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Zeitschriftenartikel zum Thema "Protein LMs"
1
Garcia, Natalia, Ayman Al-Hendy, Edmund C. Baracat, Katia Candido Carvalho und Qiwei Yang. „Targeting Hedgehog Pathway and DNA Methyltransferases in Uterine Leiomyosarcoma Cells“. Cells 10, Nr. 1 (31.12.2020): 53. http://dx.doi.org/10.3390/cells10010053.
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Uterine leiomyosarcoma (LMS) is an aggressive tumor that presents a poor prognosis, high rates of recurrence, and metastasis. Because of its rarity, there is no information available concerning LMS molecular mechanisms of origin and development. Here, we assessed the expression profile of Hedgehog (HH) signaling pathway markers and the effects of their pharmacological inhibition on uterine smooth muscle (UTSM), leiomyoma, and LMS cells. Additionally, we also evaluated the effects of DNMTs inhibition on LMS cell behavior. Cell proliferation, migration and apoptosis rates were evaluated by MTT, Scratch, and Annexin V assays, respectively. RNA expression and protein levels were assessed by qRT-PCR and Western blot. We found that SMO and GLIs (1, 2, and 3) expression was upregulated in LMS cells, with increased nuclear levels of GLI proteins. Treatment with LDE225 (SMOi) and Gant61 (GLIi) resulted in a significant reduction in Glis protein levels in LMS (p < 0.05). Additionally, the expression of DNMT (1, 3a, and 3b), as well as GLI1 nuclear expression, was significantly decreased after treatment with HH inhibitor in LMS cells. Our results showed that blocking of SMO, GLI, and DNMTs is able to inhibit LMS proliferation, migration, and invasion. Importantly, the combination of those treatments exhibited a potentiated effect on LMS malignant features due to HH pathway deactivation.
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Plaat, Boudewijn E. C., Harry Hollema, Willemina M. Molenaar, Gerben H. Torn Broers, Justin Pijpe, Mirjam F. Mastik, Harald J. Hoekstra, Eva van den Berg, Rik J. Scheper und Winette T. A. van der Graaf. „Soft Tissue Leiomyosarcomas and Malignant Gastrointestinal Stromal Tumors: Differences in Clinical Outcome and Expression of Multidrug Resistance Proteins“. Journal of Clinical Oncology 18, Nr. 18 (18.09.2000): 3211–20. http://dx.doi.org/10.1200/jco.2000.18.18.3211.
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PURPOSE: Several studies have reported clinical behavior and chemotherapy resistance in leiomyosarcomas, but these studies did not differentiate between soft tissue leiomyosarcomas (LMS) and malignant gastrointestinal stromal tumors (GIST). Multidrug resistance (MDR) has been associated with the expression of P-glycoprotein (P-gp), multidrug resistance protein (MRP1), and lung resistance protein (LRP). The aim of the present study was to compare LMS and GIST with respect to clinical outcome and MDR parameters. PATIENTS AND METHODS: Clinical outcome was evaluated in 29 patients with a primary deep-seated LMS and 26 patients with a primary malignant GIST. Paraffin-embedded material, available for 26 patients with LMS and 25 with GIST, was used for immunohistochemical detection of P-gp, MRP1, LRP, and c-kit. RESULTS: Mean overall survival (OS) was 72 months for LMS patients and 31 months for GIST patients (P < .05). Metastases occurred in 16 (59%) of 27 assessable LMS patients and in 10 (56%) of 18 assessable GIST patients. LMS predominantly metastasized to the lungs (14 of 16 patients), whereas GIST tended to spread to the liver (five of 10 patients) and the abdominal cavity (three of 10 patients; P < .001). P-gp and MRP1 expression was more pronounced in GIST than in LMS (P < .05): the mean percentage of P-gp expressing cells was 13.4% in patients with LMS and 38.4% in patients with GIST, and the mean percentage MRP1 expressing cells was 13.3% in patients with LMS and 35.4% in patients with GIST. LRP expression did not differ between LMS and GIST. c-kit was expressed in 5% of the LMS patients and in 68% of the GIST patients. CONCLUSION: LMS patients have a better survival than GIST patients, and the metastatic pattern is different. Expression of MDR proteins in LMS is less pronounced than in GIST.
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Sparić, Radmila, Mladen Andjić, Ivana Babović, Lazar Nejković, Milena Mitrović, Jelena Štulić, Miljan Pupovac und Andrea Tinelli. „Molecular Insights in Uterine Leiomyosarcoma: A Systematic Review“. International Journal of Molecular Sciences 23, Nr. 17 (27.08.2022): 9728. http://dx.doi.org/10.3390/ijms23179728.
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Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, in order to distinguish the biological and molecular origins. The authors performed a Medline and PubMed search for the years 1990–2022 using a combination of keywords on the topics to highlight the many genes and proteins involved in the pathogenesis of LMS. The mutation of these genes, in addition to the altered expression and functions of their enzymes, are potentially biomarkers of uterine LMS. Thus, the use of this molecular and protein information could favor differential diagnosis and personalized therapy based on the molecular characteristics of LMS tissue, leading to timely diagnoses and potential better outcomes for patients.
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Ceausu, Amalia Raluca, Alexandru Ciolofan, Alexandru Blidisel, Andrei Alexandru Cosma, Pusa Nela Gaje und Octavian Cretu. „Chloride Intracellular Channel Protein 1 Expression and Angiogenic Profile of Liver Metastasis of Digestive Origin“. Current Issues in Molecular Biology 45, Nr. 2 (06.02.2023): 1396–406. http://dx.doi.org/10.3390/cimb45020091.
