Ruumiliste otsustustugede arendamine võimaldamaks merede jätkusuutlikku majandamist

Väitekirja elektrooniline versioon ei sisalda publikatsiooneMeremajanduse teostamiseks on vaja eri tüüpi ruumilist infot, millele tuginevad tööriistad on hädavajalikud kriisiolukorras reageerimiseks ja erinevate stsenaariumipõhiste analüüside läbiviimisel. Doktoritöös arendati veebipõhiseid operatiivseid otsustustugesid, mis võimaldavad koguda ja analüüsida andmeid ja teadmisi ning edastada tulemusi sidusrühmadele arusaadaval viisil, et hõlbustada kokkulepete sõlmimist. Sellist lähenemist illustreerib Next-Generation Smart Response Web (NG-SRW), mis võimaldab hinnata naftareostusega seotud keskkonnariske ja leida hädaolukordadele paremaid lahendusi. Naftalekke ruumilise leviku modelleerimine ja selle visualiseerimine võimaldab hinnata võimalike meetmete eeliseid, et kujundada sobiv reageerimisstrateegia. Lisaks valmis doktoritöö käigus PlanWise4Blue (PW4B) tööriist, millega hinnatakse erinevate survetegurite kumulatiivset mõju mereelustikule. PW4B tööriista saab kasutada inimtegevuste eraldi- ja koosmõjude prognoosimiseks nii tänapäevaste kui ka tuleviku kliimamuutuste tingimustes. Tööriista katsetati Läänemere piirkonnas Eesti mereala ruumilise planeerimise protsessis uurimaks erinevate meremajandamisstsenaariumite mõju erinevatele loodusväärtustele. Tulemused julgustavad kasutama modelleerimisel põhinevaid stsenaariumarvutusi otsustusprotsessides, et uurida inimtegevuse mõju ja/või kasu ökosüsteemi teenuste osutamisele ja vastupidi. Stsenaariumianalüüse kasutades saame teada ühiskonna eelistusi selle kohta, millist tulevikku nad eelistaksid ning paraneb otsustusprotsesside läbipaistvus.The maritime economy requires different types of spatial information, on which spatial decision support tools are essential to respond to crisis situations and to carry out different scenario-based analyses. This doctoral study developed web-based operational decision support tools to collect and analyse data and insights as well as to facilitate communication and discussion with stakeholders. Such an approach is illustrated by the Next-Generation Smart Response Web (NG-SRW), which enables the assessment of environmental risks associated with oil spills and the identification of better solutions to emergencies. By integrating the analysis and visualization of dynamic spill features, the benefits of potential response actions are compared to develop an appropriate response strategy. In addition, PlanWise4Blue (PW4B), a tool to assess the cumulative impact of different human pressures on marine life, was developed during the PhD. The PW4B tool can be used to predict the individual and combined effects of human activities under both current environmental conditions and future climate change. The tool has been tested in the Baltic Sea region in the Estonian marine spatial planning process to investigate the impacts of different marine management scenarios on different nature values. The results encourage the use of modelling-based scenario calculations in decision-making processes to explore effects and/or benefits of human activities to ecosystem services provision, and vice versa. Scenario analysis can be used to include society preferences of what future would they prefer and can improve transparency in decision-making processes.https://www.ester.ee/record=b550706

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general

Possible roles of neuropeptide/transmitter and autoantibody modulation in emotional problems and aggression

The theoretical foundations of understanding psychiatric disorders are undergoing changes. Explaining behaviour and neuroendocrine cell communication leaning towards immunology represents a different approach compared to previous models for understanding complex central nervous system processes. One such approach is the study of immunoglobulins or autoantibodies, and their effect on peptide hormones in the neuro-endocrine system. In the present review, we provide an overview of the literature on neuropeptide/transmitter and autoantibody modulation in psychiatric disorders featuring emotional problems and aggression, including associated illness behaviour. Finally, we discuss the role of psycho-immunology as a growing field in the understanding of psychiatric disorders, and that modulation and regulation by IgG autoAbs represent a relatively new subcategory in psycho-immunology, where studies are currently being conducted

Increased Immune Complexes of Hypocretin Autoantibodies in Narcolepsy

International audienceBACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. METHODOLOGY: Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. PRINCIPAL FINDINGS: Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. CONCLUSION: Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation

The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial

Background Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN. Methods This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology. Discussion Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment

The effects of probiotics administration on the gut microbiome in adolescents with anorexia nervosa—A study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial

