Hat

Abnormally enhanced de novo lipid biosynthesis has been increasingly realized to play crucial roles in the initiation and progression of varieties of cancers including breast cancer. However, the mechanisms underlying the dysregulation of lipid biosynthesis in breast cancer remain largely unknown. Here, we reported that seryl tRNA synthetase (SerRS), a key enzyme for protein biosynthesis, could translocate into the nucleus in a glucose-dependent manner to suppress key genes involved in the de novo lipid biosynthesis. In normal mammary gland epithelial cells glucose can promote the nuclear translocation of SerRS by increasing the acetylation of SerRS at lysine 323. In SerRS knock-in mice bearing acetylation-defective lysine to arginine mutation, we observed increased body weight and adipose tissue mass. In breast cancer cells the acetylation and nuclear translocation of SerRS are greatly inhibited. Overexpression of SerRS, in particularly the acetylation-mimetic lysine to glutamine mutant, dramatically inhibits the de novo lipid synthesis and hence greatly suppresses the proliferation of breast cancer cells and the growth of breast cancer xenografts in mice. We further identified that HDAC4 and HDAC5 regulated the acetylation and nuclear translocation of SerRS. Thus, we identified a SerRS-meditated inhibitory pathway in glucose-induced lipid biosynthesis, which is dysregulated in breast cancer.

The stress protein p8 is a small, highly basic, unfolded, and multifunctional protein. We have previously shown that most of its functions are exerted through interactions with other proteins, whose activities are thereby enhanced or repressed. In this work we describe another example of such mechanism, by which p8 binds and negatively regulates MSL1, a histone acetyl transferase (HAT)‐associated protein, which in turn binds the DNA‐damage‐associated 53BP1 protein to facilitate DNA repair following DNA γ‐irradiation. Contrary to the HAT‐associated activity, MSL1‐dependent DNA‐repair activity is almost completely dependent on 53BP1 expression. The picture that has emerged from our findings is that 53BP1 could be a scaffold that gets the HAT MSL1‐dependent DNA‐repair activity to the sites of DNA damage. Finally, we also found that, although p8 expression is transiently activated after γ‐irradiation, it is eventually submitted to sustained down‐regulation, presumably to allow developme...

In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting 80% of cytosolic proteins in humans. The human essential gene,NAA10,encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex, also including the accessory protein, NAA15. The full spectrum of human genetic variation in this pathway is currently unknown. Here we reveal the genetic landscape of variation inNAA10andNAA15in humans. Through a genotype-first approach, one clinician interviewed the parents of 56 individuals withNAA10variants and 19 individuals withNAA15variants, which were added to all known cases (N=106 forNAA10and N=66 forNAA15). Although there is clinical overlap between the two syndromes, functional assessment demonstrates that the overall level of functioning for the probands withNAA10variants is significantly lower than the probands withNAA15variants. The phenotypic spectrum includes variable levels of intellectual disability, de...

Carcinogenesis is a complicated process that involves the deregulation of epigenetics, resulting in cellular transformational events, such as proliferation, differentiation, and metastasis. Most chromatin-modifying enzymes utilize metabolites as co-factors or substrates and thus are directly dependent on such metabolites as acetyl-coenzyme A, S-adenosylmethionine, and NAD+. Here, we show that using specific siRNA to deplete a tumor of VDAC1 not only led to reprograming of the cancer cell metabolism but also altered several epigenetic-related enzymes and factors. VDAC1, in the outer mitochondrial membrane, controls metabolic cross-talk between the mitochondria and the rest of the cell, thus regulating the metabolic and energetic functions of mitochondria, and has been implicated in apoptotic-relevant events. We previously demonstrated that silencing VDAC1 expression in glioblastoma (GBM) U-87MG cell-derived tumors, resulted in reprogramed metabolism leading to inhibited tumor growth,...

The National Library of Russia (henceforth NLR) has a valuable collection of Oriental manuscripts (about 26 thousand items), mainly Hebrew and Arabographic codices and documents. The predominance of the Near Eastern and Middle Eastern materials here, which the author of the present article had a chance to note elsewhere, is a feature characteristic of the collection of the NLR as a whole.

This study aimed to identify trypanosomes infecting cattle in Malawi in order to understand the importance of cattle in the transmission dynamics of Human African Trypanosomiasis (HAT) and Animal African Trypanosomosis (AAT). A total of 446 DNA samples from cattle blood from three regions of Malawi were screened for African trypanosomes by ITS1 PCR. The obtained amplicons were sequenced using a portable next-generation sequencer, MinION, for validation. Comparison of the results from ITS1 PCR and MinION sequencing showed that combining the two methods provided more accurate species identification than ITS1 PCR alone. Further PCR screening targeting the serum resistance-associated (SRA) gene was conducted to detect Trypanosoma brucei rhodesiense. Trypanosoma congolense was the most prevalent Trypanosoma sp., which was found in Nkhotakota (10.8%; 20 of 185), followed by Kasungu (2.5%; 5 of 199). Of note, the prevalence of T. b. rhodesiense detected by SRA PCR was high in Kasungu and N...

