Interactions between intracerebral human immunodeficiency virus-1 glycoprotein 120 and systemic heroin on expression of messenger ribonucleic acid (mRNA) of inducible nitric oxide synthase, interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2 in hippocampus and cortex brain tissue of the Lewis rat

Neurological complications caused by interactions of the immune system and the nervous system commonly occur in human immunodeficiency virus patients (HIV). Intravenous drug users, including heroin users, have increased rates of HIV-induced pathology in the brain. Glycoprotein 120 (gp120), a coat protein of HIV, has been implicated as a possible causative factor. These experiments examined an in vivo model of HIV infection in the brain by injecting gp120 into the lateral ventricles of Lewis rats with and without systemic heroin administration. The effects of gp120 and heroin were measured in expression of messenger RNA (mRNA) for the important proinflammatory mediators inducible nitric oxide synthase, interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2 in hippocampus and cortex tissue. The results of these experiments indicate that heroin may uniquely alter the acute effects of gp120 in the rat brain on mRNA, allowing increased expression of interleukin-1β and inducible nitric oxide mRNA

Effects of heroin on sickness behavior and proinflammatory mediators in associated brain regions

Proinflammatory mediators in the brain are associated with a constellation of adaptive behaviors known as sickness behaviors. Although many studies have confirmed peripheral immunosuppressive effects of opiates, none have demonstrated effects of heroin or any other opiate on immune responses within the central nervous system. The following experiments examined the effects of heroin on brain proinflammatory mediators alone and during an immune challenge, and the effects that heroin has on sickness behaviors and proinflammatory mediators in associated brain regions. Experiments in Chapter 2 established that heroin produces a reliable, short-term hyperthermia that is not reversed by pre-treatment of indomethacin, nor does it correlate with increased proinflammatory mediators in the hypothalamus, the area of the brain most associated with temperature changes. However, we did show that in the presence of an immune challenge (lipopolysaccharide, LPS), heroin appeared to have a suppressive effect on some proinflammatory mediators 90 minutes after treatment. In Chapter 3, we further investigated these findings and examined both LPS-induced fever response and increased proinflammatory mediators in the hypothalamus, and determined that heroin has a suppressive effect on all proinflammatory mediators measured. In addition to the proinflammatory mediator suppression, heroin also attenuated fever production induced by LPS. In Chapter 4, we examined the effects of heroin on LPS-induced proinflammatory mediators in the hippocampus, a region associated with behavioral depression. As in the hypothalamus, the hippocampus exhibited suppressed proinflammatory mediators when heroin treatment occurred concurrently with LPS treatment, although the hippocampus selectively showed these effects in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Additionally, heroin treatment diminished behavioral depression induced by LPS. Taken together, these studies indicated that although heroin produced hyperthermia, heroin treatment does not acutely elevate proinflammatory mediators in the brain (Chapter 2), and when it is given in the presence of LPS, heroin has an immunosuppressive effect on both production of proinflammatory mediators and sickness behaviors (Chapters 3 and 4). Overall, these experiments demonstrate that heroin suppresses immune responses in the brain that are normally key parts of the process of producing adaptive sickness behaviors

An Economic History of Ellis County, Kansas

Like many American rural communities in the second decade of the twenty-first century, Ellis County faces tough decisions regarding economic development, population growth, and sustainable strategies. This paper examines the history of the region since the early twentieth century, tracing the evolution of various industries—from oil to farming—and the different ways the community responded to the area and nation’s economic shifts. This “big picture” view of Ellis County operates as a starting point for strategizing paths forward for area residents

Diesel Exhaust Activates & Primes Microglia: Air Pollution, Neuroinflammation, & Regulation of Dopaminergic Neurotoxicity

BACKGROUND: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood. OBJECTIVES: Here, we sought to address the brain-region-specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity. METHODS: Rats were exposed to DE (2.0, 0.5, and 0 mg/m3) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron-glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms. RESULTS: Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuroinflammation. Analysis by brain region revealed that DE increased TNFα (tumor necrosis factor-α), IL-1β, IL-6, MIP-1α (macrophage inflammatory protein-1α) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNFα at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 μg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFα release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 μg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity. CONCLUSIONS: Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity

CNTRICS Final Task Selection: Long-term Memory

Long-term memory (LTM) is a multifactorial construct, composed of different stages of information processing and different cognitive operations that are mediated by distinct neural systems, some of which may be more responsible for the marked memory problems that limit the daily function of individuals with schizophrenia. From the outset of the CNTRICS initiative, this multidimensionality was appreciated, and an effort was made to identify the specific memory constructs and task paradigms that hold the most promise for immediate translational development. During the second CNTRICS meeting, the LTM group identified item encoding and retrieval and relational encoding and retrieval as key constructs. This article describes the process that the LTM group went through in the third and final CNTRICS meeting to select nominated tasks within the 2 LTM constructs and within a reinforcement learning construct that were judged most promising for immediate development. This discussion is followed by each nominating authors' description of their selected task paradigm, ending with some thoughts about future directions.Psycholog

A conserved dimorphism-regulating histidine kinase controls the dimorphic switching in Paracoccidioides brasiliensis

Paracoccidioides brasiliensis and P. lutzii, thermally dimorphic fungi, are the causative agents of paracoccidioidomycosis (PCM). Paracoccidioides infection occurs when conidia or mycelium fragments are inhaled by the host, which causes the Paracoccidioides cells to transition to the yeast form. The development of disease requires conidia inside the host alveoli to differentiate into yeast cells in a temperature-dependent manner. We describe the presence of a two-component signal transduction system in P. brasiliensis, which we investigated by expression analysis of a hypothetical protein gene (PADG_07579) that showed high similarity with the dimorphism-regulating histidine kinase (DRK1) gene of Blastomyces dermatitidis and Histoplasma capsulatum. This gene was sensitive to environmental redox changes, which was demonstrated by a dose-dependent decrease in transcript levels after peroxide stimulation and a subtler decrease in transcript levels after NO stimulation. Furthermore, the higher PbDRK1 levels after treatment with increasing NaCl concentrations suggest that this histidine kinase can play a role as osmosensing. In the mycelium-yeast (M -> Y) transition, PbDRK1 mRNA expression increased 14-fold after 24 h incubation at 37A degrees C, consistent with similar observations in other virulent fungi. These results demonstrate that the PbDRK1 gene is differentially expressed during the dimorphic M -> Y transition. Finally, when P. brasiliensis mycelium cells were exposed to a histidine kinase inhibitor and incubated at 37A degrees C, there was a delay in the dimorphic M -> Y transition, suggesting that histidine kinases could be targets of interest for PCM therapy.CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Brazil)FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/Brazil)Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Unidade Jose Alencar, St Sao Nicolau 210,4 Floor, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Farmaceut, R Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilUniv Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Unidade Jose Alencar, St Sao Nicolau 210,4 Floor, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Farmaceut, R Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilCNPq: 478023/2013-8FAPESP: 2014/13961-1FAPESP: 2015/09727-6Web of Scienc

Book Reviews

Book Reviews: the Water of Life, a Jungian Journey Through Hawaiian Myth by Rita Knipe; Before the Horror: the Population of Hawai'i on the Eve of Western Contact by David E. Stannard; Observations and Interpretation of Hawaiian Volcanism and Seismicity 1779-1955. An Annotated Bibliography and Subject Index by Thomas L. Wright and Taeko Jane Takahashi; An Account of Two Voyages to the South Seas, to Australia, New Zealand, Oceania 1826-1829 in the Corvette Astrolabe; and to the Straits of Magellan, Chile, Oceania, Southeast Asia, Australia, Antarctica, New Zealand, and the Torres Strait 1837-1840 in the Corvettes Astrolabe and Zelee. by Jules S. C. Dumont d'Urville, Translated and edited by Helen Rosenman; Paths of Duty: American Missionary Wives in Nineteenth-Century Hawaii by Patricia Grimshaw; Journal of Stephen Reynolds Edited by Pauline King; Moramona: the Mormons in Hawaii by R. Lanier Britsch; the Peopling of Hawai'i by Eleanor C. Nordyk

Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1) at Weanling Age

Neonatal foals respond poorly to conventional vaccines. These vaccines typically target T-helper (Th) cell dependent B-cell activation. However, Th2-cell immunity is impaired in foals during the first three months of life. In contrast, neonatal basophils are potent interleukin-4 (IL-4) producers. The purpose of this study was to develop a novel vaccine triggering the natural capacity of neonatal basophils to secrete IL-4 and to evaluate if vaccination resulted in B-cell activation and antibody production against EHV-1 glycoprotein C (gC). Neonatal vaccination was performed by oral biotinylated IgE (IgE-bio) treatment at birth followed by intramuscular injection of a single dose of streptavidin-conjugated gC/IL-4 fusion protein (Sav-gC/IL-4) for crosslinking of receptor-bound IgE-bio (group 1). Neonates in group 2 received the intramuscular Sav-gC/IL-4 vaccine only. Group 3 remained non-vaccinated at birth. After vaccination, gC antibody production was not detectable. The ability of the vaccine to induce protection was evaluated by an EHV-1 challenge infection after weaning at 7 months of age. Groups 1 and 2 responded to EHV-1 infection with an earlier onset and overall significantly increased anti-gC serum antibody responses compared to control group 3. In addition, group 1 weanlings had a decreased initial fever peak after infection indicating partial protection from EHV-1 infection. This suggested that the neonatal vaccination induced a memory B-cell response at birth that was recalled at weanling age after EHV-1 challenge. In conclusion, early stimulation of neonatal immunity via the innate arm of the immune system can induce partial protection and increased antibody responses against EHV-1.Funding for this project was provided by the Harry M. Zweig Memorial Fund for Equine Research at Cornell University ‘A Novel Strategy to Boost Antibody Production to EHV-1 in Neonates’ (http://vet.cornell.edu/research/Zweig/). Monoclonal antibody development for horse cell surface markers and cytokines was supported by USDA grant #2005-01812 ‘The US Veterinary Immune Reagent Network’ and #2015-67015-23072 ‘Equine Immune Reagents: Development of monoclonal antibodies to improve the analysis of immunity in horses’ (https://nifa.usda.gov/).Peer Reviewe

Detection of forest disturbance across California using deep-learning on PlanetScope imagery

California forests have recently experienced record breaking wildfires and tree mortality from droughts, However, there is inadequate monitoring, and limited data to inform policies and management strategies across the state. Although forest surveys and satellite observations of forest cover changes exist at medium to coarse resolutions (30–500 m) annually, they remain less effective in mapping small disturbances of forest patches (<5 m) occurring multiple times a year. We introduce a novel method of tracking California forest cover using a supervised U-Net deep learning architecture and PlanetScope’s Visual dataset which provides 3-band RGB (Red, Green, and Blue) mosaicked imagery. We created labels of forest and non-forest to train the U-Net model to map tree cover based on a semi-unsupervised classification method. We then detected changes of tree cover and disturbance with the U-Net model, achieving an overall accuracy of 98.97% over training data set, and 95.5% over an independent validation dataset, obtaining a precision of 82%, and a recall of 74%. With the predicted tree cover mask, we created wall to wall monthly tree cover maps over California at 4.77 m resolution for 2020, 2021, and 2022. These maps were then aggregated in a post-processing step to develop annual maps of disturbance, while accounting for the time of disturbance and other confounding factors such as topography, phenological and snow cover variability. We compared our high-resolution disturbance maps with wildfire GIS survey data from CALFIRE, and satellite-based forest cover changes and achieved an F-1 score of 54% and 88% respectively. The results suggest that high-resolution maps capture variability of forest disturbance and fire that wildfire surveys and medium resolution satellite products cannot. From 2020 to 2021, California maintained 30,923.5 sq km of forest while 5,994.9 sq km were disturbed. The highest observed forest loss rate was located at the Sierra Nevada mountains at 21.4% of the forested area being disturbed between 2020 and 2021. Our findings highlight the strong potential of deep learning and high-resolution RGB optical imagery for mapping complex forest ecosystems and their changes across California, as well as the application of these techniques on a national to global scale

Sub-Meter Tree Height Mapping of California using Aerial Images and LiDAR-Informed U-Net Model

Tree canopy height is one of the most important indicators of forest biomass, productivity, and species diversity, but it is challenging to measure accurately from the ground and from space. Here, we used a U-Net model adapted for regression to map the canopy height of all trees in the state of California with very high-resolution aerial imagery (60 cm) from the USDA-NAIP program. The U-Net model was trained using canopy height models computed from aerial LiDAR data as a reference, along with corresponding RGB-NIR NAIP images collected in 2020. We evaluated the performance of the deep-learning model using 42 independent 1 km$^2$ sites across various forest types and landscape variations in California. Our predictions of tree heights exhibited a mean error of 2.9 m and showed relatively low systematic bias across the entire range of tree heights present in California. In 2020, trees taller than 5 m covered ~ 19.3% of California. Our model successfully estimated canopy heights up to 50 m without saturation, outperforming existing canopy height products from global models. The approach we used allowed for the reconstruction of the three-dimensional structure of individual trees as observed from nadir-looking optical airborne imagery, suggesting a relatively robust estimation and mapping capability, even in the presence of image distortion. These findings demonstrate the potential of large-scale mapping and monitoring of tree height, as well as potential biomass estimation, using NAIP imagery.Comment: 29 pages, 9 figures, submitted to Remote Sensing in Ecology and Conservation (RSEC