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Chloride intracellular channel 1 (CLIC1) is involved in cell migration and metastasis. The histological growth patterns of liver metastasis are as follows: desmoplastic (d-HGP), replacement (r-HGP), pushing (p-HGP), and mixed. The aim of this study was to evaluate the relation between HGP, angiogenesis, and CLIC1 expression. Materials and Methods: A total of 40 cases of primary tumors and their LM: d-HGP (12 cases), r-HGP (13 cases), and p-HGP (15 cases), were evaluated through simple and double immunostaining. CLIC1 assessment was conducted as follows: scores of 0 (less than 10% of positive cells), 1 (10–30%), 2 (30–50%), or 3 (more than 50%) were assigned. Heterogeneous CLIC1 expression was found. CLIC1 in primary tumors correlated with grade G for all cases of LM with a p-HGP (p = 0.004). The CLIC1 score for LMs with an r-HGP correlated with grade G of the corresponding primary tumor (p = 0.027). CLIC1 and CD34+/Ki67+ vessels (p = 0.006) correlated in primary tumors. CLIC1 in primary tumors correlated with CD34+/Ki67+ vessels of LMs with a d HGP (p = 0.024). Conclusions: The CLIC1 score may have prognostic value, mainly for LMs with a p-HGP and r-HGP, and therapeutic value for LMs with a d-HGP.
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Safonova, L. A., M. M. Bobrova, O. I. Agapova, A. Yu Arkhipova, A. V. Goncharenko und I. I. Agapov. „FIBROIN SILK BASED FILMS FOR RAT’S FULL-THICKNESS SKIN WOUND REGENERATION“. Russian Journal of Transplantology and Artificial Organs 18, Nr. 3 (17.11.2016): 74–84. http://dx.doi.org/10.15825/1995-1191-2016-3-74-84.
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Aimof this study is to research an effect of silk fi broin fi lms fabricated by casting method upon Wistar rat’s full-thickness skin wound regeneration.Materials and methods.4 different kinds of fi lms with protein concentration equal to 20 mg/ml were fabricated: fi lms from silk fi broin aqueous solution, fi lms from silk fi broin formic acid solution, fi lms from silk fi broin aqueous solution containing 30% collagen by weight, fi lms from silk fi broin formic acid solution containing 30% collagen by weight. All kinds of fi lms were fabricated by casting method on polished Tefl on surface. Scanning electron microscopy was applied to research fi lms’ surface structure. Cytotoxicity test of the fi lms was realized on mouse 3T3 fi broblasts model by MTT assay. Manufactured fi lms were utilized to regenerate full-thickness skin wounds in Wistar rats.Results.It was shown that fi lms’ surface was characterized by micro- and nanorelief in the form of roughness. The proliferative activity of mouse 3T3 fi broblasts increased during 7 days of cytotoxicity test. Fabricated fi lms enlarge the regeneration rate of full-thickness Wistar rat skin wounds an average of 25%. Histological analysis indicated structural skin restoration without any infl ammatory tissue.Conclusion.All fabricated fi lms are non-cytotoxic and characterized by appropriate structure for the adhesion and proliferation of fi broblasts. The application of fi lms for full-thickness skin wound regeneration increases its restoration rate which is confi rmed by histological examination.
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Azzimato, Valerio, Jennifer Jager, Ping Chen, Cecilia Morgantini, Laura Levi, Emelie Barreby, André Sulen et al. „Liver macrophages inhibit the endogenous antioxidant response in obesity-associated insulin resistance“. Science Translational Medicine 12, Nr. 532 (26.02.2020): eaaw9709. http://dx.doi.org/10.1126/scitranslmed.aaw9709.
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Obesity and insulin resistance are risk factors for nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. Because no approved medication nor an accurate and noninvasive diagnosis is currently available for NAFLD, there is a clear need to better understand the link between obesity and NAFLD. Lipid accumulation during obesity is known to be associated with oxidative stress and inflammatory activation of liver macrophages (LMs). However, we show that although LMs do not become proinflammatory during obesity, they display signs of oxidative stress. In livers of both humans and mice, antioxidant nuclear factor erythroid 2–related factor 2 (NRF2) was down-regulated with obesity and insulin resistance, yielding an impaired response to lipid accumulation. At the molecular level, a microRNA-targeting NRF2 protein, miR-144, was elevated in the livers of obese insulin-resistant humans and mice, and specific silencing of miR-144 in murine and human LMs was sufficient to restore NRF2 protein expression and the antioxidant response. These results highlight the pathological role of LMs and their therapeutic potential to restore the impaired endogenous antioxidant response in obesity-associated NAFLD.
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Böhm, Michael J., Ralf Marienfeld, Daniela Jäger, Kevin Mellert, Adrian von Witzleben, Silke Brüderlein, Mathias Wittau et al. „Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib“. Sarcoma 2019 (21.01.2019): 1–10. http://dx.doi.org/10.1155/2019/3914232.
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Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G0/G1-phase arrest with decreased S/G2fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare thesein vitrofindings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (n=99patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients.
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De Gregorio, Amelie, Inga Bekes, Nikolaus de Gregorio, Sophia Andres, Diego Hoffmeister, Tatjana Swerev, Thomas W. P. Friedl, Wolfgang Janni und Florian Ebner. „Comparison of preoperative serum VEGF in leiomyosarcoma and uterus myomatosus patients: A proof of concept study.“ Journal of Clinical Oncology 37, Nr. 15_suppl (20.05.2019): e17117-e17117. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e17117.
