Heart Failure Symptom Biology in Response to Ventricular Assist Device Implantation.

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation. OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF. METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], depression [Patient Health Questionnaire], and anxiety [Brief Symptom Inventory]) and peripheral biomarkers of myocardial stretch, systemic inflammation, and hypervolumetric mechanical stress were measured before implantation with a commercially available LVAD and again at 30, 90, and 180 days after LVAD implantation. Latent growth curve and parallel process modeling were used to describe changes in symptoms and biomarkers and the degree to which they change in parallel in response to LVAD implantation. RESULTS: In response to LVAD implantation, changes in myocardial stretch were closely associated with changes in early and subtle physical symptoms as well as depression, and changes in hypervolumetric stress were closely associated with changes in pain severity and wake disturbances. Changes in systemic inflammation were not closely associated with changes in physical or affective symptoms in response to LVAD implantation. CONCLUSIONS: These findings provide new insights into the many ways in which symptoms and biomarkers provide concordant or discordant information about LVAD response

Probing the Coevolution of Supermassive Black Holes and Galaxies Using Gravitationally Lensed Quasar Hosts

In the present-day universe, supermassive black hole masses (MBH) appear to be strongly correlated with their galaxy's bulge luminosity, among other properties. In this study, we explore the analogous relationship between MBH, derived using the virial method, and the stellar R-band bulge luminosity (Lr) or stellar bulge mass (M*) at epochs of 1 < z < 4.5 using a sample of 31 gravitationally lensed AGNs and 20 non-lensed AGNs. At redshifts z > 1.7 (10--12 Gyrs ago), we find that the observed MBH--Lr relation is nearly the same (to within ~0.3 mag) as it is today. When the observed Lr are corrected for luminosity evolution, this means that the black holes grew in mass faster than their hosts, with the MBH/M* mass ratio being a factor of > 4(+2)(-1) times larger at z > 1.7 than it is today. By the redshift range 1<z<1.7 (8-10 Gyrs ago), the MBH/M* ratio is at most two times higher than today, but it may be consistent with no evolution. Combining the results, we conclude that the ratio MBH/M* rises with look-back time, although it may saturate at ~6 times the local value. Scenarios in which moderately luminous quasar hosts at z>1.7 were fully formed bulges that passively faded to the present epoch are ruled out.Comment: ApJ accepted, includes Referee comments and statistics to better quantify the statistical significance of results. 23 pages, 11 figures, 4 table

History of Galaxy Interactions and their Impact on Star Formation over the Last 7 Gyr from GEMS

We perform a comprehensive estimate of the frequency of galaxy mergers and their impact on star formation over z~0.24--0.80 (lookback time T_b~3--7 Gyr) using 3698 (M*>=1e9 Msun) galaxies with GEMS HST, COMBO-17, and Spitzer data. Our results are: (1) Among 790 high mass (M*>=2.5e10 Msun) galaxies, the visually-based merger fraction over z~0.24--0.80, ranges from 9%+-5% to 8%+-2%. Lower limits on the major and minor merger fractions over this interval range from 1.1% to 3.5%, and 3.6% to 7.5%, respectively. This is the first approximate empirical estimate of the frequency of minor mergers at z<1. For a visibility timescale of ~0.5 Gyr, it follows that over T_b~3--7 Gyr, ~68% of high mass systems have undergone a merger of mass ratio >1/10, with ~16%, 45%, and 7% of these corresponding respectively to major, minor, and ambiguous `major or minor' mergers. The mean merger rate is a few x 1e-4 Gyr-1 Mpc-3. (2) We compare the empirical merger fraction and rate for high mass galaxies to a suite of Lambda CDM-based models: halo occupation distribution models, semi-analytic models, and hydrodynamic SPH simulations. We find qualitative agreement between observations and models such that the (major+minor) merger fraction or rate from different models bracket the observations, and show a factor of five dispersion. Near-future improvements can now start to rule out certain merger scenarios. (3) Among ~3698 M*>=1e9 Msun galaxies, we find that the mean SFR of visibly merging systems is only modestly enhanced compared to non-interacting galaxies over z~0.24--0.80. Visibly merging systems only account for less than 30% of the cosmic SFR density over T_b~3--7 Gyr. This suggests that the behavior of the cosmic SFR density over the last 7 Gyr is predominantly shaped by non-interacting galaxies.Comment: Accepted for Publication in the Astrophysical Journal. 17 pages of text, 21 figures, 3 tables. Uses emulateapj5.st

