Functional dissociation of behavioral effects from acetylcholine and glutamate released from cholinergic striatal interneurons

In the striatum, cholinergic interneurons (CINs) have the ability to release both acetylcholine and glutamate, due to the expression of the vesicular acetylcholine transporter (VAChT) and the vesicular glutamate transporter 3 (VGLUT3). However, the relationship these neurotransmitters have in the regulation of behavior is not fully understood. Here we used reward-based touchscreen tests in mice to assess the individual and combined contributions of acetylcholine/glutamate co-transmission in behavior. We found that reduced levels of the VAChT from CINs negatively impacted dopamine signalling in response to reward, and disrupted complex responses in a sequential chain of events. In contrast, diminished VGLUT3 levels had somewhat opposite effects. When mutant mice were treated with haloperidol in a cue-based task, the drug did not affect the performance of VAChT mutant mice, whereas VGLUT3 mutant mice were highly sensitive to haloperidol. In mice where both vesicular transporters were deleted from CINs, we observed altered reward-evoked dopaminergic signalling and behavioral deficits that resemble, but were worse, than those in mice with specific loss of VAChT alone. These results demonstrate that the ability to secrete two different neurotransmitters allows CINs to exert complex modulation of a wide range of behaviors

Cholinergic Modulation of Behaviour

The cholinergic system is one of the most influential and essential signalling systems in the body. In the brain, cholinergic neurons innervate many brain regions where they influence a wide variety of behaviours. However, the precise role of each cholinergic region on distinct types of behaviour is not well known. Furthermore, in recent years there has been evidence that many cholinergic neurons in the brain have a capacity for co-transmission. Yet the functional significance of secreting two classical neurotransmitters from the same neuron is still largely unidentified. In this thesis, we investigated how different cholinergic nuclei modulate behavioural functions. To do that we selectively eliminated acetylcholine (ACh) release from cholinergic neurons of the striatum, brainstem and basal forebrain in mice. We then evaluated cognitive and non-cognitive behaviours using classical behavioural tests as well as sophisticated automated touchscreens tasks. In the striatum cholinergic interneurons are known to co-release ACh and glutamate (Glu), so we focused our investigation on how the individual neurotransmitters modulate striatal-dependent behaviours. We demonstrated that ACh modulates cognitive behaviours such as cognitive flexibility, extinction and cue detection. Glu released from striatal cholinergic interneurons also affects striatal-dependent behaviours but usually in an opposing manner to ACh, so, a balance between ACh and Glu is critical to regulating behaviours. As dopaminergic signalling in the striatum is widely influenced by ACh and Glu released by cholinergic interneurons, we also investigated how dopaminergic signalling changes while animals are performing a striatal-dependent cognitive task. In the brainstem, we showed that ACh influences motor functions and stress but does not have a major impact on cognition. However, stress induced by brainstem ACh-deficiency can interfere with results from cognitive tasks. In the forebrain, we find that ACh signalling is essential for maintaining social memory. Decreased cholinergic signalling in the hippocampus and cortex lead to deficits in social recognition. In conclusion, we demonstrate the complexity that ACh brings into behavioural regulation and how changes in its release can contribute to the pathophysiology of diseases such as Parkinson’s disease and Alzheimer’s disease. Ultimately, this data helps define novel pharmacological mechanisms tailored to improve specific cholinergic-mediated symptoms

Automatic detection of differences that occures onAndroid user interfaces

Android-applikationers användargränssnitt kan se annorlunda ut på olika Android-enheteroch det är svårt att anpassa en applikation efter alla enheter då det finns så många unikamodeller. Målet med arbetet var att framställa ett verktyg som kunde med hjälp av ett korrektdefinierat gränssnitt, upptäcka skillnader i gränssnittet mellan olika Android-enheter.Ett egenutvecklat verktyg framställdes och hade en hög precision. Verktyget kunde bådaupptäcka skillnader och rapportera hur stor skillnaden var mellan gränssnitten.User interfaces can look different on different Android devices and it is difficult to tailor anapplication to all Android devices. The goal with this project was to develop a tool that canuse a correct image of a user-interface and find differences in other images taken from otherAndroid devices. A tool was developed from scratch and it proved accurate in most cases.The tool could both find differences and report how large the difference was

