Characterization of herpes simplex virus 2 primary microRNA transcript regulation

In order to understand factors that may influence latency-associated transcription and latency-associated transcript (LAT) phenotypes, we studied the expression of the herpes simplex virus 2 (HSV-2) LAT-associated microRNAs (miRNAs). We mapped the transcription initiation sites of all three primary miRNA transcripts and identified the ICP4-binding sequences at the transcription initiation sites of both HSV-2 LAT (pri-miRNA for miR-I and miR-II, which target ICP34.5, and miR-III, which targets ICP0) and L/ST (a pri-miRNA for miR-I and miR-II) but not at that of the primary miR-H6 (for which the target is unknown). We confirmed activity of the putative HSV-2 L/ST promoter and found that ICP4 trans-activates the L/ST promoter when the ICP4-binding site at its transcription initiation site is mutated, suggesting that ICP4 may play a dual role in regulating transcription of L/ST and, consequently, of miR-I and miR-II. LAT exon 1 (containing LAT enhancer sequences), together with the LAT promoter region, comprises a bidirectional promoter required for the expression of both LAT-encoded miRNAs and miR-H6 in latently infected mouse ganglia. The ability of ICP4 to suppress ICP34.5-targeting miRNAs and to activate lytic viral genes suggests that ICP4 could play a key role in the switch between latency and reactivation. IMPORTANCE The HSV-2 LAT and viral miRNAs expressed in the LAT region are the most abundant viral transcripts during HSV latency. The balance between the expression of LAT and LAT-associated miRNAs and the expression of lytic viral transcripts from the opposite strand appears to influence whether individual HSV-infected neurons will be latently or productively infected. The outcome of neuronal infection may thus depend on regulation of gene expression of the corresponding primary miRNAs. In the present study, we characterize promoter sequences responsible for miRNA expression, including identification of the primary miRNA 5′ ends and evaluation of ICP4 response. These findings provide further insight into the virus' strategy to tightly control expression of lytic cycle genes (especially the neurovirulence factor, ICP34.5) and suggest a mechanism (via ICP4) for the transition from latency to reactivated productive infection

The chaperone balance hypothesis: The importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management

Recent evidence shows divergence between the concentrations of extracellular 70 kDa heat shock protein [eHSP70] and its intracellular concentrations [iHSP70] in people with type 2 diabetes (T2DM). A vital aspect regarding HSP70 physiology is its versatility to induce antagonistic actions, depending on the location of the protein. For example, iHSP70 exerts a powerful anti-inflammatory effect, while eHSP70 activates proinflammatory pathways. Increased eHSP70 is associated with inflammatory and oxidative stress conditions, whereas decreased iHSP70 levels are related to insulin resistance in skeletal muscle. Serum eHSP70 concentrations are positively correlated with markers of inflammation, such as C-reactive protein, monocyte count, and TNF-a, while strategies to enhance iHSP70 (e.g., heat treatment, chemical HSP70 inducers or coinducers, and physical exercise) are capable of reducing the inflammatory profile and the insulin resistance state. Here, we present recent findings suggesting that imbalances in the HSP70 status, described by the [eHSP70]/[iHSP70] ratio, may be determinant to trigger a chronic proinflammatory state that leads to insulin resistance and T2DM development. This led us to hypothesize that changes in this ratio value could be used as a biomarker for the management of the inflammatory response in insulin resistance and diabetes

Continuum Halos in Nearby Galaxies -- an EVLA Survey (CHANG-ES) -- II: First Results on NGC 4631