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e17117 Background: The preoperative differentiation of a uterine fibroid from a sarcoma is still a pending clinical problem. Currently with the suspicion of a sarcoma (LMS) the more invasive open surgical approach is recommended to minimise the risk of LMS fragmentation and distribution. In a minority of cases, a malignancy is indicated by clinical suspicion, pre-surgical imaging or routine serum blood samples (SBS). Our hypothesis postulates higher VEGF levels in LMS compared to fibroid patients in the pre-surgical SBS. To assess this hypothesis, SBS were taken from patients with the clinical suspicion of LMS after informed consent and analysed after histology confirmed the diagnosis. Methods: Case series of patients with suspected LMS over a 4year time period. Analysis was performed via SBS collected from LMS- and fibroid patients before surgery. Serum VEGF protein was measured by ELISA. The final tumor histology was obtained from the report of the institutional pathologist. VEGF-serum levels were then compared between fibroid and LMS patients using the non-parametric Mann-Whitney U test. Results: 25 patient SBS were collected prior to surgery. In 9 cases the histopathology confirmed a LMS, with heterogeneous pTNM classifications. On average, VEGF serum levels were higher in the LMS patients as compared to the fibroid patients (628,96 pg/ml vs 351,91 pg/ml; further statistics see Table 1); however, the difference was not statistically significant (Mann-Whitney-U Test, p = 0.141). Conclusions: This proof-of-concept study with a small sample size of pre-surgical SBS indicates that VEGF serum levels may be increased in patients with histologically confirmed LMS; however, larger sample sizes are needed to validate our findings. If additional studies confirm a pronounced increase in pre-surgical serum VEGF levels in LMS patients, serum VEGF levels might routinely be used to assess the risk for a LMS in patients presenting with clinical uterine fibroids. [Table: see text]
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Terés, Raul, Paula Cerdà, Ana Sebio, Pablo Gallardo, Aida Bujosa, Maria Borrell, Berta Martin et al. „Evaluation of dystrophin expression by immunohistochemistry as a prognostic factor in leiomyosarcomas (LMS).“ Journal of Clinical Oncology 39, Nr. 15_suppl (20.05.2021): e23525-e23525. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e23525.
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e23525 Background: Leiomyosarcomas (LMS) are soft tissue sarcomas that derive from smooth muscle cells and can arise anywhere in the body (most frequently in extremities, uterus or retroperitoneum). The clinical prognostic factors are well established but molecular factors influencing prognostic are unknown. The DMD gene, which codifies for the dystrophin protein, has been proposed as tumour suppressor gene in LMS. The aim of our study is to evaluate dystrophin expression in LMS and its relation with the patient prognosis. Methods: A total of 103 patients (pts) with LMS were analysed. Clinical and pathological data were collected retrospectively from patients’ electronic board system. Dystrophin expression was analysed by immunohistochemistry (IHC) in paraffin embedded tissue LMS samples using the Novocastra NCL-DYS2 (Leica Biosystems). Semiquantitative assessment of the staining was classified from score 0 to 3 (0 = no dystrophin expression, 1 = low expression, 2 = moderate expression, 3 = high expression). Results: Of all 103 pts, 70 (68%) had localized disease and the majority of tumours were larger than 5 cm (75%). The most frequent locations of primary LMS were extremities (n = 31; 30.1%), uterus (n = 23; 23.2%) and retroperitoneum (n = 21; 20.4%). Most LMS were high grade (G): 7 pts G1 (6.8%), 35 pts G2 (34%) 2 and 53 pts G3 (51.5%). 50 of all grade LMS (48.6%) had loss of dystrophin expression (score 0), 17 (16.5%) had score 1, 23 (22.3%) score 2 and 10 (9.7%) score 3. Loss/low dystrophin expression measured as score 0 or 1, was more frequent in grade 3 LMS compared to grade 2 or grade 1 (77.4% vs. 57.1% vs. 16.7%; p = 0.005). There were no differences in dystrophin loss between localized or metastatic disease at diagnosis (64.2% vs. 72.2%; p > 0.05). In our series, loss or reduced dystrophin expression did not correlate with the risk of relapse in localized patients or overall survival in metastatic patients. Conclusions: Loss of dystrophin expression is a common event in LMS. Loss/low dystrophin expression is more frequent in grade 3 LMS compared to grade 2 and grade 1 LMS. Loss of dystrophin expression did not correlate with risk of relapse or overall survival in our series. Additional genetic evaluations to study DMD in LMS are underway.
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Gonzalez-Molina, Jordi, Paula Hahn, Raul Maia Falcão, Georgia Kokaraki, Jorge Estefano de Souza, Tirzah Braz Petta Lajus, Kaisa Lehti und Joseph W. Carlson. „Abstract 6096: The microarchitecture and fibrillar collagen expression of leiomyosarcoma are associated with malignancy“. Cancer Research 82, Nr. 12_Supplement (15.06.2022): 6096. http://dx.doi.org/10.1158/1538-7445.am2022-6096.
