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Through all its transformations and reinventions over the past century, \"Sin City\" has consistently been regarded by artists and cultural critics as expressing in purest form, for better or worse, an aesthetic and social order spawned by neon signs and institutionalized indulgence. In other words, Las Vegas provides a codex with which to confront the problems of the West and to track the people, materials, ideas, and virtual images that constitute postregional space.Morta Las Vegas considers Las Vegas and the problem of regional identity in the American West through a case study of a single episode of the television crime drama CSI: Crime Scene Investigation. Delving deep into the interwoven events of the episode titled \"4 x 4,\" but resisting a linear, logical case-study approach, the authors draw connections between the city--a layered and complex world--and the violent, uncanny mysteries of a crime scene. Morta Las Vegas reveals nuanced issues characterizing the emergence of a postregional West, moving back and forth between a geographical and a procedural site and into a place both in between and beyond Western identity.

Coat protein complex I (COP-I) mediates the retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Mutation of the COPA gene, encoding one of the COP-I subunits (α-COP), causes an immune dysregulatory disease known as COPA syndrome. The molecular mechanism by which the impaired retrograde transport results in autoinflammation remains poorly understood. Here we report that STING, an innate immunity protein, is a cargo of the retrograde membrane transport. In the presence of the disease-causative α-COP variants, STING cannot be retrieved back to the ER from the Golgi. The forced Golgi residency of STING results in the cGAS-independent and palmitoylation-dependent activation of the STING downstream signaling pathway. Surf4, a protein that circulates between the ER/ ER-Golgi intermediate compartment/ Golgi, binds STING and α-COP, and mediates the retrograde transport of STING to the ER. The STING/Surf4/α-COP complex is disrupted in the presence of the disease-causative α-COP variant. We also find that the STING ligand cGAMP impairs the formation of the STING/Surf4/α-COP complex. Our results suggest a homeostatic regulation of STING at the resting state by retrograde membrane traffic and provide insights into the pathogenesis of COPA syndrome. COPA regulates Golgi to ER transport, and mutations lead to autoinflammation and disease through poorly understood mechanisms. Here, the authors show that disease-causing COPA variants prevent STING transport from the Golgi to the ER, leading to cGAS-independent activation of the STING pathway.

Studies in mice reveal that CREB regulated transcription coactivator 2 (CRTC2) acts as a mediator of mTOR signalling in the liver to regulate SREBP1-controlled lipid homeostasis during feeding and diabetes; overexpression of a CRTC2 mutant defective for mTOR regulation improves the lipogenic program and insulin sensitivity in obese mice. Hepatic control of lipid metabolism SREBP1 is an important transcriptional regulator of lipogenesis. Upon insulin stimulation, it is transported from the endoplasmic reticulum to the Golgi where it is processed, then shuttled to the nucleus to induce genes involved in cholesterol and fatty acid synthesis. From studies in mice, Yiguo Wang and colleagues show that the CREB regulated transcription coactivator 2 (CRTC2) acts as a mediator of mTOR signalling in the liver to regulate SREBP1-controlled lipid homeostasis during feeding and diabetes. CRTC2 can disrupt SREBP1 processing and transport by competing with binding to a subunit of COPII. During feeding, mTOR signalling inhibits the action of CRTC2 on SREBP1 processing. Overexpression of a CRTC2 mutant defective for mTOR regulation improves the lipogenic program and insulin sensitivity in obese mice. Abnormal accumulation of triglycerides in the liver, caused in part by increased de novo lipogenesis, results in non-alcoholic fatty liver disease and insulin resistance 1 , 2 . Sterol regulatory element-binding protein 1 (SREBP1), an important transcriptional regulator of lipogenesis, is synthesized as an inactive precursor that binds to the endoplasmic reticulum (ER). In response to insulin signalling, SREBP1 is transported from the ER to the Golgi in a COPII-dependent manner, processed by proteases in the Golgi, and then shuttled to the nucleus to induce lipogenic gene expression 3 , 4 , 5 ; however, the mechanisms underlying enhanced SREBP1 activity in insulin-resistant obesity and diabetes remain unclear. Here we show in mice that CREB regulated transcription coactivator 2 (CRTC2) 6 functions as a mediator of mTOR 7 signalling to modulate COPII-dependent SREBP1 processing. CRTC2 competes with Sec23A, a subunit of the COPII complex 8 , to interact with Sec31A, another COPII subunit, thus disrupting SREBP1 transport. During feeding, mTOR phosphorylates CRTC2 and attenuates its inhibitory effect on COPII-dependent SREBP1 maturation. As hepatic overexpression of an mTOR-defective CRTC2 mutant in obese mice improved the lipogenic program and insulin sensitivity, these results demonstrate how the transcriptional coactivator CRTC2 regulates mTOR-mediated lipid homeostasis in the fed state and in obesity.

