235 research outputs found

    Traceable GISAXS measurements for pitch determination of a 25 nm self-assembled polymer grating

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    The feature sizes of only a few nanometers in modern nanotechnology and next-generation microelectronics continually increase the demand for suitable nanometrology tools. Grazing incidence small-angle X-ray scattering (GISAXS) is a versatile technique to measure lateral and vertical sizes in the nm-range, but the traceability of the obtained parameters, which is a prerequisite for any metrological measurement, has not been demonstrated so far. In this work, the first traceable GISAXS measurements, demonstrated with a self-assembled block copolymer grating structure with a nominal pitch of 25 nm, are reported. The different uncertainty contributions to the obtained pitch value of 24.83(9) nm are discussed individually. The main uncertainty contribution results from the sample-detector distance and the pixel size measurement, whereas the intrinsic asymmetry of the scattering features is of minor relevance for the investigated grating structure. The uncertainty analysis provides a basis for the evaluation of the uncertainty of GISAXS data in a more general context, for example in numerical data modeling.Comment: 9 pages, 6 figures; submitted to Journal of Applied Crystallograph

    Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

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    PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1Ξ± co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined theΒ crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1Ξ±-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

    Bacteroides fragilis aortic arch pseudoaneurysm: case report with review

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    We present a case of 58-year-old woman with underlying diabetes mellitus, hepatitis C virus-related liver cirrhosis, and total hysterectomy for uterine myoma 11 moths ago, who was diagnosed ruptured aortic arch mycotic pseudoaneurysm after a certain period of survey for her unknown fever cause. After emergent surgery with prosthetic graft interposition, all her blood cultures and tissue cultures revealed pathogen with Bacteroides fragilis. Although mycotic aneurysms have been well described in literatures, an aneurysm infected solely with Bacteroides fragilis is unusual, with only eight similar cases in the literature. Here we reported the only female case with her specific clinical and management course and summarized all reported cases of mycotic aneurysm caused by Bacteroides fragilis to clarify their conditions and treatments, alert the difficulty in diagnosis, and importance of highly suspicious

    Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth

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    Enterovirus 71 (EV71) is associated with severe neurological disorders in children, and has been implicated as the infectious agent in several large-scale outbreaks with mortalities. Upon infection, the viral RNA is translated in a cap-independent manner to yield a large polyprotein precursor. This mechanism relies on the presence of an internal ribosome entry site (IRES) element within the 5β€²-untranslated region. Virus–host interactions in EV71-infected cells are crucial in assisting this process. We identified a novel positive IRES trans-acting factor, far upstream element binding protein 1 (FBP1). Using binding assays, we mapped the RNA determinants within the EV71 IRES responsible for FBP1 binding and mapped the protein domains involved in this interaction. We also demonstrated that during EV71 infection, the nuclear protein FBP1 is enriched in cytoplasm where viral replication occurs. Moreover, we showed that FBP1 acts as a positive regulator of EV71 replication by competing with negative ITAF for EV71 IRES binding. These new findings may provide a route to new anti-viral therapy

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

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    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

    Cryptococcus neoformans Mediator Protein Ssn8 Negatively Regulates Diverse Physiological Processes and Is Required for Virulence

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    Cryptococcus neoformans is a ubiquitously distributed human pathogen. It is also a model system for studying fungal virulence, physiology and differentiation. Light is known to inhibit sexual development via the evolutionarily conserved white collar proteins in C. neoformans. To dissect molecular mechanisms regulating this process, we have identified the SSN8 gene whose mutation suppresses the light-dependent CWC1 overexpression phenotype. Characterization of sex-related phenotypes revealed that Ssn8 functions as a negative regulator in both heterothallic a-Ξ± mating and same-sex mating processes. In addition, Ssn8 is involved in the suppression of other physiological processes including invasive growth, and production of capsule and melanin. Interestingly, Ssn8 is also required for the maintenance of cell wall integrity and virulence. Our gene expression studies confirmed that deletion of SSN8 results in de-repression of genes involved in sexual development and melanization. Epistatic and yeast two hybrid studies suggest that C. neoformans Ssn8 plays critical roles downstream of the Cpk1 MAPK cascade and Ste12 and possibly resides at one of the major branches downstream of the Cwc complex in the light-mediated sexual development pathway. Taken together, our studies demonstrate that the conserved Mediator protein Ssn8 functions as a global regulator which negatively regulates diverse physiological and developmental processes and is required for virulence in C. neoformans
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