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Abstract The expression, abundance, and microarchitecture of fibrillar collagens are associated with tumor development and aggressiveness in various carcinomas. However, the impact of fibrillar collagens on mesenchymal tumors is less understood. While uterine leiomyomas, also known as fibroids, are characterized by high fibrillar collagen deposition and depend on ECM signaling for cell proliferation, the impact of fibrillar collagens on malignant uterine leiomyosarcomas has not been explored. Thus, identifying malignancy and aggressiveness-associated features of the fibrillar collagen-leiomyosarcoma crosstalk may provide novel biomarkers and therapeutic targets for these aggressive tumors. We used publicly available RNAseq data and performed RNAseq and picrosirius red analysis of fiber microarchitecture in a cohort of normal myometrium (MM; n =68 ), leiomyoma (LM; n = 66), and leiomyosarcoma (LMS; n = 67) tissues. Furthermore, we cultured patient-derived primary cells (4 MM, 3 LM, and 4 LMS) on collagen I-functionalized polyacrylamide gels at stiffness ranging from 0.5 to 115 kPa, covering the physiological and pathological stiffness, to investigate distinct behaviors between cell types, including proliferation, migration, and activity of the ECM stiffness molecular rheostat YAP/TAZ. At the protein level, analysis of fibrillar collagen microarchitecture revealed that LMS tumors present reduced fibrillar collagen density and hyphal growth units and enhanced fiber endpoints compared to both MM and LM. At the gene expression level, however, LMS tumors did not show reduced fibrillar collagen expression, instead they exhibited enhanced matrix metalloproteinase expression, particularly of MMP14. Furthermore, COL11A1 was specifically upregulated in LMS tumors and its expression was associated with poor prognosis. Finally, in vitro response of MM, LM, and LMS cells to collagen I at defined stiffness showed that LMS cell migration, proliferation, and subcellular localization of YAP/TAZ are less sensitive to substrate stiffness than in MM and LM cells, although the response varied between distinct donors. In conclusion, we show that LMS tumors typically present low fibrillar collagen protein expression likely due to enhanced degradation. In addition, collagen I adhesion and stiffness have a lower impact on malignant LMS cells than on MM and LM, which may explain their ability to grow in low-collagen microenvironments. Furthermore, this study shows that COL11A1 is a potential biomarker with prognostic value in leiomyosarcoma. Citation Format: Jordi Gonzalez-Molina, Paula Hahn, Raul Maia Falcão, Georgia Kokaraki, Jorge Estefano de Souza, Tirzah Braz Petta Lajus, Kaisa Lehti, Joseph W. Carlson. The microarchitecture and fibrillar collagen expression of leiomyosarcoma are associated with malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6096.
Dissertationen zum Thema "Protein LMs"
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Batzenschlager, Morgane. „Diversité fonctionnelle des protéines GIPs/MZT1 (Gamma-tubulin complex protein 3- Interacting Proteins/Mitotic spindle organiZing proTein1) à l'interface nucléo-cytoplasmique chez Arabidopsis thaliana“. Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ030.
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Chez Arabidopsis, l’enveloppe nucléaire constitue un site de nucléation des microtubules à partir des complexes à gamma-tubuline. Conservées des plantes à l'Homme, les protéines GIPs/MZT1 ont été initialement découvertes comme partenaires d’AtGCP3. J’ai consacré ma thèse à la caractérisation moléculaire et fonctionnelle des AtGIPs et de leurs partenaires à l’interface nucléocytoplasmique. Mes résultats confirment l’appartenance des GIPs aux complexes à gamma-tubuline, et démontrent leur association entre elles et avec TSA1 (TonSoKu [TSK]-Associating protein 1) et l'histone centromérique CenH3. Les interactions génétiques entre les gènes GIPs, TSA1 et TSK révèlent des anomalies sévères à l'échelle de l'organisme, des cellules et des noyaux. Les mutants gip1gip2 démontrent une diminution de la cohésion des régions centromériques. L’ensemble de nos résultats suggère un rôle des AtGIPs dans un continuum nucléocytoplasmique inédit, la régulation de l'architecture nucléaire et du centromèreIn Arabidopsis, the nuclear envelope is a nucleation center where gamma-tubulin complexes initiate the polymerization of microtubules. Conserved from plants to humans, GIPs/MZT1 proteins were initially discovered as AtGCP3 interacting partners. Our investigations were devoted to the molecular and functional characterization of AtGIPs and their associated proteins at the nucleocytoplasmic interface. We confirmed that AtGIPs are integral components of gamma-tubulin complexes, and showed that they interact with each other, TSA1 (TonSoKu [TSK]-Associating protein 1) and centromeric histone H3 (CenH3). Genetic interactions between GIPs, TSA1 and TSK reveal severe defects at the organism, cellular and nuclear scales. gip1gip2 mutants exhibit a decrease of centromeric and pericentromeric cohesion. Altogether, this is the first evidence for the role of a gamma–tubulin complex component in the structural maintenance of centromeric regions, and in defining nuclear morphology and architecture
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Ghanim, Mustafa. „Les aspects génétiques des démences frontotemporales“. Paris 6, 2010. http://www.theses.fr/2010PA066039.
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Guillaud, Laurent. „Étude de la localisation et du rôle fonctionnel des protéines STOP dans les cellules neuronales“. Université Joseph Fourier (Grenoble ; 1971-2015), 1998. http://www.theses.fr/1998GRE10160.
