Nitric oxide donation lowers blood pressure in adrenocorticotrophic hormone-induced hypertensive rats.

Adrenocorticotrophic hormone (ACTH) elevates systolic blood pressure (SBP) and lowers plasma reactive nitrogen intermediates in rats. We assessed the ability of NO donation from isosorbide dinitrate (ISDN) to prevent or reverse the hypertension caused by ACTH. In the prevention study, male Sprague Dawley rats were treated with ACTH (0.2 mg/kg/day) or saline control for 8 days, with either concurrent ISDN (100 mg/kg/day) via the drinking water or water alone. Animals receiving ISDN via the drinking water were provided with nitrate-free water for 8 hours every day. In the reversal study ISDN (100 mg/kg) or vehicle was given as a single oral dose on day 8. SBP was measured daily by the indirect tail-cuff method in conscious, restrained rats. ACTH caused a significant increase in SBP compared with saline (P < 0.0015). In the prevention study, chronic administration of ISDN (100 mg/kg/day) did not affect the SBP in either group. In the reversal study, ISDN significantly lowered SBP in ACTH-treated rats at 1 and 2.5 hours (132 +/- 3 mmHg (1 h) and 131 +/- 2 mmHg (2.5 h) versus 143 +/- 3 mmHg (0 h), P < 0.002), but not to control levels. It had no effect in control (saline treated) rats. In conclusion, the lowering of SBP by NO donation is consistent with the notion that ACTH-induced hypertension involves an impaired bioavailability or action of NO in vivo

Learning and Recognition of a Non-conscious Sequence of Events in Human Primary Visual Cortex

Published Online: March 03, 2016Human primary visual cortex (V1) has long been associated with learning simple low-level visual discriminations [1] and is classically considered outside of neural systems that support high-level cognitive behavior in contexts that differ from the original conditions of learning, such as recognition memory [2, 3]. Here, we used a novel fMRI-based dichoptic masking protocol—designed to induce activity in V1, without modulation from visual awareness—to test whether human V1 is implicated in human observers rapidly learning and then later (15–20 min) recognizing a non-conscious and complex (secondorder) visuospatial sequence. Learning was associated with a change in V1 activity, as part of a temporo-occipital and basal ganglia network, which is at variance with the cortico-cerebellar network identified in prior studies of ‘‘implicit’’ sequence learning that involved motor responses and visible stimuli (e.g., [4]). Recognition memory was associated with V1 activity, as part of a temporo-occipital network involving the hippocampus, under conditions that were not imputable to mechanisms associated with conscious retrieval. Notably, the V1 responses during learning and recognition separately predicted non-conscious recognition memory, and functional coupling between V1 and the hippocampus was enhanced for old retrieval cues. The results provide a basis for novel hypotheses about the signals that can drive recognition memory, because these data (1) identify human V1 with a memory network that can code complex associative serial visuospatial information and support later nonconscious recognition memory-guided behavior (cf. [5]) and (2) align with mouse models of experiencedependent V1 plasticity in learning and memory [6].This work was supported by the Wellcome Trust (WT073735MA; C.R.R. and C.K.; http://www.wellcome.ac.uk/), the Medical Research Council (UK, 89631; D.S.; http://www.mrc.ac.uk/), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford (C.R.R., C.A.A., and C.K.; http://oxfordbrc.nihr.ac.uk/), and the Dementias and Neurodegenerative Diseases Research Network (C.A.A.; https://www.crn.nihr.ac.uk/dementia)

SN2013fs and SN2013fr: Exploring the circumstellar-material diversity in Type II supernovae

We present photometry and spectroscopy of SN2013fs and SN2013fr in the first 100 days post-explosion. Both objects showed transient, relatively narrow H$\alpha$ emission lines characteristic of SNeIIn, but later resembled normal SNeII-P or SNeII-L, indicative of fleeting interaction with circumstellar material (CSM). SN2013fs was discovered within 8hr of explosion. Its light curve exhibits a plateau, with spectra revealing strong CSM interaction at early times. It is a less luminous version of the transitional SNIIn PTF11iqb, further demonstrating a continuum of CSM interaction intensity between SNeII-P and IIn. It requires dense CSM within 6.5$\times$10$^{14}$~cm of the progenitor, from a phase of advanced pre-SN mass loss shortly before explosion. Spectropolarimetry of SN2013fs shows little continuum polarization, but noticeable line polarization during the plateau phase. SN2013fr morphed from a SNIIn at early times to a SNII-L. After the first epoch its narrow lines probably arose from host-galaxy emission, but the bright, narrow H$\alpha$ emission at early times may be intrinsic. As for SN2013fs, this would point to a short-lived phase of strong CSM interaction if proven to be intrinsic, suggesting a continuum between SNeIIn and II-L. It is a low-velocity SNII-L, like SN2009kr but more luminous. SN2013fr also developed an IR excess at later times, due to warm CSM dust that require a more sustained phase of strong pre-SN mass loss.Comment: MNRAS accepted. 28 pages, 23 figures, 8 table