The Visual Making of a Regional Society. Photography and Amazonian History

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The reasons for unusable lipemic blood plasma in transfusion treatment

Introduction/Objective The increased presence of lipid particles in blood is one of most common reasons that transfusion units are unusable. The risk factors for lipemic plasma in donated blood are not completely known. The aim of this study is to identify the factors that influence plasma to be fatty so that we can prevent further storage costs and eliminate unusable transfusion units. Methods This case–control study was conducted in 2017, and 1552 respondents were included in the study. The control group included 1502 subjects whose blood was not lipemic, while 50 patients with lipemic blood were selected for the case group. The presence of lipemic blood was assessed by inspec-tion, while data were collected by clinical laboratory tests and a questionnaire. Results Our findings show that multiple blood donors with lipemic blood were significantly older (p < 0.0005) and have higher systolic and diastolic pressure (p < 0.0005), high triglyceride levels (p < 0.0005), and lower levels of hemoglobin (p < 0.0005). Additionally, the presence of lipemic plasma was associated with female sex (p = 0.002), blood type (p = 0.016), heart disease (p < 0.0005), smoking (p < 0.005), diabetes (p = 0.001), lipid intake prior to blood donation (p < 0.005) and venipuncture therapy (p < 0.0005). Systolic pressure is a reliable predictor of lipemic blood (AUROC = 0.901, p < 0.0005). Conclusion Our study provided a rational explanation and identified some of the risk factors that may help identify potential donors with lipemic blood

The presence of antibodies in anti-Lewis system in our pregnant women

In this paper we have shown 3625 testing blood samples of pregnant women from 2005 to 2010 on the presence of irregular antibodies in Lewis system, which was done by routine methods, and by using appropriate “screening” tests and the panel for identification of antibodies. In addition to other antibodies, anti-Lewis antibodies were found in 0.2%, as follows: anti- Lea in 5, anti- Leb in 2, but anti- Lea+b weren’t found. We have confirmed that the phenotype Le (a-b-) in pregnant women is significantly more active versus tested population. If the anti- Lea antibodies (IgM class) are harmless, the rare anti- Leb antibodies (IgG class) could be dangerous for the fetus. Although the clinical significance of anti-Le antibody has not been fully proven, and although their immunogenicity is low, we suggest test these antibodies in all pregnant women in relationship to their essential role in the transfusions, the sensitization of the fetus and the risk of hemolysis

Modified technique of vaginal hysterectomy, placing polypropylene mesh TOT Sling and IVS methods in solving the associated static disorders of female genital organs and stress incontinentio urinae

Introduction: static disorders of female genital organs, present a problem and a professional challenge for any gynecologist who deals with the operational uroginecology. Frequent relapses of these disorders, after using the classical surgical techniques, have led to new research, technological progress in the production of polypropylene grafts and development of modern operational approaches to these problems. Newer surgical techniques haveled to the construction of retaining polypropylene mesh, in terms of solving the disorders. Stress incontinentio urinae (SUI) and strengthening of the pelvic bottom, as well as prevention of a relapse Rectocoella and Enterocoella.The aim of the study was to present a modification of the classical techniques of vaginal hysterectomy, taking into consideration the recommendations of the authority in the field of vaginal surgery. Also, it indicates the great importance of introducing operational techniques of application polypropylene mesh grafts in correction in the following SUI and strengthening of the pelvic bottom… Case: we present a case of sexagenarian patient with total prolapse of the uterus, followed by the SUI of the middle level, and with evident Rectocoellomi Enterocoella. At council has decided to do a modified technique of total vaginal hysterectomy (TVH), and after that, we did a setting of semi rigid polypropylene mesh by transobtural (TOT Sling) method, in order to obtain SUI correction, and setting of intravaginal slings (IVS) by polypropylene mesh, in order to make a correction of Rectocoellae and Enterocoellae. The surgery has been done in spinal anesthesia. Operative and postoperative flows occurred regularly. The catheter was removed the third postoperative day. The patient urinates spontaneously without residue, controls the micturition. Fifth postoperative day the patient passed faeces, proper and controlled, and was dismissed to home care, for recovered. Discussion and conclusion: problems of our female patient were solved using the described technique and interdisciplinary approach.We removed the prolapsed uterus, solved the problem of SUI and strengthened the pelvic bottom. Interdisciplinary solving of the static disorder of female genital organs is necessary, in order to achieve optimal solving of these problems. The controls after a month, after three and six months, showed that our patient has no subjective discomfort, micturitionis orderly, controlled and there is no sign of Cistocoellae and Enterocoellae. Ultrasound finding is neat, after micturition there is no resudue. The patient lives a normal life and has returned to normal life activities. We think that these techniques are, currently, in our conditions, the ideal approach to solve these problem

