417 research outputs found

    Drebrin is a novel connexin-43 binding partner that links gap junctions to the submembrane cytoskeleton

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    AbstractBackground: Connexins form gap junctions that mediate the transfer of ions, metabolites, and second messengers between contacting cells. Many aspects of connexin function, for example cellular transport, plaque assembly and stability, and channel conductivity, are finely tuned and likely involve proteins that bind to connexins' cytoplasmic domains. However, little is known about such regulatory proteins. To identify novel proteins that interact with the COOH-terminal domain of Connexin-43 (Cx43), the most widely expressed connexin family member, we applied a proteomics approach to screen fractions of mouse tissue homogenates for binding partners.Results: Drebrin was recovered as a binding partner of the Cx43 COOH-terminal domain from mouse brain homogenate. Drebrin had previously been described as an actin binding protein that diminishes in brains during Alzheimer's disease. The novel Drebrin-Cx43 interaction identified by proteomics was confirmed by colocalization of endogenous proteins in astrocytes and Vero cells, coimmunoprecipitation, electron microscopy, electrophysiology, coexpression of both proteins with fluorescent tags, and live-cell FRET analysis. Depletion of Drebrin in cells with siRNA results in impaired cell-cell coupling, internalization of gap junctions, and targeting of Cx43 to a degradative pathway.Conclusions: We conclude that Drebrin is required for maintaining Cx43-containing gap junctions in their functional state at the plasma membrane. It is thus possible that Drebrin may interact with gap junctions in zones of cell-cell contacts in a regulated fashion in response to extracellular signals. The rearrangement or disruption of interactions between connexins and the Drebrin-containing submembrane cytoskeleton directs connexins to degradative cellular pathways

    Beta-COP localizes mainly to the cis-Golgi side in exocrine pancreas.

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    Influence of uncorrelated overlayers on the magnetism in thin itinerant-electron films

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    The influence of uncorrelated (nonmagnetic) overlayers on the magnetic properties of thin itinerant-electron films is investigated within the single-band Hubbard model. The Coulomb correlation between the electrons in the ferromagnetic layers is treated by using the spectral density approach (SDA). It is found that the presence of nonmagnetic layers has a strong effect on the magnetic properties of thin films. The Curie temperatures of very thin films are modified by the uncorrelated overlayers. The quasiparticle density of states is used to analyze the results. In addition, the coupling between the ferromagnetic layers and the nonmagnetic layers is discussed in detail. The coupling depends on the band occupation of the nonmagnetic layers, while it is almost independent of the number of the nonmagnetic layers. The induced polarization in the nonmagnetic layers shows a long-range decreasing oscillatory behavior and it depends on the coupling between ferromagnetic and nonmagnetic layers.Comment: 9 pages, RevTex, 6 figures, for related work see: http://orion.physik.hu-berlin.d

    Beyond the Womb and the Tomb: Identity, (Dis)embodiment and the Life Course

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    Grounded in the authors’ theoretical and ethnographic work on pregnancy and social life after death, this article explores the ways in which the body is involved in processes of identification. With a focus on the embodied nature of social identity, the article nonetheless problematizes a model of the life course that begins at the moments of birth and ends at death. Instead, it offers a more extended temporal perspective and examines other ways in which identity may be claimed, for example, via material objects and practices which evoke the body as imagined or remembered. By documenting pre-birth and post-mortem identity-making of this kind, it demonstrates how the unborn and the dead may come into social existence. In addition, a cultural privileging of both the body and visuality is shown to shore up the capacity of material objects and practices to shape social identities in a highly selective fashion. The article therefore proposes that models of the life course need to accommodate the meanings of pre-birth and post-mortem materialities and so incorporate a conceptualization of social identity as contested, relational and inevitably incomplete

    Multilab Direct Replication of Flavell, Beach, and Chinsky (1966): Spontaneous Verbal Rehearsal in a Memory Task as a Function of Age

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    Work by Flavell, Beach, and Chinsky indicated a change in the spontaneous production of overt verbalization behaviors when comparing young children (age 5) with older children (age 10). Despite the critical role that this evidence of a change in verbalization behaviors plays in modern theories of cognitive development and working memory, there has been only one other published near replication of this work. In this Registered Replication Report, we relied on researchers from 17 labs who contributed their results to a larger and more comprehensive sample of children. We assessed memory performance and the presence or absence of verbalization behaviors of young children at different ages and determined that the original pattern of findings was largely upheld: Older children were more likely to verbalize, and their memory spans improved. We confirmed that 5- and 6-year-old children who verbalized recalled more than children who did not verbalize. However, unlike Flavell et al., substantial proportions of our 5- and 6-year-old samples overtly verbalized at least sometimes during the picture memory task. In addition, continuous increase in overt verbalization from 7 to 10 years old was not consistently evident in our samples. These robust findings should be weighed when considering theories of cognitive development, particularly theories concerning when verbal rehearsal emerges and relations between speech and memory

    International differences in employee silence motives: Scale validation, prevalence, and relationships with culture characteristics across 33 Countries

