from the apical surface of the epididymal epithelial cells. Additionally, an association of MIF with the outer dense fibers of luminal spermatozoa was demonstrated. Data obtained in this study suggest MIF release by an apocrine secretion mode in the bovine epididymis. Furthermore, MIF localized in the basal cells of the epithelium and in the connective tissue could be responsible for regulating the migration of macrophages in order to avoid contact of immune cells with spermatozoa that carry a wide range of potent antigens. Copyright (c) 2006 S. Karger AG, Basel

Confound-leakage: confound removal in machine learning leads to leakage

BACKGROUND: Machine learning (ML) approaches are a crucial component of modern data analysis in many fields, including epidemiology and medicine. Nonlinear ML methods often achieve accurate predictions, for instance, in personalized medicine, as they are capable of modeling complex relationships between features and the target. Problematically, ML models and their predictions can be biased by confounding information present in the features. To remove this spurious signal, researchers often employ featurewise linear confound regression (CR). While this is considered a standard approach for dealing with confounding, possible pitfalls of using CR in ML pipelines are not fully understood. RESULTS: We provide new evidence that, contrary to general expectations, linear confound regression can increase the risk of confounding when combined with nonlinear ML approaches. Using a simple framework that uses the target as a confound, we show that information leaked via CR can increase null or moderate effects to near-perfect prediction. By shuffling the features, we provide evidence that this increase is indeed due to confound-leakage and not due to revealing of information. We then demonstrate the danger of confound-leakage in a real-world clinical application where the accuracy of predicting attention-deficit/hyperactivity disorder is overestimated using speech-derived features when using depression as a confound. CONCLUSIONS: Mishandling or even amplifying confounding effects when building ML models due to confound-leakage, as shown, can lead to untrustworthy, biased, and unfair predictions. Our expose of the confound-leakage pitfall and provided guidelines for dealing with it can help create more robust and trustworthy ML models

Differential binding studies applying functional protein microarrays and surface plasmon resonance

A variety of different in vivo and in vitro technologies provide comprehensive insights in protein-protein interaction networks. Here we demonstrate a novel approach to analyze, verify and quantify putative interactions between two members of the S100 protein family and 80 recombinant proteins derived from a proteome-wide protein expression library. Surface plasmon resonance (SPR) using Biacore technology and functional protein microarrays were used as two independent methods to study protein-protein interactions. With this combined approach we were able to detect nine calcium-dependent interactions between Arg-Gly-Ser-(RGS)-His6 tagged proteins derived from the library and GST-tagged S100B and S100A6, respectively. For the protein microarray affinity-purified proteins from the expression library were spotted onto modified glass slides and probed with the S100 proteins. SPR experiments were performed in the same setup and in a vice-versa approach reversing analytes and ligands to determine distinct association and dissociation patterns of each positive interaction. Besides already known interaction partners, several novel binders were found independently with both detection methods, albeit analogous immobilization strategies had to be applied in both assays

Identification of proteins from Mycobacterium tuberculosis missing in attenuated Mycobacterium bovis BCG strains.

A proteome approach, combining high-resolution two-dimensional electrophoresis (2-DE) with mass spectrometry, was used to compare the cellular protein composition of two virulent strains of Mycobacterium tuberculosis with two attenuated strains of Mycobacterium bovis Bacillus Calmette-Guerin (BCG), in order to identify unique proteins of these strains. Emphasis was given to the identification of M. tuberculosis specific proteins, because we consider these proteins to represent putative virulence factors and interesting candidates for vaccination and diagnosis of tuberculosis. The genome of M. tuberculosis strain H37Rv comprises nearly 4000 predicted open reading frames. In contrast, the separation of proteins from whole mycobacterial cells by 2-DE resulted in silver-stained patterns comprising about 1800 distinct protein spots. Amongst these, 96 spots were exclusively detected either in the virulent (56 spots) or in the attenuated (40 spots) mycobacterial strains. Fifty-three of these spots were analyzed by mass spectrometry, of which 41 were identified, including 32 M. tuberculosis specific spots. Twelve M. tuberculosis specific spots were identified as proteins, encoded by genes previously reported to be deleted in M. bovis BCG. The remaining 20 spots unique for M. tuberculosis were identified as proteins encoded by genes that are not known to be missing in M. bovis BCG

Late Proterozoic Patsy Springs Canyon, Adelaide Geosyncline: Submarine or Subaerial Origin?

