Bats are the only mammals capable of powered flight. In flight, bats consume up to 20 times more oxygen per hour than under basal conditions. This is twice the increase reported for running mammals of the same body sizes. Birds are the only other group of vertebrate capable of powered flight. By plotting morphological and physiological parameters against body mass for bats, terrestrial mammals, and birds, we can observe to what extent these parameters permit high rates of oxygen delivery necessary for flight. In this study we analyzed basal metabolic rate, heart mass, and hematocrit, and compared how differently they scale in the afore-mentioned groups. We found that larger heart masses are associated with the ability to fly; hematocrit values for birds change markedly with body size, while those for mammals and bats are nearly independent of body size; and that BMR scales differently in all three groups.

Neuro-computational models allow to study the brain mechanisms involved in intelligent behavior and extract essential computational principles which can be implemented in cognitive systems. They are a promising solution to achieve a brain-like artificial intelligence that can compete with natural intelligence on realistic behaviors. A crucial property of intelligent behavior is motivation, defined as the incentive to interact with the world in order to achieve specific goals, either extrinsic (obtaining rewards such as food or money, or avoiding pain) or intrinsic (satisfying one’s curiosity, fun). In the human brain, motivated or goal-directed behavior depends on a network of different structures, including the prefrontal cortex, the basal ganglia and the limbic system. Dopamine, a neurotransmitter associated with reward processing, plays a central role in coordinating the activity of this network. It structures processing in high-level cognitive areas along a limbic-associative-motor gradient and impacts the learning capabilities of the whole system. In this habilitation thesis, I present biologically-constrained neuro-computational models which investigate the role of dopamine in visual object categorization and memory retrieval (Vitay and Hamker, 2008), reinforcement learning and action selection (Vitay and Hamker, 2010), the updating, learning and maintenance of working memory (Schroll et al., 2012) and timing processes (Vitay and Hamker, 2014). These models outline the many mechanisms by which the dopaminergic system regulates cognitive and emotional behavior: bistable processing modes in the cerebral cortex, modulation of synaptic transmission and plasticity, allocation of cognitive resources and signaling of relevant events. Finally, I present a neural simulator able to simulate a variety of neuro-computational models efficiently on parallel architectures (Vitay et al., 2015). / Neuronale Modelle nach dem Vorbild des Gehirns bieten die Möglichkeit intelligente, kognitive Prozesse nicht nur besser zu verstehen, sondern sie stellen auch eine vielversprechende Lösung dar, um eine Gehirn-ähnliche künstliche Intelligenz für Wahrnehmung und Verhaltensweisen zu erreichen, die mit natürlicher Intelligenz konkurrieren kann. Eine entscheidende Eigenschaft von intelligentem Verhalten ist Motivation, definiert als der Anreiz mit der Welt zu interagieren, um bestimmte Ziele zu erreichen, sei es extrinsisch (Belohnungen wie Nahrung oder Geld zu erhalten oder die Vermeidung von Schmerzen) oder intrinsisch (die Neugier zu befriedigen, Spaß zu haben). Im menschlichen Gehirn basiert motiviertes oder zielgerichtetes Verhalten auf einem Netzwerk von verschiedenen Strukturen, einschließlich des präfrontalen Cortex, der Basalganglien und des limbischen Systems. Dopamin, ein Neurotransmitter, welcher der Belohnungsverarbeitung zugeordnet wird, spielt eine zentrale Rolle bei der Koordination der Aktivität in diesem Netzwerk. Es strukturiert die Verarbeitung in High-Level-kognitiven Bereichen entlang eines limbischen-assoziativ-motor Gradienten und beinflusst die Lernfähigkeit des gesamten Systems. In dieser Habilitation, präsentiere ich biologisch motivierte neuronale Modelle, die die Rolle von Dopamin in der visuellen Objektkategorisierung und Gedächtnisabruf (Vitay and Hamker, 2008), Reinforcement Lernen und Aktionsauswahl (Vitay and Hamker, 2010), Aktualisierung, Lernen und Aufrechterhaltung von Arbeitsgedächtnis (Schroll et al., 2012) und Timing Prozessen (Vitay and Hamker, 2014) untersuchen. Diese Modelle beschreiben Mechanismen, durch die das dopaminerge System kognitives und emotionales Verhalten reguliert: bistabile Verarbeitungsmodi in der Hirnrinde, Plastizität und Modulation der synaptischen Übertragung, Zuweisung von kognitiven Ressourcen und Signalisierung von relevanten Ereignissen. Schließlich beschreibe ich einen neuronalen Simulator, der in in der Lage ist, eine Vielzahl von neuronalen Modellen effizient auf parallelen Architekturen zu simulieren (Vitay et al., 2015).

