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Journal articles on the topic 'Viral tracer'
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McLeod, Malcolm, Jacqueline Aislabie, James Smith, Rhonda Fraser, Alexandra Roberts, and Matthew Taylor. "Viral and Chemical Tracer Movement through Contrasting Soils." Journal of Environmental Quality 30, no. 6 (November 2001): 2134–40. http://dx.doi.org/10.2134/jeq2001.2134.
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Flexman, J. A., S. Minoshima, Yongmin Kim, S. Miyoshi, B. L. Lewellen, and D. J. Cross. "A viral envelope as a vehicle for tracer, drug, and gene delivery." IEEE Engineering in Medicine and Biology Magazine 25, no. 4 (July 2006): 70–75. http://dx.doi.org/10.1109/memb.2006.1657790.
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Pomeranz, Lisa E., Ashley E. Reynolds, and Christoph J. Hengartner. "Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine." Microbiology and Molecular Biology Reviews 69, no. 3 (September 2005): 462–500. http://dx.doi.org/10.1128/mmbr.69.3.462-500.2005.
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SUMMARY Pseudorabies virus (PRV) is a herpesvirus of swine, a member of the Alphaherpesvirinae subfamily, and the etiological agent of Aujeszky's disease. This review describes the contributions of PRV research to herpesvirus biology, neurobiology, and viral pathogenesis by focusing on (i) the molecular biology of PRV, (ii) model systems to study PRV pathogenesis and neurovirulence, (iii) PRV transsynaptic tracing of neuronal circuits, and (iv) veterinary aspects of pseudorabies disease. The structure of the enveloped infectious particle, the content of the viral DNA genome, and a step-by-step overview of the viral replication cycle are presented. PRV infection is initiated by binding to cellular receptors to allow penetration into the cell. After reaching the nucleus, the viral genome directs a regulated gene expression cascade that culminates with viral DNA replication and production of new virion constituents. Finally, progeny virions self-assemble and exit the host cells. Animal models and neuronal culture systems developed for the study of PRV pathogenesis and neurovirulence are discussed. PRV serves as a self-perpetuating transsynaptic tracer of neuronal circuitry, and we detail the original studies of PRV circuitry mapping, the biology underlying this application, and the development of the next generation of tracer viruses. The basic veterinary aspects of pseudorabies management and disease in swine are discussed. PRV infection progresses from acute infection of the respiratory epithelium to latent infection in the peripheral nervous system. Sporadic reactivation from latency can transmit PRV to new hosts. The successful management of PRV disease has relied on vaccination, prevention, and testing.
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Song, C. Kay, Gary J. Schwartz, and Timothy J. Bartness. "Anterograde transneuronal viral tract tracing reveals central sensory circuits from white adipose tissue." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 296, no. 3 (March 2009): R501—R511. http://dx.doi.org/10.1152/ajpregu.90786.2008.
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The origins of the sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) have been defined using the transneuronal viral retrograde tract tracer, pseudorabies virus. Activation of this SNS innervation is acknowledged as the principal initiator of WAT lipolysis. The central control of WAT lipolysis may require neural feedback to a brain-SNS-WAT circuit via WAT afferents. Indeed, conventional tract tracing studies have demonstrated that peripheral pseudounipolar dorsal root ganglion (DRG) sensory cells innervate WAT. The central nervous system projections of WAT afferents remain uncharted, however, and form the focus of the present study. We used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer, to define the afferent circuits projecting from WAT to the central nervous system. Siberian hamster inguinal (IWAT) or epididymal WAT was injected with H129 and the neuraxis processed for HSV-1 immunoreactivity. We found substantial overlap in the pattern of WAT sensory afferent projections with multiple SNS outflow sites along the neuraxis, suggesting the possibility of WAT sensory-SNS circuits that could regulate WAT SNS drive and thereby lipolysis. Previously, we demonstrated that systemic 2-deoxy-d-glucose (2DG) elicited increases in the SNS drive to IWAT. Here, we show that systemic 2DG administration also significantly increases multiunit spike activity arising from decentralized IWAT afferents. Collectively, these data provide structural and functional support for the existence of a sensory WAT pathway to the brain, important in the negative feedback control of lipid mobilization.
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Lo, Liching, and David J. Anderson. "A Cre-Dependent, Anterograde Transsynaptic Viral Tracer for Mapping Output Pathways of Genetically Marked Neurons." Neuron 72, no. 6 (December 2011): 938–50. http://dx.doi.org/10.1016/j.neuron.2011.12.002.
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Schneider, Karin, and Paul Massa. "SHP-1 regulates neuroinvasion of neurotropic virus into the CNS (VIR5P.1035)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 144.18. http://dx.doi.org/10.4049/jimmunol.192.supp.144.18.
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Abstract Viral infections in the central nervous system (CNS) may have devastating clinical consequences to the host. Neurotropic virus infections often begin in peripheral tissues, which then spread to the CNS via peripheral nerves following entry into nerve terminals by receptor-mediated endocytosis and subsequent retrograde axonal transport into the CNS compartment. In our lab, a possible novel role for the protein tyrosine phosphatase, SHP-1, in regulating neuroinvasion via peripheral nerves of a neurotropic virus (Theiler’s Murine Encephalomyelitis Virus, TMEV) is being investigated. Preliminary data using immunohistochemistry of TMEV showed extensive staining of spinal cord neurons after intraperitoneal inoculation in mice with a null mutation in the SHP-1 gene (me/me mice) compared to wild type mice. Further, intramuscular (IM) inoculations of TMEV caused virus infection in spinal cord neurons and subsequent paralysis of SHP-1-deficient mice but not of wild type mice. IM and intraperitoneal injections (IP) of retrograde axonal transport tracers fluorogold and horseradish peroxidase showed increased tracer levels in the spinal cords of SHP-1-deficient mice compared to wild type mice. Therefore, we propose SHP-1 may play a role in regulating viral neuroinvasion by controlling retrograde axonal transport from peripheral sites of infection. In this sense, SHP-1 may play novel roles in antiviral responses including inhibition of virus invasion and spreading in the CNS.
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Gostine, Andrew, David Gostine, Jack Short, Arjun Rustagi, Jennifer Cadnum, Curtis Donskey, and Tim Angelotti. "Evaluating the Utility of UV Lamps to Mitigate the Spread of Pathogens in the ICU." Applied Sciences 10, no. 18 (September 11, 2020): 6326. http://dx.doi.org/10.3390/app10186326.
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Contaminated surfaces in a hospital serve as reservoirs for pathogen spread. The aim of this study was to evaluate UV lights in preventing the spread of a DNA tracer in an intensive care unit (ICU) through sterilization of highly touched surfaces. In a prospective trial, a non-pathogenic DNA virus was inoculated onto surfaces in an ICU patient room. Investigators swabbed frequently touched surfaces in non-inoculated ICU rooms at 24, 48, and 96 h post inoculation. Culture specimens were analyzed for the presence of viral DNA via PCR. After baseline data were obtained, UV lights were deployed in a standardized fashion onto vitals monitors, ventilators, keyboards, and intravenous (IV) pumps. Inoculation and culturing were then repeated. Prior to UV implementation, the DNA tracer disseminated to 10.10% of tested surfaces in non-inoculated rooms at 48 h. Post UV light deployment, only 1.20% of surfaces tested positive for the DNA tracer after 48 h. UV decontamination significantly retarded the spread of the virus DNA, with a relative reduction of 90% at 48 h from 10.10% of surfaces pre UV to 1.20% of surfaces post UV (p < 0.0001). UV decontamination holds the potential to confer protection to patients by reducing the number of surfaces that can serve as a nidus for transfer.
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Paul, J. H., J. B. Rose, J. Brown, E. A. Shinn, S. Miller, and S. R. Farrah. "Viral tracer studies indicate contamination of marine waters by sewage disposal practices in key largo, Florida." Applied and environmental microbiology 61, no. 6 (1995): 2230–34. http://dx.doi.org/10.1128/aem.61.6.2230-2234.1995.
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Ryu, Vitaly, and Timothy J. Bartness. "Short and long sympathetic-sensory feedback loops in white fat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 306, no. 12 (June 15, 2014): R886—R900. http://dx.doi.org/10.1152/ajpregu.00060.2014.
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We previously demonstrated white adipose tissue (WAT) innervation using the established WAT retrograde sympathetic nervous system (SNS)-specific transneuronal viral tract tracer pseudorabies virus (PRV152) and showed its role in the control of lipolysis. Conversely, we demonstrated WAT sensory innervation using the established anterograde sensory system (SS)-specific transneuronal viral tracer, the H129 strain of herpes simplex virus-1, with sensory nerves showing responsiveness with increases in WAT SNS drive. Several brain areas were part of the SNS outflow to and SS inflow from WAT between these studies suggesting SNS-SS feedback loops. Therefore, we injected both PRV152 and H129 into inguinal WAT (IWAT) of Siberian hamsters. Animals were perfused on days 5 and 6 postinoculation after H129 and PRV152 injections, respectively, and brains, spinal cords, sympathetic, and dorsal root ganglia (DRG) were processed for immunohistochemical detection of each virus across the neuroaxis. The presence of H129+PRV152-colocalized neurons (∼50%) in the spinal segments innervating IWAT suggested short SNS-SS loops with significant coinfections (>60%) in discrete brain regions, signifying long SNS-SS loops. Notably, the most highly populated sites with the double-infected neurons were the medial part of medial preoptic nucleus, medial preoptic area, hypothalamic paraventricular nucleus, lateral hypothalamus, periaqueductal gray, oral part of the pontine reticular nucleus, and the nucleus of the solitary tract. Collectively, these results strongly indicate the neuroanatomical reality of the central SNS-SS feedback loops with short loops in the spinal cord and long loops in the brain, both likely involved in the control of lipolysis or other WAT pad-specific functions.