Le virus de la leucemie bovine (BLV) est un retrovirus B-lymphotrope qui a ete identifie comme l’agent etiologique de la leucose bovine enzootique. L’infection par le BLV se caracterise par l’absence de viremie due a la latence du virus dans la majorite des cellules infectees. Cette latence resulte de la repression transcriptionnelle du provirus in vivo; elle favorise tres probablement le developpement tumoral en permettant aux cellules infectees d’echapper au systeme immunitaire de l’hote. Cependant, la transcription du BLV peut etre activee de maniere rapide et tres efficace par la proteine virale TaxBLV. La trans-activation par TaxBLV joue un role crucial dans la pathogenese associee au BLV car elle permet la production de nouvelles particules virales necessaires a la propagation du virus. Au cours de notre travail de these, nous avons etudie differents mecanismes impliques au cours de ces deux phases cles (latence et trans-activation par TaxBLV) de l’expression du BLV.Le promote...

Sulfamides guide intermolecular chlorine transfer to gamma-C(sp<sup>3</sup>) centers. This unusual position-selectivity arises because accessed sulfamidyl radical intermediates engage in otherwise rare 1,6-hydrogen-atom transfer processes. The disclosed chlorine-transfer reaction relies on a light-initiated radical chain-propagation mechanism to oxidize C(sp<sup>3</sup>)-H bonds.

In 2009–2010, an archaeological excavation was carried out at 1 Sadowa Street in the so-called Lower City of Gdańsk/Poland (former Danzig), during which a considerable number of artefacts of organic materials were discovered, including a well-preserved felt hat from a 17th/18th century layer of a building. The aim of the activities undertaken by the Authors of this paper was to establish the chronology of the hat, determine how it was made, identify the material, and perform an in-depth analysis of its form compared with other finds of thiskind using basic research methods. The employed methods included the typological method, a case study as well as organoleptic and microscopic methods for identifying the item and determining the degree of material biodegradation. The following research techniques wereadopted: technological textile, felt, etc. analysis including observation of the surface with a stereoscopic microscope, material analysis with an optical microscope, and XRF spectrom...

Histone post-translational modifications (PTMs) such as acetylation and methylation are known to affect chromatin higher order structures. Primary targets of these modifications include basic residues present at N-terminus tail region of core histones. Four histone acetyltransferase (HAT) genes have been identified in trypanosomatids. HAT1, HAT3 and HAT4 of Leishmania donovani have been partially characterized. However, there is no report about HAT2 of Leishmania donovani. Lysine residues present on the N-terminal tail of Leishmania donovani histone H4 are conserved in other trypanosomatids and humans. PTMs of lysines modulate various functions at chromatin level. The four histone acetyltransferases encoded in Leishmania genome were over-expressed to analyse their functional activity. All four HATs were found actively acetylating core histones H3/H4. Similar to L. donovani HAT3 and HAT4, HAT2 was found to be a member of MYST family protein and have SAS2 type domain. Over-expression ...

In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.

katedra: KHT; přílohy: 1 CD; rozsah: 50 s., 2 s. dotaznik přilohBakalářská práce se zabývá popularizací a propagací technologie výroby plstěných klobouků firmy Tonak, a.s. Pro názornou obrazovou ukázku technologie byl vytvořen krátký dokumentární film, který má široké veřejnosti pomoci pochopit proces výroby plstěných klobouků. Srozumitelnost dokumentárního filmu byla ověřena marketingovým výzkumem, pro který byla použita metoda dotazování. Jednotlivé kapitoly popisují technologický postup výroby plstěných klobouků a teorii marketingového výzkumu. Praktická část vypovídá o propagaci technologie, výrobě dokumentárního filmu, informacích a výsledcích zjištěných marketingovým výzkumem. Z výzkumu vyplývá, že dokumentární film o technologii výroby klobouků je srozumitelný, spotřebitel si uvědomuje složitost a náročnost výroby klobouků. Díky tomuto faktu také příznivěji vnímá cenu plstěných pokrývek hlavy.This bachelor´s essay deals with popularization and propagation of the felt hat prod...

This study aimed to identify trypanosomes infecting cattle in Malawi in order to understand the importance of cattle in the transmission dynamics of Human African Trypanosomiasis (HAT) and Animal African Trypanosomosis (AAT). A total of 446 DNA samples from cattle blood from three regions of Malawi were screened for African trypanosomes by ITS1 PCR. The obtained amplicons were sequenced using a portable next-generation sequencer, MinION, for validation. Comparison of the results from ITS1 PCR and MinION sequencing showed that combining the two methods provided more accurate species identification than ITS1 PCR alone. Further PCR screening targeting the serum resistance-associated (SRA) gene was conducted to detect Trypanosoma brucei rhodesiense. Trypanosoma congolense was the most prevalent Trypanosoma sp., which was found in Nkhotakota (10.8%; 20 of 185), followed by Kasungu (2.5%; 5 of 199). Of note, the prevalence of T. b. rhodesiense detected by SRA PCR was high in Kasungu and N...

Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the NAA10 gene have been described. After the advent of whole exome sequencing, many NAA10 variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females. The NAA10 gene lies in the Xq28 region and encodes the catalytic subunit of the major N-terminal acetyltransferase complex NatA, which acetylates almost half the human proteome. Here, we present a young female carrying a de novo NAA10 [NM_003491:c.247C > T, p.(Arg83Cys)] variant. The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy. Our attempt is to expand and compare genotype–phenotype correlation in females with NAA10-related syndrome. A detailed clinical description could...

In the following article, we analyze the traditions of Mongolian Tuvans (Tsengel sum of Bayan-Ölgii province, Tsagaannuur sum of Khövsgöl province, Hovd province) related to the worship of belt (girdle). We describe various rites, omens, and concepts related to girdles which are still observed in Tuvan daily life. We also list similar rites and omens in the cultures of Mongolians, Russian Tuvans, and Buryats. Our article is based on long-term field observations.

In Ottoman tradition of thought the Prophet Muhammad represents the complete human being (al-insan al-kamil), who has reached the highest psychological, physical and spiritual stage of being. In this case the main purpose of the hilya as a work of calligraphy and illumination is to aesthetically evoke the physical appearance and moral character of the Prophet Muhammad. Moreover, the complex symbolism of the hilya as an expression of prophetic glory also reflects the cosmological thought of the Ottoman community. The subject of this article is to examine the classical hilya design attributed to the famous Ottoman calligrapher Hâfiz Osman in the context of calligraphy-illumination interaction and number symbolism. Examining classical examples of Turkish-Islamic arts of the book, we will try to observe that the conventional hilya design passed through various stages during the process of its formation. In this case the theoretical roots of Hâfiz Osman's hilya form and the probability of his inspiration by the aesthetic designs of the previous periods will be examined through the decorative manuscripts in religious and non-religious topics. Keywords: Hilya, Hâfiz Osman, Ottoman arts of the book, calligraphy, illumination, numeral symbolism. Öz: Osmanlı düşünce geleneğinde Hz. Muhammed, psikolojik, fiziksel ve manevi açıdan en yüce varlık mertebesine ulaşmış yetkin insanı (el-insanü'l-kamil) temsil etmektedir. Bu bakımdan, hat ve tezhip sanatının uygulandığı bir eser olarak hilyenin asıl amacı, Hz. Muhammed'in fiziksel görünüşünün ve ahlaki özelliklerinin estetik ifadesini ortaya koymaktır. Peygamberlik makamının yüceliğini gözler önüne seren hilyedeki mürekkep sembolizm, aynı zamanda Osmanlı toplumunun kozmolojik düşüncesini de yansıtmaktadır. Bu makalenin konusu, ünlü Osmanlı hattat Hâfiz Osman'a atfedilen klasik hilye tasarımının hat-tezhip etkileşimi ve sayı sembolizmi bağlamında incelenmesidir. Makalede Türk/İslam kitap sanatlarının klasik örneklerini incelemek suretiyle, geleneksel hilye tasarımının oluşum sürecinin çeşitli aşamalardan geçtiğini irdelemeye çalışacağız. Buna binaen, Hâfiz Osman tarafından geliştirilen hilye formunun teorik kökleri araştırılacak ve gerek dini gerekse de dini olmayan konulardaki bezemeli yazmalar üzerinden sanatkarın önceki dönemlere ait estetik tasarımlardan esinlenme olasılığı incelemeye tabi tutulacaktır.

In the period 2009-2010 rescue excavations headed by Artur Ginter and Aleksander Andrzejewski were conducted at
ulica Sadowa 1 in Gdańsk. Among other finds a large collection of textiles was found in the remains of a utility building
used since the end of the 17th until the end of the 18th century.
Woollen goods are the most numerous among the textile finds. The majority of them are plain weave 1/1 (35 pieces);
twill weave 2/1 were less numerous (17 pieces). 13 pieces of felted plain weave fabrics 1/1 were also found. Moreover, 67
pieces of felt in various sizes and a piece of woollen string were isolated. Undoubtedly, the most characteristic item made
of felt is a well preserved man’s hat. Two large pieces of cloth made of plant fibre with well preserved, vivid colours are
another interesting finds. Moreover, six pieces of silk were excavated, including three patterned ones, and a silk ribbon. The
finds also include 16 pieces of knitwear six of which could be identified as the remains of socks or stockings. Most of them
are woollen, only one of them was made of silk.
Information on textile finds is a preliminary one, in the future we are going to supplement our study with detailed technological
analysis and research into the dyes used.