Centriole and basal bodies are related nine-fold symmetric microtubule-based eukaryotic organelles central to the organisation of cilia/flagella and centrosomes. Mechanisms of eukaryotic centriole and basal body assembly are mainly based on studies in animal systems. To understand which centriolar proteins are the universally important ones in the assembly across eukaryotes, a bioinformatic survey presented here investigates the distribution of centriolar and cilia-associated proteins across a diverse range of eukaryotes. This analysis showed also that the basal body function is ancestral to eukaryotes, whereas centrosomal components are specific to Holozoa (which include animals). It also suggested that the ancestor of all eukaryotes possessed a cilium/cilia not only with motility function but also with a sensory role. The most frequently conserved proteins in extant ciliated eukaryotes found in this analysis included SAS-6, SAS-4 and WDR16. To test whether these proteins are also important for basal body assembly in distantly-related species to metazoan and other model organisms where the proteins have been studied to date, the proteins were investigated in Trypanosoma brucei. I used a combination of genetic tools and microscopy techniques to demonstrate that SAS-6 but not SAS-4 is essential for basal body assembly in T. brucei. I showed that WDR16 is a stably integrated component of the transition zone and axoneme but not the basal body. Furthermore, I identified a novel SAS-6 like protein which localises to a position consistent with the basal plate and has the capacity to form into filaments. This thesis provides new insights into the evolution of centrioles and basal bodies, and into the function of conserved centriole proteins in T. brucei, a distantly-related organism to animals.

Parkinson's disease (PD) is characterized by debilitating impairments in motor control arising from pathophysiological alterations in basal ganglia circuitry and function. In this research thesis two main approaches, namely electrical recording and stimulation, are combined in order to better understand motor performance in Parkinson's disease and ways it might be improved. Three main types of motor behaviors are studied: discrete ballistic movement, repetitive movement, and motor adaptation. <ul><li>First, deep brain stimulation (DBS) of the subthalamic nucleus (STN) was shown to improve the velocity of discrete, ballistic movements in PD. The neural correlates of ballistic movements were then studied by recording from the STN of PD patients, revealing onset of beta-range desynchronization prior to, and gamma-range frequency synchronization during, performance of fast arm reaches. To determine a causal role for these oscillatory frequencies in motor behavior, the motor cortex of healthy humans was stimulated at either beta or gamma frequency during a 'go/no-go' grip force task. Beta stimulation resulted in slower force generation on 'go' trials but enhanced inhibition during 'no-go' trials, whereas gamma stimulation resulted in faster force generation on 'go' trials.</li> <li>Second, STN DBS resulted in improved repetitive tapping performance in PD patients through a reduction in variability. Recordings from the STN demonstrated that repetitive movement was accompanied by a substantial and persistent suppression of beta oscillatory activity.</li> <li>Third, Parkinson's patients were tested on a motor adaptation task, revealing intact learning but impaired retention of a visuomotor rotation. Application of direct current stimulation of the motor cortex resulted in enhanced adaptation during both learning and retention in PD patients and healthy controls.</li> <li>These results causally implicate the basal ganglia and oscillatory activity in motor control, provide insight into the neuronal mechanisms of motor performance and adaptation, and demonstrate promising new avenues for enhancing motor control in Parkinson's disease.</li></ul>

