The Legal Adaptation of British Settlers in Turkey

This article is based on a fieldwork project conducted by the authors in the Muğla region of western Turkey. The region is the locale for a significant level of settlement by British people, within the wider context of settlement by groups of other EU nationals in western Turkey. Based on a series of interviews with British settlers and Turkish locals, it examines the factors which affect the process of legal adaptation of the former group. It identifies and discusses the place of British settlers within the larger Turkish legal order, their integration into Turkish life, and the extent to which different socio-legal disabilities and advantages affect this process. The article also casts some light on the extent to which, given the level of British immigration into the area, Turkish officialdom is prepared for their presence

β-Defensins Activate Human Mast Cells Via Mas-Related Gene X2

Human β-defensins (hBDs) stimulate degranulation in rat peritoneal mast cells in vitro and cause increased vascular permeability in rats in vivo. In this study, we sought to determine whether hBDs activate murine and human mast cells and to delineate the mechanisms of their regulation. hBD2 and hBD3 did not induce degranulation in murine peritoneal or bone marrow-derived mast cells (BMMC) in vitro and had no effect on vascular permeability in vivo. By contrast, these peptides induced sustained Ca2+ mobilization and substantial degranulation in human mast cells, with hBD3 being more potent. Pertussis toxin (PTx) had no effect on hBD-induced Ca2+ mobilization, but La3+ and 2-aminoethoxydiphenyl borate (a dual inhibitor of inositol 1,4,5-triphosphate receptor and transient receptor potential channels) caused substantial inhibition of this response. Interestingly, degranulation induced by hBDs was substantially inhibited by PTx, La3+, or 2-aminoethoxydiphenyl borate. Whereas human mast cells endogenously express G protein-coupled receptor, Mas-related gene X2 (MrgX2), rat basophilic leukemia, RBL-2H3 cells, and murine BMMCs do not. Silencing the expression of MrgX2 in human mast cells inhibited hBD-induced degranulation, but had no effect on anaphylatoxin C3a-induced response. Furthermore, ectopic expression of MrgX2 in RBL-2H3 and murine BMMCs rendered these cells responsive to hBDs for degranulation. This study demonstrates that hBDs activate human mast cells via MrgX2, which couples to both PTx-sensitive and insensitive signaling pathways most likely involving Gαq and Gαi to induce degranulation. Furthermore, murine mast cells are resistant to hBDs for degranulation, and this reflects the absence of MrgX2 in these cells. Copyright©2013 by The American Association of Immunologists, Inc

Detection of PHLPP1α/β in Human and Mouse Brain by Different Anti-PHLPP1 Antibodies

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal at ~150 kDa as evidenced by its abundance in PHLPP1 KO tissues. Results suggest Cosmo antibody is a better reagent to detect PHLPP1α by Western blot. In contrast, we found it unsuitable for immunofluorescence applications in brain. Our findings caution interpretation of the ~150 kDa band detected by some PHLPP1 antibodies in rodent and human tissues. Results also recapitulate the importance of including molecular weight standards in Western blot data to simplify retrospective analysis

Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death

High fidelity and effective adaptive changes of the cell and tissue metabolism to changing environments require strict coordination of numerous biological processes. Multicellular organisms developed sophisticated signaling systems of monitoring and responding to these different contexts. Among these systems, oxygenated lipids play a significant role realized via a variety of re-programming mechanisms. Some of them are enacted as a part of pro-survival pathways that eliminate harmful or unnecessary molecules or organelles by a variety of degradation/hydrolytic reactions or specialized autophageal processes. When these “partial” intracellular measures are insufficient, the programs of cells death are triggered with the aim to remove irreparably damaged members of the multicellular community. These regulated cell death mechanisms are believed to heavily rely on signaling by a highly diversified group of molecules, oxygenated phospholipids (PLox). Out of thousands of detectable individual PLox species, redox phospholipidomics deciphered several specific molecules that seem to be diagnostic of specialized death programs. Oxygenated cardiolipins (CLs) and phosphatidylethanolamines (PEs) have been identified as predictive biomarkers of apoptosis and ferroptosis, respectively. This has led to decoding of the enzymatic mechanisms of their formation involving mitochondrial oxidation of CLs by cytochrome c and endoplasmic reticulum-associated oxidation of PE by lipoxygenases. Understanding of the specific biochemical radical-mediated mechanisms of these oxidative reactions opens new avenues for the design and search of highly specific regulators of cell death programs. This review emphasizes the usefulness of such selective lipid peroxidation mechanisms in contrast to the concept of random poorly controlled free radical reactions as instruments of non-specific damage of cells and their membranes. Detailed analysis of two specific examples of phospholipid oxidative signaling in apoptosis and ferroptosis along with their molecular mechanisms and roles in reprogramming has been presented

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Phosphatidylserine Targets Single-Walled Carbon Nanotubes to Professional Phagocytes In Vitro and In Vivo

Broad applications of single-walled carbon nanotubes (SWCNT) dictate the necessity to better understand their health effects. Poor recognition of non-functionalized SWCNT by phagocytes is prohibitive towards controlling their biological action. We report that SWCNT coating with a phospholipid “eat-me” signal, phosphatidylserine (PS), makes them recognizable in vitro by different phagocytic cells - murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c) allowed for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PS-coating can be utilized for targeted delivery of SWCNT with specified cargoes into professional phagocytes, hence for therapeutic regulation of specific populations of immune-competent cells

Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments.

BACKGROUND: Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. RESULTS: Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. CONCLUSIONS: Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment

Do Political Attitudes Matter for Epistemic Decisions of Scientists?

The epistemic attitudes of scientists, such as epistemic tolerance and authoritarianism, play important roles in the discourse about rivaling theories. Epistemic tolerance stands for the mental attitude of an epistemic agent, e.g., a scientist, who is open to opposing views, while epistemic authoritarianism represents the tendency to uncritically accept views of authorities. Another relevant epistemic factor when it comes to the epistemic decisions of scientists is the skepticism towards the scientific method. However, the question is whether these epistemic attitudes are influenced by their sociopolitical counterparts, such as the researcher's degree of conservatism. To empirically investigate the interplay between epistemic and sociopolitical attitudes of scientists, we conducted a survey with researchers (N = 655) across different disciplines. We propose scales for measuring epistemic tolerance and epistemic authoritarianism, as well as a scale for detecting the participants' readiness to question the scientific method. Furthermore, we investigate the relationship between epistemic tolerance and epistemic authoritarianism on the one hand, and career stage and sociopolitical views on the other hand. Interestingly, our study found only small correlations between the participants' degree of conservatism and their epistemic attitudes. This suggests that political views, against common argumentation, actually do not play an important role in one's scientific decisions. Moreover, social scientists scored higher on the epistemic tolerance and lower on the epistemic authoritarianism scale than natural scientists. Finally, the results indicate that natural scientists question the scientific method less than social scientists