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Marson, L., and A. Z. Murphy. "Identification of neural circuits involved in female genital responses in the rat: a dual virus and anterograde tracing study." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291, no. 2 (August 2006): R419—R428. http://dx.doi.org/10.1152/ajpregu.00864.2005.
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The spinal and peripheral innervation of the clitoris and vagina are fairly well understood. However, little is known regarding supraspinal control of these pelvic structures. The multisynaptic tracer pseudorabies virus (PRV) was used to map the brain neurons that innervate the clitoris and vagina. To delineate forebrain input on PRV-labeled cells, the anterograde tracer biotinylated dextran amine was injected in the medial preoptic area (MPO), ventromedial nucleus of the hypothalamus (VMN), or the midbrain periaqueductal gray (PAG) 10 days before viral injections. These brain regions have been intimately linked to various aspects of female reproductive behavior. After viral injections (4 days) in the vagina and clitoris, PRV-labeled cells were observed in the paraventricular nucleus (PVN), Barrington’s nucleus, the A5 region, and the nucleus paragigantocellularis (nPGi). At 5 days postviral administration, additional PRV-labeled cells were observed within the preoptic region, VMN, PAG, and lateral hypothalamus. Anterograde labeling from the MPO terminated among PRV-positive cells primarily within the dorsal PVN of the hypothalamus, ventrolateral VMN (VMNvl), caudal PAG, and nPGi. Anterograde labeling from the VMN terminated among PRV-positive cells in the MPO and lateral/ventrolateral PAG. Anterograde labeling from the PAG terminated among PRV-positive cells in the PVN, ventral hypothalamus, and nPGi. Transynaptically labeled cells in the lateral hypothalamus, Barrington’s nucleus, and ventromedial medulla received innervation from all three sources. These studies, together, identify several central nervous system (CNS) sites participating in the neural control of female sexual responses. They also provide the first data demonstrating a link between the MPO, VMNvl, and PAG and CNS regions innervating the clitoris and vagina, providing support that these areas play a major role in female genital responses.
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Husak, Paul J., Timothy Kuo, and L. W. Enquist. "Pseudorabies Virus Membrane Proteins gI and gE Facilitate Anterograde Spread of Infection in Projection- Specific Neurons in the Rat." Journal of Virology 74, no. 23 (December 1, 2000): 10975–83. http://dx.doi.org/10.1128/jvi.74.23.10975-10983.2000.
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ABSTRACT The membrane proteins gI and gE of Pseudorabies virus(PRV) are required for viral invasion and spread through some neural pathways of the rodent central nervous system. Following infection of the rat retina with wild-type PRV, virus replicates in retinal ganglion neurons and anterogradely spreads to infect all visual centers in the brain. By contrast, gI and gE null mutants do not infect a specific subset of the visual centers, e.g., the superior colliculus and the dorsal lateral geniculate nucleus. In previous experiments, we suggested that the defect was not due to inability to infect projection-specific retinal ganglion cells, because mixed infection of a gE deletion mutant and a gI deletion mutant restored the wild-type phenotype (i.e., genetic complementation occurred). In the present study, we provide direct evidence that gE and gI function to promote the spread of infection after entry into primary neurons. We used stereotaxic central nervous system injection of a fluorescent retrograde tracer into the superior colliculus and subsequent inoculation of a PRV gI-gE double null mutant into the eye of the same animal to demonstrate that viral antigen and fluorescent tracer colocalize in retinal ganglion cells. Furthermore, we demonstrate that direct injection of a PRV gI-gE double null mutant into the superior colliculus resulted in robust infection followed by retrograde transport to the eye and replication in retinal ganglion neuron cell bodies. These experiments provide additional proof that the retinal ganglion cells projecting to the superior colliculus are susceptible and permissive to gE and gI mutant viruses. Our studies confirm that gI and gE specifically facilitate anterograde spread of infection by affecting intracellular processes in the primary infected neuron such as anterograde transport in axons or egress from axon terminals.
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Jocius, Donatas, Donatas Vajauskas, Kipras Mikelis, Skirmante Jokubauskiene, Jolita Jakutiene, Kestutis Strupas, and Algirdas E. Tamosiunas. "Quantitative Assessment of Liver Impairment in Chronic Viral Hepatitis with [99mTc]Tc-Mebrofenin: A Noninvasive Attempt to Stage Viral Hepatitis-Associated Liver Fibrosis." Medicina 58, no. 10 (September 23, 2022): 1333. http://dx.doi.org/10.3390/medicina58101333.
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Background and objectives—Chronic viral hepatitis B and C infections are one of the leading causes of chronic liver impairment, resulting in liver fibrosis and liver cirrhosis. An early diagnosis with accurate liver fibrosis staging leads to a proper diagnosis, thus tailoring correct treatment. Both invasive and noninvasive techniques are used in the diagnosis and staging of chronic liver impairment. Those techniques include liver biopsy, multiple serological markers (as either single tests or combined panels), and imaging examinations, such as ultrasound or magnetic resonance elastography. Nuclear medicine probes may also be employed in staging liver fibrosis, although the literature scarcely reports this. The purpose of our study was to investigate whether a dynamic liver scintigraphy with [99mTc]Tc-mebrofenin has any value in staging or grading chronic liver damage. Materials and Methods—We prospectively enrolled patients with chronic viral hepatitis B and C infection referred for liver biopsy. All patient underwent dynamic liver scintigraphy with 99mTc-mebrofenin prior to liver biopsy. Dynamic liver scintigraphy was performed immediately after intravenous tracer injection for 30 min scanning time. Multiple scintigraphy parameters were calculated (whole liver lobe and focal area time to peak (TTP), 30 min to peak ratio (30/peak), whole lobe and focal area slope index in 350 s (slope_350). Liver biopsy took place shortly after imaging. Results—We found that many dynamic scintigraphic parameters are positively or negatively associated with different stages of liver fibrosis. The main parameters that showed most value are the ratio between 30 min and the peak of the dynamic curve (30/peak_dex (ratio)), and liver clearance corrected for body surface area and liver area (LCL_m2_dm2 (%/min/m2/dm2)). Conclusions—Our present study proves that conducting dynamic liver scintigraphies with [99mTc]Tc-mebrofenin has potential value in staging liver fibrosis. The benefits of this method, including whole liver imaging and direct imaging of the liver function, provide an advantage over presently used quantitative imaging modalities.
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Sélas, B., A. Lakel, Y. Andres, and P. Le Cloirec. "Wastewater reuse in on-site wastewater treatment: bacteria and virus movement in unsaturated flow through sand filter." Water Science and Technology 47, no. 1 (January 1, 2003): 59–64. http://dx.doi.org/10.2166/wst.2003.0016.
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In on-site wastewater treatment plants, effluents are pre-treated by septic tank and treated by soil infiltration or sand filtration systems, with unsaturated flow conditions. These systems remove efficiently carbon, nitrogen and suspended solids. But for microbial pollution, the treatment efficiency depends on the hydrodynamic behaviour and filtering media characteristics. Contamination of superficial water and groundwater due to pathogenic viruses and pathogenic bacteria is responsible for many diseases. The objective of this study is to approach the mechanisms and operating conditions to control bacteria and virus release in the environment. Experiments were carried out on reactors of different length packed with sand. Hydraulic load of 90 cm.d−1 with a pulse periodic flow was used. The influence of chemical composition of the solution on the treatment efficiency has also been studied. For the first time, the residence time distribution (RTD) has been studied using a conservative tracer (KI), to determine the main hydrodynamic parameters. For the second time, the RTD with bacterial and viral tracers (E. coli, bacteriophage MS2) was applied, with the aim to define microbial behaviour in filtering media, including adsorption and filtration phenomena. This work allowed us to determine retardation factors according to the hydraulic loads and chemical composition.
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Noble, Rachel T., Steven M. Allen, Angelia D. Blackwood, Weiping Chu, Sunny C. Jiang, Greg L. Lovelace, Mark D. Sobsey, Jill R. Stewart, and Douglas A. Wait. "Use of viral pathogens and indicators to differentiate between human and non-human fecal contamination in a microbial source tracking comparison study." Journal of Water and Health 1, no. 4 (December 1, 2003): 195–207. http://dx.doi.org/10.2166/wh.2003.0021.
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Assays for the detection and typing of adenoviruses, enteroviruses and F+ specific coliphages were performed on samples created as part of a national microbial source tracking methods comparison study. The samples were created blind to the researchers, and were inoculated with a variety of types of fecal contamination source (human, sewage, dog, seagull and cow) and mixtures of sources. Viral tracer and pathogen assays demonstrated a general ability to discriminate human from non-human fecal contamination. For example, samples inoculated with sewage were correctly identified as containing human fecal contamination because they contained human adenovirus or human enterovirus. In samples containing fecal material from individual humans, human pathogen analysis yielded negative results probably because the stool samples were taken from healthy individuals. False positive rates for the virus-based methods (0–8%) were among the lowest observed during the methods comparison study. It is suggested that virus-based source tracking methods are useful for identification of sewage contamination, and that these methods may also be useful as an indication of the public health risk associated with viral pathogens. Overall, virus-based source tracking methods are an important approach to include in the microbial source tracking ‘toolbox’.