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La differenciation neuronale et les principales fonctions neuronales necessitent une forte stabilisation du cytosquelette microtubulaire. Les neurones contiennent une large proportion de microtubules qui resistent au froid et aux drogues depolymerisantes, et qui de plus possedent une dynamique fortement ralentie. L'origine de cette stabilisation n'est toujours pas clairement definie. Au cours de ce travail, nous avons etudie le role des proteines stop, une proteine regulee par la calmoduline, prealablement isolee a partir d'une population de microtubules stables au froid presente dans des cytosols de cerveaux de rats. Nous avons montre que dans les cellules neuronales, l'expression des proteines stop et des isoformes de proteines stop augmente au cours de la differenciation. Ces proteines sont associees a une large proportion de microtubules neuronaux et sont concentrees sur les microtubules stables au froid, resistants aux drogues et a longue duree de vie. L'inhibition des proteines stop abolit completement la stabilite au froid et aux drogues des microtubules presents dans les neurites preformes et empeche la formation de nouvelles extensions. Il apparait clairement que les proteines stop sont les principaux responsables du haut degre de stabilisation des microtubules observe dans les cellules neuronales et sont apparemment necessaires a la formation normale des extensions axodendritiques.
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Durand, Jean-Pierre. „Contribution a l'etude du groupe des proteines nucleaires de faible mobilite electrophoretique (lmg)“. Nantes, 1988. http://www.theses.fr/1988NANT2010.
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Obiol, Pardo Cristian. „Disrupting the protein-protein recognition in cancer pathways by molecular modeling“. Doctoral thesis, Universitat de Barcelona, 2008. http://hdl.handle.net/10803/2759.
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Cancer is the second disease leading cause of death in industrialized countries. Although early detection and more efficient drugs are responsible of the reduction of mortality, several cancers still present difficult treatments and low survival rates. Conventional drugs only exhibit moderate therapeutic index between cancer and normal tissues but recent advances are focused to improve lesstoxic treatments. Hence, new drugs must target specific signaling pathways involved in cell growth and proliferation. Concerning this aim, two mechanism involved in cancer disease, named apoptosis (or programmed cell death) and pentose phosphate pathway, have been selected in this work to search new inhibitors to target crucial proteins of both cell routes.Overexpression of antiapoptotic genes has been correlated with tumor growth and resistance to
chemotherapy, thus many efforts have been done to block the activity of XIAP and Survivin, central proteins acting in apoptosis and studied in the present work. Moreover, the two most active proteins detected in both the oxidative and nonoxidative branches of the pentose phosphate pathway, Glucose-6-Phosphate Dehydrogenase (G6PDH) and Transketolase (TKT), have been also selected in this thesis.
Molecular Modeling methods, covering topics in protein and peptide recognition, molecular dynamics, pharmacophore generation, database searching, docking and scoring in virtual screening and binding free energy prediction, have been applied with success to discover new active molecules inhibitors of XIAP, Survivin, G6PDH and TKT proteins.
TÍTULO: "Ruptura del reconocimiento proteína-proteína en rutas tumorales mediante modelización
molecular".
TEXTO:
El cáncer es el segunda causa de muerte por enfermedad en los paises industrializados. A pesar de la existencia de métodos eficaces de detección precoz y tratamientos cada vez más efectivos responsables de la reducción de mortalidad, algunos tipos de tumores presentan todavía tratamientos difíciles y bajos índices de supervivencia. Los fármacos convencionales sólo exhiben un índice terapéutico moderado, entre células sanas y tumorales, por ello los avances recientes se centran en encontrar tratamientos menos tóxicos para esta enfermedad. Así pues, los fármacos del futuro deberán incidir en rutas biológicas específicas, involucrando el crecimiento celular y la
proliferación descontrolada. Siguiendo este planteamiento, en este trabajo se han seleccionado dos mecanismos biológicos involucrados en el cáncer, llamados apoptosis (o muerte celular programada) y ruta de las pentosas fosfato, con el objetivo de encontrar nuevos inhibidores de las proteínas más sensibles de ambas rutas.
La sobreexpresión de genes antiapoptóticos se ha correlacionado con el crecimiento tumoral y la
resistencia a los tratamientos habituales. Así, se está trabajando en entender el funcionamiento de dos proteínas importantes de esta ruta, el XIAP y el Survivin, las cuales se han seleccionado en este trabajo, debido a que todavía no existen fármacos en el mercado que actúen sobre estas dos proteínas y debido a que su interés terapéutico se ha demostrado claramente.
Por otro lado, en este trabajo también se han estudiado las dos proteínas más activas detectadas en la rama oxidativa y no oxidativa de la ruta de las pentosas fosfato, la Glucosa-6-Fosfato Deshidrogenasa y la Transketolasa.
El objetivo principal ha consistido en aplicar métodos de la Modelización Molecular, que cubren
tópicos recientes, como el reconocimiento de péptidos y proteínas, la búsqueda en bases de datos, el anclaje y evaluación del cribado virtual de compuestos y la predicción de energías libres de unión, para encontrar nuevos inhibidores de las proteínas XIAP, Survivin, Glucosa-6-Fosfato Deshidrogenasa y Transketolasa.
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Masoud, Kinda. „Caractérisation moléculaire et fonctionnelle des protéines GIPs (Gamma-tubulin complex protein 3-Interacting Proteins) d'Arabidopsis thaliana“. Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ011/document.
