<p>Women with pregestational diabetes have a 2-5 fold increased risk of giving birth to malformed babies compared with non-diabetic women. Diabetes-induced oxidative stress in maternal and embryonic tissues has been implicated in the teratogenic process. The malformations are likely to be induced before the seventh week of pregnancy, when the yolk sac is partly responsible for the transfer of metabolites to the embryo, and the uterine blood flow to the implantation site determines the net amount of nutrients available to the conceptus. We aimed to evaluate the effect on embryogenesis caused by a diabetes-induced disturbance in yolk sac morphology, uterine blood flow or altered maternal antioxidative status in conjunction with a varied severity of the maternal diabetic state.</p><p>We investigated to which extent maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes (SOD, CAT, GPX), vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis associated proteins (Bax, Bcl-2, Caspase-3) in the yolk sacs of rat embryos on gestational days 10 and 11. We found that maternal diabetes impairs, and that FA supplementation restores, yolk sac vessel morphology, and that maternal diabetes is associated with increased apoptotic rate in embryos and yolk sacs, as well as impaired SOD gene expression. We assessed uterine blood flow with a laser-Doppler-flow-meter and found increased blood flow to implantation sites of diabetic rats compared with controls. Furthermore, resorbed and malformed offspring showed increased and decreased blood flow to their implantation sites, respectively. In mice with genetically altered CuZnSOD levels, maternal diabetes increased embryonic dysmorphogenesis irrespective of CuZnSOD expression. We thus found the maternal diabetic state to be a major determinant of diabetic embryopathy and that the CuZnSOD status exerts a partial protection for the embryo in diabetic pregnancy. </p>

La stimulation du récepteur de la rénine/prorénine [(P) RR], un membre récemment découvert du système rénine-angiotensine (SRA), augmente l'activité du SRA et des voies de signalisation angiotensine II-indépendante. Pour étudier l'impact potentiel du (P)RR dans le développement de l`obésité, nous avons émis l'hypothèse que les souris déficientes en (P)RR uniquement dans le tissus adipeux (KO) auront une diminution du poids corporel en ciblant le métabolisme du tissu adipeux, l'activité locomoteur et/ou la prise alimentaire. Ainsi, des souris KO ont été générées en utilisant la technologie Cre/Lox. Le gain de poids et la prise alimentaire ont été évalués hebdomadairement dans les mâles et femelles KO et de type sauvage (WT) pendant 4 semaines alors qu’ils étaient maintenu sur une diète normal. De plus, un groupe de femelles a été placé pour 6 semaines sur une diète riche en gras et en glucides (HF/HC). La composition corporelle et l'activité ambulatoire ont été évaluées par l’EchoMRI et à l’aide de cages Physioscan, respectivement. Les tissus adipeux ont été prélevés et pesés. De plus, les gras péri-gonadaux ont été utilisés pour le microarray. Finalement, le niveaux d'expression d'ARNm du (P)RR ont été évalués. Comme le gène du (P)RR est situé sur le chromosome X, les mâles étaient des KOs complets et les femelles étaient des KOs partielles. Les souris KO avaient un poids corporel significativement plus petit par rapport à WT, les différences étant plus prononcées chez les mâles. De plus, les femelles KOs étaient résistantes à l'obésité lorsqu'elles ont été placées sur la diète HF/HC et donc elles avaient significativement moins de masse grasse par rapport aux WTs. L’analyse histologique des gras péri-gonadaux des KOs nous ont dévoilés qu’il avait une réduction du nombre d'adipocytes mais de plus grande taille. Bien qu'il n'y ait eu aucun changement dans la consommation alimentaire, une augmentation de près de 3 fois de l'activité ambulatoire a été détectée chez les mâles. De plus, nous avons observé que leurs tibias étaient de longueur réduite ce qui suggère fortement l'affection de leur développement. Les gras péri-gonadaux des souris KO avaient une expression réduite de l`ABLIM2 (Actin binding LIM protein family, member 2) qui est associé avec le diabète de type II chez l'humain. Ainsi, les données recueillies suggèrent fortement que le (P)RR est impliquée dans la régulation du poids corporelle. / Stimulation of the (pro)renin receptor [(P)RR], a recently discovered member of the renin-angiotensin system (RAS), increases the activity of the RAS and stimulates angiotensin II-independent signaling pathways. To investigate the possible impact of the (P)RR on obesity development, we hypothesized that mice deficient in the (P)RR specifically in their adipose tissue (KO) would have a decrease in body weight by targeting adipose tissue metabolism, locomotor activity and/or food intake. As such, KO mice were generated using the Cre/Lox technology. Weekly weight gain and food intake were assessed in both male and female KO and wild-type (WT) littermates for 4 weeks on a normal diet. A group of females were also placed for an additional 6 weeks on a high-fat/high-carbohydrate diet (HF/HC). Body composition and physical activity were evaluated using EchoMRI and Physioscan cages, respectively. Adipose tissues were collected and weighed at sacrifice. Moreover, perigonadal fat was used for Gene assay and histological analysis. (P)RR mRNA expression levels were evaluated using real-time PCR. Different circulating metabolites and proteinuria were measured by ELISA kits. As the (P)RR gene is located on the X chromosome, males were complete KOs and females were partial KOs. KO body weights were significantly lower compared to WTs, the differences being more pronounced in males. Female KOs were resistant to obesity development when placed on a HF/HC diet and as such, had significantly smaller fat mass as well as lower circulating leptin levels compared to WTs. All KO perigonadal fat had a reduced number of adipocytes but of bigger size. Although there were no changes in food intake, an almost 3-fold increase in activity was detected in males. Moreover, they presented with shorter tibial length which strongly suggests that they may have developmental issues. Gonadal fat of KO mice showed a reduced expression of ABLIM2 gene (Actin binding LIM protein family, member 2) which is associated with type II diabetes in humans. Conversely, no obvious changes in glycemia were detected while tendencies for lower proteinuria could be observed. The data collected thus strongly suggests that the (P)RR is implicated in body weight regulation.