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Liu, I.-Li, Yi-Chun Lin, Yong-Chong Lin, Cai-Zhen Jian, Ivan-Chen Cheng, and Hui-Wen Chen. "A Novel Immunochromatographic Strip for Antigen Detection of Avian Infectious Bronchitis Virus." International Journal of Molecular Sciences 20, no. 9 (May 6, 2019): 2216. http://dx.doi.org/10.3390/ijms20092216.
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Avian infectious bronchitis virus (IBV) causes considerable economic losses in the poultry industry worldwide, including Taiwan. IBV is among the most important pathogens in chickens, and it spreads rapidly among flocks. In addition to dozens of known serotypes, new viral variants have emerged due to the viral evolution and antigenic variation in IBVs. Therefore, the development of a sensitive, specific, and easily performed assay is crucial for the rapid detection and surveillance of IBV infections. A rapid and simple immunochromatographic strip (ICS) was developed in this study by employing monoclonal antibodies against spike and nucleocapsid proteins of IBV as the tracer and the capture antibody. The ICS showed high specificity in detecting IBV antigens, including several IBV genotypes and novel variants, as opposed to three other common avian respiratory viruses. The detection limit of the strip reached 104.4 50% embryo-infective dose. Moreover, in the experimental chicken model, the strip test demonstrated consistency in detecting IBV with RT-PCR gene detection. Taken together, this antigen detection strip has the potential to serve as an on-farm rapid test for IBV; therefore, it may facilitate surveillance and control of the disease.
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Gitis, Vitaly, Avner Adin, Abed Nasser, Jenny Gun, and Ovadia Lev. "Fluorescent dye labeled bacteriophages—a new tracer for the investigation of viral transport in porous media: 1. Introduction and characterization." Water Research 36, no. 17 (October 2002): 4227–34. http://dx.doi.org/10.1016/s0043-1354(02)00163-x.
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Abed, Riyad E., and Moatasem Al-Salih. "Transmitted Water Disease, Assessment of Immunopathogenesis of Chronic Hepatitis B and The Carrier State of Disease." Asian Journal of Water, Environment and Pollution 18, no. 4 (November 18, 2021): 101–7. http://dx.doi.org/10.3233/ajw210049.
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The transmission of viral hepatitis type B (HBV) is of significant public health concern. The infection result depends on how well the virus interacts with the host and in particular, on the ability to respond inherently and adaptively to the humoral and cellular immunity. The purpose of this study is to evaluate clinical, immunology and tracer status (viral). This study showed the relationship between the immune and chronic conditions of Iraqi patients who are chronic hepatitis virus B or HBV carriers. The study included (111) chronically-viral hepatitis type (b) and (112) hepatitis virus surface antigen type (b) healthy carriers from out of patients. The result of this study proved that a non-significant correlation was observed between cellular immune response (CD4 and CD8) among chronic hepatitis B patients. For CD8+ lymphocytes: there was a highly significant decrease (P<0.001) in the percentage means of the CD8+ cells in CHB patients, as compared with the carrier groups. For CD4+ lymphocytes: there was a slight decrease in the percentage of these lymphocytes in the peripheral blood of the patients, as compared with the carrier groups, a non-significant importance was recorded between them. The percentage of cytotoxic T-lymphocyte CD8+ was significantly decreased in CHB patients as compared to the carrier group. One of the deciding factors for the form of infection, and the immune response, which developed in accordance with a number of other biochemical factors and genes is chronic hepatitis B immunopathogénesis and carrier condition with the level of cellular immunity.
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Murphy, Keegan T., Gary J. Schwartz, Ngoc Ly T. Nguyen, Jennifer M. Mendez, Vitaly Ryu, and Timothy J. Bartness. "Leptin-sensitive sensory nerves innervate white fat." American Journal of Physiology-Endocrinology and Metabolism 304, no. 12 (June 15, 2013): E1338—E1347. http://dx.doi.org/10.1152/ajpendo.00021.2013.
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Leptin, the primary white adipose tissue (WAT) adipokine, is thought to convey lipid reserve information to the brain via the circulation. Because WAT responds to environmental/internal signals in a fat pad-specific (FPS) manner, systemic signals such as leptin would fail to communicate such distinctive information. Saturation of brain leptin transport systems also would fail to convey increased lipid levels beyond that point. WAT possesses sensory innervation exemplified by proven sensory-associated peptides in nerves within the tissue and by viral sensory nerve-specific transneuronal tract tracer, H129 strain of herpes simplex virus 1 labeling of dorsal root ganglia (DRG) pseudounipolar neurons, spinal cord and central sensory circuits. Leptin as a paracrine factor activating WAT sensory innervation could supply the brain with FPS information. Therefore, we tested for and found the presence of the long form of the leptin receptor (Ob-Rb) on DRG pseudounipolar neurons immunohistochemically labeled after injections of Fluorogold, a retrograde tract tracer, into inguinal WAT (IWAT). Intra-IWAT leptin injections (300 ng) significantly elevated IWAT nerve spike rate within 5 min and persisted for at least 30 min. Intra-IWAT leptin injections also induced significant c-Fos immunoreactivity (ir), indicating neural activation across DRG pseudounipolar sensory neurons labeled with Fluorogold IWAT injections. Intraperitoneal leptin injection did not increase c-Fos-ir in DRG or the arcuate nucleus, nor did it increase arcuate signal transducer and activator of transcription 3 phosphorylation-ir. Collectively, these results strongly suggest that endogenous leptin secreted from white adipocytes functions as a paracrine factor to activate spinal sensory nerves innervating the tissue.
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Gitis, Vitaly, Avner Adin, Abed Nasser, Jenny Gun, and Ovadia Lev. "Fluorescent dye labeled bacteriophages—a new tracer for the investigation of viral transport in porous media: 2. Studies of deep-bed filtration." Water Research 36, no. 17 (October 2002): 4235–42. http://dx.doi.org/10.1016/s0043-1354(02)00164-1.
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Drokhlyansky, Eugene, Didem Göz Aytürk, Timothy K. Soh, Ryan Chrenek, Elaine O’Loughlin, Charlotte Madore, Oleg Butovsky, and Constance L. Cepko. "The brain parenchyma has a type I interferon response that can limit virus spread." Proceedings of the National Academy of Sciences 114, no. 1 (December 15, 2016): E95—E104. http://dx.doi.org/10.1073/pnas.1618157114.
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The brain has a tightly regulated environment that protects neurons and limits inflammation, designated “immune privilege.” However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate–putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.
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Curanović, D., M. G. Lyman, C. Bou-Abboud, J. P. Card, and L. W. Enquist. "Repair of the UL21 Locus in Pseudorabies Virus Bartha Enhances the Kinetics of Retrograde, Transneuronal Infection In Vitro and In Vivo." Journal of Virology 83, no. 3 (November 19, 2008): 1173–83. http://dx.doi.org/10.1128/jvi.02102-08.
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ABSTRACT The attenuated pseudorabies virus (PRV) strain Bartha contains several characterized mutations that affect its virulence and ability to spread through neural circuits. This strain contains a small genomic deletion that abrogates anterograde spread and is widely used as a retrograde-restricted neural circuit tracer. Previous studies showed that the retrograde-directed spread of PRV Bartha is slower than that of wild-type PRV. We used compartmented neuronal cultures to characterize the retrograde defect and identify the genetic basis of the phenotype. PRV Bartha is not impaired in retrograde axonal transport, but transneuronal spread among neurons is diminished. Repair of the UL21 locus with wild-type sequence restored efficient transneuronal spread both in vitro and in vivo. It is likely that mutations in the Bartha UL21 gene confer defects that affect infectious particle production, causing a delay in spread to presynaptic neurons and amplification of infection. These events manifest as slower kinetics of retrograde viral spread in a neural circuit.
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Hassin, D., R. Fixler, Y. Shimoni, E. Rubinstein, S. Raz, M. S. Gotsman, and Y. Hasin. "Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes." American Journal of Physiology-Cell Physiology 252, no. 1 (January 1, 1987): C10—C16. http://dx.doi.org/10.1152/ajpcell.1987.252.1.c10.
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The “lethal hit” induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by 45Ca tracer measurements after loading the myocytes with 45Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. These changes in action potentials and contractions were reversible either by washout with the normal medium or by the addition of verapamil. The amount of total exchangeable calcium in the cultured myocytes, 1 h after exposure to CTL, was significantly increased. This increase was prevented by pretreatment with verapamil. (ABSTRACT TRUNCATED AT 250 WORDS)
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Bamshad, Maryam, C. Kay Song, and Timothy J. Bartness. "CNS origins of the sympathetic nervous system outflow to brown adipose tissue." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, no. 6 (June 1, 1999): R1569—R1578. http://dx.doi.org/10.1152/ajpregu.1999.276.6.r1569.
