Role of Chronic Stress-Induced Neuroinflammation in Rodent Locus Coeruleus Physiology and Anxiety-Like Behaviors

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC activity which correlates with rodent anxietylike behaviors. Recent studies have also implicated neuroinflammation mediated by microglia as a risk factor in mood and anxiety disorders. Despite their association with anxiety disorders, the combined contributions of stress and inflammation in potentially driving LC neuroadaptations, and their potential contribution to neuropsychiatric disorders have not been well explored. This dissertation addresses the knowledge gap in the complex roles of stress and neuroinflammation in the etiology of anxiety disorders. Our results demonstrate increased rodent anxiety-like behaviors in the elevated plus maze (EPM) and increased LC spontaneous firing via ex-vivo electrophysiology in adolescent rats exposed to chronic stress. Surprisingly, despite similarities in anxiety-like behavior, chronic stress induces a sex-dependent LC neuroinflammation. A significant increase in activated microglia and expression of pro-inflammatory genes, cd74 and il-6, within the LC were noted in male but not female adolescent rats. Interestingly, modulation of the chronic stress-induced LC neuroinflammation through minocycline administration showed a trend for reversal of chronic stress effects in rodent anxiety-like behaviors and LC physiology. Our results suggest that chronic stress induces LC neuroinflammation, leading to rodent anxiety-like behaviors and alterations in LC neuronal physiology. Overall, our results establish the LC as an anatomical site of convergence for pro-stress and pro-inflammatory cues and imply a possible role for chronic stress-induced neuroinflammation in driving LC neuroadaptations leading to anxiety-like phenotypes

Socioeconomic Status and Protest Politics

This brief shall focus upon protest politics in the most recent years like the famous protests against the Vietnam War and the Civil Rights movement as well as examples from today like the protest against stricter immigration laws and a 700-mile fence between the Mexican and American border and how exactly members from different socioeconomic backgrounds participated in these demonstrations

The Subcellular Localization of the Uncharacterized Human Disease-Associated Protein Potassium Channel Tetramerization Domain 13 (KCTD13)

Human KCTD (potassium (K+) channel tetramerization domain (KCTD) proteins make up a family of 26 largely uncharacterized human proteins containing a single N-terminal BTB/POZ domain most closely related to the T1 domain of potassium channels. KCTDs have been implicated in a variety of human diseases including cancer and neurological disorders. KCTD13 (also known as BACURD1, PDIP1 and POLDIP1), encoded on human chromosome 16p11.2, has been recently implicated in human disease, including neurological disorders and autism spectrum disorder (ASD). However, the molecular mechanisms are unknown. To gain insight on the function of KCTD13, and the family of uncharacterized KCTD proteins, the subcellular localization of expressed KCTD13 was determined, leading to the hypothesis that KCTD13 may have a role in the a protein quality control pathway possibly required for mitochondrial maintenance. Localization of epitope-tagged KCTD13 in mammalian cells was analyzed by immunofluorescence microscopy. Results indicate that KCTD13 forms distinct cytoplasmic structures that co-localize with the E3-ubiquitin ligase Cullin-3 (Cul-3) and mitochondrial organelles. Interestingly, uncoupling of mitochondria by treatment of cells with carbonyl cyanide m-chlorophenyl hydrazone (CCCP) intensifies the co-localization of expressed KCTD13 with the mitochondria and cul-3, suggesting a potential role in the clearance of damaged mitochondrial organelles or components thereof. Further supporting this hypothesis, KCTD13 also co-localizes with autophagy markers LC3, ATG12 and ATG13. KCTD13 also partially localizes with the endosome markers RAB5 and prominently localizes with late endosome marker RAB7. Taken together, these findings are consistent with a potential role of KCTD13 in mitochondrial homeostasis and provide a new perspective in the understanding of molecular mechanisms contributing to ASD and other diseases in which KCTD13 mutations may contribute

Social Media and Democracy

Has social media disrupted the concept of democracy? This complex question has become more pressing than ever as social media have become a ubiquitous part of democratic societies worldwide. This chapter discusses social media’s effects at three critical levels of democratic politics (personal relationships among democratic citizens, national politics, and international politics) and argues that social media pressures the conceptual limits of democracy. This new digital communication infrastructure challenges some of the fundamental elements of the concept of democracy. By giving citizens and non-citizens equal substantive access to online political debates that shape the political agenda, social media has drastically expanded and opened up the notion of demos and public sphere (the communicative space where citizens come together to form and exchange opinions and define collective problems), and misaligned the conceptual relationship of public sphere with the idea of demos. These conclusions have multiple implications. They indicate engineers’ and designers’ new political responsibility, novel normative challenges for research in political and moral philosophy, security and legal frameworks, and ultimately they shed light on how to do politics in digital democratic societies

Native-Born Citizens and Naturalized Citizens – Differences in Voting Behavior within the United States

Native born citizens have different voting behavior than do naturalized citizens. Although both groups have the right to vote, native born citizens are more likely to vote than naturalized citizens. These differences are attributed to education, residential mobility, and length of time in the United States among other factors

Disruption of the prostaglandin metabolome and characterization of the pharmaceutical exposome in fish exposed to wastewater treatment works effluent as revealed by nanoflow-nanospray mass spectrometry-based metabolomics

Fish can be exposed to a complex mixture of chemical contaminants, including pharmaceuticals, present in discharges of wastewater treatment works (WwTWs) effluents. There is little information on the effects of effluent exposure on fish metabolism, especially the small molecule signaling compounds which are the biological target of many pharmaceuticals. We applied a newly developed sensitive nanoflow-nanospray mass spectrometry nontargeted profiling technique to identify changes in the exposome and metabolome of roach (Rutilus rutilus) exposed to a final WwTWs effluent for 15 days. Effluent exposure resulted in widespread reduction (between 50% and 90%) in prostaglandin (PG) profiles in fish tissues and plasma with disruptions also in tryptophan/serotonin, bile acid and lipid metabolism. Metabolite disruptions were not explained by altered expression of genes associated with the PG or tryptophan metabolism. Of the 31 pharmaceutical metabolites that were detected in the effluent exposome of fish, 6 were nonsteroidal anti-inflammatory drugs but with plasma concentrations too low to disrupt PG biosynthesis. PGs, bile acids, and tryptophan metabolites are important mediators regulating a diverse array of physiological systems in fish and the identity of wastewater contaminants disrupting their metabolism warrants further investigation on their exposure effects on fish health

Efecto cicatrizante de los extractos etanólicos de hojas y brácteas de cynara cardunculus l. (alcachofa) en heridas inducidas en ratones albinos

La investigación tuvo como objetivo principal determinar el efecto cicatrizante de los extractos etanólicos de hojas y brácteas de Cynara cardunculus L. “alcachofa” en heridas inducidas en ratones albinos de la especie Mus musculus. Para la determinación de los componentes químicos se realizó una marcha fitoquímica, hallándose flavonoides y alcaloides. Utilizando técnicas cromatográficas y espectrofotometría UV-Vis, se propuso la estructura de cuatro flavonas: 3´,4´,5,6,7- pentahidroxi-8 -metoxi flavona; 4´,5,6,7- tetrahidroxi-8 -metoxi flavona; 5,6,7- trihidroxi-4´,8 -dimetoxi flavona y 5,6,7- trihidroxi-8 -metoxi flavona.The main objective of this research was to determine the wound healing effect of ethanolic extracts of leaves and bracts of Cynara cardunculus L. “artichoke” in wounds induced in albino mice Mus musculus . To determine the chemical compounds of ethanolic extracts, phytochemical screening was performed, revealing the presence of flavonoids and alkaloids. Metabolites Chromatographic techniques and UV-Vis spectrophotometry were used to propose the structure of four flavonoids: 5,6,7,3´,4'- pentahydroxy- 8 -methoxyflavone; 5,6,7,4´-tetrahydroxy-8-methoxyflavone; 5,6,7-trihydroxy-4’,8-dimethoxyflavone and 5,6,7-trihydroxy-8-methoxyflavone

Taking Blockchain Seriously

In the present techno-political moment it is clear that ignoring or dismissing the hype surrounding blockchain is unwise, and certainly for regulatory authorities and governments who must keep a grip on the technology and those promoting it, in order to ensure democratic accountability and regulatory legitimacy within the blockchain ecosystem and beyond. Blockchain is telling (and showing) us something very important about the evolution of capital and neoliberal economic reason, and the likely impact in the near future on forms and patterns of work, social organization, and, crucially, on communities and individuals who lack influence over the technologies and data that increasingly shape and control their lives. In this short essay I introduce some of the problems in the regulation of blockchain and offer counter-narratives aimed at cutting through the hype fuelling the ascendency of this most contemporary of technologies

Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

I'll take that to go:Big data bags and minimal identifiers for exchange of large, complex datasets

Big data workflows often require the assembly and exchange of complex, multi-element datasets. For example, in biomedical applications, the input to an analytic pipeline can be a dataset consisting thousands of images and genome sequences assembled from diverse repositories, requiring a description of the contents of the dataset in a concise and unambiguous form. Typical approaches to creating datasets for big data workflows assume that all data reside in a single location, requiring costly data marshaling and permitting errors of omission and commission because dataset members are not explicitly specified. We address these issues by proposing simple methods and tools for assembling, sharing, and analyzing large and complex datasets that scientists can easily integrate into their daily workflows. These tools combine a simple and robust method for describing data collections (BDBags), data descriptions (Research Objects), and simple persistent identifiers (Minids) to create a powerful ecosystem of tools and services for big data analysis and sharing. We present these tools and use biomedical case studies to illustrate their use for the rapid assembly, sharing, and analysis of large datasets