ABSTRACT In humans, advanced malignancies are often targeted with broad-spectrum cytotoxic drugs that engender several detrimental side effects, in addition to their primary usage for eradicating cancerous cells. One of the lesser-researched of these effects, histological distortion of the olfactory system impedes a patient's ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from chemotherapy. Recent studies have indicated that cytotoxic drugs can damage gustatory epithelia immediately following administration (Mukherjee & Delay, 2011, 2013). We sought to observe the histological effects that cyclophosphamide (CYP), one of the oldest and most popular alkylating antineoplastic agents, may have on the murine main olfactory epithelium (MOE) and vomeronasal organ (VNO). We utilized two immunohistochemical antibodies to label cells in the olfactory epithelia: anti-Ki67, a marker strictly associated with cell proliferation; and, anti-Keratin 5, a marker for the cytoskeleton of horizontal basal cells. Twenty-eight C57BL/6 mice were administered a single intraperitoneal injection of CYP (75 mg/kg), while 20 control mice were administered saline, all at approximately seven weeks of age. Mice were euthanized at days one, two, six, 14, 30, and 45 post injection; subsequently, they were perfused with 4% paraformaldehyde, decalcified, cryoprotected, cryosectioned, and incubated with anti-Ki67 and anti-Keratin 5 antibodies, sequentially. Quantification results by fluorescent imaging of labeled sections revealed a significant decrease in the number of proliferative cells in the MOE and VNO of CYP-injected mice within the first 10 days post injection, followed by a compensatory period of increased cell proliferation through day 45 post injection, compared to saline-injected mice. Co-localization of horizontal basal cells and proliferative cells in the MOE and VNO of CYP-injected mice was significantly amplified at approximately 14 and 45 days post injection, respectively, compared to saline-injected mice. Our results suggest that administration of CYP can rapidly depress the populations of proliferative cells in the murine MOE and VNO; consequently, horizontal basal cells may afford restoration of the proliferative cell populations in the murine MOE and VNO, 14 to 45 days post injection, respectively.

The basal ganglia (BG) is a complex set of heavily interconnected nuclei located in the central part of the brain that receives inputs from the several areas of the cortex and projects via the thalamus back to the prefrontal and motor cortical areas. Despite playing a significant part in multiple brain functions, the physiology of the BG and associated disorders like dystonia remain poorly understood. Dystonia is a devastating condition characterized by ineffective, twisting movements, prolonged co-contractions and contorted postures. Evidences suggest that it occurs due to abnormal discharge patterning in BG-thalamocortocal (BGTC) circuitry. The central purpose of this study was to understand the electrophysiology of BGTC circuitry and its role in motor control and dystonia. Toward this goal, an advanced multi-target multi-unit recording and analysis system was utilized, which allows simultaneous collection and analysis of multiple neuronal units from multiple brain nuclei. Over the cause of this work, neuronal data from the globus pallidus (GP), subthalamic nucleus (STN), entopenduncular nucleus (EP), pallidal receiving thalamus (VL) and motor cortex (MC) was collected from normal, lesioned and dystonic rats under awake, head restrained conditions. The results have shown that the neuronal population in BG nuclei (GP, STN and EP) were characterized by a dichotomy of firing patterns in normal rats which remains preserved in dystonic rats. Unlike normals, neurons in dystonic rat exhibit reduced mean firing rate, increased irregularity and burstiness at resting state. The chaotic changes that occurs in BG leads to inadequate hyperpolarization levels within the VL thalamic neurons resulting in a shift from the normal bursting mode to an abnormal tonic firing pattern. During movement, the dystonic EP generates abnormally synchronized and elongated burst duration which further corrupts the VL motor signals. It was finally concluded that the loss of specificity and temporal misalignment between motor neurons leads to corrupted signaling to the muscles resulting in dystonic behavior. Furthermore, this study reveals the importance of EP output in controlling firing modes occurring in the VL thalamus.