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Brown adipose tissue (BAT) plays a critical role in cold- and diet-induced thermogenesis. Although BAT is densely innervated by the sympathetic nervous system (SNS), little is known about the central nervous system (CNS) origins of this innervation. The purpose of the present experiment was to determine the neuroanatomic chain of functionally connected neurons from the CNS to BAT. A transneuronal viral tract tracer, Bartha’s K strain of the pseudorabies virus (PRV), was injected into the interscapular BAT of Siberian hamsters. The animals were killed 4 and 6 days postinjection, and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord, brain stem, midbrain, and forebrain. The intensity of labeled neurons in the forebrain varied from heavy infections in the medial preoptic area and paraventricular hypothalamic nucleus to few infections in the ventromedial hypothalamic nucleus, with moderate infections in the suprachiasmatic and lateral hypothalamic nuclei. These results define the SNS outflow from the brain to BAT for the first time in any species.
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Wang, Yida. "The Influence and Mechanism of the Nervous System and Other Factors Inducing Anxiety-like Behavior in Animal Models." Lecture Notes in Education Psychology and Public Media 30, no. 1 (December 7, 2023): 160–66. http://dx.doi.org/10.54254/2753-7048/30/20231617.
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Researches on the actions that trigger anxiety is being undertaken gradually, which has shown that anxiety is a common occurrence. In order to gain a comprehensive understanding of the influences and mechanisms of the nervous system and other factors inducing anxiety-like behaviors, this paper employs an animal model as its research topic in order to better understand how the nervous system and other elements impact anxiety and its mechanism. Using optogenetic activation, chemical genetics, electrophysiology, total internal reflection fluorescence (TIRF) imaging, immunoelectron microscopy, viral tracer, and other techniques, this study examines the interaction between the immune and neurological systems in a simulated animal model. The development of the NAc-VTA circuit, the nucleus accumbens, the ventromedial prefrontal cortexs action mechanism, and three other elements, show that the nervous system and related components may induce anxiety-like behavior in a mouse-based animal model and that these factors can also create or obstruct the regulatory pathway for anxiety-like behavior. Human anxiety can be controlled using this knowledge.
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ZHANG, Fan, Li-bin WU, Ling HU, Zi-jian WU, Shuai CUI, Qing YU, and Rong-lin CAI. "Study on the central neural pathway and the relationship between the heart and small intestine via a dual neural tracer." PLOS ONE 17, no. 11 (November 22, 2022): e0277644. http://dx.doi.org/10.1371/journal.pone.0277644.
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Despite very different functions, studies increasingly report that there may be a potential central nervous anatomical connection between the heart and the small intestine. In this study, the central nervous anatomical relationship between the heart and small intestine was studied via a viral tracer. Pseudorabies virus (PRV) syngeneic strains with different fluorescent reporter genes (eGFP or mRFP) were microinjected into the heart walls and small intestinal walls of male C57BL/6J using glass microelectrode. The results showed that the co-labeled nuclei in the brain were lateral periaqueductal gray (LPAG) and ventrolateral periaqueductal gray (VLPAG) in the midbrain, mesencephalic trigeminal nucleus (Me5), and motor trigeminal nucleus anterior digastric Part (5Adi) in the pons. The co-labeled sites in the spinal cord were intermediolateral column (IML) in the second thoracic vertebra, IML and lamina 7 of the spinal gray (7SP) in the third thoracic vertebra, and IML in the fourth thoracic vertebra. Our data show that there is a neuroanatomical connection between the small intestine and the heart in the central nervous system (CNS). Neuroanatomical integration of the heart and small intestine may provide a basis for revealing the physiological and pathological interactions between the circulatory and digestive systems. The interactions may be mediated more effectively through sympathetic nerves.
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Hartimath, SV, O. Draghiciu, T. Daemen, H. W. Nijman, A. van Waarde, R. A. J. O. Dierckx, and E. F. J. de Vries. "Therapy-Induced Changes in CXCR4 Expression in Tumor Xenografts Can Be Monitored Noninvasively with N-[11C]Methyl-AMD3465 PET." Molecular Imaging and Biology 22, no. 4 (December 4, 2019): 883–90. http://dx.doi.org/10.1007/s11307-019-01447-x.
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Abstract Purpose Chemokine CXCL12 and its receptor CXCR4 are constitutively overexpressed in human cancers. The CXCL12-CXCR4 signaling axis plays an important role in tumor progression and metastasis, but also in treatment-induced recruitment of CXCR4-expressing cytotoxic immune cells. Here, we aimed to demonstrate the feasibility of N-[11C]methyl-AMD3465 positron emission tomography (PET) to monitor changes in CXCR4 density in tumors after single-fraction local radiotherapy or in combination with immunization. Procedure TC-1 cells expressing human papillomavirus antigens E6 and E7 were inoculated into the C57BL/6 mice subcutaneously. Two weeks after tumor cell inoculation, mice were irradiated with a single-fraction 14-Gy dose of X-ray. One group of irradiated mice was immunized with an alpha-viral vector vaccine, SFVeE6,7, and another group received daily injections of the CXCR4 antagonist AMD3100 (3 mg/kg -intraperitoneal (i.p.)). Seven days after irradiation, all animals underwent N-[11C]methyl-AMD3465 PET. Results PET imaging showed N-[11C]methyl-AMD3465 uptake in the tumor of single-fraction irradiated mice was nearly 2.5-fold higher than in sham-irradiated tumors (1.07 ± 0.31 %ID/g vs. 0.42 ± 0.05 % ID/g, p < 0.01). The tumor uptake was further increased by 4-fold (1.73 ± 0.17 % ID/g vs 0.42 ± 0.05 % ID/g, p < 0.01) in mice treated with single-fraction radiotherapy in combination with SFVeE6,7 immunization. Administration of AMD3100 caused a 4.5-fold reduction in the tracer uptake in the tumor of irradiated animals (0.24 ± 0.1 % ID/g, p < 0.001), suggesting that tracer uptake is indeed due to CXCR4-mediated chemotaxis. Conclusion This study demonstrates the feasibility of N-[11C]methyl-AMD3465 PET imaging to monitor treatment-induced changes in the density of CXCR4 receptors in tumors and justifies further evaluation of CXCR4 as a potential imaging biomarker for evaluation of anti-tumor therapies.
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Vaughan, Cheryl H., and Timothy J. Bartness. "Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 302, no. 9 (May 1, 2012): R1049—R1058. http://dx.doi.org/10.1152/ajpregu.00640.2011.
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Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (Tc) and IBAT (TIBAT) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. TIBAT and Tc were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.
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El Omri, Halima, Zsolt Hascsi, Ruba Taha, Lajos Szabados, Hesham El Sabah, Amna Gamiel, and Ibrahim Al Hijji. "Tubercular Meningitis and Lymphadenitis Mimicking a Relapse of Burkitt's Lymphoma on 18F-FDG-PET/CT: A Case Report." Case Reports in Oncology 8, no. 2 (May 7, 2015): 226–32. http://dx.doi.org/10.1159/000430768.
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Tuberculosis (TB) can present with various forms and can occasionally be mistaken for malignancy. Hereby, we report a 53-year-old man diagnosed and treated for Burkitt's lymphoma in 2009 who achieved a complete remission confirmed by a computed tomography (CT) scan. During the follow-up 2 years later, he complained of left hip pain that warranted investigation with magnetic resonance imaging and whole-body 18F-fludeoxyglucose-positron emission tomography (FDG-PET)/CT which showed a benign lesion in the left hip associated with multiple lymph nodes in the chest and abdomen not amenable for biopsy. A follow-up PET/CT scan a few months later showed intense tracer uptake in the lymph nodes with size progression and appearance of new lymph nodes suspicious of lymphoma relapse. The patient was asymptomatic, and all investigations including viral and connective tissue disease studies were negative. Also the tuberculin skin test and QuantiFERON were negative. Lymph node biopsy was planned; however, the patient presented a few days earlier with fever, headache and photophobia. Cerebrospinal fluid (CSF) examination confirmed meningitis with lymphocytic pleocytosis and elevated protein. The CSF Gram stain, culture, viral and acid-fast bacilli were negative. CSF flow cytometry and cytopathology confirmed polyclonal lymphocytosis and suggested reactive causes. CSF TB culture grew Mycobacterium tuberculosis. Mediastinal lymph node biopsy also confirmed TB lymphadenitis. Four antituberculosis drugs were started. One year later, a PET/CT scan showed regression of all the involved lymph nodes. This case highlights the importance of excluding TB in patients with suspected malignancy, especially if they belong to endemic regions, and the increasing role of 18F-FDG-PET/CT in the early detection of extrapulmonary TB.
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Leutwyler, Kristin. "Viral Tracers." Scientific American 274, no. 3 (March 1996): 18. http://dx.doi.org/10.1038/scientificamerican0396-18.
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Frank, E., and J. R. Sanes. "Lineage of neurons and glia in chick dorsal root ganglia: analysis in vivo with a recombinant retrovirus." Development 111, no. 4 (April 1, 1991): 895–908. http://dx.doi.org/10.1242/dev.111.4.895.
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We used retrovirus-mediated gene transfer to study the lineage of neural crest cells in chick embryos. Individual crest cells were infected before they migrated from the neural tube, and their clonal progeny were subsequently revealed in sensory ganglia and associated structures by a histochemical stain for the viral gene product (lacZ). We found that crest cells were multipotential in several respects. (1) Many clones contained both ventrolateral (VL) and dorsomedial (DM) neurons, which had been suggested to be lineally distinct. (2) Many clones contained both large and small neurons, which are known to innervate distinct targets. (3) Many clones contained multiple glial subtypes, e.g. both Schwann cells, which ensheath axons, and satellite cells, which ensheath neuronal somata. (4) Many clones contained both neurons and glial cells. On the other hand, a sizeable minority of clones was homogenous, e.g. they contained only neurons or only glial cells—suggesting that some progenitors may be, or become, restricted in potential. Finally, this study provides the first opportunity to compare directly the two methods currently available for tracing cell lineage in vertebrate embryos, retroviral infection and tracer injection: our results and those of Bronner-Fraser and Fraser (1989), who used the latter method, provide complementary but consistent views of crest lineage.