We present the first results from the CHANG-ES survey, a new survey of 35 edge-on galaxies to search for both in-disk as well as extra-planar radio continuum emission. The motivation and science case for the survey are presented in a companion paper (Paper I). In this paper (Paper II), we outline the observations and data reduction steps required for wide-band calibration and mapping of EVLA data, including polarization, based on C-array test observations of NGC 4631. With modest on-source observing times (30 minutes at 1.5 GHz and 75 minutes at 6 GHz for the test data) we have achieved best rms noise levels of 22 and 3.5 $\mu$Jy beam$^{-1}$ at 1.5 GHz and 6 GHz, respectively. New disk-halo features have been detected, among them two at 1.5 GHz that appear as loops in projection. We present the first 1.5 GHz spectral index map of NGC 4631 to be formed from a single wide-band observation in a single array configuration. This map represents tangent slopes to the intensities within the band centered at 1.5 GHz, rather than fits across widely separated frequencies as has been done in the past and is also the highest spatial resolution spectral index map yet presented for this galaxy. The average spectral index in the disk is $\bar\alpha_{1.5 GHz}\,=\,-0.84\,\pm\,0.05$ indicating that the emission is largely non-thermal, but a small global thermal contribution is sufficient to explain a positive curvature term in the spectral index over the band. Two specific star forming regions have spectral indices that are consistent with thermal emission. Polarization results (uncorrected for internal Faraday rotation) are consistent with previous observations and also reveal some new features. On broad scales, we find strong support for the notion that magnetic fields constrain the X-ray emitting hot gas.Comment: Accepted to the Astronomical Journal, Version 2 changes: Added acknowledgement to NRA

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Continuum Halos in Nearby Galaxies -- an EVLA Survey (CHANG-ES) -- I: Introduction to the Survey

We introduce a new survey to map the radio continuum halos of a sample of 35 edge-on spiral galaxies at 1.5 GHz and 6 GHz in all polarization products. The survey is exploiting the new wide bandwidth capabilities of the Karl G. Jansky Very Large Array (i.e. the Expanded Very Large Array, or EVLA) in a variety of array configurations (B, C, and D) in order to compile the most comprehensive data set yet obtained for the study of radio halo properties. This is the first survey of radio halos to include all polarization products. In this first paper, we outline the scientific motivation of the survey, the specific science goals, and the expected improvements in noise levels and spatial coverage from the survey. Our goals include investigating the physical conditions and origin of halos, characterizing cosmic ray transport and wind speed, measuring Faraday rotation and mapping the magnetic field, probing the in-disk and extraplanar far-infrared - radio continuum relation, and reconciling non-thermal radio emission with high-energy gamma-ray models. The sample size allows us to search for correlations between radio halos and other properties, including environment, star formation rate, and the presence of AGNs. In a companion paper (Paper II) we outline the data reduction steps and present the first results of the survey for the galaxy, NGC 4631.Comment: 17 pages, 1 figure, accepted to the Astronomical Journal, Version 2 changes: added acknowledgement to NRA

Assessing hydrological controls on the lithium isotope weathering tracer

To investigate the impact of riverine discharge and weathering intensity on lithium isotopes (δ7Li) in a mono-lithological terrain, this study examines the dissolved load and leached suspended load (exchangeable, oxide, and clay fractions) from Icelandic rivers spanning a wide range of discharge, weathering rates, and weathering intensity. The δ7Lidissolved co-varies inversely with the discharge, confirming that water-rock interaction time is a primary control on the secondary mineral formation that fractionates Li isotopes. The “boomerang” shape observed in global rivers between the weathering intensity (i.e. W/D = weathering rate/denudation rate) and δ7Lidissolved also exists for these basaltic rivers at low to medium W/D. However, these rivers do not extend to such low δ7Lidissolved values as seen in the global compilation at low W/D, indicating that there is a lithological control on this relationship arising from the type of the lithology-specific secondary minerals forming and their precipitation rates. In addition, the Δ7Lix-dissolved between each leached solid phase and the dissolved load also co-varies with discharge. At low discharge (long water-rock interaction times), Δ7Lix-dissolved values agree with experimentally-determined equilibrium values, whereas less fractionated values are observed at higher discharge (shorter water-rock interaction times). As a result, there is a different relationship between W/D and Δ7Liclay-source in this basaltic terrain than previously reported from global multi-lithological river sediment samples, with clay leachates from Iceland more closely mimicking the boomerang shape of the dissolved load. However, the relationship between δ7Li and weathering processes is complicated because the fractionation between the clay fraction and the dissolved load is not constant but varies with both W/D and discharge. Overall, this study confirms the utility of Li isotopes as a tracer of modern and palaeo-weathering processes, and also has important implications for the specific interpretations of detrital δ7Li values, which may be more sensitive to weathering parameters than previously thought