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Les microtubules constituent l’un des réseaux du cytosquelette des cellules eucaryotes. Ils jouent un rôle central dans de multiples fonctions comme la division cellulaire, les trafics intracellulaires et la morphogenèse cellulaire. Chez les plantes supérieures, les microtubules (MTs) forment différents réseaux qui s'assemblent au cours du cycle cellulaire. Cette spécificité nécessite un recrutement régulé des complexes de nucléation des MTs à l’enveloppe nucléaire, au cortex et au niveau de MTs préexistants, qui sont des sites de nucléation caractérisés. L'équipe d’A.C. Schmit (IBMP, CNRS, Strasbourg), dans laquelle j'ai effectué mon travail de thèse, se focalise sur la caractérisation des complexes de nucléation des MTs (γ-TuRCs) et la régulation de l'assemblage du fuseau mitotique chez les plantes. Deux nouvelles protéines associées au γ-TuRC ont été mises en évidence par une interaction directe avec l'un de ses composants AtGCP3. Ces protéines, AtGIP1 et AtGIP2 (GCP3 Interacting Protein 1 et 2), sont très conservées au cours de l'évolution, mais leur fonction reste totalement inconnue. Mon travail a été consacré à la caractérisation de cette nouvelle classe de protéines dans le but de comprendre leur rôle. Nos résultats suggèrent que l'association des protéines GIPs aux γ-TuRCs participe à la régulation de leur activité et à la formation d'un fuseau mitotique robuste. Le profil de localisation des protéines GIPs au cours du cycle cellulaire et les phénotypes observés chez les mutants "perte de fonction" gip1gip2 indiquent que ces protéines interviennent dans le recrutement des γ-TuRCs, la nucléation des MTs, l’assemblage du fuseau mitotique, le déroulement du cycle cellulaire et l'organisation des méristèmes. L’étude des mécanismes de régulation de cette famille de protéines a été initiée. Nos résultats ont permis d’identifier GIP1comme un substrat de la kinase Aurora1 in vitro. Les résultats d’expérience de complémentation avec des phosphomutants GIP1 indiquent que la/les fonction(s) des GIPs pourrai(en)t être dépendante(s) de la phosphorylation par la kinase Aurora1, qui est un régulateur avéré du cycle cellulaire. L’ensemble de mes travaux a ainsi contribué à la caractérisation de nouveaux acteurs du cytosquelette microtubulaire. Une meilleure connaissance de leur réseau d'interaction (interactome) ainsi que l’étude de leur homologue humain pourraient ouvrir de nouvelles perspectives de recherche dans le contrôle de la division cellulaire et la lutte contre le cancerMicrotubules (MTs) constitute one of the cytoskeletal networks in eukaryotic cells. They are involved in various processes such as cell division, intracellular transport and cell morphogenesis. In higher plants, MTs can be organized into dynamic structures, which undergo continual assembly and disassembly during the cell cycle. This specificity requires the recruitment of the nucleation complexes of the MTs to the nuclear envelope, to the cortex and to pre-existing MTs. The work of A. C. Schmit’s team (IBMP, CNRS, Strasbourg), in which I did my thesis, focuses on the characterization of MT nucleation complexes (γ-TuRCs) and the regulation of mitotic spindle assembly in plants. We have identified small proteins interacting with Gamma-tubulin Complex Protein 3 (GCP) and named GIP1 and GIP2 (GCP3-Interacting Proteins). The aim of these studies was to characterize this new class of proteins in order to understand their role. It shows that GIPs are conserved among eukaryotes and suggests that their association with the γ-TuRC participates in the regulation of their activity and the formation of a robust mitotic spindle. The localization of GIPs during the cell cycle and the phenotypes observed in T-DNA insertional gip1gip2 double mutants indicatethat GIPs are required for the recruitment of γ-TuRCs, MT nucleation, spindle assembly, cell cycle regulation and stem cell maintenance. Likewise, in vitro assays showed that GIP1 is a novel substrate for Aurora kinase1, which is a well known cell cycle regulator. The results of complementation experiments with GIP1 phosphomutants indicate that the phosphorylation of GIPs may be required for their function(s). Altogether, our results have contributed to the characterization of a new class of proteins involved in MT nucleation/organization and functions. The study of the interaction network (interactome) of GIPs and oftheir homologues could open new ways of research in the control of cell division and in the fight against cancer
7
Kwan, Ann Hau Yu. „Protein Design Based on a PHD Scaffold“. Thesis, The University of Sydney, 2004. http://hdl.handle.net/2123/564.