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    Employee silence, the withholding of work-related ideas, questions, or concerns from someone who could effect change, has been proposed to hamper individual and collective learning as well as the detection of errors and unethical behaviors in many areas of the world. To facilitate cross-cultural research, we validated an instrument measuring four employee silence motives (i.e., silence based on fear, resignation, prosocial, and selfish motives) in 21 languages. Across 33 countries (N = 8,222) representing diverse cultural clusters, the instrument shows good psychometric properties (i.e., internal reliabilities, factor structure, measurement invariance). Results further revealed similarities and differences in the prevalence of silence motives between countries, but did not necessarily support cultural stereotypes. To explore the role of culture for silence, we examined relationships of silence motives with the societal practices cultural dimensions from the GLOBE Program. We found relationships between silence motives and power distance, institutional collectivism, and uncertainty avoidance. Overall, the findings suggest that relationships between silence and cultural dimensions are more complex than commonly assumed. We discuss the explanatory power of nations as (cultural) units of analysis, our social scientific approach, the predictive value of cultural dimensions, and opportunities to extend silence research geographically, methodologically, and conceptuallyinfo:eu-repo/semantics/publishedVersio

    Abortive Autophagy Induces Endoplasmic Reticulum Stress and Cell Death in Cancer Cells

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    Autophagic cell death or abortive autophagy has been proposed to eliminate damaged as well as cancer cells, but there remains a critical gap in our knowledge in how this process is regulated. The goal of this study was to identify modulators of the autophagic cell death pathway and elucidate their effects on cellular signaling and function. The result of our siRNA library screenings show that an intact coatomer complex I (COPI) is obligatory for productive autophagy. Depletion of COPI complex members decreased cell survival and impaired productive autophagy which preceded endoplasmic reticulum stress. Further, abortive autophagy provoked by COPI depletion significantly altered growth factor signaling in multiple cancer cell lines. Finally, we show that COPI complex members are overexpressed in an array of cancer cell lines and several types of cancer tissues as compared to normal cell lines or tissues. In cancer tissues, overexpression of COPI members is associated with poor prognosis. Our results demonstrate that the coatomer complex is essential for productive autophagy and cellular survival, and thus inhibition of COPI members may promote cell death of cancer cells when apoptosis is compromised

    Holding blame at bay? ‘Gene talk’ in family members’ accounts of schizophrenia aetiology

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    We provide the first detailed analysis of how, for what purposes and with what consequences people related to someone with a diagnosis of schizophrenia use ‘gene talk'. The article analyses findings from a qualitative interview study conducted in London and involving 19 participants (mostly women). We transcribed the interviews verbatim and analysed them using grounded theory methods. We analyse how and for what purposes participants mobilized ‘gene talk' in their affectively freighted encounter with an unknown interviewer. Gene talk served to (re)position blame and guilt, and was simultaneously used imaginatively to forge family history narratives. Family members used ‘gene talk' to recruit forebears with no psychiatric diagnosis into a family history of mental illness, and presented the origins of the diagnosed family member's schizophrenia as lying temporally before, and hence beyond the agency of the immediate family. Gene talk was also used in attempts to dislodge the distressing figure of the schizophrenia-inducing mother. ‘Gene talk', however, ultimately displaced, rather than resolved, the (self-)blame of many family members, particularly mothers. Our article challenges the commonly expressed view that genetic accounts will absolve family members' sense of (self-)blame in relation to their relative's/relatives' diagnosis

    Transmembrane protein PERP is a component of tessellate junctions and of other junctional and non-junctional plasma membrane regions in diverse epithelial and epithelium-derived cells

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    Protein PERP (p53 apoptosis effector related to PMP-22) is a small (21.4 kDa) transmembrane polypeptide with an amino acid sequence indicative of a tetraspanin character. It is enriched in the plasma membrane and apparently contributes to cell-cell contacts. Hitherto, it has been reported to be exclusively a component of desmosomes of some stratified epithelia. However, by using a series of newly generated mono- and polyclonal antibodies, we show that protein PERP is not only present in all kinds of stratified epithelia but also occurs in simple, columnar, complex and transitional epithelia, in various types of squamous metaplasia and epithelium-derived tumors, in diverse epithelium-derived cell cultures and in myocardial tissue. Immunofluorescence and immunoelectron microscopy allow us to localize PERP predominantly in small intradesmosomal locations and in variously sized, junction-like peri- and interdesmosomal regions (“tessellate junctions”), mostly in mosaic or amalgamated combinations with other molecules believed, to date, to be exclusive components of tight and adherens junctions. In the heart, PERP is a major component of the composite junctions of the intercalated disks connecting cardiomyocytes. Finally, protein PERP is a cobblestone-like general component of special plasma membrane regions such as the bile canaliculi of liver and subapical-to-lateral zones of diverse columnar epithelia and upper urothelial cell layers. We discuss possible organizational and architectonic functions of protein PERP and its potential value as an immunohistochemical diagnostic marker
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