COPII mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Five essential proteins assemble into a two-layer architecture, with the inner layer thought to regulate coat assembly and cargo recruitment, and the outer coat forming cages assumed to scaffold membrane curvature. Here we visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers. We demonstrate the physiological importance of these interactions using genetic and biochemical approaches. Mutagenesis reveals that the inner coat alone can provide membrane remodelling function, with organisational input from the outer coat. These functional roles for the inner and outer coats significantly move away from the current paradigm, which posits membrane curvature derives primarily from the outer coat. We suggest these interactions collectively contribute to coat organisation and membrane curvature, providing a structural framework to understand regulatory mechanisms of COPII trafficking and secretion. Cytosolic coat proteins capture secretory cargo and sculpt membrane carriers for intracellular transport, such as COPII which mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Here authors visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers.

Most proteins destined for the extracellular space or various intracellular compartments must traverse the intracellular secretory pathway. The first step is the recruitment and transport of cargoes from the endoplasmic reticulum (ER) lumen to the Golgi apparatus by coat protein complex II (COPII), consisting of five core proteins. Additional ER transmembrane proteins that aid cargo recruitment are referred to as cargo receptors. Gene duplication events have resulted in multiple COPII paralogs present in the mammalian genome. Here, we review the functions of each COPII protein, human disorders associated with each paralog, and evidence for functional conservation between paralogs. We also provide a summary of current knowledge regarding two prototypical cargo receptors in mammals, LMAN1 and SURF4, and their roles in human health and disease.

Eukaryotic cells employ membrane-bound carriers to transport cargo between compartments in a process essential to cell functionality. Carriers are generated by coat complexes that couple cargo capture to membrane deformation. The COPII coat mediates export from the endoplasmic reticulum by assembling in inner and outer layers, yielding carriers of variable shape and size that allow secretion of thousands of diverse cargo. Despite detailed understanding of COPII subunits, the molecular mechanisms of coat assembly and membrane deformation are unclear. Here we present a 4.9 Å cryo-tomography subtomogram averaging structure of in vitro-reconstituted membrane-bound inner coat. We show that the outer coat (Sec13–Sec31) bridges inner coat subunits (Sar1–Sec23–Sec24), promoting their assembly into a tight lattice. We directly visualize the membrane-embedded Sar1 amphipathic helix, revealing that lattice formation induces parallel helix insertions, yielding tubular curvature. We propose that regulators like the procollagen receptor TANGO1 modulate this mechanism to determine vesicle shape and size. The COPII coat assembles in two concentric layers and mediates protein export from the endoplasmic reticulum. Here the authors present the 4.9 Å resolution cryo-tomography and subtomogram averaging structure of the membrane bound COPII inner coat that was obtained by in vitro reconstitution and discuss mechanistic implications.

Proteins traverse the eukaryotic secretory pathway through membrane trafficking between organelles. The coat protein complex II (COPII) mediates the anterograde transport of newly synthesized proteins from the endoplasmic reticulum, engaging cargoes with a wide range of size and biophysical properties. The native architecture of the COPII coat and how cargo might influence COPII carrier morphology remain poorly understood. Here we reconstituted COPII-coated membrane carriers using purified Saccharomyces cerevisiae proteins and cell-derived microsomes as a native membrane source. Using cryo-electron tomography with subtomogram averaging, we demonstrate that the COPII coat binds cargo and forms largely spherical vesicles from native membranes. We reveal the architecture of the inner and outer coat layers and shed light on how spherical carriers are formed. Our results provide insights into the architecture and regulation of the COPII coat and advance our current understanding of how membrane curvature is generated. The authors reconstituted coat protein complex II vesicles from native membranes and used cryo-electron tomography and subtomogram averaging to reveal the arrangement of inner and outer coat layers on cargo-containing coated vesicles.

