Identification of calcium-binding proteins associated with the human sperm plasma membrane

<p>Abstract</p> <p>Background</p> <p>The precise composition of the human sperm plasma membrane, the molecular interactions that define domain specific functions, and the regulation of membrane associated proteins during the capacitation process, still remain to be fully understood. Here, we investigated the repertoire of calcium-regulated proteins associated with the human sperm plasma membrane.</p> <p>Methods</p> <p>Surface specific radioiodination was combined with two-dimensional gel electrophoresis, a 45Ca-overlay assay, computer assisted image analysis and mass spectrometry to identify calcium-binding proteins exposed on the human sperm surface.</p> <p>Results</p> <p>Nine acidic 45Ca-binding sperm proteins were excised from stained preparative 2D gels and identified by mass spectrometry. Five of the calcium binding proteins; HSPA2 (HSP70-1), HSPA5 (Bip), HYOU1 (ORP150), serum amyloid P-component (SAP) and protein kinase C substrate 80K-H (80K-H) were found to be accessible to Iodo-Bead catalyzed 125I-labelling on the surface of intact human sperm. Agglutination and immunofluorescence analysis confirmed that SAP is situated on the plasma membrane of intact, motile sperm as well as permeabilized cells. Western blot analysis showed increased phosphorylation of human sperm 80K-H protein following in vitro capacitation. This is the first demonstration of the 80K-H protein in a mammalian sperm.</p> <p>Conclusion</p> <p>The presence of SAP on the surface of mature sperm implies that SAP has a physiological role in reproduction, which is thought to be in the removal of spermatozoa from the female genital tract via phagocytosis. Since 80K-H is a Ca2+-sensor recently implicated in the regulation of both inositol 1,4,5-trisphosphate receptor and transient receptor potential (TRP) cation channel activities, its detection in sperm represents the first direct signaling link between PKC and store-operated calcium channels identified in human sperm.</p

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Comparing the response of birds and butterflies to vegetation-based mountain ecotones using boundary detection approaches

Mountains provide an opportunity to examine changes in biodiversity across environmental gradients and areas of transition (ecotones). Mountain ecotones separate vegetation belts. Here, we aimed to examine whether transition areas for birds and butterflies spatially correspond with ecotones between three previously described altitudinal vegetation belts on Mt. Hermon, northern Israel. These include the Mediterranean Maquis, xero-montane open forest and Tragacanthic mountain steppe vegetation belts. We sampled the abundance of bird and butterfly species in 34 sampling locations along an elevational gradient between 500 and 2200 m. We applied wombling, a boundary-detection technique, which detects rapid changes in a continuous variable, in order to locate the transition areas for bird and butterfly communities and compare the location of these areas with the location of vegetation belts as described in earlier studies of Mt. Hermon. We found some correspondence between the areas of transition of both bird and butterfly communities and the ecotones between vegetation belts. For birds and butterflies, important transitions occurred at the lower vegetation ecotone between Mediterranean maquis and the xero-montane open forest vegetation belts, and between the xero-montane open forest and the mountain steppe Tragacanthic belts. While patterns of species turnover with elevation were similar for birds and butterflies, the change in species richness and diversity with elevation differed substantially between the two taxa. Birds and butterflies responded quite similarly to the elevational gradient and to the shift between vegetation belts in terms of species turnover rates. While the mechanisms generating these patterns may differ, the resulting areas of peak turnover in species show correspondence among three different taxa (plants, birds and butterflies)

The rejection of industrial democracy by Berle and Means and the emergence of the ideology of managerialism.

One distinctive feature of the American variant of capitalism is the near absence of any of the industrial democracy institutions found in many European firms. This article examines ideology as a factor behind the absence of industrial democracy institutions in the United States. It focuses on the early 1930s, when the ideology of managerialism was being formulated by Adolf Berle and Gardiner Means, the authors of a book that had a well-documented influence on American business culture. As the article shows, many American firms in the 1910s and 1920s experimented with worker representation systems that contemporaries called industrial democracy. Berle and Means were aware of these moves to democratize the American workplace, but they rejected all forms of industrial democracy. The article advances an explanation for their rejection and thereby contributes to our understanding why the United States did not take the path towards democracy within companies

Microglia in neurodegenerative disease

Microglia, the resident macrophages of the CNS, are exquisitely sensitive to brain injury and disease, altering their morphology and phenotype to adopt a so-called activated state in response to pathophysiological brain insults. Morphologically activated microglia, like other tissue macrophages, exist as many different phenotypes, depending on the nature of the tissue injury. Microglial responsiveness to injury suggests that these cells have the potential to act as diagnostic markers of disease onset or progression, and could contribute to the outcome of neurodegenerative diseases. The persistence of activated microglia long after acute injury and in chronic disease suggests that these cells have an innate immune memory of tissue injury and degeneration. Microglial phenotype is also modified by systemic infection or inflammation. Evidence from some preclinical models shows that systemic manipulations can ameliorate disease progression, although data from other models indicates that systemic inflammation exacerbates disease progression. Systemic inflammation is associated with a decline in function in patients with chronic neurodegenerative disease, both acutely and in the long term. The fact that diseases with a chronic systemic inflammatory component are risk factors for Alzheimer disease implies that crosstalk occurs between systemic inflammation and microglia in the CNS