Thirteen essays by scholars from seven countries discuss the political use and abuse of history in the recent decades with particular focus on Central and Eastern Europe (Hungary, Poland, Estonia, ...Moldova, Ukraine, Russia as case studies), but also includes articles on Germany, Japan and Turkey, which provide a much needed comparative dimension. The main focus is on new conditions of political utilization of history in post-communist context, which is characterized by lack of censorship and political pluralism. The phenomenon of history politics became extremely visible in Central and Eastern Europe in the past decade, and remains central for political agenda in many countries of the regions. Each essay is a case study contributing to the knowledge about collective memory and political use of history, offering a new theoretical twist. The studies look at actors (from political parties to individual historians), institutions (museums, Institutes of National remembrance, special political commissions), methods, political rationale and motivations behind this phenomenon.
The Gram-negative outer membrane is an important barrier that provides protection against toxic compounds, which include antibiotics and host innate immune molecules such as cationic antimicrobial ...peptides. Recently, significant research progress has been made in understanding the biogenesis, regulation, and functioning of the outer membrane, including a recent paper from the laboratory of Dr. Brett Finlay at the University of British Columbia (J. van der Heijden et al., mBio 7:e01238-16, 2016, http://dx.doi.org/10.1128/mBio.01541-16). These investigators demonstrate that toxic oxygen radicals, such as those found in host tissues, regulate outer membrane permeability by altering the outer membrane porin protein channels to regulate the influx of oxygen radicals as well as β-lactam antibiotics. This commentary provides context about this interesting paper and discusses the prospects of utilizing increased knowledge of outer membrane biology to develop new antibiotics for antibiotic-resistant Gram-negative bacteria.
Despite theoretical postulations that individuals' conformity to masculine norms is differentially related to mental health-related outcomes depending on a variety of contexts, there has not been any ...systematic synthesis of the empirical research on this topic. Therefore, the authors of this study conducted meta-analyses of the relationships between conformity to masculine norms (as measured by the Conformity to Masculine Norms Inventory-94 and other versions of this scale) and mental health-related outcomes using 78 samples and 19,453 participants. Conformity to masculine norms was modestly and unfavorably associated with mental health as well as moderately and unfavorably related to psychological help seeking. The authors also identified several moderation effects. Conformity to masculine norms was more strongly correlated with negative social functioning than with psychological indicators of negative mental health. Conformity to the specific masculine norms of self-reliance, power over women, and playboy were unfavorably, robustly, and consistently related to mental health-related outcomes, whereas conformity to the masculine norm of primacy of work was not significantly related to any mental health-related outcome. These findings highlight the need for researchers to disaggregate the generic construct of conformity to masculine norms and to focus instead on specific dimensions of masculine norms and their differential associations with other outcomes.
Public Significance Statement
This study synthesized findings from 19,453 participants across 78 samples regarding the relationships between conformity to masculine norms and mental health-related outcomes. In general, individuals who conformed strongly to masculine norms tended to have poorer mental health and less favorable attitudes toward seeking psychological help, although the results differed depending on specific types of masculine norms.
Abnormalities of lipid metabolism often lead to pathologic lipid accumulation in the vessel wall, oxidative and chronic inflammatory sequelae and the formation of atherosclerotic lesions, ultimately ...leading to clinical events. Oxidation of lipoproteins, and in particular low density lipoprotein (LDL), is a seminal even that mediates many pro-atherogenic and pro-inflammatory pathways. Many in vivo mechanisms exist to oxidize LDL, including transition metals such as divalent iron cations, heme, as well as a number of different enzyme systems, such as lipoxygenases, myeloperoxidase, NADPH oxidases, and nitric oxide synthases. Oxidized LDL is taken up in an unregulated fashion. By macrophages leading to foam cell formation, ultimately generating a potent pro-inflammatory milieu. Minimally modified LDL also induces proinflammatory effects in macrophages, including cytoskeletal rearrangements and macropinocytosis, generation of reactive oxygen species, survival of foam cells, reduced phagocytic capacity toward apoptotic cells, and expression of inflammatory genes, many of these effects mediated through toll-like receptor-4. Using the scientific knowledge gained from understanding these pathways, antibodies binding well-defined oxidation-specific epitopes have been generated and are being used in translational clinical applications. In particular, assays measuring oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB) predict the presence and progression of femoral, carotid and coronary artery disease and predict new cardiovascular events independent of established risk factors. Human oxidation-specific antibodies have also been successfully used to image the extent and regression of experimental atherosclerotic lesions using nuclear and magnetic resonance imaging approaches. If validated and translated to humans, this imaging approach may provide a means to non-invasively detect, quantitate and monitor extent of atherosclerosis and potentially image high risk plaques. Further understanding of the role of oxidation of lipoproteins may allow more rational targeted diagnostic and therapeutic modalities in clinical applications.