Assessing hydrological controls on the lithium isotope weathering tracer

To investigate the impact of riverine discharge and weathering intensity on lithium isotopes (δ7Li) in a mono-lithological terrain, this study examines the dissolved load and leached suspended load (exchangeable, oxide, and clay fractions) from Icelandic rivers spanning a wide range of discharge, weathering rates, and weathering intensity. The δ7Lidissolved co-varies inversely with the discharge, confirming that water-rock interaction time is a primary control on the secondary mineral formation that fractionates Li isotopes. The “boomerang” shape observed in global rivers between the weathering intensity (i.e. W/D = weathering rate/denudation rate) and δ7Lidissolved also exists for these basaltic rivers at low to medium W/D. However, these rivers do not extend to such low δ7Lidissolved values as seen in the global compilation at low W/D, indicating that there is a lithological control on this relationship arising from the type of the lithology-specific secondary minerals forming and their precipitation rates. In addition, the Δ7Lix-dissolved between each leached solid phase and the dissolved load also co-varies with discharge. At low discharge (long water-rock interaction times), Δ7Lix-dissolved values agree with experimentally-determined equilibrium values, whereas less fractionated values are observed at higher discharge (shorter water-rock interaction times). As a result, there is a different relationship between W/D and Δ7Liclay-source in this basaltic terrain than previously reported from global multi-lithological river sediment samples, with clay leachates from Iceland more closely mimicking the boomerang shape of the dissolved load. However, the relationship between δ7Li and weathering processes is complicated because the fractionation between the clay fraction and the dissolved load is not constant but varies with both W/D and discharge. Overall, this study confirms the utility of Li isotopes as a tracer of modern and palaeo-weathering processes, and also has important implications for the specific interpretations of detrital δ7Li values, which may be more sensitive to weathering parameters than previously thought

Planning for Sustainability in Small Municipalities: The Influence of Interest Groups, Growth Patterns, and Institutional Characteristics

How and why small municipalities promote sustainability through planning efforts is poorly understood. We analyzed ordinances in 451 Maine municipalities and tested theories of policy adoption using regression analysis.We found that smaller communities do adopt programs that contribute to sustainability relevant to their scale and context. In line with the political market theory, we found that municipalities with strong environmental interests, higher growth, and more formal governments were more likely to adopt these policies. Consideration of context and capacity in planning for sustainability will help planners better identify and benefit from collaboration, training, and outreach opportunities

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

Modelling hair follicle growth dynamics as an excitable medium

The hair follicle system represents a tractable model for the study of stem cell behaviour in regenerative adult epithelial tissue. However, although there are numerous spatial scales of observation (molecular, cellular, follicle and multi follicle), it is not yet clear what mechanisms underpin the follicle growth cycle. In this study we seek to address this problem by describing how the growth dynamics of a large population of follicles can be treated as a classical excitable medium. Defining caricature interactions at the molecular scale and treating a single follicle as a functional unit, a minimal model is proposed in which the follicle growth cycle is an emergent phenomenon. Expressions are derived, in terms of parameters representing molecular regulation, for the time spent in the different functional phases of the cycle, a formalism that allows the model to be directly compared with a previous cellular automaton model and experimental measurements made at the single follicle scale. A multi follicle model is constructed and numerical simulations are used to demonstrate excellent qualitative agreement with a range of experimental observations. Notably, the excitable medium equations exhibit a wider family of solutions than the previous work and we demonstrate how parameter changes representing altered molecular regulation can explain perturbed patterns in Wnt over-expression and BMP down-regulation mouse models. Further experimental scenarios that could be used to test the fundamental premise of the model are suggested. The key conclusion from our work is that positive and negative regulatory interactions between activators and inhibitors can give rise to a range of experimentally observed phenomena at the follicle and multi follicle spatial scales and, as such, could represent a core mechanism underlying hair follicle growth