The Discursive Problematization of Death, Dehumanization and Sociocultural identity: An Analysis of 'The Walking Dead'

<p>The zombie is a significant cultural figure which is represented and produced as being symptomatic of and relevant to contemporary concerns about death and dehumanization. This thesis will focus on the ways that death and dehumanization are changing and being negotiated within popular cultural representations and discourses regarding zombies, particularly in Frank Darabont’s television series The Walking Dead. The thesis will consider the way in which the figure of the zombie is representative of issues and discourses that are indicative of a problematization of the category of the human, and the notion of the transcendental. This will involve an examination of the changing narratives of the body, with particular regard to consumerism and the insistence of the body as a major site of the truth and value of the self, in contrast to the horrifying bodily form of the zombie. The thesis will also examine the way that dehumanization is problematized in The Walking Dead, where the human/non-human distinction is shown to be increasingly precarious and difficult to sustain. Further, the thesis will examine how the zombie is represented as manifesting the collapse of identity, as agents become alienated from the social discourses, narratives and values which constitute and categorize the subject.</p>

The Discursive Problematization of Death, Dehumanization and Sociocultural identity: An Analysis of 'The Walking Dead'

<p>The zombie is a significant cultural figure which is represented and produced as being symptomatic of and relevant to contemporary concerns about death and dehumanization. This thesis will focus on the ways that death and dehumanization are changing and being negotiated within popular cultural representations and discourses regarding zombies, particularly in Frank Darabont’s television series The Walking Dead. The thesis will consider the way in which the figure of the zombie is representative of issues and discourses that are indicative of a problematization of the category of the human, and the notion of the transcendental. This will involve an examination of the changing narratives of the body, with particular regard to consumerism and the insistence of the body as a major site of the truth and value of the self, in contrast to the horrifying bodily form of the zombie. The thesis will also examine the way that dehumanization is problematized in The Walking Dead, where the human/non-human distinction is shown to be increasingly precarious and difficult to sustain. Further, the thesis will examine how the zombie is represented as manifesting the collapse of identity, as agents become alienated from the social discourses, narratives and values which constitute and categorize the subject.</p>

Fibroblastic reticular cells provide a supportive niche for lymph node-resident macrophages

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis. The T cell paracortical zone is a major site of macrophage efferocytosis of apoptotic cells, but key factors controlling this niche are undefined. Here we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Macrophages co-localised with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that most reticular cells expressed master macrophage regulator CSF1. Functional assays showed that CSF1R signalling was sufficient to support macrophage development. In the presence of LPS, FRCs underwent a mechanistic switch and maintained support through CSF1R-independent mechanisms. These effects were conserved between mouse and human systems. Rapid loss of macrophages and monocytes from LNs was observed upon genetic ablation of FRCs. These data reveal a critically important role for FRCs in the creation of the parenchymal macrophage niche within LNs.

The enpp4 ectonucleotidase regulates kidney patterning signalling networks in Xenopus embryos

The enpp ectonucleotidases regulate lipidic and purinergic signalling pathways by controlling the extracellular concentrations of purines and bioactive lipids. Although both pathways are key regulators of kidney physiology and linked to human renal pathologies, their roles during nephrogenesis remain poorly understood. We previously showed that the pronephros was a major site of enpp expression and now demonstrate an unsuspected role for the conserved vertebrate enpp4 protein during kidney formation in Xenopus. Enpp4 over-expression results in ectopic renal tissues and, on rare occasion, complete mini-duplication of the entire kidney. Enpp4 is required and sufficient for pronephric markers expression and regulates the expression of RA, Notch and Wnt pathway members. Enpp4 is a membrane protein that binds, without hydrolyzing, phosphatidylserine and its effects are mediated by the receptor s1pr5, although not via the generation of S1P. Finally, we propose a novel and non-catalytic mechanism by which lipidic signalling regulates nephrogenesis.