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Woodard, J. P., W. Chen, E. O. Keku, S. C. Liu, J. G. Lecce, and J. M. Rhoads. "Altered jejunal potassium (Rb+) transport in piglet rotavirus enteritis." American Journal of Physiology-Gastrointestinal and Liver Physiology 265, no. 2 (August 1, 1993): G388—G393. http://dx.doi.org/10.1152/ajpgi.1993.265.2.g388.
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To determine the mechanisms of K+ loss in viral diarrhea, K+ fluxes (estimated by tracer Rb+ flows) across piglet jejunum in Ussing chambers were determined. Normal jejunum was characterized by an indomethacin-sensitive short-circuit current and a small K+ secretory flow. Rotavirus-infected gut secreted K+ at high rates, probably resulting from increased prostaglandin generation because secretion was abolished by indomethacin. Tissues pretreated with indomethacin responded to 8-bromoadenosine 3',5'-cyclic monophosphate acid and 16,16-dimethyl-prostaglandin E2 with K+ secretion. The secretory response in rotavirus-infected jejunum was no greater than that in normal tissue. Serosal addition of Ca2+ ionophore A23187 caused K+ secretion in normal but not rotavirus-infected jejunum. To inhibit the basolateral uptake of K+ and reduce the driving force for secretion, ouabain was added to the bath. Ouabain unmasked a K+ absorptive process in normal intestine, which was not seen in rotavirus-infected tissue. K+ absorption was inhibited by 3-(cyanomethyl)-2-methyl-8-(phenyl-methoxy)imidazo (1,2 alpha)pyridine (Sch-28080) and omeprazole. We speculate that the high fecal K+ losses observed in human rotavirus enteritis might be caused by an imbalance between K+ secretion and an impaired apical K+ absorptive mechanism in the crypt-type epithelium.
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Zimmermann, Christine, and Hanspeter Pircher. "A Novel Approach to Visualize Polyclonal Virus-Specific CD8 T Cells In Vivo." Journal of Immunology 162, no. 9 (May 1, 1999): 5178–82. http://dx.doi.org/10.4049/jimmunol.162.9.5178.
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Abstract Recent technical breakthroughs in generating soluble MHC class I-peptide tetramers now allow the direct visualization of virus-specific CD8 T cells after infection in vivo. However, this technique requires the knowledge of the immunodominant viral epitopes recognized by T cells. Here, we describe an alternative approach to visualize polyclonal virus-specific CD8 T cells in vivo using a simple adoptive transfer system. In our approach, C57BL/6 (Thy1.2) mice were infected with lymphocytic choriomeningitis virus, vesicular stomatitis virus, or vaccinia virus to induce virus-specific memory T cells. Tracer T cells (2 × 106) from these virus-immune mice were adoptively transferred into nonirradiated (C57BL/6 × B6.PL-Thy-1a)F1 mice. After infection of the F1-recipient mice with the appropriate virus, the transferred cells expanded vigorously, and on day 8 postinfection 60–80% of total CD8 T cells were of donor T cell origin. Under the same conditions memory CD4 T cells gave rise to at least 10 times less cell numbers than memory CD8 T cells. The transfer system described here not only allows to visualize effector and memory CD8 T cells in vivo but also to isolate them for further in vitro characterization without knowing the epitopes recognized by these Ag-specific CD8 T cells.
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Filatov, Ekaterina, Alex P. Rudecki, Alina-Geta Constantin, and Sarah Louise Gray. "Identification of PACAP-Expressing Neurons in the Hypothalamic Origins of Sympathetic Outflow Tracts Terminating in Brown Adipose Tissue of Mice." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A541. http://dx.doi.org/10.1210/jendso/bvab048.1102.
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Abstract Adaptive thermogenesis in brown adipose tissue is stimulated by the sympathetic nervous system (SNS) in response to cold stress. Using retrograde viral transneuronal tract tracers, previous studies have identified that the paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), and median preoptic nucleus (MnPO) contain neurons that are part of sympathetic outflow tracts to brown adipose tissue, presumptively involved in SNS stimulation of interscapular brown adipose tissue (iBAT). Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is a peptide hormone known to regulate energy homeostasis, acting in both the central (CNS) and peripheral nervous system (PNS). Mice lacking PACAP have impaired adrenergic-induced thermogenesis and a cold-sensitive phenotype. In the CNS, PACAP is highly expressed in the VMH, MnPO, and PVN of the hypothalamus. Injection of PACAP into the VMN increased core body temperature and sympathetic nerve activity to brown adipose tissue. While these studies show exogenous PACAP can activate sympathetic outflow tracts to brown adipose tissue, they do not confirm that endogenously expressed PACAP induces sympathetic nerve activity as an adaptive mechanism to cold stress, or if sympathetic outflow tracts originating in the hypothalamus express PACAP. We hypothesize that PACAP is expressed in neurons of sympathetic outflow tracts originating in the hypothalamus. To test this hypothesis, PACAP-eGFP transgenic mice were injected with the retrograde neural tracer, pseudorabies virus tagged with β-galactosidase (β-gal, PRV-BaBlu), in iBAT where postganglionic nerves innervate the tissue. Five-days post-infection, animals were culled, brains removed and cryosectioned. Neurons positive for green fluorescent protein (eGFP) and/or β-gal immunoreactivity (ir) were identified by immunohistochemistry in serial coronal and sagittal brain cryo-sections. Co-occurrence of eGFP-ir and β-gal-ir, inferred PACAP expressing neurons present in sympathetic outflow tracts (ImageJ). Co-occurrence was identified in several structures in the hypothalamus and thalamus. In conclusion, this study presents neuroanatomical evidence for populations of PACAPinergic neurons in the hypothalamus that are part of sympathetic outflow tracts to brown adipose tissue, providing further evidence of a central role for PACAP in regulating energy homeostasis.
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Shydlovska, О. А., Е. N. Andriychuk, and T. A. Kompanets. "The spectrum of viruses isolated from Pulsatilla pratensis (Ranunculaceae) a native plant of Ukraine." Biosystems Diversity 24, no. 1 (March 21, 2016): 234–39. http://dx.doi.org/10.15421/011629.
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The article is devoted to virus screening of wild plants of Ukraine’s flora. The object of the research is the Red Book plant Pulsatilla pratensis (L.) Mill., which grows on the territory of Kanev Nature Reserve. Isolated isometric infectious virus-like particles with diameters of 34, 36, 43, 47, 50 and 57 nm were isolated from selected plants of P. pratensis. In our research, determination of the infectious nature of the pathogen, host range, concentration of viruses in plants, species identity and virus isolation from the mixture in mixed viral infections were carried with using indicator plants. The typical viral symptoms were observed on indicator plants: browning of the leaf plate, mottling, chlorosis and necrosis. All symptoms were systemic and could be caused by a variety of viruse species. Virions with sizes from 34 to 43 nm produced the necrotic and chlorotic spotting on Chenopodium amaranticolor Coste and Reyn. On the other hand, virions with sizes from 47 to 57 nm produced the necrosis, chlorosis and deformation of the leaf plates on Cucumis sativus L. That is not typical for viruses previously discovered on P. pratensis. The viruses isolated in these plants viruses were cumulated in small concentrations and rapidly lost their infectivity. The number of isolated viruses was insufficient for their identification. Four bacteriophage isolates with long phage tails of different size were isolated from P. pratensis roots and radical soil. The biological (lytic) activity towards the tracer bacteria, the morphology of negative colonies, and bacteriophage protein structure were characterized. According to our research, it is possible to divide phages into three subgroups that probably correspond to three different types of viruses. Results of the polypeptide analysis may reflect an evolutionary process in a population of phages that had a common ancestor. Comparison of phage proteins of different hosts shows a variety of molecular weights of polypeptides comprising up to several dozens of proteins. The results of the current work lay the basis for studying the spread of viruses in nature and determination of their relationships in biocenoses.
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Kroeger, D., J. A. Thundercliffe, A. Phung, C. Geraci, R. DeLuca, S. Bragg, E. Arrigoni, and T. E. Scammell. "0156 Activation of Glutamatergic PPT Neurons and Their Projections Promotes Arousal, and Distinct Wake Behaviors." Sleep 43, Supplement_1 (April 2020): A61—A62. http://dx.doi.org/10.1093/sleep/zsaa056.154.
