91 research outputs found
MCM-GINS and MCM-MCM interactions in vivo visualised by bimolecular fluorescence complementation in fission yeast
No full textBackground: Each of the three individual components of the CMG complex (Cdc45, MCM and GINS) is essential for chromosomal DNA replication in eukaryotic cells, both for the initiation of replication at origins and also for normal replication fork progression. The MCM complex is a DNA helicase that most likely functions as the catalytic core of the replicative helicase, unwinding the parental duplex DNA ahead of the moving replication fork, whereas Cdc45 and the GINS complex are believed to act as accessory factors for MCM. Results:To investigate interactions between components of the CMG complex, we have used bimolecular fluorescence complementation (BiFC) in the fission yeast Schizosaccharomyces pombe for the first time, to analyse protein-protein interactions between GINS and MCM subunits expressed from their native chromosomal loci. We demonstrate interactions between GINS andMCM in the nuclei of exponentially-growing fission yeast cells and on chromatin in binucleate S-phase cells. In addition we present evidence of MCM-MCM interactions in diploid fission yeast cells. As with GINS-MCM interactions, MCM-MCM interactions also occur on chromatin in S-phase cells. Conclusion: Bimolecular fluorescence complementation can be used in fission yeast to visualise interactions between two of the three components of the CMG complex, offering the prospect that this technique could in the future be used to allow studies on replication protein dynamics in living S. pombe cells.Peer reviewe
LBVS no decoys
No full textTwo datasets for Ligand-Based Virtual Screening (LBVS) benchmarking without decoys.
If you use them, please cite the original datasets:
@article{butkiewicz2013,
title={Benchmarking ligand-based virtual High-Throughput Screening
with the PubChem database},
author={Butkiewicz, Mariusz and Lowe, Edward W and Mueller, Ralf and
Mendenhall, Jeffrey L and Teixeira, Pedro L and
Weaver, C David and Meiler, Jens},
journal={Molecules},
volume={18},
number={1},
pages={735--756},
year={2013},
publisher={Multidisciplinary Digital Publishing Institute},
doi={10.3390/molecules18010735}
}
@article{Lagarde2014,
author = {Lagarde, Nathalie and Ben Nasr, Nesrine and Jérémie, Aurore and
Guillemain, Hélène and Laville, Vincent and Labib, Taoufik and
Zagury, Jean-François and Montes, Matthieu},
title = {NRLiSt BDB, the Manually Curated Nuclear Receptors Ligands and
Structures Benchmarking Database},
journal = {Journal of Medicinal Chemistry},
volume = {57},
number = {7},
pages = {3117-3125},
year = {2014},
doi = {10.1021/jm500132p},
note ={PMID: 24666037},
URL = {http://dx.doi.org/10.1021/jm500132p},
eprint = {http://dx.doi.org/10.1021/jm500132p}
Response to: "timing of administration of indocyanine green for fluorescence-guided surgery in pancreatic cancer: response to Shirakawa et al."
Get PDFThis is the response article to correspondence article received for our published article in BMC surgery titled "A prospective single-center protocol for using near-infrared fluorescence imaging with indocyanine green during staging laparoscopy to detect small metastasis from pancreatic cancer". Peter L. Labib, MBChB pointed out the necessity to administer indocyanine green intravenously in separate timing for detection of metastasis in liver and peritoneum. Preoperative injection is suitable to detect hepatic metastasis and intraoperative injection is reported to be well suited to detect peritoneal metastasis. However, we could not find the usefulness of intraoperative injection of indocyanine green for detecting peritoneal metastasis in cases with staging laparoscopy prior to this study. We employed this study protocol with only preoperative injection of indocyanine green to simplify the procedure with consideration of probably more frequent cases of hepatic metastasis that is difficult to detect with white-light imaging than those of peritoneal metastasis
WALI NIKAH DALAM KOMPILASI HUKUM ISLAM PERSPEKTIF MASYARAKAT DESA CATURTUNGGAL KECAMATAN DEPOK KABUPATEN SLEMAN
Get PDFMarriage guardian is one of marriage pillars that must be fulfilled by the Indonesian muslim community when they want to perform a marriage. However, this pillar has been a discrimination issue. This is understandable as the entitlement is only reserved for a man. It is mentioned in Article 20 Paragraph (1) from the Compilation of Islamic Laws, stating that "The person acting as marriage guardian is a man who meets the criteria of Islamic laws, including muslim, akil, and balig". This has served as the basis for this research which attempted to explore the discrimination issue from the perspective of society, with its discussion focused on how the society views the provisions of marriage guardian as mentioned in Article 20 Paragraph (1) from the Compilation of Islamic Laws and what serves as the basis for the construction of such view.