The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians

The eutherian placenta is a major site for parental genetic conflict. Here, we identify the X-linked Mbnl3 gene as a novel player in this dispute. Mbnl3 belongs to an RNA binding protein family whose members regulate alternative splicing and other aspects of RNA metabolism in association with cellular differentiation. We find that, in eutherians, Mbnl3 has become specifically expressed in placenta and has undergone accelerated sequence evolution leading to changes in its RNA binding specificities. Although its molecular roles are partly redundant with those of Mbnl2, Mbnl3 has also acquired novel biological functions. In particular, whereas Mbnl2;Mbnl3 double knockout mice display severe placental maturation defects leading to strong histological and functional abnormalities, Mbnl3 knockout alone results in increased placental growth and favors placental and fetal resource allocation during limiting conditions.

Optimization of ROS measurement and localization in plant tissues: challenges and solutions v1

During the last decade, there has been a huge interest in understanding the role of reactive oxygen species (ROS) in plant signalling transduction pathways. This understanding requires precise quantification of ROS levels in each cell and each cellular compartment. However, the current methods of ROS detection and measuring are limited. This paper revisits the existing ROS detection methods and discuss general guidelines for applying them to specific cases. Introduction All plants require molecular oxygen for survival (Mittler, 2017). ROS formation naturally occurred during electron transport through all membranes which, in turn, regulate DNA repair systems, cell cycle, phytohormone-dependent signalling and pathogen integration (Huang et al., 2019). In the non-photosynthetic plant tissue, the mitochondrial electron transport system of oxidative phosphorylation is the major site for ROS generation (Dourmap et al., 2020). While in photosynthetic tissue, electron transport between stroma and thylakoid is the primary ROS source (Asada, 2006). On plasma membranes and on endoplasmic reticulum membranes, ROS is mainly produced via NADPH oxidases (Foreman et al., 2003).Cell wall peroxidases are another source of apoplastic ROS (Torres, 2010). In addition, peroxisomes can be considered as the major site of intracellular hydrogen peroxide (H2O2) production (Sandalio et al., 2021). Major ROS produced by cellular processes are superoxide (O2-), H2O2, and hydroxyl radical (∙OH). Superoxide is rapidly converted to H2O2 by superoxide dismutase enzymes (SODs; Cu/Zn-SOD in chloroplasts and cytoplasm, Fe-SOD and Mn-SOD in mitochondria). Hydroxyl radicals are thus generated in the cell wall, plasma membrane, and intracellularly by a range of peroxidases, superoxide dismutases, NADPH oxidases, and transition metal catalysts (Richards et al., 2015). Because of the cellular and biochemical damage caused by oxidative stress (Huang et al., 2019), ROS levels should be precisely controlled in each subcellular compartment and each cell type. ROS are highly reactive molecules rapidly subjected to scavenging or degradation, in processes that are highly sensitive to any environmental change, therefore making ROS extremely unstable and difficult to directly detect. Transferring of the plants to buffers with non-physiological pH can be considered as an abiotic stress factor and it eventually might change endogenous ROS levels (Choudhury et al., 2017). However, many established protocols for ROS measurement (Dunand et al., 2007, Jambunathan, 2010, Rodríguez & Taleisnik, 2012) included the soaking of plant tissues on non-physiological buffers, which might alter steady-state ROS levels. Several methods have been used for ROS localization and they rely on histochemistry, fluorescent dyes, and spectrophotometric measurements (Mittler et al., 2011). Histochemistry Histochemical methods are based on the oxidation of dyes in the presence of ROS, resulting in the production of insoluble precipitates. For example, nitro blue tetrazolium (NBT) chloride reacted with O2- to generate water-insoluble di-formazan, while 3-3-diaminobenzidine (DAB) is oxidized by H2O2 in the presence of peroxidases with formation of a dark-brown precipitate (Jambunathan, 2010). Fluorescent dyes Some chemical dyes became fluorescent after oxidation by ROS, like H2DCFDA, DHE or Amplex red (Ortega-Villasante et al., 2016). These dyes can be used for direct ROS localization. Spectrophotometric methods They allow to quantitatively determine ROS level after tissue homogenization, such as the determination of H2O2 levels with 3,5-dichloro-2-hydroxybenzensulfonic acid (DCHBS)in conjunction with 4-aminoantipyrine (AAP) (Van Gestelen et al., 1998). There methods were summarised in the graphical abstracts. Here we provide several detailed protocols for ROS localization and quantification under physiological conditions, aimed to improve current methods and to minimize artefacts.