Objective Knowledge on gut?brain interaction might help to develop new therapies for patients with anorexia nervosa (AN), as severe starvation-induced changes of the microbiome (MI) do not normalise with weight gain. We examine the effects of probiotics supplementation on the gut MI in patients with AN. Method This is a study protocol for a two-centre double-blind randomized-controlled trial comparing the clinical efficacy of multistrain probiotic administration in addition to treatment-as-usual compared to placebo in 60 patients with AN (13?19 years). Moreover, 60 sex- and age-matched healthy controls are included in order to record development-related changes. Assessments are conducted at baseline, discharge, 6 and 12 months after baseline. Assessments include measures of body mass index, psychopathology (including eating-disorder-related psychopathology, depression and anxiety), neuropsychological measures, serum and stool analyses. We hypothesise that probiotic administration will have positive effects on the gut microbiota and the treatment of AN by improvement of weight gain, gastrointestinal complaints and psychopathology, and reduction of inflammatory processes compared to placebo. Conclusions If probiotics could help to normalise the MI composition, reduce inflammation and gastrointestinal discomfort and increase body weight, its administration would be a readily applicable additional component of multi-modal AN treatment

Caffeine Modulates Food Intake Depending on the Context That Gives Access to Food: Comparison With Dopamine Depletion

Caffeine is a methylxanthine consumed in different contexts to potentiate alertness and reduce fatigue. However, caffeine can induce anxiety at high doses. Caffeine is also a minor psychostimulant that seems to act as an appetite suppressant, but there are also reports indicating that it could stimulate appetite. Dopamine also is involved in food motivation and in behavioral activation. In the present series of experiments, we evaluated the effects of acute administration of caffeine on food consumption under different access conditions. CD1 male adult mice had access to highly palatable food (50% sucrose) in a restricted but habitual context, under continuous or intermittent access as well as under anxiogenic, or effortful conditions. Caffeine (2.5-20.0 mg/kg) increased intake at the highest dose under familiar continuous and intermittent access. However, this high dose reduced food intake in the dark-light paradigm. In contrast, a dopamine-depleting agent, tetrabenazine (TBZ; 1.0-8.0 mg/kg) did not affect food intake in any of those experimental conditions. In the T-maze-barrier task that evaluates seeking and taking of food under effortful conditions, caffeine (10.0 mg/kg) decreased latency to reach the food, but did not affect selection of the high-food density arm that required more effort, or the total amount of food consumed. In contrast, TBZ (4.0 mg/kg) reduced selection of the high food density arm with the barrier, thus affecting amount of food consumed. Interestingly, a small dose of caffeine (5.0 mg/kg) was able to reverse the anergia-inducing effects produced by TBZ in the T-maze. These results suggest that caffeine can potentiate or suppress food consumption depending on the context. Moreover, caffeine did not change appetite, and did not impair orientation toward food under effortful conditions, but it rather helped to achieve the goal by improving speed and by reversing performance to normal levels when fatigue was induced by dopamine depletion

A Spontaneous Mutation in Contactin 1 in the Mouse

Mutations in the gene encoding the immunoglobulin-superfamily member cell adhesion molecule contactin1 (CNTN1) cause lethal congenital myopathy in human patients and neurodevelopmental phenotypes in knockout mice. Whether the mutant mice provide an accurate model of the human disease is unclear; resolving this will require additional functional tests of the neuromuscular system and examination of Cntn1 mutations on different genetic backgrounds that may influence the phenotype. Toward these ends, we have analyzed a new, spontaneous mutation in the mouse Cntn1 gene that arose in a BALB/c genetic background. The overt phenotype is very similar to the knockout of Cntn1, with affected animals having reduced body weight, a failure to thrive, locomotor abnormalities, and a lifespan of 2–3 weeks. Mice homozygous for the new allele have CNTN1 protein undetectable by western blotting, suggesting that it is a null or very severe hypomorph. In an analysis of neuromuscular function, neuromuscular junctions had normal morphology, consistent with previous studies in knockout mice, and the muscles were able to generate appropriate force when normalized for their reduced size in late stage animals. Therefore, the Cntn1 mutant mice do not show evidence for a myopathy, but instead the phenotype is likely to be caused by dysfunction in the nervous system. Given the similarity of CNTN1 to other Ig-superfamily proteins such as DSCAMs, we also characterized the expression and localization of Cntn1 in the retinas of mutant mice for developmental defects. Despite widespread expression, no anomalies in retinal anatomy were detected histologically or using a battery of cell-type specific antibodies. We therefore conclude that the phenotype of the Cntn1 mice arises from dysfunction in the brain, spinal cord or peripheral nervous system, and is similar in either a BALB/c or B6;129;Black Swiss background, raising a possible discordance between the mouse and human phenotypes resulting from Cntn1 mutations