A general role for TANGO1, encoded by MIA3, in secretory pathway organization and function

Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum (ER), which is an essential process in eukaryotic cells. In vertebrates, the MIA3 gene encodes two major forms of transport and Golgi organization protein 1 (TANGO1S and TANGO1L), which have previously been implicated in selective trafficking of procollagen. Using genome engineering of human cells, light microscopy, secretion assays, genomics and proteomics, we show that disruption of the longer form, TANGO1L, results in relatively minor defects in secretory pathway organization and function, including having limited impacts on procollagen secretion. In contrast, loss of both long and short forms results in major defects in cell organization and secretion. These include a failure to maintain the localization of ERGIC53 (also known as LMAN1) and SURF4 to the ER–Golgi intermediate compartment and dramatic changes to the ultrastructure of the ER–Golgi interface. Disruption of TANGO1 causes significant changes in early secretory pathway gene and protein expression, and impairs secretion not only of large proteins, but of all types of secretory cargo, including small soluble proteins. Our data support a general role for MIA3/TANGO1 in maintaining secretory pathway structure and function in vertebrate cells

Competitive nationalism:state, class, and the forms of capital in devolved Scotland

Devolved government in Scotland actively reconstitutes the unequal conditions of social class reproduction. Recognition of state-led class reconstitution draws upon the social theory of Bourdieu. Our analysis of social class in devolved Scotland revisits theories that examine the state as a `power container'. A range of state-enabling powers regulate the legal, economic, social, and cultural containers of class relations as specific forms of what Bourdieu called economic, social, and cultural `capital'. The preconditions of class reproduction are structured in direct ways by the Scottish state as a wealth container but also, more indirectly, as a cultural container and a social container. Competitive nationalism in the devolved Scottish state enacts neoliberal policies as a class- specific worldview but, at the same time, discursively frames society as a panclass national fraternity in terms of distinctive Scottish values of welfare nationalism. Nationalism is able to express this ambiguity in symbolic ways in which the partisan language of social class cannot

High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer’s and Parkinson’s disease

IntroductionAlzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative conditions characterized by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis.MethodsHere, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterize bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases.Results and discussionThis study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease etiology

Functional genomics of drought stress response in rice: transcript mapping of annotated unigenes of an indica rice (Oryza sativa L. cv. Nagina 22)

Rice being one of the widely cultivated cereals across diverse agroecological systems, is prone to high yield losses due to recurring droughts. In India, drought is a major constraint of rice production and accounts for as much as 15% of yield losses during some years. Conventional plant breeding techniques though cumbersome and time-consuming, have been immensely helpful in releasing drought-tolerant varieties. However, this is not adequate to cope up with the future demand for rice, as drought seems to spread to more regions and seasons across the country. Understanding the genes that govern rice plant architecture and response to drought stress is urgently needed to enhance breeding rice with improved drought tolerance. In order to identify genes associated with drought stress response and their temporal and spatial regulation, we took the genomic approach. By generating a large set of expressed sequence tags (ESTs) from cDNA libraries of drought-stressed seedlings and transcript profiling, we identified 589 genes presumed to be involved in drought stress. These 5814 ESTs are assembled into 2094 contigs and localized onto chromosome arms. We present here the physical map of the 2094 unigene set along with 589 annotated putative stress responsive genes of rice. Further, using ESTs, a few of drought quantitative trait loci (QTLs) have been dissected and putative candidate genes identified. This will be useful to rice researchers as ready reference source for breeding through developing candidate gene markers, molecular dissection of QTLs associated with drought stress and map-based cloning

Simulating temporal evolution of pressure in two-phase flow in porous media

We have simulated the temporal evolution of pressure due to capillary and viscous forces in two-phase drainage in porous media. We analyze our result in light of macroscopic flow equations for two-phase flow. We also investigate the effect of the trapped clusters on the pressure evolution and on the effective permeability of the system. We find that the capillary forces play an important role during the displacements for both fast and slow injection rates and both when the invading fluid is more or less viscous than the defending fluid. The simulations are based on a network simulator modeling two-phase drainage displacements on a two-dimensional lattice of tubes.Comment: 12 pages, LaTeX, 14 figures, Postscrip

Corticosterone pattern-dependent glucocorticoid receptor binding and transcriptional regulation within the liver

Ultradian glucocorticoid rhythms are highly conserved across mammalian species, however, their functional significance is not yet fully understood. Here we demonstrate that pulsatile corticosterone replacement in adrenalectomised rats induces a dynamic pattern of glucocorticoid receptor (GR) binding at ~3,000 genomic sites in liver at the pulse peak, subsequently not found during the pulse nadir. In contrast, constant corticosterone replacement induced prolonged binding at the majority of these sites. Additionally, each pattern further induced markedly different transcriptional responses. During pulsatile treatment, intragenic occupancy by active RNA polymerase II exhibited pulsatile dynamics with transient changes in enrichment, either decreased or increased depending on the gene, which mostly returned to baseline during the inter-pulse interval. In contrast, constant corticosterone exposure induced prolonged effects on RNA polymerase II occupancy at the majority of gene targets, thus acting as a sustained regulatory signal for both transactivation and repression of glucocorticoid target genes. The nett effect of these differences were consequently seen in the liver transcriptome as RNA-seq analysis indicated that despite the same overall amount of corticosterone infused, twice the number of transcripts were regulated by constant corticosterone infusion, when compared to pulsatile. Target genes that were found to be differentially regulated in a pattern-dependent manner were enriched in functional pathways including carbohydrate, cholesterol, glucose and fat metabolism as well as inflammation, suggesting a functional role for dysregulated glucocorticoid rhythms in the development of metabolic dysfunction

SAGUARO: Time-domain Infrastructure for the Fourth Gravitational-wave Observing Run and Beyond

We present upgraded infrastructure for Searches after Gravitational Waves Using ARizona Observatories (SAGUARO) during LIGO, Virgo, and KAGRA's fourth gravitational-wave (GW) observing run (O4). These upgrades implement many of the lessons we learned after a comprehensive analysis of potential electromagnetic counterparts to the GWs discovered during the previous observing run. We have developed a new web-based target and observation manager (TOM) that allows us to coordinate sky surveys, vet potential counterparts, and trigger follow-up observations from one centralized portal. The TOM includes software that aggregates all publicly available information on the light curves and possible host galaxies of targets, allowing us to rule out potential contaminants like active galactic nuclei, variable stars, solar-system objects, and preexisting supernovae, as well as to assess the viability of any plausible counterparts. We have also upgraded our image-subtraction pipeline by assembling deeper reference images and training a new neural network-based real-bogus classifier. These infrastructure upgrades will aid coordination by enabling the prompt reporting of observations, discoveries, and analysis to the GW follow-up community, and put SAGUARO in an advantageous position to discover kilonovae in the remainder of O4 and beyond. Many elements of our open-source software stack have broad utility beyond multimessenger astronomy, and will be particularly relevant in the "big data" era of transient discoveries by the Vera C. Rubin Observatory.Comment: submitted to AAS Journal