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Abstract Introduction The pedunculopontine tegmental (PPT) region in the brainstem is crucial for the regulation of sleep/wake states. We recently showed that chemogenetic activation of glutamatergic PPT neurons promotes wakefulness for several hours. Here we used optogenetic activation of these neurons to further investigate the mechanisms and pathways through which PPT glutamatergic neurons produce wakefulness. Methods Using vGlut2-cre mice, we transfected neurons in the PPT region with a viral vector coding for cre-dependent ChR2 tagged with fluorescent mCherry and implanted bilateral optical fibers above the PPT nuclei as well as EEG/EMG leads. Two weeks later, we administered blue laser light to activate ChR2-expressing neurons and recorded sleep/wake states. Results Activation of ChR2-expressing glutamatergic neurons during NREM sleep rapidly elicited wakefulness in a stimulation-frequency dependent manner, with higher frequencies producing wake more quickly and with longer duration. Random, automated stimulation for 10 s at 5 Hz over 24 h revealed that activation of glutamatergic PPT neurons produces rapid arousals form NREM sleep. Importantly, stimulation did not wake mice from REM sleep, suggesting that glutamatergic PPT signaling does not interfere with REM sleep. To map the target areas through which PPT glut neurons produce wakefulness, we used a viral tracer to visualize PPT glutamatergic projections, and then optogenetically stimulated terminals in 1) basal forebrain, 2) lateral hypothalamus, 3) thalamus, and 4) substantia nigra. We found that stimulating terminals in all of these regions woke mice from NREM sleep, and stimulating terminals in the basal forebrain and lateral hypothalamus produced a number of active wake behaviors such as locomotion. In contrast, stimulation of PPT glut soma and terminals in the thalamus and substantia nigra results mainly in quiet wakefulness. Conclusion Glutamatergic PPT neurons potently promote arousal from NREM sleep but not REM sleep, and the resulting wake behavior is modulated by different projection targets. Support NIH grant P01 - HL095491
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Talha, Sheikh M., Teppo Salminen, Deepti A. Chugh, Sathyamangalam Swaminathan, Tero Soukka, Kim Pettersson, and Navin Khanna. "Inexpensive Designer Antigen for Anti-HIV Antibody Detection with High Sensitivity and Specificity." Clinical and Vaccine Immunology 17, no. 3 (January 20, 2010): 335–41. http://dx.doi.org/10.1128/cvi.00283-09.
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ABSTRACT A novel recombinant multiepitope protein (MEP) has been designed that consists of four linear, immunodominant, and phylogenetically conserved epitopes, taken from human immunodeficiency virus (HIV)-encoded antigens that are used in many third-generation immunoassay kits. This HIV-MEP has been evaluated for its diagnostic potential in the detection of anti-HIV antibodies in human sera. A synthetic MEP gene encoding these epitopes, joined by flexible peptide linkers in a single open reading frame, was designed and overexpressed in Escherichia coli. The recombinant HIV-MEP was purified using a single affinity step, yielding >20 mg pure protein/liter culture, and used as the coating antigen in an in-house immunoassay. Bound anti-HIV antibodies were detected by highly sensitive time-resolved fluorometry, using europium(III) chelate-labeled anti-human antibody. The sensitivity and specificity of the HIV-MEP were evaluated using Boston Biomedica worldwide HIV performance, HIV seroconversion, and viral coinfection panels and were found to be comparable with those of commercially available anti-HIV enzyme immunoassay (EIA) kits. The careful choice of epitopes, high epitope density, and an E. coli-based expression system, coupled with a simple purification protocol and the use of europium(III) chelate-labeled tracer, provide the capability for the development of an inexpensive diagnostic test with high degrees of sensitivity and specificity.
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Gao, Hong, and Andrei V. Derbenev. "Synaptic and extrasynaptic transmission of kidney-related neurons in the rostral ventrolateral medulla." Journal of Neurophysiology 110, no. 11 (December 1, 2013): 2637–47. http://dx.doi.org/10.1152/jn.00155.2013.
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The rostral ventrolateral medulla (RVLM) is a critical component of the sympathetic nervous system regulating homeostatic functions including arterial blood pressure. Using the transsynaptic retrograde viral tracer PRV-152, we identified kidney-related neurons in the RVLM. We found that PRV-152-labeled RVLM neurons displayed an unusually large persistent, tonic current to both glutamate, via N-methyl-d-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA)/kainate receptors, and to γ-aminobutyric acid (GABA), via GABAAreceptors, in the absence of large-scale phasic neurotransmission with whole cell patch-clamp recordings. A cocktail of potent NMDA and AMPA/kainate ionotropic glutamate receptor antagonists AP-5 (50 μM) and CNQX (10 μM) revealed a two-component somatic tonic excitatory current with an overall amplitude of 42.6 ± 13.4 pA. Moreover, application of the GABAAreceptor blockers gabazine (15 μM) and bicuculline (30 μM) revealed a robust somatic tonic inhibitory current with an average amplitude of 196.3 ± 39.3 pA. These findings suggest that the tonic current plays a role in determining the resting membrane potential, input resistance, and firing rate of RVLM neurons. The magnitude of the tonic inhibitory current demonstrates that GABAergic inhibition plays a critical role in regulation of kidney-related RVLM neurons. Our results indicate that the GABAergic tonic current may determine the basal tone of firing activity in kidney-related RVLM neurons.
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Huddleston, Gloria G., C. Kay Song, Jacquelyn C. Paisley, Timothy J. Bartness, and Andrew N. Clancy. "Gonadal steroid receptors colocalize with central nervous system neurons projecting to the rat prostate gland." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 6 (June 2007): R2196—R2205. http://dx.doi.org/10.1152/ajpregu.00667.2006.
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Mating-induced Fos-immunoreactive (-ir) cells are colocalized with androgen receptors (AR), estrogen receptors (ER), or both in limbic and hypothalamic areas known to mediate male rat mating behavior. A steroid-responsive neural network might govern copulatory behavior in male laboratory rats that is analogous to the network described in female rats that governs the lordosis response. This hypothesized network in males may synchronize and coordinate sexual behavioral responses with physiological responses of the genitals and the internal organs of reproduction. Therefore, the pseudorabies virus (PRV; Bartha strain), a transneuronal, viral retrograde tract tracer, was microinjected into the prostate gland to label this network. After 7 days, brains from infected animals were processed for immunohistochemical labeling of AR, ER, and PRV. The majority of PRV-ir cells exhibited either AR or ER immunoreactivity in the medial preoptic area, median preoptic nucleus, bed nucleus of stria terminalis, hypothalamic paraventricular nucleus, and zona incerta, areas known to play roles in male rat mating behavior. Other structures such as the central tegmental field/subparafascicular nucleus of the thalamus, central nucleus of the amygdala, and medial amygdala, also important in the display of male copulatory behavior, were less reliably labeled. Collectively, a steroid receptor-containing neuronal circuit, largely contained in the diencephalon, was revealed that likely is involved in the autonomic control of the prostate gland and the consummatory aspects of male rat mating behavior.
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Bamshad, Maryam, Victor T. Aoki, M. Gregory Adkison, Wade S. Warren, and Timothy J. Bartness. "Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 275, no. 1 (July 1, 1998): R291—R299. http://dx.doi.org/10.1152/ajpregu.1998.275.1.r291.
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White adipose tissue (WAT) is innervated by postganglionic sympathetic nervous system (SNS) neurons, suggesting that lipid mobilization could be regulated by the SNS [T. G. Youngstrom and T. J. Bartness. Am. J. Physiol. 268 ( Regulatory Integrative Comp. Physiol. 37): R744–R751, 1995]. A viral transsynaptic retrograde tract tracer, the pseudorabies virus (PRV), was used to identify the origins of the SNS outflow from the brain to WAT neuroanatomically. PRV was injected into epididymal or inguinal WAT (EWAT and IWAT, respectively) of Siberian hamsters and IWAT of rats. PRV-infected neurons were visualized by immunocytochemistry and found in the spinal cord, brain stem (medulla, nucleus of the solitary tract, caudal raphe nucleus, C1 and A5 regions), midbrain (central gray), and several areas within the forebrain. The general pattern of infection of WAT in both species was more similar than different and resembled that seen after PRV injections into the adrenal medulla in rats (A. M. Strack, W. B. Sawyer, J. H. Hughes, K. B. Platt, and A. D. Loewy. Brain Res. 491: 156–162, 1989). EWAT versus IWAT injected hamsters had relatively less labeling in the suprachiasmatic, dorsomedial, and arcuate nuclei. Overall, it appeared that the SNS innervation of WAT originates from the general SNS outflow of the central nervous system and therefore may play a significant role in lipid mobilization.
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Chou, Hui-Wen, Chih-Lin Huang, Yu-Chih Lin, Yusen Eason Lin, and Wei-Chuan Chen. "Experimental Observation of Isolative Efficacy of a Solid Coupling Medium in Extracorporeal Shock Wave Lithotripsy—Implications to Nosocomial Infection Prevention." Pathogens 11, no. 10 (September 27, 2022): 1103. http://dx.doi.org/10.3390/pathogens11101103.
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Introduction: Extracorporeal shock wave lithotripsy (ESWL) is a well-established, popular treatment choice for renal stones. Traditionally, the semi-liquid gel is used as a coupling medium in ESWL. During ESWL, body fluid or blood might transmit between the patients when the probe or gel used in the procedure is contaminated and cause potential nosocomial infections. To solve this problem, we developed a solid coupling medium (isolation coupling pad, referred to as “icPad”) between the patient’s skin and the probe as a shock wave transmission medium to prevent contamination. This study aimed to investigate the isolative efficacy of the icPad in blocking the permeation of microbes. Method: Rhodamine 6G (a fluorescent dye) was used as a tracer to simulate the microorganisms. The penetration of the fluorescent dye on the longitudinal section of the icPad was observed by a microscope after the dye was placed on the body side of the icPad for 40 min. After the shock wave, icPad was extracted with 75% ethanol, and fluorescence intensity was measured with a fluorescence spectrometer. Results: Our results revealed that the body side of icPad is free of fluorescent dye during lithotripsy. Qualitative analysis results confirmed that icPad has an isolative effect on simulating contaminants such as bacteria or viruses. Conclusion: In this in vitro phantom study, a proprietary icPad can be an isolative coupling medium and is speculated to avoid cross-contamination of bacterial or viral infection during ESWL.