Immunodeficient honey bee (Apis mellifera) colonies suffer from broad range of parasites including eukaryotic protozoa. Despite this fact, the eukaryotic parasites are still poorly documented in the Czech Republic. The presence of eukaryotic parasites (Nosema ceranae, Nosema apis, Crithidia mellificae and Apicystis bombi) was observed in different apiaries in the Czech Republic. The samples were taken in 9 apiaries in 53 beehives during the 2014/2015 season. From each beehive, 10 adult of honey bees were taken from the peripheral comb in triplicate. DNA was isolated from every sample of honey bees. The parasites were detected by polymerase chain reaction (PCR) with specific primers. The treatment fall of parasitic mite Varroa destructor was obtained from beekeepers for season of 2014. Crithidia mellificae was detected by 5 types of specific primers (SEF, SER; SSU, SSU rRNA, Cyt b, Tryp cyt b) and positive amplicons were cloned and sequenced. The obtained sequences were compared with GeneBank and showed similarity from 98-100% to sequences of Lotmaria passim (Trypanosomatid). Crithidia mellificae was not detected. L. passim had prevalence of 79,2% and is reported in the Czech Republic for the first time. Primer Tryp-cyt b is recommended for the routine detection of L. passim. Nosema ceranae was...

La triadine est une famille de protéines du muscle squelettique. Quatre isoformes de la triadine ont été clonées: Trisk 95, Trisk 51, Trisk 49 et Trisk 32. Ce sont des protéines transmembranaires du reticulum sarcoplasmique (RS). Trisk 95 et Trisk 51 sont localisées dans la triade où elles sont associées au récepteur de la ryanodine (RyR), un canal calcique. Trisk 49 et Trisk 32 sont localisées dans le RS longitudinal. Il a été montré que Trisk 95 régule les relâchements de Ca2+ du RyR. L'objectif de ce travail de thèse a été d'étudier les fonctions des triadines dans le muscle squelettique grâce à différentes approches et techniques complémentaires. Dans un premier temps, Trisk 95 et de Trisk 51 ont été étudiées par surexpression in vivo dans les muscles de souris. La caractérisation de ces muscles a permis de mettre en évidence l'association du RyR avec la cavéoline, une protéine de la membrane plasmique. Dans un second temps, la fonction de Trisk 32 a été étudiée dans le muscle squelettique. L'étude précise de sa localisation a permis de montrer qu'elle est localisée dans la triade, dans le RS longitudinal, et à proximité des mitochondries. Des expériences de co-immunoprécipitation ont révélé qu'elle est associée avec le RyR et avec le récepteur de l'IP3. De par ses partenaires, Trisk 32 semble jouer un rôle dans la régulation de nombreux mécanismes impliquant le Ca2+. Enfin, le gène de la triadine a été invalidé chez la souris. Cette souris KO triadine présente une faiblesse musculaire et des défauts dans l'ultrastructure de la triade. Ces résultats indiquent qu'en plus de sa fonction de régulation des relâchements de Ca2+ la triadine pourrait avoir un rôle structural.