A significant aspect of Late Proterozoic sedimentation in the Adelaide Geosyncline, South Australia, is the presence of kilometre-deep erosional incisions which have been termed canyons. These structures were formerly described to be of submarine origin, cut and filled in an inferred basin-slope setting by subaqueous processes. Subsequent detailed research, particularly on a specific incision known as Patsy Springs Canyon, indicates that sedimentary structures within some of the canyon-filling sediments are indicative of deposition above fair weather wave base. In addition, an unusual carbonate unit, which is observed to veneer upper portions of canyon shoulders and to contribute to carbonate breccias interbedded with canyon-fill, has a stable isotope signature which may imply a non-marine origin. The presence of the carbonate veneer, where it is in situ, suggests that at least upper portions of the canyons could have been emergent during the canyon-filling phase. Considering these observations, and combining them with regional stratigraphical relationships, an alternative model for canyon genesis is proposed involving subaerial erosion and subsequent filling by coastal onlap. Such a model requires base-level changes of the order of 1 km, in order to account for observed canyon cutting and filling. Vertical movements associated with halokinesis, or thermally-induced uplift of the order of 1 km, could have resulted in the observed erosional events. Alternatively, a Messinian-style evaporitic lowering of base-level is currently receiving serious attention. With present knowledge this mechanism most satisfactorily explains all observations

The BrainMap strategy for standardization, sharing, and meta-analysis of neuroimaging data

<p>Abstract</p> <p>Background</p> <p>Neuroimaging researchers have developed rigorous community data and metadata standards that encourage meta-analysis as a method for establishing robust and meaningful convergence of knowledge of human brain structure and function. Capitalizing on these standards, the BrainMap project offers databases, software applications, and other associated tools for supporting and promoting quantitative coordinate-based meta-analysis of the structural and functional neuroimaging literature.</p> <p>Findings</p> <p>In this report, we describe recent technical updates to the project and provide an educational description for performing meta-analyses in the BrainMap environment.</p> <p>Conclusions</p> <p>The BrainMap project will continue to evolve in response to the meta-analytic needs of biomedical researchers in the structural and functional neuroimaging communities. Future work on the BrainMap project regarding software and hardware advances are also discussed.</p

Influence of Processing Pipeline on Cortical Thickness Measurement

In recent years, replicability of neuroscientific findings, specifically those concerning correlates of morphological properties of gray matter (GM), have been subject of major scrutiny. Use of different processing pipelines and differences in their estimates of the macroscale GM may play an important role in this context. To address this issue, here, we investigated the cortical thickness estimates of three widely used pipelines. Based on analyses in two independent large-scale cohorts, we report high levels of within-pipeline reliability of the absolute cortical thickness-estimates and comparable spatial patterns of cortical thickness-estimates across all pipelines. Within each individual, absolute regional thickness differed between pipelines, indicating that in-vivo thickness measurements are only a proxy of actual thickness of the cortex, which shall only be compared within the same software package and thickness estimation technique. However, at group level, cortical thickness-estimates correlated strongly between pipelines, in most brain regions. The smallest between-pipeline correlations were observed in para-limbic areas and insula. These regions also demonstrated the highest interindividual variability and the lowest reliability of cortical thickness-estimates within each pipeline, suggesting that structural variations within these regions should be interpreted with caution

Dynamic stabilization zone structure of jet diffusion flames from liftoff to blowout

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76733/1/AIAA-23512-341.pd