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The plant homeodomain (PHD) is a protein domain of ~45�100 residues characterised by a Cys4-His-Cys3 zinc-binding motif. When we commenced our study of the PHD in 2000, it was clear that the domain was commonly found in proteins involved in transcription. Sequence alignments indicate that while the cysteines, histidine and a few other key residues are strictly conserved, the rest of the domain varies greatly in terms of both amino acid composition and length. However, no structural information was available on the PHD and little was known about its function. We were therefore interested in determining the structure of a PHD in the hope that this might shed some light on its function and molecular mechanism of action. Our work began with the structure determination of a representative PHD, Mi2b-P2, and this work is presented in Chapter 3. Through comparison of this structure with the two other PHD structures that were determined during the course of our work, it became clear that PHDs adopt a well-defined globular fold with a superimposable core region. In addition, PHDs contain two loop regions (termed L1 and L3) that display increased flexibility and overlay less well between the three PHD structures available. These L1 and L3 regions correspond to variable regions identified earlier in PHD sequence alignments, indicating that L1 and L3 are probably not crucial for the PHD fold, but are instead likely to be responsible for imparting function(s) to the PHD. Indeed, numerous recent functional studies of PHDs from different proteins have since demonstrated their ability in binding a range of other proteins. In order to ascertain whether or not L1 and L3 were in fact dispensable for folding, we made extensive mutations (including both insertions and substitutions) in the loop regions of Mi2b-P2 and showed that the structure was maintained. We then went on to illustrate that a new function could be imparted to Mi2b-P2 by inserting a five-residue CtBP-binding motif into the L1 region and showed this chimera could fold and bind CtBP. Having established that the PHD could adopt a new binding function, we next sought to use combinatorial methods to introduce other novel functions into the PHD scaffold. Phage display was selected for this purpose, because it is a well-established technique and has been used successfully to engineer zinc-binding domains by other researchers. However, in order to establish this technique in our laboratory, we first chose a control system in which two partner proteins were already known to interact in vitro. We chose the protein complex formed between the transcriptional regulators LMO2 and ldb1 as a test case. We have examined this interaction in detail in our laboratory, and determined its three-dimensional structure. Furthermore, inappropriate formation of this complex is implicated in the onset of T-cell acute lymphoblastic leukemia. We therefore sought to use phage display to engineer ldb1 mimics that could potentially compete against wild-type ldb1 for LMO2, and this work is described in Chapter 4. Using a phage library containing ~3 x 10 7 variants of the LMO2-binding region of ldb1, we isolated mutants that were able to interact with LMO2 with higher affinity and specificity than wild-type ldb1. These ldb1 mutants represent a first step towards finding potential therapeutics for treating LMO-associated diseases. Having established phage display in our laboratory, we went on to search for PHD mutants that could bind selected target proteins. This work is described in Chapter 5. We created three PHD libraries with eight randomized residues in each of L1, L3 or in both loops of the PHD. These PHD libraries were then screened against four target proteins. After four rounds of selection, we were able to isolate a PHD mutant (dubbed L13-FH6) that could bind our test protein Fli-ets. This result demonstrates that a novel function can be imparted to the PHD using combinatorial methods and opens the way for further work in applying the PHD scaffold to other protein design work. In summary, the work detailed in Chapters 3 and 5 demonstrates that the PHD possesses many of the properties that are desirable for a protein scaffold for molecular recognition, including small size, stability, and a well-characterised structure. Moreover, the PHD motif possesses two loops (L1 and L3) of substantial size that can be remodeled for target binding. This may lead to an enhancement of binding affinities and specificities over other small scaffolds that have only one variable loop. In light of the fact that PHDs are mainly found in nuclear proteins, it is reasonable to expect that engineered PHDs could be expressed and function in an intracellular environment, unlike many other scaffolds that can only function in an oxidizing environment. Therefore, our results together with other currently available genomic and functional information indicate PHD is an excellent candidate for a scaffold that could be used to modify cellular processes. Appendices 1 and 2 describe completed bodies of work on unrelated projects that I have carried out during the course of my PhD candidature. The first comprises the invention and application of DNA sequences that contain all N-base sequences in the minimum possible length. This work is presented as a reprint of our recently published paper in Nucleic Acids Research. The second Appendix describes our structural analysis of an antifreeze protein from the shorthorn sculpin, a fish that lives in the Arctic and Antarctic oceans. This work is presented as a manuscript that is currently under review at the Journal of the American Chemical Society.
8
Kwan, Ann Hau Yu. „Protein Design Based on a PHD Scaffold“. University of Sydney. Molecular and Microbial Biosciences, 2004. http://hdl.handle.net/2123/564.
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The plant homeodomain (PHD) is a protein domain of ~45�100 residues characterised by a Cys4-His-Cys3 zinc-binding motif. When we commenced our study of the PHD in 2000, it was clear that the domain was commonly found in proteins involved in transcription. Sequence alignments indicate that while the cysteines, histidine and a few other key residues are strictly conserved, the rest of the domain varies greatly in terms of both amino acid composition and length. However, no structural information was available on the PHD and little was known about its function. We were therefore interested in determining the structure of a PHD in the hope that this might shed some light on its function and molecular mechanism of action. Our work began with the structure determination of a representative PHD, Mi2b-P2, and this work is presented in Chapter 3. Through comparison of this structure with the two other PHD structures that were determined during the course of our work, it became clear that PHDs adopt a well-defined globular fold with a superimposable core region. In addition, PHDs contain two loop regions (termed L1 and L3) that display increased flexibility and overlay less well between the three PHD structures available. These L1 and L3 regions correspond to variable regions identified earlier in PHD sequence alignments, indicating that L1 and L3 are probably not crucial for the PHD fold, but are instead likely to be responsible for imparting function(s) to