Deletion of the trpc4 gene and its role in simple and complex strategic learning

The TRPC4 ion channel is expressed extensively in corticolimbic and a subpopulation of midbrain dopamine neurons. While TRPC4 knockout (KO) rats exhibit reduced sociability and social exploration, little is known about the role of TRPC4 in motivation and learning. To identify a function for TRPC4 channels in learning processes  we tested TRPC4 KO and normal wild type (WT) rats. TRPC4 KO and WT rats exhibited no differences in Y-­maze learning or simple discrimination learning. Furthermore, on a more complex serial reversal shift task designed  to assess strategic learning where the reward and non-­reward cues were repeatedly reversed between training sessions both TRPC4 KO and WT rats   performed equally well. Finally, we found no   performance differences when using a conditional reversal shift task where a tone signals the reversal of reward and non-reward cues within sessions. These data suggest that although TRPC4 channels may play a role in social interaction/anxiety  they exert a minimal role in simple and complex strategic learning

The Forum: Spring 2005

Spring 2005 journal of the Honors Program at the University of North Dakota. The issue includes stories, poems, essays and art by undergraduate students.https://commons.und.edu/und-books/1056/thumbnail.jp

The Forum: Spring 2004

Spring 2004 journal of the Honors Program at the University of North Dakota. The issue includes stories, poems, essays and art by undergraduate students.https://commons.und.edu/und-books/1054/thumbnail.jp

Taller plants have lower rates of molecular evolution

Rates of molecular evolution have a central role in our understanding of many aspects of species' biology. However, the causes of variation in rates of molecular evolution remain poorly understood, particularly in plants. Here we show that height account

NETWORK DOS MEDIADORES LIPÍDICOS COM DOENÇAS AUTOIMUNES: UMA REVISÃO DE LITERATURA

Lipid mediators are organic molecules released in the inflammatory process that can be related to both physiological and pathological actions, as well as autoimmune diseases. At the onset of inflammation, pro-inflammatory lipid mediators contribute to vasodilation and recruitment of neutrophils; In the final stages, anti-inflammatory activation occurs, when the resolution process begins, resulting in the recruitment of cells at the injury site. Autoimmune diseases are able to arise from an exacerbated immune response, although etiologically distinct, these diseases are unified through the presence of unregulated immune components. This study sought to correlate the different lipid mediators with autoimmune diseases: Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hashimoto's Thyroiditis and Multiple Sclerosis through a literature review. Bibliographic review using the academic Google, Medline, PubMed and SciELO as databases. The search was carried out on articles published from 2000 to 2020, in Portuguese and / or English. From the study it is possible to understand how a complexity of the immunoregulation of lipid mediators can elucidate the pathogenesis of autoimmune diseases, in addition to guiding future treatment strategies.Los mediadores lipídicos son moléculas orgánicas liberadas en el proceso inflamatorio que pueden estar relacionadas tanto con acciones fisiológicas como patológicas, así como con enfermedades autoinmunes. Al inicio de la inflamación, los mediadores lipídicos proinflamatorios contribuyen a la vasodilatación y al reclutamiento de neutrófilos; en las etapas finales, ocurre la activación antiinflamatoria, cuando comienza el proceso de resolución, reduciendo el reclutamiento de células en el sitio de la lesión. Las enfermedades autoinmunes pueden surgir de la respuesta inmune exacerbada, aunque etiológicamente distintas, estas enfermedades se unifican a través de la presencia de componentes inmunes no regulados. Este estudio busca correlacionar los diferentes mediadores lipídicos con enfermedades autoinmunes: artritis reumatoide, lupus eritematoso sistémico, tiroiditis de Hashimoto y esclerosis múltiple a través de una revisión de la literatura. Revisión bibliográfica utilizando las bases de datos académicas Google, Medline, PubMed y SciELO. La búsqueda se realizó sobre artículos publicados entre 2000 y 2020, en portugués y / o inglés. A partir de este estudio es posible comprender cómo la complejidad de la inmunorregulación de los mediadores lipídicos puede dilucidar la patogenia de las enfermedades autoinmunes, además de orientar futuras estrategias de tratamiento.Os mediadores lipídicos são moléculas orgânicas liberadas no processo inflamatório que podem estar relacionados tanto às ações fisiológicas quanto patológicas, como nas doenças autoimunes. No início da inflamação, mediadores lipídicos pró inflamatórios contribuem para vasodilatação e recrutamento de neutrófilos; nos estágios finais ocorre ativação anti-inflamatória, quando se inicia o processo de resolução, reduzindo o recrutamento de células no local da lesão. As doenças autoimunes são capazes de surgir a partir da resposta imune exacerbada, embora etiologicamente distintas, essas doenças são unificadas por meio da presença de componentes imunológicos desregulados. Este estudo buscou correlacionar os diferentes mediadores lipídicos com as doenças autoimunes: Artrite Reumatoide, Lúpus Eritematoso Sistêmico, Tireoidite de Hashimoto e Esclerose Múltipla por meio de uma revisão de literatura. Revisão bibliográfica utilizando como bases de dados o Google acadêmico, Medline, PubMed e SciELO. A busca foi realizada em artigos publicados no período de 2000 a 2020, em português e/ou inglês. A partir deste estudo é possível compreender como a complexidade da imunorregulação dos mediadores lipídicos pode elucidar a patogênese das doenças autoimunes, além de guiar futuras estratégias de tratamento

