This nuanced study traces how Chinese came to view death as an
opportunity to fashion and convey social identities and memories
during the medieval period (200-1000) and the Tang dynasty
(618-907), ...specifically. As Chinese society became increasingly
multicultural and multireligious, to achieve these aims people
selectively adopted, portrayed, and interpreted various acts of
remembrance. Included in these were new and evolving burial,
mourning, and commemorative practices: joint-burials of spouses,
extended family members, and coreligionists; relocation and
reburial of bodies; posthumous marriage and divorce; interment of a
summoned soul in the absence of a body; and many changes to the
classical mourning and commemorative rites that became the norm
during the period. Individuals independently constructed the
socio-religious meanings of a particular death and the handling of
corpses by engaging in and reviewing acts of remembrance. Drawing
on a variety of sources, including hundreds of newly excavated
entombed epitaph inscriptions, Inscribing Death illuminates the
process through which the living-and the dead-negotiated this
multiplicity of meanings and how they shaped their memories and
identities both as individuals and as part of collectives. In
particular, it details the growing emphasis on remembrance as an
expression of filial piety and the grave as a focal point of
ancestral sacrifice. The work also identifies different modes of
construction and representation of the self in life and death,
deepening our understanding of ancestral worship and its changing
modus operandi and continuous shaping influence on the most
intimate human relationships-thus challenging the current
monolithic representation of ancestral worship as an extension of
families rather than individuals in medieval China.
The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome ...activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Essentials
Mitochondrial hyperpolarization enhances the conversion of platelets to a procoagulant phenotype.
Mitochondrial calcium uniporter (MCU) function is essential in procoagulant platelet ...formation.
Mitochondrial calcium uniporter deletion does not impact other aspects of platelet activation.
Ablation of MCU results in the emergence of a permeability transition pore‐independent pathway.
Summary
Background
Procoagulant platelets comprise a phenotypically distinct subpopulation of activated platelets with high‐level phosphatidylserine externalization. When initiated by co‐stimulation with thrombin and a glycoprotein VI (GPVI) agonist, the transition to the procoagulant phenotype is mediated by extracellular calcium entry and mitochondrial permeability transition pore (mPTP) formation.
Objectives
The intracellular mechanisms coordinating these distinct cytoplasmic and mitochondrial processes remain unclear. The mitochondrial calcium uniporter (MCU) protein is a central component of the transmembrane ion channel that allows the passage of Ca2+ from the cytosol into the mitochondrial matrix. Here we investigate the role of the MCU in the regulation of procoagulant platelet formation.
Results
Procoagulant platelet formation was directly correlated with pre‐stimulatory mitochondrial transmembrane potential, a key determinant of calcium flux from the cytoplasm to the mitochondria. The role of MCU in the regulation of procoagulant platelet formation was investigated using MCU null platelets. Procoagulant platelet formation in MCU null platelets was significantly decreased coincident with decreased mPTP formation. In contrast, neither granule release nor initial integrin activation was altered in response to stimulation. In the genomic absence of MCU, developmental induction of an alternative intracellular pathway partially rescued procoagulant platelet formation.
Conclusion
These results identify a key role for the mitochondrial calcium uptake channel in the regulation of mPTP‐mediated procoagulant platelet formation and suggest a novel pharmacologic target for procoagulant‐platelet‐related pathologies.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective: Given the overlap among depressive symptoms, disordered eating, and overweight, identifying shared risk factors for these conditions may inform public health interventions. This study ...aimed to examine cross-sectional and prospective relationships among these 3 conditions, and identify potential shared eating-related and psychosocial variable risk factors (i.e., body dissatisfaction, dieting, teasing experiences). Method: A population-based sample (n = 1,902) self-reported depressive symptoms, disordered eating (binge eating, extreme weight control behaviors), weight status, and several putative risk factors (body satisfaction, dieting frequency, weight-related teasing) at 5-year intervals spanning early/middle adolescence, middle adolescence/early young adulthood, and early/middle young adulthood. Results: There was moderate overlap among depressive symptoms, disordered eating, and overweight at each time point, and moderate stability in each condition over time. Body dissatisfaction and dieting were the most potent shared risk factors for later depressive symptoms, disordered eating, and overweight among males and females (ps < .05). Conclusions: Depressive symptoms, disordered eating, and overweight share several risk factors, including dieting and body dissatisfaction, which may be effective targets for interventions aiming to simultaneously prevent these 3 conditions.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