Aim: To study the way in which cop culture is transmitted, by examining the phenomena and cases that have been identified in the main areas of police culture: professional characteristics, values, canteen culture, code of silence.Methodology: The author uses qualitative research, document and content analysis.Findings: Research in the main areas of cop culture shows that deviant behaviour is rarely achieved by immediate action, by showing 'example'. One possible mode of transmission is mainly through verbalisation, which may be a kind of testing phase, followed by deviant behaviour. The detection of such cases is made more difficult by the characteristics of the police profession – (uncritical) loyalty, need for trust, conformity or empathy – thus helping to maintain and reproduce an inappropriate cop culture.Value: Describes the role of morale in cop culture and police profession. Cél: A zsarukultúra átörökítési módjának feltárása annak főbb területein – rendőrszakmai jellemzők, értékek, kantin-kultúra, hallgatás kódja – feltárt jelenségek, megtörtént esetek vizsgálatával.Módszertan: A szerző kvalitatív kutatást, dokumentum- és tartalomelemzést alkalmaz.Megállapítások: A zsarukultúra főbb területein végzett kutatások rámutatnak arra, hogy a deviáns magatartások ritkán valósulnak meg azonnal tettek, „példamutatás” által. Az egyik lehetséges átörökítési mód elsősorban a szóbeliség útján valósul meg, ami egyfajta tesztelési fázis is lehet, amit később deviáns magatartás követ(het). Az ilyen esetek felfedését pedig a rendőri hivatás jellemzői – (kritikátlan) lojalitás, bizalom szüksége, konformitás vagy empátia – nehezítik meg, ezáltal segítve a helytelen zsarukultúra konzerválódását és ismételt átörökítését.Érték: A morál szerepének ismertetése a zsarukultúrában és a rendőri hivatásban.

The origin and cellular complexity of eukaryotes represent a major enigma in biology. Current data support scenarios in which an archaeal host cell and an alphaproteobacterial (mitochondrial) endosymbiont merged together, resulting in the first eukaryotic cell. The host cell is related to Lokiarchaeota, an archaeal phylum with many eukaryotic features. The emergence of the structural complexity that characterizes eukaryotic cells remains unclear. Here we describe the ‘Asgard’ superphylum, a group of uncultivated archaea that, as well as Lokiarchaeota, includes Thor-, Odin- and Heimdallarchaeota. Asgard archaea affiliate with eukaryotes in phylogenomic analyses, and their genomes are enriched for proteins formerly considered specific to eukaryotes. Notably, thorarchaeal genomes encode several homologues of eukaryotic membrane-trafficking machinery components, including Sec23/24 and TRAPP domains. Furthermore, we identify thorarchaeal proteins with similar features to eukaryotic coat proteins involved in vesicle biogenesis. Our results expand the known repertoire of ‘eukaryote-specific’ proteins in Archaea, indicating that the archaeal host cell already contained many key components that govern eukaryotic cellular complexity. This work describes the Asgard superphylum, an assemblage of diverse archaea that comprises Odinarchaeota, Heimdallarchaeota, Lokiarchaeota and Thorarchaeota, offering insights into the earliest days of eukaryotic cells and their complex features. Archaea with eukaryotic tendencies Although the origin of eukaryotic cells from prokaryotic ancestors remains an enigma, it has become clear that the root of eukaryotes lies among a group of prokaryotes known as archaea. The recent identification of newly described archaea belonging to the Asgard superphylum, including Lokiarchaeota and Thorarchaeota, revealed a group of prokaryotes containing many proteins and genetic sequences that are otherwise found only in eukaryotes. Thijs Ettema and colleagues extend the search for eukaryotic roots by describing further additions to the Asgard superphylum: the Odinarchaeota and Heimdallarchaeota. The new Asgard genomes encode homologues of several components of eukaryotic membrane-trafficking machineries, suggesting that the archaeal ancestor of eukaryotes was well equipped to evolve the complex cellular features that are characteristic of eukaryotic cells.