Sectional soot model coupled to tabulated chemistry for Diesel RANS simulations

International audienceIn future Euro norms, the soot volume fraction and the soot number density will be regulated. Car manufacturersneed therefore accurate soot models for piston engine emissions prediction in order to developfuture engine concepts. This paper addresses this question by coupling a sectional soot model with a tabulatedcombustion model for RANS simulations of Diesel engines. The sectional soot model, based on thework of Netzell et al. (2007), is implemented in the IFP-C3D RANS CFD code. At each time and location,transport equations are solved for several soot sections, including source terms for collisional and chemicalprocesses. The soot model is coupled to a tabulated combustion model derived from the EngineApproximated Diffusion Flame one (EADF) (Michel and Colin, 2013). It allows to represent the minor speciesrequired by the soot model with a much lower computational cost than a kinetic solver. In order toevaluate the soot model coupled to the resulting combustion model called Variable PressureHomogeneous Tabulated Chemistry (VPTHC), it is compared to the same soot model directly coupledto a complex chemistry solver. As this comparison can hardly be performed on a real Diesel engine casedue to the very high CPU time involved by the chemical solver, it is performed on a variable volume andfuel/air ratio case which retains the essential features of a Diesel engine. Results show that the proposedcoupling recovers with reasonable accuracy the evolution of the soot volume fraction and distribution.Finally, an experimental database of Diesel operating points is simulated. The database includes pointswith a commercial Diesel fuel and the computed surrogate (30% 1-Methylnaphthalene and 70% Decanein liquid volume) to validate the models against the experiments. Soot yields predictions from the modelshow an improvement against the current standards and reach industrial target of accuracy for most ofthe database while the model also provides a good estimation of the soot particles distributions in size

The influence of the expression of steroid receptors on angiogenesis, proliferation and apoptosis in myomas of pre-and postmenopausal women

© 2019, Serbia Medical Society. All rights reserved. Introduction/Objective The aim of this study was to determine the effects of the estrogen and progesterone receptor status on angiogenesis, proliferation, and apoptosis of myoma cells in premenopausal (PreM) and postmenopausal (PostM) women. Methods This was a cross section; clinical-experimental, retrospective, non-interventional study in the field of the study of fundamental pathogenesis mechanisms of disease using pathohistological materials from the existing archive. The research included 76 patients diagnosed with uterine leiomyomas, operatively treated in the Clinic for Gynecology and Obstetrics, Clinical Centre Kragujevac, Serbia. According to the menstrual status, we formed two experimental subgroups. The first group was PreM women (n = 35; 46.2 ± 5.02 years old), and the second group was PostM women (n = 41; 60.25 ± 5.41 years old). Hema-toxylin-eosin staining for myoma and myometrium was conducted, as well as immunohistochemistry for ERα, ERβ, PRа, vascular endothelial growth factor, endoglin, Ki67, and caspase-3. Results Progesterone receptor was overexpressed in myoma and myometrium of PreM compared to myoma and myometrium of PostM women. Expression of caspase-3 was a statistically significant increase in PostM women compared to PreM group. ERα and ERβ were not changed among groups neither in myoma nor in myometrium samples. Conclusion According to our data, PRа had higher influence on apoptosis and cell growth than estrogen receptors. Since PRа was increased in PreM in both myoma and myometrium, probably this expression led further to lower expression of apoptotic marker in PreM women