Carbenoxolone induced depression of rhythmogenesis in the pre-Bötzinger Complex

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Enhanced Cellular Immunity in Shrimp (Litopenaeus vannamei) after ‘Vaccination’

It has long been viewed that invertebrates rely exclusively upon a wide variety of innate mechanisms for protection from disease and parasite invasion and lack any specific acquired immune mechanisms comparable to those of vertebrates. Recent findings, however, suggest certain invertebrates may be able to mount some form of specific immunity, termed ‘specific immune priming’, although the mechanism of this is not fully understood (see Textbox S1). In our initial experiments, either formalin-inactivated Vibrio harveyi or sterile saline were injected into the main body cavity (haemocoel) of juvenile shrimp (Litopenaeus vannamei). Haemocytes (blood cells) from V. harveyi-injected shrimp were collected 7 days later and incubated with a 1∶1 mix of V. harveyi and an unrelated Gram positive bacterium, Bacillus subtilis. Haemocytes from ‘vaccinated’ shrimp showed elevated levels of phagocytosis of V. harveyi, but not B. subtilis, compared with those from saline-injected (non-immunised) animals. The increased phagocytic activity was characterised by a significant increase in the percentage of phagocytic cells. When shrimp were injected with B. subtilis rather than vibrio, there was no significant increase in the phagocytic activity of haemocytes from these animals in comparison to the non-immunised (saline injected) controls. Whole haemolymph (blood) from either ‘immunised’ or non-immunised’ shrimp was shown to display innate humoral antibacterial activity against V. harveyi that was absent against B. subtilis. However, there was no difference in the potency of antibacterial activity between V. harveyi-injected shrimp and control (saline injected) animals showing that ‘vaccination’ has no effect on this component of the shrimp's immune system. These results imply that the cellular immune system of shrimp, particularly phagocytosis, is capable of a degree of specificity and shows the phenomenon of ‘immune priming’ reported by other workers. However, in agreement with other studies, this phenomenon is not universal to all potential pathogens

Surrogate Markers for Time-Varying Treatments and Outcomes

BACKGROUND: A surrogate marker is a variable commonly used in clinical trials to guide treatment decisions when the outcome of ultimate interest is not available. A good surrogate marker is one where the treatment effect on the surrogate is a strong predictor of the effect of treatment on the outcome. We review the situation when there is one treatment delivered at baseline, one surrogate measured at one later time point, and one ultimate outcome of interest and discuss new issues arising when variables are time-varying. METHODS: Most of the literature on surrogate markers has only considered simple settings with one treatment, one surrogate, and one outcome of interest at a fixed time point. However, more complicated time-varying settings are common in practice. In this article, we describe the unique challenges in two settings, time-varying treatments and time-varying surrogates, while relating the ideas back to the causal-effects and causal-association paradigms. CONCLUSION: In addition to discussing and extending popular notions of surrogacy to time-varying settings, we give examples illustrating that one can be misled by not taking into account time-varying information about the surrogate or treatment. We hope this article has provided some motivation for future work on estimation and inference in such settings

The Central Engines of 19 LINERs as Viewed by Chandra

Using archival Chandra observations of 19 LINERs we explore the X-ray properties of their inner kiloparsec to determine the origin of their nuclear X-ray emission, to investigate the presence of an AGN, and to identify the power source of the optical emission lines. The relative numbers of LINER types in our sample are similar to those in optical spectroscopic surveys. We find that diffuse, thermal emission is very common and is concentrated within the central few hundred parsec. The average spectra of the hot gas in spirals and ellipticals are very similar to those of normal galaxies. They can be fitted with a thermal plasma (kT~0.5 keV) plus a power law (photon index of 1.3-1.5) model. There are on average 3 detected point sources in their inner kiloparsec with L(0.5-10 keV)~10^37-10^40 erg/s. The average cumulative luminosity functions for sources in spirals and ellipticals are identical to those of normal galaxies. In the innermost circle of 2.5" radius in each galaxy we find an AGN in 12 of the 19 galaxies. The AGNs contribute a median of 60% of the 0.5-10 keV luminosity of the central 2.5" region, they have luminosities of 10^37-10^39 erg/s (Eddington ratios 10^-8 to 10^-5). The ionizing luminosity of the AGNs is not enough to power the observed optical emission lines in this particular sample. Thus, we suggest that the lines are powered either by the mechanical interaction of an AGN jet (or wind) with the circumnuclear gas, or by stellar processes, e.g. photoionization by post-AGB stars or young stars.Comment: Accepted by Ap.J. 23 pages, 8 figures, emulatepj format, images of fig 1 not included, for complete PDF preprint see http://www.astro.psu.edu/users/mce/preprints