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Song, C. Kay, Cheryl H. Vaughan, Erin Keen-Rhinehart, Ruth B. S. Harris, Denis Richard, and Timothy J. Bartness. "Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 295, no. 2 (August 2008): R417—R428. http://dx.doi.org/10.1152/ajpregu.00174.2008.
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A precise understanding of neural circuits controlling lipid mobilization and thermogenesis remains to be determined. We have been studying the sympathetic nervous system (SNS) contributions to white adipose tissue (WAT) lipolysis largely in Siberian hamsters. Central melanocortins are implicated in the control of the sympathetic outflow to WAT, and, moreover, the melanocortin 4 receptors (MC4-R) appear to be principally involved. We previously found that acute third ventricular melanotan II (MTII; an MC3/4-R agonist) injections increase sympathetic drive (norepinephrine turnover) to interscapular brown adipose tissue (IBAT) and IBAT temperature. Here we tested whether MC4-R mRNA is expressed in IBAT SNS outflow neurons using in situ hybridization for the former and injections of the transneuronal viral retrograde tract tracer, pseudorabies virus (PRV) into IBAT, for the latter. Significant numbers of double-labeled cells for PRV and MC4-R mRNA were found across the neuroaxis (mean of all brain sites ∼60%), including the hypothalamic paraventricular nucleus (PVH; ∼80%). Acute parenchymal MTII microinjections into the PVH of awake, freely-moving hamsters, using doses below those able to increase IBAT temperature when injected into the third ventricle, increased IBAT temperature for as long as 4 h, as measured by temperature transponders implanted below the tissue. Collectively, these data add significant support to the view that central melanocortins are important in controlling IBAT thermogenesis via the SNS innervation of this tissue, likely through the MC4-Rs.
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Verzijl, Dennis, Carlos P. Fitzsimons, Marie van Dijk, James P. Stewart, Henk Timmerman, Martine J. Smit, and Rob Leurs. "Differential Activation of Murine Herpesvirus 68- and Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORF74 G Protein-Coupled Receptors by Human and Murine Chemokines." Journal of Virology 78, no. 7 (April 1, 2004): 3343–51. http://dx.doi.org/10.1128/jvi.78.7.3343-3351.2004.
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ABSTRACT Infection of mice with murine gammaherpesvirus 68 (MHV-68) is a well-characterized small animal model for the study of gammaherpesvirus infection. MHV-68 belongs to the same herpesvirus family as herpesvirus saimiri (HVS) of New World squirrel monkeys and human herpesvirus 8 (HHV-8) (also referred to as Kaposi's sarcoma-associated herpesvirus [KSHV]). The open reading frame ORF74 of HVS, KSHV, and MHV-68 encodes a protein with homology to G protein-coupled receptors and chemokine receptors in particular. ORF74 of KSHV (human ORF74 [hORF74]) is highly constitutively active and has been implicated in the pathogenesis of Kaposi's sarcoma. MHV-68-encoded ORF74 (mORF74) is oncogenic and has been implicated in viral replication and reactivation from latency. Here, we show that mORF74 is a functional chemokine receptor. Chemokines with an N-terminal glutamic acid-leucine-arginine (ELR) motif (e.g., KC and macrophage inflammatory protein 2) act as agonists on mORF74, activating phospholipase C, NF-κB, p44/p42 mitogen-activated protein kinase, and Akt signaling pathways and inhibiting formation of cyclic AMP. Using 125I-labeled CXCL1/growth-related oncogene α as a tracer, we show that murine CXCL10/gamma interferon-inducible protein 10 binds mORF74, and functional assays show that it behaves as an antagonist for this virally encoded G protein-coupled receptor. Profound differences in the upstream activation of signal transduction pathways between mORF74 and hORF74 were found. Moreover, in contrast to hORF74, no constitutive activity of mORF74 could be detected.
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Torres, Hayden, Clara Huesing, David H. Burk, Adrien J. R. Molinas, Winfried L. Neuhuber, Hans-Rudolf Berthoud, Heike Münzberg, Andrei V. Derbenev, and Andrea Zsombok. "Sympathetic innervation of the mouse kidney and liver arising from prevertebral ganglia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 321, no. 3 (September 1, 2021): R328—R337. http://dx.doi.org/10.1152/ajpregu.00079.2021.
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The sympathetic nervous system (SNS) plays a crucial role in the regulation of renal and hepatic functions. Although sympathetic nerves to the kidney and liver have been identified in many species, specific details are lacking in the mouse. In the absence of detailed information of sympathetic prevertebral innervation of specific organs, selective manipulation of a specific function will remain challenging. Despite providing major postganglionic inputs to abdominal organs, limited data are available about the mouse celiac-superior mesenteric complex. We used tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DbH) reporter mice to visualize abdominal prevertebral ganglia. We found that both the TH and DbH reporter mice are useful models for identification of ganglia and nerve bundles. We further tested if the celiac-superior mesenteric complex provides differential inputs to the mouse kidney and liver. The retrograde viral tracer, pseudorabies virus (PRV)-152 was injected into the cortex of the left kidney or the main lobe of the liver to identify kidney-projecting and liver-projecting neurons in the celiac-superior mesenteric complex. iDISCO immunostaining and tissue clearing were used to visualize unprecedented anatomical detail of kidney-related and liver-related postganglionic neurons in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia compared with TH-positive neurons. Kidney-projecting neurons were restricted to the suprarenal and aorticorenal ganglia, whereas only sparse labeling was observed in the celiac-superior mesenteric complex. In contrast, liver-projecting postganglionic neurons were observed in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia, suggesting spatial separation between the sympathetic innervation of the mouse kidney and liver.
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Nguyen, Ngoc Ly T., Candace L. Barr, Vitaly Ryu, Qiang Cao, Bingzhong Xue, and Timothy J. Bartness. "Separate and shared sympathetic outflow to white and brown fat coordinately regulates thermoregulation and beige adipocyte recruitment." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 312, no. 1 (January 1, 2017): R132—R145. http://dx.doi.org/10.1152/ajpregu.00344.2016.
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White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer, with unique fluorescent reporters into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian hamsters to define SNS pathways to both. To test the functional importance of SNS coordinated control of BAT and WAT, we exposed hamsters with denervated SNS nerves to IBAT to 4°C for 16–24 h and measured core and fat temperatures and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in fat tissues. Overall, there were more SNS neurons innervating IBAT than IWAT across the neuroaxis. However, there was a greater percentage of singly labeled IWAT neurons in midbrain reticular nuclei than singly labeled IBAT neurons. The hindbrain had ~30–40% of doubly labeled neurons while the forebrain had ~25% suggesting shared SNS circuitry to BAT and WAT across the brain. The raphe nucleus, a key region in thermoregulation, had ~40% doubly labeled neurons. Hamsters with IBAT SNS denervation maintained core body temperature during acute cold challenge and had increased beige adipocyte formation in IWAT. They also had increased IWAT NETO, temperature, and UCP1 expression compared with intact hamsters. These data provide strong neuroanatomical and functional evidence of WAT and BAT SNS cross talk for thermoregulation and beige adipocyte formation.
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Song, C. Kay, Raven M. Jackson, Ruth B. S. Harris, Denis Richard, and Timothy J. Bartness. "Melanocortin-4 receptor mRNA is expressed in sympathetic nervous system outflow neurons to white adipose tissue." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 289, no. 5 (November 2005): R1467—R1476. http://dx.doi.org/10.1152/ajpregu.00348.2005.
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Energy balance results from the coordination of multiple pathways affecting energy expenditure and food intake. Candidate neuropeptides involved in energy balance are the melanocortins. Several species, including Siberian hamsters studied here, decrease and increase food intake in response to stimulation and blockade of the melanocortin 4-receptor (MC4-R). In addition, central application of the MC3/4-R agonist melanotan-II decreases body fat (increases lipolysis) beyond that accounted for by its ability to decrease food intake. Because an increase in the sympathetic nervous system drive to white adipose tissue (WAT) is the principal initiator of lipolysis, we tested whether the sympathetic outflow circuitry from brain to WAT contained MC4-R mRNA expressing cells. This was accomplished by labeling the sympathetic outflow to inguinal WAT using the pseudorabies virus (PRV), a transneuronal retrograde viral tract tracer, and then processing the brain for colocalization of PRV immunoreactivity with MC4-R mRNA, the latter assessed by in situ hybridization. MC4-R mRNA was impressively colocalized in PRV-labeled cells (approximately greater than 60%) in many brain areas across the neuroaxis, including those typically implicated in lipid mobilization (e.g., hypothalamic paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, lateral hypothalamic area), as well as those not traditionally identified with lipolysis (e.g., preoptic area, subzona incerta of the lateral hypothalamus, periaqueductal gray, solitary nucleus). These data provide compelling neuroanatomical evidence that could underlie a direct central modulation of the sympathetic outflow to WAT by the melanocortins through the MC4-Rs resulting in changes in lipid mobilization and adiposity.