Effects of Duodenal 5-Hydroxytryptophan Perfusion on Melatonin Synthesis in GI Tract of Sheep

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10–50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day.

Unique Gut Microbiome in HIV Patients on Antiretroviral Therapy (ART) Suggests Association with Chronic Inflammation

Chronic inflammation is a hallmark of HIV infection and is associated with the development and progression of age-related comorbidities. Although the gastrointestinal tract is a major site of HIV replication and CD4 + T-cell depletion, the role of HIV-associated imbalance of gut microbiome in chronic inflammation is unclear.

Compartmentalization of Resistance-Associated Substitutions in HIV/HCV-Infected Patients: Possible Correlation with Infecting HCV Genotype

Resistance-associated substitutions (RASs) may exist prior to treatment and contribute to the failure of treatment with direct-acting antivirals (DAAs). As the major site of HCV replication, naturally occurring variants with RASs may segregate into the liver. In the present study, we performed viral population sequencing to retrospectively investigate the NS3 and NS5A RAS profiles in 34 HIV/HCV coinfected patients naïve to anti-HCV treatment who underwent diagnostic liver biopsy between 2000 and 2006 and had liver and plasma samples available. Sixteen were infected by HCV genotype (GT) 1a, 11 by GT3a, and 7 by GT4d. The analysis of the NS3 domain in GT1a showed a difference in strain between the liver and plasma in three cases, with a preponderance of specific RASs in the liver compartment. In GT4d samples, 6/7 coupled liver and plasma samples were concordant with no RASs. Sequence analysis of the NS5A domain showed the presence of RASs in the livers of 2/16 patients harboring GT1a but not in the corresponding plasma. In GT4d, NS5A RASs were detected in 7/7 liver tissues and 5/7 plasma samples. NS3 domain and NS5A domain were found to be conserved in plasma and livers of patients infected with GT3a. Thus, RASs within GT1a and GT4d more likely segregate into the liver and may explain the emergence of resistant strains during DAA treatment.

Comparison of the Mechanical Properties Between the Convex and Concave Inner/Apical Surfaces of the Developing Cerebrum

The inner/apical surface of the embryonic brain wall is important as a major site for cell production by neural progenitor cells (NPCs). We compared the mechanical properties of the apical surfaces of two neighboring but morphologically distinct cerebral wall regions in mice from embryonic day (E) E12–E14. Through indentation measurement using atomic force microscopy (AFM), we first found that Young’s modulus was higher at a concave-shaped apical surface of the pallium than at a convex-shaped apical surface of the ganglionic eminence (GE). Further AFM analysis suggested that contribution of actomyosin as revealed with apical surface softening by blebbistatin and stiffness of dissociated NPCs were both comparable between pallium and GE, not accounting for the differential apical surface stiffness. We then found that the density of apices of NPCs was greater, with denser F-actin meshwork, in the apically stiffer pallium than in GE. A similar correlation was found between the decreasing density between E12 and E14 of NPC apices and the declining apical surface stiffness in the same period in both the pallium and the GE. Thus, one plausible explanation for the observed difference (pallium &gt; GE) in apical surface stiffness may be differential densification of NPC apices. In laser ablation onto the apical surface, the convex-shaped GE apical surface showed quicker recoils of edges than the pallial apical surface did, with a milder inhibition of recoiling by blebbistatin than in pallium. This greater pre-stress in GE may provide an indication of how the initially apically concave wall then becomes an apically convex “eminence.”