Three LINERs Under the Chandra X-Ray Microscope

We use X-ray observations of three galaxies hosting LINERs (NGC 404, NGC 4736, NGC 4579) with Chandra to study their power sources. We find very diverse properties within this small group: NGC 404 has an X-ray-faint nucleus with a soft, thermal spectrum, NGC 4736 harbors a plethora of discrete X-ray sources in and around its nucleus, and NGC 4579 has a dominant nuclear point source embedded in a very extended, diffuse nebulosity. From their multi- wavelength properties we conclude the following: the nucleus of NGC 404 is the site of a weak, compact starburst, whose X-ray emission is due to gas heated by stellar winds and supernovae, NGC 4736 is in a recent or aging starburst phase, where the X-ray emission is dominated by a dense cluster of X-ray binaries, and NGC 4579 is powered by accretion onto a supermassive black hole. We detect 39 discrete sources in NGC 4736 and 21 in NGC 4579, most with L_X > 10^37 erg/s. One source in the disk of NGC 4579 could be an ultraluminous X-ray binary with L_X (2-10 keV) = 9x10^39 erg/s, but it could also be a background quasar. The most luminous discrete sources have simple power-law spectra, which along with their luminosities suggest that these are X-ray binaries accreting near or above the Eddington rate for a neutron star. By comparing the luminosity functions of discrete X-ray sources in these and other galaxies we find a potential connection between the age of the stellar population and the slope of the cumulative X-ray source luminosity function: galaxies with primarily old stellar populations have steeper luminosity functions than starburst galaxies. We suggest that this difference results from the contribution of high-mass X-ray binaries from the young stellar population to the upper end of the luminosity function.Comment: To appear in the Astrophysical Journal. Enlarged views of images available at http://www.astro.psu.edu/users/mce/preprints/preprint_index.htm

Characterization of novel canine bocaviruses and their association with respiratory disease

We report the first identification, genetic characterization and disease association studies of several novel species of canine bocaviruses (CBoV). Evolutionary analysis confirmed that CBoV are genetically distinct from the only other known canine bocavirus, minute virus of canines, with which they share less than 63, 62 and 64 % protein identity in NS, NP and VP genes, respectively. Comparative genetic analysis of 37 VP gene variants found in diseased and healthy animals showed that these novel viruses are genetically highly diverse and are common in canine respiratory infections that have remained undetected until now. Interestingly, we observed that a CBoV genotype with a unique deletion in the VP2 gene was significantly more prevalent in animals with respiratory diseases compared with healthy animals

New research directions on disparities in obesity and type 2 diabetes

Obesity and type 2 diabetes disproportionately impact U.S. racial and ethnic minority communities and lowâ income populations. Improvements in implementing efficacious interventions to reduce the incidence of type 2 diabetes are underway (i.e., the National Diabetes Prevention Program), but challenges in effectively scalingâ up successful interventions and reaching atâ risk populations remain. In October 2017, the National Institutes of Health convened a workshop to understand how to (1) address socioeconomic and other environmental conditions that perpetuate disparities in the burden of obesity and type 2 diabetes; (2) design effective prevention and treatment strategies that are accessible, feasible, culturally relevant, and acceptable to diverse population groups; and (3) achieve sustainable health improvement approaches in communities with the greatest burden of these diseases. Common features of guiding frameworks to understand and address disparities and promote health equity were described. Promising research directions were identified in numerous areas, including study design, methodology, and core metrics; program implementation and scalability; the integration of medical care and social services; strategies to enhance patient empowerment; and understanding and addressing the impact of psychosocial stress on disease onset and progression in addition to factors that support resiliency and health.This report discusses a workshop convened by the National Institutes of Health to understand how to (1) address socioeconomic and other environmental conditions that perpetuate disparities in the burden of obesity and type 2 diabetes; (2) design effective prevention and treatment strategies that are accessible, feasible, culturally relevant, and acceptable to diverse population groups; and (3) achieve sustainable health improvement approaches in communities with the greatest burden of these diseases.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154507/1/nyas14270_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154507/2/nyas14270.pd