Lipid rafts as a therapeutic target Sviridov, Dmitri; Mukhamedova, Nigora; Miller, Yury I.
Journal of lipid research,
05/2020, Letnik:
61, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by ...lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting “pathological” lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.
Most rare diseases still lack approved treatments despite major advances in research providing the tools to understand their molecular basis, as well as legislation providing regulatory and economic ...incentives to catalyse the development of specific therapies. Addressing this translational gap is a multifaceted challenge, for which a key aspect is the selection of the optimal therapeutic modality for translating advances in rare disease knowledge into potential medicines, known as orphan drugs. With this in mind, we discuss here the technological basis and rare disease applicability of the main therapeutic modalities, including small molecules, monoclonal antibodies, protein replacement therapies, oligonucleotides and gene and cell therapies, as well as drug repurposing. For each modality, we consider its strengths and limitations as a platform for rare disease therapy development and describe clinical progress so far in developing drugs based on it. We also discuss selected overarching topics in the development of therapies for rare diseases, such as approval statistics, engagement of patients in the process, regulatory pathways and digital tools.
Highlights • Sex differences in cognitive abilities are changing and vary across nations. • Some differences are found in infancy but depend on task characteristics. • Fraternal-twin studies help ...establish the role of prenatal androgens. • International data help explain the role of economic prosperity and gender equity. • Modifying biological and environmental factors could maximize cognitive potential.
This meta-analysis, spanning 5 decades of Draw-A-Scientist studies, examined U.S. children's gender-science stereotypes linking science with men. These stereotypes should have weakened over time ...because women's representation in science has risen substantially in the United States, and mass media increasingly depict female scientists. Based on 78 studies (N = 20,860; grades K-12), children's drawings of scientists depicted female scientists more often in later decades, but less often among older children. Children's depictions of scientists therefore have become more gender diverse over time, but children still associate science with men as they grow older. These results may reflect that children observe more male than female scientists in their environments, even though women's representation in science has increased over time.
Gram-negative bacteria are surrounded by two membrane bilayers separated by a space termed the periplasm. The periplasm is a multipurpose compartment separate from the cytoplasm whose distinct ...reducing environment allows more efficient and diverse mechanisms of protein oxidation, folding, and quality control. The periplasm also contains structural elements and important environmental sensing modules, and it allows complex nanomachines to span the cell envelope. Recent work indicates that the size or intermembrane distance of the periplasm is controlled by periplasmic lipoproteins that anchor the outer membrane to the periplasmic peptidoglycan polymer. This periplasm intermembrane distance is critical for sensing outer membrane damage and dictates length of the flagellar periplasmic rotor, which controls motility. These exciting results resolve longstanding debates about whether the periplasmic distance has a biological function and raise the possibility that the mechanisms for maintenance of periplasmic size could be exploited for antibiotic development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Monocyte and Macrophage Dynamics During Atherogenesis Ley, Klaus; Miller, Yury I; Hedrick, Catherine C
Arteriosclerosis, thrombosis, and vascular biology,
2011-July, 2011-Jul, 2011-07-00, 20110701, Letnik:
31, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Vascular inflammation is associated with and in large part driven by changes in the leukocyte compartment of the vessel wall. Here, we focus on monocyte influx during atherosclerosis, the most common ...form of vascular inflammation. Although the arterial wall contains a large number of resident macrophages and some resident dendritic cells, atherosclerosis drives a rapid influx of inflammatory monocytes (Ly-6C in mice) and other monocytes (Ly-6C in mice, also known as patrolling monocytes). Once in the vessel wall, Ly-6C monocytes differentiate to a phenotype consistent with inflammatory macrophages and inflammatory dendritic cells. The phenotype of these cells is modulated by lipid uptake, Toll-like receptor ligands, hematopoietic growth factors, cytokines, and chemokines. In addition to newly recruited macrophages, it is likely that resident macrophages also change their phenotype. Monocyte-derived inflammatory macrophages have a short half-life. After undergoing apoptosis, they may be taken up by surrounding macrophages or, if the phagocytic capacity is overwhelmed, can undergo secondary necrosis, a key event in forming the necrotic core of atherosclerotic lesions. In this review, we discuss these and other processes associated with monocytic cell dynamics in the vascular wall and their role in the initiation and progression of atherosclerosis.
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