<p>This essay is the result of a field study in Ko Lanta in Thailand, during October-December 2009. The purpose of the study was to document the traditional religion of Urak Lawoi and to analyze in what way their life and beliefs have changed during the last 20 years.</p><p>Urak Lawoi is the name of one of the sea nomadic ethnic groups who lives along the shores of Myanmar, Thailand and Malaysia. They are spread on many of the islands in the Andaman Sea archipelago and Ko Lanta is the main settlement. Ural Lawoi is regarded as the indigenous people of the island and they live there as a minority with Muslims and Thai-Chinese.</p><p>The traditional religion of Urak Lawoi is built upon the animistic belief of their ancestors. The religious leader and link between the spirit world and the humans is the To Maw. The family bonds are strong in the Urak Lawoi community and the elders play an important role in life and after death, when they can keep on watching out for their offspring. For the living it is important to do the rituals and ceremonies in the right way to obtain good luck and avoid bad luck.</p><p>In the last 20 years Ko Lanta has experienced a tremendous process of change caused by the increasing tourism. The conditions of the Urak Lawoi and their way of life have dramatically changed. The modern society with money economy, new technical solutions and a rationalized large-scale fishing has rapidly changed their way of life. The tsunami catastrophe, and the following attention from help organizations and missionary activities, has escalated the process. The traditional religion and culture of the Urak Lawoi is still present on the island but it is declining and changing under the influence of the constant pressure from other interests.</p>

Women with pregestational diabetes have a 2-5 fold increased risk of giving birth to malformed babies compared with non-diabetic women. Diabetes-induced oxidative stress in maternal and embryonic tissues has been implicated in the teratogenic process. The malformations are likely to be induced before the seventh week of pregnancy, when the yolk sac is partly responsible for the transfer of metabolites to the embryo, and the uterine blood flow to the implantation site determines the net amount of nutrients available to the conceptus. We aimed to evaluate the effect on embryogenesis caused by a diabetes-induced disturbance in yolk sac morphology, uterine blood flow or altered maternal antioxidative status in conjunction with a varied severity of the maternal diabetic state. We investigated to which extent maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes (SOD, CAT, GPX), vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis associated proteins (Bax, Bcl-2, Caspase-3) in the yolk sacs of rat embryos on gestational days 10 and 11. We found that maternal diabetes impairs, and that FA supplementation restores, yolk sac vessel morphology, and that maternal diabetes is associated with increased apoptotic rate in embryos and yolk sacs, as well as impaired SOD gene expression. We assessed uterine blood flow with a laser-Doppler-flow-meter and found increased blood flow to implantation sites of diabetic rats compared with controls. Furthermore, resorbed and malformed offspring showed increased and decreased blood flow to their implantation sites, respectively. In mice with genetically altered CuZnSOD levels, maternal diabetes increased embryonic dysmorphogenesis irrespective of CuZnSOD expression. We thus found the maternal diabetic state to be a major determinant of diabetic embryopathy and that the CuZnSOD status exerts a partial protection for the embryo in diabetic pregnancy.