Field performance of switchgrass plants engineered for reduced recalcitrance

Switchgrass (Panicum virgatum L.) is a promising perennial bioenergy crop that achieves high yields with relatively low nutrient and energy inputs. Modification of cell wall composition for reduced recalcitrance can lower the costs of deconstructing biomass to fermentable sugars and other intermediates. We have engineered overexpression of OsAT10, encoding a rice BAHD acyltransferase and QsuB, encoding dehydroshikimate dehydratase from Corynebacterium glutamicum, to enhance saccharification efficiency in switchgrass. These engineering strategies demonstrated low lignin content, low ferulic acid esters, and increased saccharification yield during greenhouse studies in switchgrass and other plant species. In this work, transgenic switchgrass plants overexpressing either OsAT10 or QsuB were tested in the field in Davis, California, USA for three growing seasons. No significant differences in the content of lignin and cell wall-bound p-coumaric acid or ferulic acid were detected in transgenic OsAT10 lines compared with the untransformed Alamo control variety. However, the transgenic overexpressing QsuB lines had increased biomass yield and slightly increased biomass saccharification properties compared to the control plants. This work demonstrates good performance of engineered plants in the field, and also shows that the cell wall changes in the greenhouse were not replicated in the field, emphasizing the need to validate engineered plants under relevant field conditions

Chemotaxis of Cell Populations through Confined Spaces at Single-Cell Resolution

Cell migration is crucial for both physiological and pathological processes. Current in vitro cell motility assays suffer from various drawbacks, including insufficient temporal and/or optical resolution, or the failure to include a controlled chemotactic stimulus. Here, we address these limitations with a migration chamber that utilizes a self-sustaining chemotactic gradient to induce locomotion through confined environments that emulate physiological settings. Dynamic real-time analysis of both population-scale and single-cell movement are achieved at high resolution. Interior surfaces can be functionalized through adsorption of extracellular matrix components, and pharmacological agents can be administered to cells directly, or indirectly through the chemotactic reservoir. Direct comparison of multiple cell types can be achieved in a single enclosed system to compare inherent migratory potentials. Our novel microfluidic design is therefore a powerful tool for the study of cellular chemotaxis, and is suitable for a wide range of biological and biomedical applications

The Flagellar Regulator fliT Represses Salmonella Pathogenicity Island 1 through flhDC and fliZ

Salmonella pathogenicity island 1 (SPI1), comprising a type III section system that translocates effector proteins into host cells, is essential for the enteric pathogen Salmonella to penetrate the intestinal epithelium and subsequently to cause disease. Using random transposon mutagenesis, we found that a Tn10 disruption in the flagellar fliDST operon induced SPI1 expression when the strain was grown under conditions designed to repress SPI1, by mimicking the environment of the large intestine through the use of the intestinal fatty acid butyrate. Our genetic studies showed that only fliT within this operon was required for this effect, and that exogenous over-expression of fliT alone significantly reduced the expression of SPI1 genes, including the invasion regulator hilA and the sipBCDA operon, encoding type III section system effector proteins, and Salmonella invasion of cultured epithelial cells. fliT has been known to inhibit the flagellar machinery through repression of the flagellar master regulator flhDC. We found that the repressive effect of fliT on invasion genes was completely abolished in the absence of flhDC or fliZ, the latter previously shown to induce SPI1, indicating that this regulatory pathway is required for invasion control by fliT. Although this flhDC-fliZ pathway was necessary for fliT to negatively control invasion genes, fliZ was not essential for the repressive effect of fliT on motility, placing fliT high in the regulatory cascade for both invasion and motility

Smoking and Genetic Risk Variation Across Populations of E uropean, A sian, and A frican A merican Ancestry—A Meta‐Analysis of Chromosome 15q25

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91126/1/gepi21627.pd

Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila

The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower