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Natural environmental factors and anthropogenic disturbances can modulate gene expression,resulting in alteration of organismal phenotype. In the first part of my thesis project, I used Drosophila melanogaster as a model to understand the mechanisms by which 24-hour light-dark cycles can regulate rhythmic changes in the chromatin to generate circadian rhythms of gene expression and orchestrate daily biological rhythms in insects. I observed that two circadian clock proteins, CLOCK and TIMELESS, regulate daily rhythmicity in the binding of BRAHMA, a chromatin remodeler, to DNA spanning clockcontrolled genes to facilitate their rhythmic gene expression cycles. Moreover, because TIMELESS degrades in the presence of light, my results provide new insights into how light affects DNA structure and gene expression. In the second part of my thesis project, I investigated the molecular mechanisms by which the fruit pest Drosophila suzukii adapt to insecticide applications and develop resistance. Specifically, I performed RNA sequencing analysis on D. suzukii flies that are either susceptible or resistant to common insecticides to determine genetic mechanisms underlying insecticide resistance in this agricultural pest. My results revealed that enhanced metabolic detoxification confers pyrethroid resistance while spinosad resistance is the result of both metabolic and penetration resistance. Finally, we identified alternative splicing as a potential mechanism of resistance. My results will facilitate the development of efficient molecular diagnostics to monitor insecticide resistance development in the field and enable growers to develop more informed D. suzukii spray programs to control this devastating pest more effectively.

Organismal development and cell differentiation critically depend on chromatin state transitions. However, certain developmentally regulated genes lack histone 3 lysine 9 and 27 acetylation (H3K9ac and H3K27ac, respectively) and histone 3 lysine 4 (H3K4) methylation, histone modifications common to most active genes. Here we describe a chromatin state featuring unique histone 3 lysine 14 acetylation (H3K14ac) peaks in key tissue-specific genes in Drosophila and human cells. Replacing H3K14 in Drosophila demonstrates that H3K14 is essential for expression of genes devoid of canonical histone modifications in the embryonic gut and larval wing imaginal disc, causing lethality and defective wing patterning. We find that the SWI/SNF protein Brahma (Brm) recognizes H3K14ac, that brm acts in the same genetic pathway as H3K14R, and that chromatin accessibility at H3K14ac-unique genes is decreased in H3K14R mutants. Our results show that acetylation of a single lysine is essential at genes devoid of canonical histone marks and uncover an important requirement for H3K14 in tissue-specific gene regulation.

V této práci nazvané Pojetí božství v indických tradicích? se zabývám stávajícími interpretacemi indických tradic a interpretacemi indických příběhů o významných božstvech. Konkrétně si pak kladu otázky: O jakém pojetí božství můžeme v Indii hovořit? Z jakých konceptů přitom vycházíme? Osvětlují dané interpretace dostatečně tradiční indické chápání? V první části textu objasňuji původní význam pojmu religio a úlohu pojetí božství v něm, s ohledem na proměny, ke kterým došlo s příchodem křesťanství. V následující části se pak zaměřuji na indické pojetí božství, jak je prezentované zejména v pracích českých indologů a na myšlenkový rámec, ze kterého naši badatelé vychází. V závěrečné části se věnuji konkrétním indickým bohům, Višnuovi, Šivovi, Kálí atd., a interpretacím příběhů, které o nich vypráví, přičemž se opět odvolávám převážně na českou indologickou produkci a všímám si deformací v jejich chápání, ke kterým z naší strany dochází., In my thesis titled "The Concept of Divinity in Indian Traditions?" I deal with the current interpretations of Indian traditions and interpretations of Indian stories about important deities. My particular questions are: About which concept of divinity can we talk in India? Which kind of concepts do we use? Do these interpretations clarify the traditional Indian thinking properly? In the first part of the text, I specify the original meaning of the term religio and the role of the concept of divinity in it, with regards to the changes caused by upcoming Christianity. In the next part, I focus on the Indian concept of divinity as presented mainly in the works of the Czech indologists and on the thinking framework which stands behind their interpretations. In the last part, I deal with particular Indian deities, Vishnu, Shiva, Kali, etc. and with the interpretations of the stories related to them. In this process I predominantly refer to the Czech indological publications and I am attentive to our deformations of their understanding as well., Fakulta filozofická, Dokončená práce s úspěšnou obhajobou

Circadian clocks enable organisms to anticipate daily changes in the environment and coordinate temporal rhythms in physiology and behavior with the 24-h day-night cycle. The robust cycling of circadian gene expression is critical for proper timekeeping, and is regulated by transcription factor binding, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Recently, it has become clear that dynamic alterations in chromatin landscape at the level of histone posttranslational modification and nucleosome density facilitate rhythms in transcription factor recruitment and RNAPII activity, and are essential for progression through activating and repressive phases of circadian transcription. Here, we discuss the characterization of the BRAHMA (BRM) chromatin-remodeling protein in Drosophila in the context of circadian clock regulation. By dissecting its catalytic vs. non-catalytic activities, we propose a model in which the non-catalytic activity of BRM functions to recruit repressive factors to limit the transcriptional output of CLOCK (CLK) during the active phase of circadian transcription, while the primary function of the ATP-dependent catalytic activity is to tune and prevent over-recruitment of negative regulators by increasing nucleosome density. Finally, we divulge ongoing efforts and investigative directions toward a deeper mechanistic understanding of transcriptional regulation of circadian gene expression at the chromatin level.

Manuel d'hindouisme incluant l'histoire à partir de l'époque védique jusqu'à nos jours, une présentation de la littérature brahmanique, les principales doctrines et leur évolution jusqu'à nos jours.

The cyclin-dependent kinases (CDKs) are serine/threonine specific kinases that are key regulators of the cell cycle. However, several reports indicated their roles in other pathways. Therefore, it is important to identify novel CDK substrates in order to gain a better understanding of the pathways they regulate and in turn, the diseases where they are deregulated. In this thesis, I describe two substrates; Brahma (Brm), an ATPase subunit of the SWI/SNF chromatin remodeling complex and Breast Cancer Metastasis Suppressor 1 (BRMS1), a metastasis suppressor in human cancers. Brm has long been modeled to be part of the pRb/E2F complex, regulating entry into S phase of the cell cycle. In addition, several studies have indicated that Brm interacts with Cyclin E and CDKs. Here, I demonstrate that Drosophila Brm is phosphorylated in vitro by both Cyclin A and Cyclin E/CDK2. Furthermore, using Drosophila as an animal model, a phospho-mimic of Brm was able to bypass the developmental G1 arrest in the wing discs’ zone of non-proliferating cells (ZNC), indicating its role in inhibiting S phase entry. In addition, based on the phenotypes obtained from the expression of Brm phospho-mutants and the current literature, I postulate that CDK-mediated phosphorylation of Brm also has roles in maintaining genomic stability, cell signaling and expression of cell adhesion systems. Our laboratory had previously identified the regulation of Drosophila EGFR/Ras signaling by Brm-DN and its antagonism by Gem. In this thesis, I have further characterised the roles of Brm-DN and Gem in Drosophila development and have identified Rhomboid (a positive regulator of EGFR/Ras signaling) to be the target gene that is transcriptionally regulated by Brm and Gem. Finally, BRMS1 is a metastasis suppressor, better known to exert its functions by being a part of the SAP30/mSin3/HDAC complex to modulate transcription. Furthermore, it was previously reported to be in complex with RBP1, a CDK substrate, which i

Circadian clocks enable organisms to anticipate daily changes in the environment and coordinate temporal rhythms in physiology and behavior with the 24-h day-night cycle. The robust cycling of circadian gene expression is critical for proper timekeeping, and is regulated by transcription factor binding, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Recently, it has become clear that dynamic alterations in chromatin landscape at the level of histone posttranslational modification and nucleosome density facilitate rhythms in transcription factor recruitment and RNAPII activity, and are essential for progression through activating and repressive phases of circadian transcription. Here, we discuss the characterization of the BRAHMA (BRM) chromatin-remodeling protein in Drosophila in the context of circadian clock regulation. By dissecting its catalytic vs. non-catalytic activities, we propose a model in which the non-catalytic activity of BRM functions to recruit repressive factors to limit the transcriptional output of CLOCK (CLK) during the active phase of circadian transcription, while the primary function of the ATP-dependent catalytic activity is to tune and prevent over-recruitment of negative regulators by increasing nucleosome density. Finally, we divulge ongoing efforts and investigative directions toward a deeper mechanistic understanding of transcriptional regulation of circadian gene expression at the chromatin level.

Sanggar temple is located on Penanjakan slope.. The hill is part of Wonogriyo of Pusungmalang village, Puspo regency, Pasuruan district. Sanggar temple suspected as place of worship to the God Brahma who dwells in Mount Bromo. On a series of research carried out in 2005-2008 by Yogyakarta Centre of Archaeology were found several short inscriptions around the temple to be praises used in religious rituals it is allegedly the people in the region. The tradition to sing praises by  until the spread of Islam in Java. The adoption of Islam influence changes lasted praises. The contents of such literatur review espeally ancient writings are used to prove the assumptin., Candi Sanggar berada di lereng Gunung Penanjakan yang merupakan anak Gunung Bromo, secara administrative terletak di Dusun Wonogriyo, Desa Pusungmalang, Kecamatan Puspo, Kabupaten Pasuruan. Candi Sanggar diduga sebagai tempat pemujaan kepada Brahma yang bersemayam di Gunung Bromo.Pada waktu Balai Arkeologi Yogyakarta melakukan penelitian tahun 2005 – 2008, ditemukan beberapa prasasti pendek, diantaranya 2 buah angka tahun / Candrasengkala, dan sebuah prasasti pendek yang belum terpecahkan maknanya meskipun sudah terbaca per kata. Dugaan sementara, prasasti tersebut berkaitan dengan puji-pujian yang diucapkan sebagai pelengkap suatu aktivitas keagamaan yang pernah dikenal masyarakat sekitar situs tersebut. Tradisi menembangkan sebuah pujian berlangsung hingga masa masuk dan berkembangnya pengaruh Islam di Jawa, dengan penambahan unsur-unsur yang bernafaskan Islam. Makalah ini bertujuan untuk membuktikan kebenaran dugaan tersebut, melalui studi pustaka terutama naskah-naskah kuna yang ada sangkut pautnya dengan tema makalah ini.

Ve své práci jsem se zaměřila na rozdíly a problémy v interpretacích, které vznikají při přenášení obsahů jedné kulturní tradice do kulturního rámce tradice jiné, značně odlišné. Na konkrétním případě staroindických upanišad argumentuji to, jak jsou badatelé, kteří usilují o věrné tlumočení těchto obsahů, ovlivněni a limitováni rámcem doby a společnosti, ve které žijí. Porovnání významů původních sanskrtských pojmů v upanišadách a jejich překladů do západních jazyků je dokladem toho, jak chápe naše západní tradice, založená na křesťanství, tradice indické., I focused in my work on differencess and problems in interpretations that appear in transfering the content of one culture tradition into the frame of another tradition, quite dissimilar. I used the specific case of the ancient Upanishads to show, how the scholars, that trying to interpret these contents truly are influeded by the specifics of their time and society they live in. The comparison of the original sanskrit terms in the Upanishads and their translations into western languages are the proof of how our western tradition, which is based on Christianism , understands the traditions of India., Katedra religionistiky, 1) Čtení posudků 2) Obhajoba studentky, Dokončená práce s úspěšnou obhajobou

The human protein Brahma (Brm), encoded by the SMARCA2 gene, is one of the two mutually exclusive ATPase subunits of the mammalian SWI/SNF-BAF chromatin-remodelling complex. Brm-containing BAF complexes are enriched in neurons, where they play crucial roles in the regulation of genes involved in neuronal differentiation. Moreover, it has been reported that Brm associates with components of the spliceosome to regulate the inclusion of alternative internal exons. While investigating with splicing-sensitive microarrays the gene expression changes triggered by mitochondrial stress, I found that Brm is strongly downregulated in SH-SY5Y human neuroblastoma cells overexpressing the SOD1 (G93A) protein, one of the genetic causes of Amyotrophic Lateral Sclerosis (ALS). I found that this downregulation is due to a mitochondrial stress-induced impairment in the SMARCA2 promoter activity. Among the genes deregulated at the splicing level by SOD1 (G93A) expression, I identified several targets that are regulated by alternative 3’ terminal exon usage in a Brm-dependent manner. Specifically, I found that Brm promotes the skipping of the proximal terminal exon in five out of six genes that were analyzed. In order to define the molecular mechanism that allow to Brm to modulate the choice of alternative 3’ terminal exons, I used one of these genes, RPRD1A, as a model. I found that Brm inhibits the choice of the proximal RPRD1A last exon by directly localizing in its genomic region. In turn, the absence of Brm at the level of the proximal last exon is concomitant with a change in the processivity of the RNA Polymerase II, an observation consistent with the “terminal exon pausing” event. I hypothesized a model where Brahma may recruit the Bard1-Cstf complex on the RPRD1A proximal last exon, a complex known to inhibit the 3’ end processing of the pre-mRNA. These observations suggest an inhibitory role for Brm, which is exerted both at the level of the cotranscriptional choice of the pro, 1692, open, open, Fontana, Fontana, G