“Big in Japan: The Novel” chronicles the struggles of American Kent Richman, has-been gaijin-tarento. The novel alternates between a collage of tabloid articles, letters, YouTube video, excerpts from an unfinished memoir, manga story boards, botched interviews, notes scribbled on napkins, and a third-person narrative. Set primarily in central Japan, “Big in Japan” is at once a satire of celebrity, a study of personality, a romance and a mystery. Kent Richman—John Lennon look-a-like known as RI-CHU-MAN-SAN! and husband to popular model Kumiko Sato—was a regular on the nightly game show The Strange Bonanza, despite having little talent beyond his resemblance to the popular Beatle. Following a foolish affair with a young Quebecois named Monique Martine, Kent and Kumi’s celebrity world is shattered when Monique’s husband, Australian Denis Ozman—an edgy, violent shock comic—seeks his revenge on Kent and, by default, Kumi. The “Ozman Incident,” as it becomes known in the Asian press, escalates Kent and Kumi to new levels of celebrity, but impels them to abandon stardom and Japan for a new beginning on an island in the Gulf of Thailand. In Thailand, Kent and Kumi try to make a new start, but Kumi is unable to forgive Kent for what Ozman did to them and paradise quickly goes sour. In the frenzy of a passing storm, Kumi disappears with a local entrepreneur named Darren. Kent’s search for her leads him to Bangkok and a painful but puzzling discovery. When we first meet Kent, he has returned from Thailand without Kumi, who has vanished. He is unemployed, abandoned by his once adoring public, and penniless, living in a capsule hotel. Kent’s failings are aggravated by a minor drug habit that leads him to often comical, painful, and revealing extremes. At the heart of Kent’s troubles are the unanswered questions about Kumi’s disappearance and his fall from grace. Once a star, he both abhors and misses his former life. What begins as an attempt to exorcise nagging questions becomes an aimless and dangerous plunge into obsession: why did Kumi disappear, where did she go and what will he do now?

This essay is the result of a field study in Ko Lanta in Thailand, during October-December 2009. The purpose of the study was to document the traditional religion of Urak Lawoi and to analyze in what way their life and beliefs have changed during the last 20 years. Urak Lawoi is the name of one of the sea nomadic ethnic groups who lives along the shores of Myanmar, Thailand and Malaysia. They are spread on many of the islands in the Andaman Sea archipelago and Ko Lanta is the main settlement. Ural Lawoi is regarded as the indigenous people of the island and they live there as a minority with Muslims and Thai-Chinese. The traditional religion of Urak Lawoi is built upon the animistic belief of their ancestors. The religious leader and link between the spirit world and the humans is the To Maw. The family bonds are strong in the Urak Lawoi community and the elders play an important role in life and after death, when they can keep on watching out for their offspring. For the living it is important to do the rituals and ceremonies in the right way to obtain good luck and avoid bad luck. In the last 20 years Ko Lanta has experienced a tremendous process of change caused by the increasing tourism. The conditions of the Urak Lawoi and their way of life have dramatically changed. The modern society with money economy, new technical solutions and a rationalized large-scale fishing has rapidly changed their way of life. The tsunami catastrophe, and the following attention from help organizations and missionary activities, has escalated the process. The traditional religion and culture of the Urak Lawoi is still present on the island but it is declining and changing under the influence of the constant pressure from other interests.

