Single-Prolonged Stress Impairs Prefrontal Cortex Control of Amygdala and Striatum in Rats

Medial prefrontal cortex (mPFC), amygdala, and striatum neurocircuitry has been shown to play an important role in post-traumatic stress disorder (PTSD) pathology in humans. Clinical studies show hypoactivity in the mPFC and hyperactivity in the amygdala and striatum of PTSD patients, which has been associated with decreased mPFC glutamate levels. The ability to refine neurobiological characteristics of PTSD in an animal model is critical in furthering our mechanistic understanding of the disease. To this end, we exposed male rats to single-prolonged stress (SPS), a validated model of PTSD, and hypothesized that traumatic stress would differentially activate mPFC subregions [prelimbic (PL) and infralimbic (IL) cortices] and increase striatal and amygdalar activity, which would be associated with decreased mPFC glutamate levels. in vivo, neural activity in the subregions of the mPFC, amygdala, and striatum was measured using manganese-enhanced magnetic resonance imaging (MEMRI), and glutamate and N-acetylaspartate (NAA) levels in the mPFC and the dorsal striatum (dSTR) were measured using proton magnetic resonance spectroscopy (1H-MRS) longitudinally, in rats exposed to SPS or control conditions. As hypothesized, SPS decreased MEMRI-based neural activity in the IL, but not PL, cortex concomitantly increasing activity within the basolateral amygdala (BLA) and dorsomedial striatum (dmSTR). 1H-MRS studies in a separate cohort revealed SPS decreased glutamate levels in the mPFC and increased NAA levels in the dSTR. These results confirm previous findings that suggest SPS causes mPFC hypoactivation as well as identifies concurrent hyperactivation in dmSTR and BLA, effects which parallel the clinical neuropathology of PTSD

Searches After Gravitational-waves Using ARizona Observatories (SAGUARO): System Overview and First Results from Advanced LIGO/Virgo's Third Observing Run

We present Searches After Gravitational-waves Using ARizona Observatories (SAGUARO), a comprehensive effort dedicated to the discovery and characterization of optical counterparts to gravitational wave (GW) events. SAGUARO utilizes ground-based facilities ranging from 1.5m to 10m in diameter, located primarily in the Northern Hemisphere. We provide an overview of SAGUARO's telescopic resources, pipeline for transient detection, and database for candidate visualization. We describe SAGUARO's discovery component, which utilizes the $5$~deg$^2$ field-of-view optical imager on the Mt. Lemmon 1.5m telescope, reaching limits of $\approx 21.3$~AB mag while rapidly tiling large areas. We also describe the follow-up component of SAGUARO, used for rapid vetting and monitoring of optical candidates. With the onset of Advanced LIGO/Virgo's third observing run, we present results from the first three SAGUARO searches following the GW events S190408an, S190425z and S190426c, which serve as a valuable proof-of-concept of SAGUARO. We triggered and searched 15, 60 and 60 deg$^{2}$ respectively, 17.6, 1.4 and 41.8 hrs after the initial GW alerts. We covered 7.8, 3.0 and 5.1\% of the total probability within the GW event localizations, reaching 3$\sigma$ limits of 19.8, 21.3 and 20.8 AB mag, respectively. Although no viable counterparts associated with these events were found, we recovered 6 known transients and ruled out 5 potential candidates. We also present Large Binocular Telescope spectroscopy of PS19eq/SN2019ebq, a promising kilonova candidate that was later determined to be a supernova. With the ability to tile large areas and conduct detailed follow-up, SAGUARO represents a significant addition to GW counterpart searches.Comment: 16 pages, 7 figures, 1 table. Accepted to ApJ

Information systems for collaborating versus transacting: Impact on manufacturing plant performance in the presence of demand volatility⋆

Research at the nexus of operations management and information systems suggests that manufacturing plants may benefit from the utilization of information systems for collaborating and transacting with suppliers and customers. The objective of this study is to examine the extent to which value generated by information systems for collaborating versus transacting is contingent upon demand volatility. We analyze a unique dataset assembled from non‐public U.S. Census Bureau data of manufacturing plants. Our findings suggest that when faced with volatile demand, plants employing information systems for collaborating with suppliers and customers experience positive and significant benefits to performance, in terms of both labor productivity and inventory turnover. In contrast, results suggest that plants employing information systems for transacting in volatile environments do not experience such benefits. Further exploratory analysis suggests that in the context of demand volatility, these two distinct dimensions of IT‐based integration have differing performance implications at different stages of the production process in terms of raw‐materials inventory and finished‐goods inventory, but not in terms of work‐in‐process inventory. Taken together, our study contributes to theoretical and managerial understanding of the contingent value of information systems in volatile demand conditions in the supply chain context.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147128/1/joom313.pd

Computing Highly Correlated Positions Using Mutual Information and Graph Theory for G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) are a superfamily of seven transmembrane-spanning proteins involved in a wide array of physiological functions and are the most common targets of pharmaceuticals. This study aims to identify a cohort or clique of positions that share high mutual information. Using a multiple sequence alignment of the transmembrane (TM) domains, we calculated the mutual information between all inter-TM pairs of aligned positions and ranked the pairs by mutual information. A mutual information graph was constructed with vertices that corresponded to TM positions and edges between vertices were drawn if the mutual information exceeded a threshold of statistical significance. Positions with high degree (i.e. had significant mutual information with a large number of other positions) were found to line a well defined inter-TM ligand binding cavity for class A as well as class C GPCRs. Although the natural ligands of class C receptors bind to their extracellular N-terminal domains, the possibility of modulating their activity through ligands that bind to their helical bundle has been reported. Such positions were not found for class B GPCRs, in agreement with the observation that there are not known ligands that bind within their TM helical bundle. All identified key positions formed a clique within the MI graph of interest. For a subset of class A receptors we also considered the alignment of a portion of the second extracellular loop, and found that the two positions adjacent to the conserved Cys that bridges the loop with the TM3 qualified as key positions. Our algorithm may be useful for localizing topologically conserved regions in other protein families