In order to explore the discrimination issue from the perspective of society, the author used Peter L. Berger's social construction theory to analyze the society’s perspective. Thus, sociological approach and field research type, as well as descriptive-explorative qualitative method were considered relevant for investigating the provisions of marriage guardian from the perspective of society. Furthermore, all informants in this research were selected using purposive sampling technique.
The results of this research consisted of: First, there were two different views regarding the provisions of marriage guardian, non-discrimination and discrimination views. The non-discrimination view was the dominant one, which was 79%. In other words, the majority of informants did not feel discriminated against by the provisions of marriage guardian in the KHI. Meanwhile, the discrimination view was 21% of the total informants. Second, by using dialectical patterns (externalization, objectivation, and internalization) in social construction theory, the basis for the construction those who thought they were not discriminated against by these provisions was because they were well-equipped with knowledge of Islamic law (marriage guardian) of Caturtunggal Village society, whose ontology was known and taught by the society, and then institutionalized to made it an objective social order with its own legitimacy. In other words, the reality existing in Caturtunggal Village society in practicing marriage guardianship which could only done by a man was guided by their a priori knowledge. Meanwhile, for the discrimination view, by using the above dialectical patterns, it can be said that although they had the desire to acts as marriage guardian, their basic construction of view was influenced by the conditions of the surrounding society
O Pedro ulterior: uma discussão axiológica a partir da tradução do apócrifo Atos de Pedro
Get PDFTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Estudos da Tradução, Florianópolis; Belo Horizonte, 2014.Esta tese tem por objetivo apresentar a tradução anotada e comentada do livro ?apócrifo? ? Atos de Pedro, obra que nos restou fragmentada nas línguas: copta, latim e grego. Para realizar tal intento procurou-se enfocar diferentes aspectos do conceito de tradução para textos sagrados, assim como as suas implicações exegéticas e tradutórias. Serviram de guia para esta tese os pressupostos teóricos de: Friedrich Daniel Ernst Schleiermacher, Eugene Albert Nida, Antoine Berman, Lawrence Venuti, e Ernst-August Gutt. A tradução é oferecida em dupla coluna: primeiramente, os textos fragmentários copto-greco-latino, comparados os fac-símiles dos manuscritos com as edições críticas de Léon Vouaux (1922), Carl Schmidt (1903); Donatien de Bruyne (1908), com respectivos aparatos críticos; na segunda coluna, a tradução em português acompanhada de comentários. Esta tese, também analisa questões como, e.g.: tradução e exegese bíblica, tradução de escritos apócrifos do ambiente cristão primitivo e literatura cristã na Antiguidade, e dentre estes, com proeminência ao valor do elemento ?gnoses? na leitura e, consequente tradução, desses textos advindos do cristianismo nascente. No labor tradutório deu-se preferência ao alcance do contexto histórico assentado à luz da crítica ? foi usado o método exegético histórico-crítico.Abstract : This thesis has as proposal: the annotated translation with commentary of the ?apocryphal? text ? Acts of Peter, a work left to us in fragmented language: Coptic, Latin and Greek. To accomplish this purpose we sought to focus on different aspects of the concepts of translation of sacred texts, as well as their exegetical and translational implications. This served as a guide for this thesis the theoretical assumptions of: Schleiermacher (F.), Nida (E.), Berman (A.), Venuti (A.) and Gutt (E-A.). The translation presented in this dual column: firstly, the fragmentary texts Coptic-Greek-Latin compared the facsimiles of manuscripts to the critical editions of Vouaux (L.; 1922), Schmidt (C.; 1903); Bruyne (D.; 1908), with their critical apparatus; in the second column, the Portuguese translation accompanied by comments. However, this thesis also examines issues such as, for example: biblical translation and exegesis, translation of apocryphal texts environment arising from the early Christian and Christian literature in Antiquity, and one of these, with prominence to the value of the element 'gnosis' in reading and, consequently, translation of these texts from early Christianity. In translational work gave preference to the scope of historical context along by the light of criticism - we used the historical-critical Exegetical method