La stimulation du récepteur de la rénine/prorénine [(P) RR], un membre récemment découvert du système rénine-angiotensine (SRA), augmente l'activité du SRA et des voies de signalisation angiotensine II-indépendante. Pour étudier l'impact potentiel du (P)RR dans le développement de l`obésité, nous avons émis l'hypothèse que les souris déficientes en (P)RR uniquement dans le tissus adipeux (KO) auront une diminution du poids corporel en ciblant le métabolisme du tissu adipeux, l'activité locomoteur et/ou la prise alimentaire. Ainsi, des souris KO ont été générées en utilisant la technologie Cre/Lox. Le gain de poids et la prise alimentaire ont été évalués hebdomadairement dans les mâles et femelles KO et de type sauvage (WT) pendant 4 semaines alors qu’ils étaient maintenu sur une diète normal. De plus, un groupe de femelles a été placé pour 6 semaines sur une diète riche en gras et en glucides (HF/HC). La composition corporelle et l'activité ambulatoire ont été évaluées par l’EchoMRI et à l’aide de cages Physioscan, respectivement. Les tissus adipeux ont été prélevés et pesés. De plus, les gras péri-gonadaux ont été utilisés pour le microarray. Finalement, le niveaux d'expression d'ARNm du (P)RR ont été évalués. Comme le gène du (P)RR est situé sur le chromosome X, les mâles étaient des KOs complets et les femelles étaient des KOs partielles. Les souris KO avaient un poids corporel significativement plus petit par rapport à WT, les différences étant plus prononcées chez les mâles. De plus, les femelles KOs étaient résistantes à l'obésité lorsqu'elles ont été placées sur la diète HF/HC et donc elles avaient significativement moins de masse grasse par rapport aux WTs. L’analyse histologique des gras péri-gonadaux des KOs nous ont dévoilés qu’il avait une réduction du nombre d'adipocytes mais de plus grande taille. Bien qu'il n'y ait eu aucun changement dans la consommation alimentaire, une augmentation de près de 3 fois de l'activité ambulatoire a été détectée chez les mâles. De plus, nous avons observé que leurs tibias étaient de longueur réduite ce qui suggère fortement l'affection de leur développement. Les gras péri-gonadaux des souris KO avaient une expression réduite de l`ABLIM2 (Actin binding LIM protein family, member 2) qui est associé avec le diabète de type II chez l'humain. Ainsi, les données recueillies suggèrent fortement que le (P)RR est impliquée dans la régulation du poids corporelle. / Stimulation of the (pro)renin receptor [(P)RR], a recently discovered member of the renin-angiotensin system (RAS), increases the activity of the RAS and stimulates angiotensin II-independent signaling pathways. To investigate the possible impact of the (P)RR on obesity development, we hypothesized that mice deficient in the (P)RR specifically in their adipose tissue (KO) would have a decrease in body weight by targeting adipose tissue metabolism, locomotor activity and/or food intake. As such, KO mice were generated using the Cre/Lox technology. Weekly weight gain and food intake were assessed in both male and female KO and wild-type (WT) littermates for 4 weeks on a normal diet. A group of females were also placed for an additional 6 weeks on a high-fat/high-carbohydrate diet (HF/HC). Body composition and physical activity were evaluated using EchoMRI and Physioscan cages, respectively. Adipose tissues were collected and weighed at sacrifice. Moreover, perigonadal fat was used for Gene assay and histological analysis. (P)RR mRNA expression levels were evaluated using real-time PCR. Different circulating metabolites and proteinuria were measured by ELISA kits. As the (P)RR gene is located on the X chromosome, males were complete KOs and females were partial KOs. KO body weights were significantly lower compared to WTs, the differences being more pronounced in males. Female KOs were resistant to obesity development when placed on a HF/HC diet and as such, had significantly smaller fat mass as well as lower circulating leptin levels compared to WTs. All KO perigonadal fat had a reduced number of adipocytes but of bigger size. Although there were no changes in food intake, an almost 3-fold increase in activity was detected in males. Moreover, they presented with shorter tibial length which strongly suggests that they may have developmental issues. Gonadal fat of KO mice showed a reduced expression of ABLIM2 gene (Actin binding LIM protein family, member 2) which is associated with type II diabetes in humans. Conversely, no obvious changes in glycemia were detected while tendencies for lower proteinuria could be observed. The data collected thus strongly suggests that the (P)RR is implicated in body weight regulation.

Title: Modules over Gorenstein rings Author: David Pospíšil Department: Department of Algebra Supervisor: Prof. RNDr. Jan Trlifaj, DSc. Supervisor's e-mail address: trlifaj@karlin.mff.cuni.cz Abstract: The dissertation collects my actual contributions to the clas- sification of (co)tilting modules and classes over Gorenstein rings. Com- pared with the original intent we get a more general result in classification of (co)tilting classes namely for general commutative noetherian rings (see the third paper in this dissertation). The dissertation consists of an introduction and three papers with coauthors. The first paper (published in Contemp. Math.) contains a classification of all (co)tilting modules and classes over 1- Gorenstein commutative rings. The second paper (published in J. Algebra) contains a classification of all tilting classes over regular rings of Krull dimen- sion 2 and also a classification of all tilting modules in the local case. Finally the third paper (preprint) contains a classification of all (co)tilting classes and also torsion pairs over general commutative noetherian rings. All these classi- fications are in terms of subsets of the spectrum of the ring and by associated prime ideals of modules. Keywords: (co)tilting module, (co)tilting class, torsion pair, Gorenstein ring, regular ring,...