Centrioles and basal bodies with their characteristic 9&plus;2 structure are found in all major eukaryotic lineages. The correlation between the occurrence of centrioles and the presence of cilia/flagella, but not centrosome-like structures, suggests that the ciliogenesis function of centrioles is ancestral. Here, it is demonstrated that the centriole domain of centrosomes emerged within the Metazoa from an ancestral state of possessing a centriole with basal body function but no functional association with a centrosome. Centrosome structures involving a centriole are metazoan innovations. When an axoneme is still present but no longer fully functional, such as the sensory cilia of Caenorhabditis elegans or, as depicted here, the flagellum of the intracellular amastigote stage of the Leishmania mexicana parasite, the basal body structure is less constrained and can depart from the canonical structure. A general view has emerged that classifies axonemes into canonical motile 9&plus;2 and noncanonical, sensory 9&plus;0 structures. This study reveals this view to be overly simplistic, and additional axonemal architectures associated with potential sensory structures should be incorporated into prevailing models. Here, a striking similarity between the axoneme structure of Leishmania amastigotes and vertebrate primary cilia is revealed. This striking conservation of ciliary structure, despite the evolutionary distance between Leishmania and mammalian cells, suggests a sensory function for the amastigote flagellum. Adding weight to a sensory hypothesis, close examination of Leishmania positioning inside the parasitophorous vacuole revealed frequent contact between the flagellum tip and the vacuole membrane. A sensory function could also explain the retention of a flagellum in Trypanosoma cruzi amastigotes, an intracellular stage that, as shown in this study, emerged independently to the Leishmania amastigote. Basal body appendages, such as pro-basal bodies and microtubule rootlets, also vary widely in their structure. Choanoflagellates, a sister group to the Metazoa, posses an extensive microtubule rootlet system that provides support for their characteristic collar tentacles. This atypical structure is reflected in the underlying molecular components of the choanoflagellate basal body. The importance of choanoflagellates as the closest known relative of metazoans was first revealed by their similarity to choanocytes, the feeding cells of sponges. Although phylogenetic analyses leave little doubt that choanoflagellates are a sister group of animals, comparisons of molecular and structural components of appendages associated with the collar tentacles highlight significant differences and questions the extent to which the collar structures of choanoflagellates and choanocytes can be assumed to be homologous. Finally, the confinement of a centriole-based centrosome to the Metazoa provides little support for the flagellar synthesis constraint as an explanation for the origin of multicellularity. There is, indeed, an apparent constraint; no flagellated or ciliated metazoan cell ever divides. This constraint, however, did not arise until after the incorporation of centrioles into the centrosome in the metazoan lineage and the co-option of centrioles as a structural and functional component of the centrosome. The flagellar synthesis constraint is therefore not an explanation for the origin of multicellularity but a consequence of it.

This thesis focuses on cognitive functions in patients after methanol poisoning. The theoretical part consists of a description of methanol, characteristics of methanol poisoning and its neurological sequelae. Methanol poisoning affects the basal ganglia, therefore we describe them and their role in cognitive processes. The theoretical part also describes a case of mass methanol poisoning in the Czech Republic in 2012-2013. The practical part compares results of a control group and a group of patients poisoned with methanol in cognitive assessment. Results show that the patients after methanol poisoning have significantly lower scores in tasks testing memory and executive functions than the control group.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical sciences Student: Veronika Krčmářová Supervisor of master thesis: PharmDr. Miroslav Kovařík Ph.D. Title of master thesis: Resting energy expenditure in patients with chronic obstructive pulmonary disease II The aim of this study was to compare the resting energy expenditure (REE) and nutritional substrate utilization among patients with chronic obstructive pulmonary disease (COPD) and control group. Previous studies have confirmed increased values of REE in COPD patients. On the basis of the increase of this parameter there was a loss of lean and muscle mass. The utilization of nutritional substrates in patients with COPD is not yet known. Our study by a total of 20 patients includes 11 patients with COPD, and 9 from the control group . The age of patients ranged from 55 to 71 years. Each patient was examined once. We determined the value of REE by indirect calorimetry and utilization of nutritional substrates. According to our results, there was an increase in REE in 82 % of patients with COPD, while only 33 % of patients from the control group was hypermetabolic. Comparing the results of REE between groups we observed REE increase by about 20 % in patients with COPD compared with the control...

1 Abstract Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Martin Jenšík Supervisor of master thesis: PharmDr. Miroslav Kovařík Ph.D. Title of master thesis: Resting energy expenditure in patients with chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is step by step moving ahead in public and scientific interest due to its fast rising in mortality rate. Contemporary studies observed a phenomena that patients with COPD have increased resting energy expenditure (REE) that leads to loss of fat free mass and total weight. Our goal was to confirm or disprove this hypothesis. Our research ran in Department of research and development at University hospital Hradec Králové. In our study participated 30 patients, 26 men and 4 women, mean age 67 ± 8 let. Every patient was once examined after twelve-hour fasting. We determined REE and substrate utilization by method of indirect calorimetry. We confirmed increased REE from the average value of REE - 122 ± 14 % predicted by Harris - Benedict equation. None patient was hypometabolic, 7 were normometabolic and 23 hypermetabolic. Substrate utilization did not differ contrary to physiological values. Furthermore we discovered correlation among fat mass, fat free mass,...