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Nguyen, Ngoc Ly T., Jessica Randall, Bruce W. Banfield, and Timothy J. Bartness. "Central sympathetic innervations to visceral and subcutaneous white adipose tissue." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 306, no. 6 (March 15, 2014): R375—R386. http://dx.doi.org/10.1152/ajpregu.00552.2013.
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There is a link between visceral white adipose tissue (WAT) and the metabolic syndrome in humans, with health improvements produced with small visceral WAT reduction. By contrast, subcutaneous WAT provides a site for lipid storage that is rather innocuous relative to ectopic lipid storage in muscle or liver. The sympathetic nervous system (SNS) is the principal initiator for lipolysis in WAT by mammals. Nothing is known, however, about the central origins of the SNS circuitry innervating the only true visceral WAT in rodents, mesenteric WAT (MWAT), which drains into the hepatic portal vein. We tested whether the central sympathetic circuits to subcutaneous [inguinal WAT (IWAT)] and visceral WAT (MWAT) are separate or shared and whether they possess differential sympathetic drives with food deprivation in Siberian hamsters. Using two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer within the same hamsters, we found some overlap (∼20–55% doubly infected neurons) between the two circuitries across the neural axis with lesser overlap proximal to the depots (spinal cord and sympathetic chain) and with more neurons involved in the innervation of IWAT than MWAT in some brain regions. Food deprivation triggered a greater sympathetic drive to subcutaneous (IWAT) than visceral (MWAT) depots. Collectively, we demonstrated both shared and separate populations of brain, spinal cord, and sympathetic chain neurons ultimately project to a subcutaneous WAT depot (IWAT) and the only visceral WAT depot in rodents (MWAT). In addition, the lipolytic stimulus of food deprivation only increased SNS drive to subcutaneous fat (IWAT).
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Bowers, Robert R., William T. L. Festuccia, C. Kay Song, Haifei Shi, Renato H. Migliorini, and Timothy J. Bartness. "Sympathetic innervation of white adipose tissue and its regulation of fat cell number." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 286, no. 6 (June 2004): R1167—R1175. http://dx.doi.org/10.1152/ajpregu.00558.2003.
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White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS), and the central origins of this innervation have been demonstrated for inguinal and epididymal WAT (iWAT and eWAT, respectively) using a viral transneuronal tract tracer, the pseudorabies virus (PRV). Although the more established role of this sympathetic innervation of WAT is as a major stimulator of lipid mobilization, this innervation also inhibits WAT fat cell number (FCN); thus, local denervation of WAT leads to marked increases in WAT mass and FCN. The purpose of this study was to extend our understanding of the SNS regulation of FCN using neuroanatomical and functional analyses. Therefore, we injected PRV into retroperitoneal WAT (rWAT) to compare the SNS outflow to this pad from what already is known for iWAT and eWAT. In addition, we tested the ability of local unilateral denervation of rWAT or iWAT to promote increases in WAT mass and FCN vs. their contralateral neurally intact counterparts. Although the overall pattern of innervation was more similar than different for rWAT vs. iWAT or eWAT, its SNS outflow appeared to involve more neurons in the suprachiasmatic and solitary tract nuclei. Denervation produced significant increases in WAT mass and FCN for both iWAT and rWAT, but FCN was increased significantly more in iWAT than in rWAT. These data suggest differences in origins of the sympathetic outflow to WAT and functional differences in the WAT SNS innervation that could contribute to the differential propensity for fat cell proliferation across WAT depots in vivo.
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Miller, Rebecca L., and Arthur D. Loewy. "5-HT neurons of the area postrema become c-Fos-activated after increases in plasma sodium levels and transmit interoceptive information to the nucleus accumbens." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 306, no. 9 (May 1, 2014): R663—R673. http://dx.doi.org/10.1152/ajpregu.00563.2013.
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Serotonergic (5-hydroxytryptamine, 5-HT) neurons of the area postrema (AP) represent one neuronal phenotype implicated in the regulation of salt appetite. Tryptophan hydroxylase (Tryp-OH, synthetic enzyme-producing 5-HT) immunoreactive neurons in the AP of rats become c-Fos-activated following conditions in which plasma sodium levels are elevated; these include intraperitoneal injections of hypertonic saline and sodium repletion. Non-Tryp-OH neurons also became c-Fos-activated. Sodium depletion, which induced an increase in plasma osmolality but caused no significant change in the plasma sodium concentration, had no effect on the c-Fos activity in the AP. Epithelial sodium channels are expressed in the Tryp-OH-immunoreactive AP neurons, possibly functioning in the detection of changes in plasma sodium levels. Since little is known about the neural circuitry of these neurons, we tested whether the AP contributes to a central pathway that innervates the reward center of the brain. Stereotaxic injections of pseudorabies virus were made in the nucleus accumbens (NAc), and after 4 days, this viral tracer produced retrograde transneuronal labeling in the Tryp-OH and non-Tryp-OH AP neurons. Both sets of neurons innervate the NAc via a multisynaptic pathway. Besides sensory information regarding plasma sodium levels, the AP→NAc pathway may also transmit other types of chemosensory information, such as those related to metabolic functions, food intake, and immune system to the subcortical structures of the reward system. Because these subcortical regions ultimately project to the medial prefrontal cortex, different types of chemical signals from visceral systems may influence affective functions.
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Balbuena-Torres, Johanna Nery, Lorena Santos-Solis, Ronald D. Navarro-Oviedo, and Cesar Augusto Cabezas-Sanchez. "Identificación del virus de hepatitis delta genotipo 3 en comunidades andinas y amazónicas del Perú." Anales de la Facultad de Medicina 84, no. 3 (August 23, 2023): 242–48. http://dx.doi.org/10.15381/anales.v84i3.24029.
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Introducción. El virus de la hepatitis delta (VHD) es el causante de la forma más severa de la hepatitis viral humana, se asocia con un riesgo alto de fibrosis al hígado y carcinoma hepatocelular (HCC). Existen 8 genotipos del VHD con diferente distribución geográfica. Objetivos. Identificar los genotipos del VHD circulante en Huanta y tres pueblos indígenas de la Amazonía peruana. Métodos. Estudio observacional y transversal, realizado en 582 muestras reactivas para anti-HBc del VHB. Por el método nRT-PCR se procesaron todos los anti VHD positivos, el genotipo fue determinado mediante secuenciamiento directo tipo Sanger y análisis filogenético del fragmento R0. Se utilizaron 111 secuencias de referencia del GenBank. Las 42 secuencias del estudio fueron editadas y ensambladas con programas bioinformáticos. El análisis filogenético y evolutivo se realizó con los programas: Beast V2.5.2, Jmodeltest v2.1.10, Tracer v1.7.1, Tree Annotator y Figtree v1.4.4. Se utilizaron los modelos Bayesianos Yule y Birth Death skyline serial, el MCMC en 30 y 80 millones respectivamente, con el relaxed uncorrelated Exponential molecular clock. Se calcularon las medidas de resumen y de tendencia central utilizando el programa en STATA 14.0. Resultados. La media de la edad fue de 38 años, el 52,8% fueron mujeres. 101 muestras fueron positivas para anticuerpos anti-VHD. El ARN del VHD fue detectado en el 49,5% de las muestras reactivas a ELISA anti-VHD. El análisis filogenético determinó la presencia del genotipo 3. Conclusiones. Se evidencia la presencia del genotipo 3 del VHD en comunidades andinas y amazónicas del Perú.
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Yu, Li-Ming, Wei-Hao Bian, Chan Wang, Bi-Xuan Zhao, and Xue Ge. "Calibration of the virial factor f in supermassive black hole masses of reverberation-mapped AGNs." Monthly Notices of the Royal Astronomical Society 488, no. 2 (July 1, 2019): 1519–34. http://dx.doi.org/10.1093/mnras/stz1766.
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ABSTRACT Using a compiled sample of 34 broad-line active galactic nuclei (AGNs) with measured H β time lags from the reverberation mapping (RM) method and measured bulge stellar velocity dispersions σ*, we calculate the virial factor f by assuming that the RM AGNs intrinsically obey the same MBH−σ* relation as quiescent galaxies, where MBH is the mass of the supermassive black hole (SMBH). Considering four tracers of the velocity of the broad-line regions (BLRs), i.e. the H β line width or line dispersion from the mean or rms spectrum, there are four kinds of the factor f. Using the H β full width at half-maximum (FWHM) to trace the BLRs velocity, we find significant correlations between the factor f and some observational parameters, e.g. FWHM, the line dispersion. Using the line dispersion to trace the BLRs velocity, these relations disappear or become weaker. It implies the effect of inclination in BLRs geometry. It also suggests that the variable f in MBH estimated from luminosity and FWHM in a single-epoch spectrum is not negligible. Using a simple model of thick-disc BLRs, we also find that, as the tracer of the BLRs velocity, H β FWHM has some dependence on the inclination, while the line dispersion σH β is insensitive to the inclination. Considering the calibrated FWHM-based factor f from the mean spectrum, the scatter of the SMBH mass is 0.39 dex for our sample of 34 low-redshift RM AGNs. For a high-redshift sample of 30 Sloan Digital Sky Survey RM AGNs with measured stellar velocity dispersions, we find that the SMBH mass scatter is larger than that for our sample of 34 low-redshift RM AGNs. It implies the possibility of evolution of the MBH−σ* relation from high-redshift to low-redshift AGNs.