Seasonal iron fluxes and iron cycling in sandy bioirrigated sediments

Permeable sediments, which represent more than 50% of the continental shelves, have been largely neglected as a potential source of Fe in current global estimates of benthic dissolved iron (Fed) fluxes. There are open questions regarding the effects of a range of factors on Fed fluxes from these deposits, including seasonal dynamics and the role of bioirrigation. To address these gaps, we performed laboratory-based sediment incubation experiments with muddy sands during summer (21 °C) and winter (7 °C). We used bioirrigation mimics to inject overlying water into the permeable sediment with patterns resembling the bioirrigation activity of the prolific bioturbating polychaete, Clymenella torquata. Newly developed in-line Fe accumulators were used to estimate Fe fluxes with a recirculating set-up. We found high Fed fluxes from sandy sediments, especially in benthic chambers with simulated bioirrigation. In the winter fluxes reached >200 µmol Fed m-2 d-1 at the onset of irrigation and then decreased over the course of a 13-day experiment while in the summer fluxes from irrigated sediments reached >100 µmol Fed m-2 d-1 and remained high throughout a 7-day experiment. Despite different geochemical expressions of Fe-S cycling and resulting porewater Fed concentrations in winter and summer, large Fed fluxes were sustained during both seasons. Solid-phase and porewater concentration profiles showed that maximum concentrations of key constituents, including total solid-phase reactive Fe, and porewater Fed and ammonium, were located closer to the sediment water interface (SWI) in irrigated cores than in non-irrigated cores due to the upward advective transport of dissolved porewater constituents. This upward transport also facilitated Fed fluxes out of the sediments, especially during times of active pumping. Our study demonstrates the potential for large Fed fluxes from sandy sediments in both summer and winter, despite relatively low standing stocks of labile organic matter and porewater Fed. The primary driver of these high fluxes was advective porewater transport, in our study induced by the activity of infaunal organisms. These results suggest that permeable sediments, which dominate shelf regions, must be explicitly considered in global estimates of benthic Fed fluxes, and cannot be simply extrapolated from estimates based on muddy sediments

Climate Change Impacts on Iowa, 2010

Climate change is already affecting the way Iowans live and work. Without action to mitigate these effects, our future responses will become more complex and costly . The following policy recommendations are offered as initial steps to help safeguard our state’s economy, environment, and residents

Specific shifts in the endocannabinoid system in hibernating brown bears

In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear's peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment

A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis

OBJECTIVE: To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG). METHODS: We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody-positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12. Secondary outcome measures included 12-month changes of the Quantitative Myasthenia Gravis Score, the Myasthenia Gravis Composite Score, Manual Muscle Testing, the Myasthenia Gravis Quality of Life, and the Myasthenia Gravis Activities of Daily Living. RESULTS: Fifty-eight patients were screened and 50 enrolled. MTX did not reduce the month 4-12 prednisone AUDTC when compared to placebo (difference MTX - placebo: -488.0 mg, 95% confidence interval -2,443.4 to 1,467.3, p = 0.26); however, the average daily prednisone dose decreased in both groups. MTX did not improve secondary measures of MG compared to placebo over 12 months. Eight participants withdrew during the course of the study (1 MTX, 7 placebo). There were no serious MTX-related adverse events. The most common adverse event was nonspecific pain (19%). CONCLUSIONS: We found no steroid-sparing benefit of MTX in MG over 12 months of treatment, despite being well-tolerated. This study demonstrates the challenges of conducting clinical trials in MG, including difficulties with recruitment, participants improving on prednisone alone, and the need for a better understanding of outcome measure variability for future clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with generalized MG MTX does not significantly reduce the prednisone AUDTC over 12 months of therapy

Developing a Series of AI Challenges for the United States Department of the Air Force

Through a series of federal initiatives and orders, the U.S. Government has been making a concerted effort to ensure American leadership in AI. These broad strategy documents have influenced organizations such as the United States Department of the Air Force (DAF). The DAF-MIT AI Accelerator is an initiative between the DAF and MIT to bridge the gap between AI researchers and DAF mission requirements. Several projects supported by the DAF-MIT AI Accelerator are developing public challenge problems that address numerous Federal AI research priorities. These challenges target priorities by making large, AI-ready datasets publicly available, incentivizing open-source solutions, and creating a demand signal for dual use technologies that can stimulate further research. In this article, we describe these public challenges being developed and how their application contributes to scientific advances