Localization and Function of Budding Yeast CENP-A Depends upon Kinetochore Protein Interactions and Is Independent of Canonical Centromere Sequence

SummaryIn many eukaryotes, the centromere is epigenetically specified and not strictly defined by sequence. In contrast, budding yeast has a specific 125 bp sequence required for kinetochore function. Despite the difference in centromere specification, budding yeast and multicellular eukaryotic centromeres contain a highly conserved histone H3 variant, CENP-A. The localization of budding yeast CENP-A, Cse4, requires the centromere DNA binding components, which are not conserved in multicellular eukaryotes. Here, we report that Cse4 localizes and functions at a synthetic kinetochore assembly site that lacks centromere sequence. The outer kinetochore Dam1-DASH and inner kinetochore CBF3 complexes are required for Cse4 localization to that site. Furthermore, the natural kinetochore also requires the outer kinetochore proteins for full Cse4 localization. Our results suggest that Cse4 localization at a functional kinetochore does not require the recognition of a specific DNA sequence by the CBF3 complex; rather, its localization depends on stable interactions among kinetochore proteins

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Characterization of different functional sites of Atg8 in Saccharomyces cerevisiae

細胞自噬作用是一種在演化上高度守衡的細胞內大分子物質分解機制，所有真核生物，從單細胞的酵母菌到哺乳動物細胞都會進行細胞自噬。當外在環境改變，例如養份供應匱乏時，細胞會藉由在細胞質內產生稱為自噬小泡的雙層膜狀構造來包裹一部分細胞質和大分子物質，甚至是整個胞器，並且運送至溶酶體或是酵母菌的液泡中進行分解。在這過程中所釋放出來的小分子，例如胺基酸等，會被用來合成新的蛋白質以幫助細胞適應改變後的環境。同時，細胞自噬作用也是維持真核細胞內部蛋白質正常代謝的重要機制。目前已經知道細胞自噬與許多退化性神經疾病亦有關聯，例如亨丁頓氏舞蹈症中的聚麩醯胺酸沉澱會誘發細胞產生自噬小泡來包裹並分解之，而失衡的細胞自噬活性與不正常累積的蛋白質聚合物造成的毒性可能是這類退化性神經疾病中神經元大量死亡的主因之一。此外細胞自噬作用也被發現和多細胞生物的胚胎發育、程式性細胞死亡、或是癌症的病理機制等皆有密切的關連。 在目前已知的31種細胞自噬相關蛋白中，Atg8是細胞自噬小泡生成過程中所必需的一種調控蛋白。它在細胞質中被合成之後會藉由一系列的後轉錄修飾作用最後在末端接上一個磷脂質。此外研究發現，細胞自噬的專一性運送物質Ape1的受體Atg19也和Atg8有直接的交互作用，顯示Atg8很可能也參與了細胞自噬作用中的被分解物篩選作用。但不論是Atg8所參與的自噬小泡生合成途徑，或被分解物篩選的確切機制皆尚不清楚。在本篇研究中，我利用定點突變的方法分離出六個Atg8表面的重要胺基酸殘基，並且將它們對應到所負責的生理功能上。其中，殘基Arg28、Tyr49和Leu50組成一個和Atg19結合的區位，同時殘基Tyr49和Leu50也是Atg8在合成後進行後轉錄修飾作用中所必須的。此外殘基Phe79會被蛋白酶Atg4所辨識來調控該修飾作用中的第一步驟，殘基Leu55則是參與在Atg4所調控的另一步驟：去脂質修飾反應。另外一個殘基，Lys48則很可能參與在Atg8所調控的自噬小泡生成作用中。Autophagy is a highly conserved membrane trafficking pathway, which is evoked during stress condition, such as nutrient starvation. Excess or abnormal intracellular macromolecules are sequestered by the double-membrane vesicle, autophagosome, and transported to the vacuole/lysosome for degradation and recycling of nutrient. The released amino acids are used in synthesis of proteins required for cells to adapt to the changed environment. Atg8 is an essential regulator for autophagosome biogenesis. It is post-translationally conjugated to lipid at its C-terminus and is proposed to be the membrane modifier that may be functionally similar to coat proteins. Besides, Atg8 also interacts directly with the autophagic cargo receptor, Atg19. We are interested in whether the Atg8-mediated vesicle expansion process and cargo sorting are coupled. Here we identified 6 residues on Atg8 surface that are required for the modification and/or physiological function of it. Residue Arg28 is specific for the cargo receptor binding; Tyr49, Leu50, Leu55, and Phe79 are involved in different steps of its post-translational modification; and Lys48 is important for perhaps the biogenesis of autophagosome.Acknowledgements ………………………………………………… 2 Abstract in Chinese ……………………………………………… 3 Abstract ………………………………………………………… 4 Introduction ……………………………………………………… 5 Materials and Methods …………………………………………11 Result ………………………………………………………………18 Discussion …………………………………………………………33 References …………………………………………………………39 Tables ………………………………………………………………52 Figures ………………………………………………………………57 Postscrip ……………………………………………………………7

Information ratings and capital structure

We examine the impact of information asymmetry on a firm\u27s capital structure decisions with a unique information rating scheme that draws from 114 measures over five dimensions of information disclosures on each firm from 2006 to 2012. We find that a firm with high (low) information rating is related to low (high) debt financing and leverage. In particular, a firm that moves from the lowest to the highest information rating experiences a 7.8% reduction in firm leverage on average. This relationship is robust to firm characteristics, incentive conflicts, and the agreement theory of Dittmar and Thakor (2007). Our results suggest that information asymmetry is in-fluential on a firm\u27s pecking order behavior independent of these effects

Dengue Outbreaks in High-Income Area, Kaohsiung City, Taiwan, 2003–2009

Kaohsiung City, a modern metropolis of 1.5 million persons, has been the focus of dengue virus activity in Taiwan for several decades. The aim of this study was to provide a temporal and spatial description of dengue virus epidemiology in Kaohsiung City by using data for all laboratory-confirmed dengue cases during 2003–2009. We investigated age- and sex-dependent incidence rates and the spatiotemporal patterns of all cases confirmed through passive or active surveillance. Elderly persons were at particularly high risk for dengue virus–related sickness and death. Of all confirmed cases, ≈75% were detected through passive surveillance activities; case-patients detected through active surveillance included immediate family members, neighbors, and colleagues of confirmed case-patients. Changing patterns of case clustering could be due to the effect of unmeasured environmental and demographic factors