A novel checkpoint in the Bcl-2–regulated apoptotic pathway revealed by murine cytomegalovirus infection of dendritic cells

Infection with murine cytomegalovirus (MCMV) has contributed to understanding many aspects of human infection and, additionally, has provided important insight to understanding complex cellular responses. Dendritic cells (DCs) are a major target for MCMV infection. Here, we analyze the effects of MCMV infection on DC viability, and show that infected DCs become resistant to apoptosis induced by growth factor deprivation. The precise contribution of changes in the expression of Bcl-2 family proteins has been assessed and a new checkpoint in the apoptotic pathway identified. Despite their resistance to apoptosis, MCMV-infected DCs showed Bax to be tightly associated with mitochondria and, together with Bak, forming high molecular weight oligomers, changes normally associated with apoptotic cell death. Exposure of a constitutively occluded Bax NH2-terminal epitope was blocked after infection. These results suggest that MCMV has evolved a novel strategy for inhibiting apoptosis and provide evidence that apoptosis can be regulated after translocation, integration, and oligomerization of Bax at the mitochondrial membrane

All the Brain\u27s a Stage for Serotonin: The Forgotten Story of Serotonin Diffusion across Cell Membranes

In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite having a positive charge, can cross cell membranes through a diffusion-like process. Multiple low-affinity, high-capacity, sodium-independent transporters, widely expressed in the brain, allow the carrier-mediated diffusion of serotonin into forebrain neurons. The amount of serotonin crossing cell membranes through this mechanism under physiological conditions is considerable. Most prominent textbooks fail to include this alternative method of serotonin uptake in the brain, and even most neuroscientists are unaware of it. This failure has limited our understanding of a key regulator of serotonergic neurotransmission, impeded research on the potential intracellular actions of serotonin in post-synaptic neurons and glial cells, and may have impeded our understanding of the mechanism by which antidepressant medications reduce depressive symptoms

Professional analysts using a large, high-resolution display

Professional cyber analysts were observed as they attempted to solve the VAST 2009 Traffic Mini Challenge using basic visualization tools and a large, high-resolution display. We discuss some of the lessons we learned about how analysts actually work and potential roles for visualization and large, high-resolution displays

Performance of Scheduling Policies in Adversarial Networks with Non-synchronized Clocks

In this paper we generalize the Continuous Adversarial Queuing Theory (CAQT) model (Blesa et al. in MFCS, Lecture Notes in Computer Science, vol. 3618, pp. 144–155, 2005) by considering the possibility that the router clocks in the network are not synchronized. We name the new model Non Synchronized CAQT (NSCAQT). Clearly, this new extension to the model only affects those scheduling policies that use some form of timing. In a first approach we consider the case in which although not synchronized, all clocks run at the same speed, maintaining constant differences. In this case we show that all universally stable policies in CAQT that use the injection time and the remaining path to schedule packets remain universally stable. These policies include, for instance, Shortest in System (SIS) and Longest in System (LIS). Then, we study the case in which clock differences can vary over time, but the maximum difference is bounded. In this model we show the universal stability of two families of policies related to SIS and LIS respectively (the priority of a packet in these policies depends on the arrival time and a function of the path traversed). The bounds we obtain in this case depend on the maximum difference between clocks. This is a necessary requirement, since we also show that LIS is not universally stable in systems without bounded clock difference. We then present a new policy that we call Longest in Queues (LIQ), which gives priority to the packet that has been waiting the longest in edge queues. This policy is universally stable and, if clocks maintain constant differences, the bounds we prove do not depend on them. To finish, we provide with simulation results that compare the behavior of some of these policies in a network with stochastic injection of packets

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142052/1/jper0257.pd