Molecular Pathogenesis of Cholangiocarcinoma
Get PDFBACKGROUND: Cholangiocarcinomas are a heterogeneous group of malignancies arising from a number of cells of origin along the biliary tree. Although most cases in Western countries are sporadic, large population-based studies have identified a number of risk factors. This review summarises the evidence behind reported risk factors and current understanding of the molecular pathogenesis of cholangiocarcinoma, with a focus on inflammation and cholestasis as the driving forces in cholangiocarcinoma development. RISK FACTORS FOR CHOLANGIOCARCINOGENESIS: Cholestatic liver diseases (e.g. primary sclerosing cholangitis and fibropolycystic liver diseases), liver cirrhosis, and biliary stone disease all increase the risk of cholangiocarcinoma. Certain bacterial, viral or parasitic infections such as hepatitis B and C and liver flukes also increase cholangiocarcinoma risk. Other risk factors include inflammatory disorders (such as inflammatory bowel disease and chronic pancreatitis), toxins (e.g. alcohol and tobacco), metabolic conditions (diabetes, obesity and non-alcoholic fatty liver disease) and a number of genetic disorders. MOLECULAR PATHOGENESIS OF CHOLANGIOCARCINOMA: Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-ɑ, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. Accumulating bile acids from cholestasis lead to reduced pH, increased apoptosis and activation of ERK1/2, Akt and NF-κB pathways that encourage cell proliferation, migration and survival. Other mediators upregulated in cholangiocarcinoma include Transforming Growth Factor-β, Vascular Endothelial Growth Factor, Hepatocyte Growth Factor and several microRNAs. Increased expression of the cell surface receptor c-Met, the glucose transporter GLUT-1 and the sodium iodide symporter lead to tumour growth, angiogenesis and cell migration. Stromal changes are also observed, resulting in alterations to the extracellular matrix composition and recruitment of fibroblasts and macrophages that create a microenvironment promoting cell survival, invasion and metastasis. CONCLUSION: Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies for this disease
The DUBASCO SCORE: A scoring system for selecting patients for consideration of bariatric surgery
No full textThe National Institute for Health and Clinical Excellence guidance states that bariatric surgery should be available as a treatment option for people with a body mass index (BMI) of > 40.0 kg/m2and those with a BMI 35.0—40.0 kg/m2and other significant disease that may be improved with weight loss. Despite this, funding criteria are different between primary care trusts (PCTs) in England and some use a cut-off BMI of > 50.0 kg/m2. However, BMI may not be the best parameter to decide on who would benefit most from bariatric surgery. We have developed a scoring system, which takes into account the number and severity of four comorbidities in addition to BMI and age. Using this scoring system, 24% of patients with BMI > 50.0 kg/m2did not score high enough, whereas 63% of patients with BMI 35.0—50.0 kg/m2had significant comorbidities and would have potentially benefited more from undergoing bariatric surgery. The advantage of using a scoring system, is that the cut-off level for referral for surgery can be adjusted up or down depending on the level of resources available, but will always identify those patients who would benefit most from surgery.</jats:p
Do some patients receive unnecessary parenteral nutrition after pancreatoduodenectomy? Results from an international multicentre study
Get PDFBACKGROUNDS/AIMS: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. METHODS: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. RESULTS: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. CONCLUSIONS: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes
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