The human protein Brahma (Brm), encoded by the SMARCA2 gene, is one of the two mutually exclusive ATPase subunits of the mammalian SWI/SNF-BAF chromatin-remodelling complex. Brm-containing BAF complexes are enriched in neurons, where they play crucial roles in the regulation of genes involved in neuronal differentiation. Moreover, it has been reported that Brm associates with components of the spliceosome to regulate the inclusion of alternative internal exons. While investigating with splicing-sensitive microarrays the gene expression changes triggered by mitochondrial stress, I found that Brm is strongly downregulated in SH-SY5Y human neuroblastoma cells overexpressing the SOD1 (G93A) protein, one of the genetic causes of Amyotrophic Lateral Sclerosis (ALS). I found that this downregulation is due to a mitochondrial stress-induced impairment in the SMARCA2 promoter activity. Among the genes deregulated at the splicing level by SOD1 (G93A) expression, I identified several targets that are regulated by alternative 3’ terminal exon usage in a Brm-dependent manner. Specifically, I found that Brm promotes the skipping of the proximal terminal exon in five out of six genes that were analyzed. In order to define the molecular mechanism that allow to Brm to modulate the choice of alternative 3’ terminal exons, I used one of these genes, RPRD1A, as a model. I found that Brm inhibits the choice of the proximal RPRD1A last exon by directly localizing in its genomic region. In turn, the absence of Brm at the level of the proximal last exon is concomitant with a change in the processivity of the RNA Polymerase II, an observation consistent with the “terminal exon pausing” event. I hypothesized a model where Brahma may recruit the Bard1-Cstf complex on the RPRD1A proximal last exon, a complex known to inhibit the 3’ end processing of the pre-mRNA. These observations suggest an inhibitory role for Brm, which is exerted both at the level of the cotranscriptional choice of the pro

[‘One day in the life of Brahma’ — On Indian Philosophy.] An enquiry into the ancient Indian concept of time, the destiny of each individual being, and the tenet of a passage of existence through cosmical ages in universal history., The interdisciplinary scientific journal Värld & Vetande (Gothenburg) was founded in 1951 by professor of astronomy Knut Lundmark. In 1983 it was edited by professor Martin Johnson, Utrecht University, and an editorial committee of distinguished academics of different disciplines.

The Manatee County Cattlemen's Association float in the 1949 De Soto parade hauls the prizewinning Brahma steer, Emperor Jr. 10th, as it passes the Standard Oil gas station. Two young Association members stand next to citrus trees at the front of the float.

Photograph of Ralph LeCocq with his Brahma bull from India.

Photo of two Brahmas on Ralph LeCocq's farm.

A bank ad featuring Ralph LeCocq and his prize Brahma crossed with Angus and Ayrshire, who has all his bank accounts at the National Bank of Commerce, Lynden Branch.

Newspaper article and photo of two of Ralph LeCocq's Brahma cows on his Lynden farm. The article describes how LeCocq imported these cows from India and plans to breed them with his Ayrshires to create quick-maturing and large beef cows.

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Photograph of Ralph LeCocq with his Brahma bull from India.

Photo of two Brahmas on Ralph LeCocq's farm.

Newspaper article and photo of two of Ralph LeCocq's Brahma cows on his Lynden farm. The article describes how LeCocq imported these cows from India and plans to breed them with his Ayrshires to create quick-maturing and large beef cows.

First Brahmas shipped in to Buitenzorg Farm.

Text on back of photo: "You are cordially invited to our First Auction Sale of the best Brahman cattle and Charollaise-Brahma cattle in America on March 17, 1953 at our ranch. Write for catalog to 25th Flr. Esperson Bldg., Houston, Texas. - C M Frost Addressed to Mr. Ralph B. LeCocq, Buitenzorg Farm, Lynden, Wash."

Photo of the Brahma bull, Sambo.

A bank ad featuring Ralph LeCocq and his prize Brahma crossed with Angus and Ayrshire, who has all his bank accounts at the National Bank of Commerce, Lynden Branch.

Photo of two Brahmas on Ralph LeCocq's farm.

Photograph of Ralph LeCocq with his Brahma bull from India.

Newspaper article and photo of two of Ralph LeCocq's Brahma cows on his Lynden farm. The article describes how LeCocq imported these cows from India and plans to breed them with his Ayrshires to create quick-maturing and large beef cows.

A bank ad featuring Ralph LeCocq and his prize Brahma crossed with Angus and Ayrshire, who has all his bank accounts at the National Bank of Commerce, Lynden Branch.

Text on back of photo: "You are cordially invited to our First Auction Sale of the best Brahman cattle and Charollaise-Brahma cattle in America on March 17, 1953 at our ranch. Write for catalog to 25th Flr. Esperson Bldg., Houston, Texas. - C M Frost Addressed to Mr. Ralph B. LeCocq, Buitenzorg Farm, Lynden, Wash."

First Brahmas shipped in to Buitenzorg Farm.

Photo of the Brahma bull, Sambo.