To cite this article: Choo KJL, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010; 65: 1205-1211. Anaphylaxis is a serious ...hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion. None of the 2496 reports identified satisfied the inclusion criteria. We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease with marked genomic instability and variable response to conventional R-CHOP (rituximab, cyclophosphamide, ...doxorubicin, vincristine and prednisone) chemotherapy. More clinically aggressive cases of DLBCLs have high level of circulating interleukin 10 (IL10) cytokine and evidence of activated intracellular STAT3 (signal transducer and activator of transcription 3) signaling. We investigated the role of IL10 and its surface receptor in supporting the neoplastic phenotype of DLBCLs. We determined that IL10RA gene is amplified in 21% and IL10RB gene in 10% of primary DLBCLs. Gene expression of IL10, IL10RA and IL10RB was markedly elevated in DLBCLs. We hypothesized that DLBCLs depend for their proliferation and survival on IL10-STAT3 signaling and that blocking the IL10 receptor (IL10R) would induce cell death. We used anti-IL10R blocking antibody, which resulted in a dose-dependent cell death in all tested activated B-cell-like subtype of DLBCL cell lines and primary DLBCLs. Response of germinal center B-cell-like subtype of DLBCL cell lines to anti-IL10R antibody varied from sensitive to resistant. Cells underwent cell cycle arrest, followed by induction of apoptosis. Cell death depended on inhibition of STAT3 and, to a lesser extent, STAT1 signaling. Anti-IL10R treatment resulted in interruption of IL10-IL10R autostimulatory loop. We thus propose that IL10R is a novel therapeutic target in DLBCLs.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mutations in ANO5 (TMEM16E) cause limb-girdle muscular dystrophy R12. Defective plasma membrane repair is a likely mechanism. Using myofibers from Ano5 knockout mice, we show that trafficking of ...several annexin proteins, which together form a cap at the site of injury, is altered upon loss of ANO5. Annexin A2 accumulates at the wound to nearly twice the level observed in WT fibers, while annexin A6 accumulation is substantially inhibited in the absence of ANO5. Appearance of annexins A1 and A5 at the cap is likewise diminished in the Ano5 knockout. These changes are correlated with an alteration in annexin repair cap fine structure and shedding of annexin-positive vesicles. We conclude that loss of annexin coordination during repair is disrupted in Ano5 knockout mice and underlies the defective repair phenotype. Although ANO5 is a phospholipid scramblase, abnormal repair is rescued by overexpression of a scramblase-defective ANO5 mutant, suggesting a novel, scramblase-independent role of ANO5 in repair.
Aims: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity.
Methods and Results: Quorum sensing inhibition was monitored using the Tn‐5 ...mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration‐dependent manner, indicating inhibition of quorum sensing.
Conclusions: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing.
Significance and Impact of the Study: The results suggest that the intake of vanilla‐containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aims/hypothesis The aim of this study was to confirm a link between mitochondrial dysfunction and type 2 diabetes. Materials and methods Cellular levels of mitochondrial proteins, cellular ...mitochondrial DNA content, and mitochondrial function and morphology were assessed by MitoTracker staining and electron microscopy, in white adipose tissue of 12-week-old male wild-type, obese (ob/ob), and diabetic (db/db) mice. Results Levels of mitochondrial proteins were found to be very similar in the livers and muscles of all the mice studied. However, levels were greatly decreased in the adipocytes of db/db mice, but not in those of the wild-type and ob/ob mice. Levels of mitochondrial DNA were also found to be considerably reduced in the adipocytes of db/db mice. MitoTracker staining and under electron microscopy revealed that the number of mitochondria was reduced in adipocytes of db/db mice. Respiration and fatty acid oxidation studies indicated mitochondrial dysfunction in adipocytes of db/db mice. Interestingly, there was an increase in mitochondria and mitochondrial protein production in adipocytes of db/db mice treated with rosiglitazone, an agent that enhances insulin sensitivity. Conclusions/interpretation Taken together, these data indicate that mitochondrial loss in adipose tissue is correlated with the development of type 2 diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Craniofacial skeletal muscle is composed of approximately 60 muscles, which have critical functions including food uptake, eye movements and facial expressions. Although craniofacial muscles have ...significantly different embryonic origin, most current skeletal muscle differentiation protocols using human induced pluripotent stem cells (iPSCs) are based on somite-derived limb and trunk muscle developmental pathways. Since the lack of a protocol for craniofacial muscles is a significant gap in the iPSC-derived muscle field, we have developed an optimized protocol to generate craniofacial myogenic precursor cells (cMPCs) from human iPSCs by mimicking key signaling pathways during craniofacial embryonic myogenesis. At each different stage, human iPSC-derived cMPCs mirror the transcription factor expression profiles seen in their counterparts during embryo development. After the bi-potential cranial pharyngeal mesoderm is established, cells are committed to cranial skeletal muscle lineages with inhibition of cardiac lineages and are purified by flow cytometry. Furthermore, identities of iPSC-derived cMPCs are verified with human primary myoblasts from craniofacial muscles using RNA sequencing. These data suggest that our new method could provide not only in vitro research tools to study muscle specificity of muscular dystrophy but also abundant and reliable cellular resources for tissue engineering to support craniofacial reconstruction surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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