the PHD. Indeed, numerous recent functional studies of PHDs from different proteins have since demonstrated their ability in binding a range of other proteins. In order to ascertain whether or not L1 and L3 were in fact dispensable for folding, we made extensive mutations (including both insertions and substitutions) in the loop regions of Mi2b-P2 and showed that the structure was maintained. We then went on to illustrate that a new function could be imparted to Mi2b-P2 by inserting a five-residue CtBP-binding motif into the L1 region and showed this chimera could fold and bind CtBP. Having established that the PHD could adopt a new binding function, we next sought to use combinatorial methods to introduce other novel functions into the PHD scaffold. Phage display was selected for this purpose, because it is a well-established technique and has been used successfully to engineer zinc-binding domains by other researchers. However, in order to establish this technique in our laboratory, we first chose a control system in which two partner proteins were already known to interact in vitro. We chose the protein complex formed between the transcriptional regulators LMO2 and ldb1 as a test case. We have examined this interaction in detail in our laboratory, and determined its three-dimensional structure. Furthermore, inappropriate formation of this complex is implicated in the onset of T-cell acute lymphoblastic leukemia. We therefore sought to use phage display to engineer ldb1 mimics that could potentially compete against wild-type ldb1 for LMO2, and this work is described in Chapter 4. Using a phage library containing ~3 x 10 7 variants of the LMO2-binding region of ldb1, we isolated mutants that were able to interact with LMO2 with higher affinity and specificity than wild-type ldb1. These ldb1 mutants represent a first step towards finding potential therapeutics for treating LMO-associated diseases. Having established phage display in our laboratory, we went on to search for PHD mutants that could bind selected target proteins. This work is described in Chapter 5. We created three PHD libraries with eight randomized residues in each of L1, L3 or in both loops of the PHD. These PHD libraries were then screened against four target proteins. After four rounds of selection, we were able to isolate a PHD mutant (dubbed L13-FH6) that could bind our test protein Fli-ets. This result demonstrates that a novel function can be imparted to the PHD using combinatorial methods and opens the way for further work in applying the PHD scaffold to other protein design work. In summary, the work detailed in Chapters 3 and 5 demonstrates that the PHD possesses many of the properties that are desirable for a protein scaffold for molecular recognition, including small size, stability, and a well-characterised structure. Moreover, the PHD motif possesses two loops (L1 and L3) of substantial size that can be remodeled for target binding. This may lead to an enhancement of binding affinities and specificities over other small scaffolds that have only one variable loop. In light of the fact that PHDs are mainly found in nuclear proteins, it is reasonable to expect that engineered PHDs could be expressed and function in an intracellular environment, unlike many other scaffolds that can only function in an oxidizing environment. Therefore, our results together with other currently available genomic and functional information indicate PHD is an excellent candidate for a scaffold that could be used to modify cellular processes. Appendices 1 and 2 describe completed bodies of work on unrelated projects that I have carried out during the course of my PhD candidature. The first comprises the invention and application of DNA sequences that contain all N-base sequences in the minimum possible length. This work is presented as a reprint of our recently published paper in Nucleic Acids Research. The second Appendix describes our structural analysis of an antifreeze protein from the shorthorn sculpin, a fish that lives in the Arctic and Antarctic oceans. This work is presented as a manuscript that is currently under review at the Journal of the American Chemical Society.
9
Moser, von Filseck Joachim. „Mécanismes du transport lipidique par les protéines ORP/Osh“. Thesis, Nice, 2014. http://www.theses.fr/2014NICE4138/document.
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Une distribution lipidique hétérogène est essentielle à l’identité et fonction des organelles, mais l’échange par trafic vésiculaire tend à annuler cette distribution. Il existe donc des mécanismes qui assurent l’homéostasie des lipides. Les protéines Osh (S. cerevisiae) et les OSBP-Related Proteins (ORP, H. sapiens), sont des transporteurs de lipides. Osh4 est capable d’échanger de l’ergostérol contre le phosphatidylinositol-4-phosphate (PI4P), présent sur l’appareil de Golgi. Utilisant des outils fluorescents mesurant avec une précision inégalée le transport de stérol et de PI4P, nous démontrons qu’Osh4 transporte du stérol contre son gradient de concentration en utilisant l’énergie d’un gradient de PI4P. Un couplage au métabolisme du PI4P permettrait à Osh4 d’alimenter le Golgi avec du stérol, ainsi créant le gradient de stérol entre ces organelles. La protéine OSBP participe, via sa capacité à connecter la membrane du RE à celle du trans-Golgi, à la création de jonctions entre ces organelles. Nous avons montré qu’OSBP, par échange stérol/PI4P, utilise le PI4P pour transférer du cholestérol au Golgi, mais également pour autoréguler sa capacité à former les jonctions. Osh6 lie la phosphatidylsérine, nous permettant d’étudier un nouveau mécanisme d’échange. Nous avons résolu la structure cristallographique d’un complexe Osh6/PI4P et avons pu observer l’échange de ces deux ligands par Osh6 entre deux membranes. Cette étude nous permet de suggérer que l’échange de PI4P avec divers lipides, via les protéines Osh/ORP, serait un mécanisme général permettant aux cellules de maintenir le gradient lipidique entre le RE et les membranes tardives de la voie sécrétoireAn uneven lipid distribution is essential for the function of eukaryotic organelles. However, exchange of material by vesicular trafficking has a tendency to perturb this distribution; mechanisms must though exist to ensure lipid homeostasis. Osh proteins (S. cerevisiae) and OSBP-Related Proteins (ORPs, H. sapiens), are lipid transfer proteins (LTPs). Osh4 is capable of exchanging ergosterol for phosphatidylinositol 4-phosphate (PI4P), found on the Golgi. Using novel fluorescent tools to measure with unprecedented precision the transport of sterol and PI4P, we find that Osh4 can transport sterol against its concentration gradient using the energy of a PI4P gradient. Coupled to phosphoinositide metabolism, this allows Osh4 to transport sterol to the trans-Golgi and create the sterol gradients observed between these organelles. OSBP participates in the creation of membrane contact sites (MCSs) via its capacity to connect ER membranes to those of the trans-Golgi. We have shown that it uses PI4P for transporting cholesterol from the ER to the trans-Golgi by sterol/PI4P counterexchange, hence also autoregulating its tethering activity. Finally, the identification of phosphatidylserine as a ligand for Osh6 allowed us to analyze the possible extrapolation of the PI4P counterexchange mechanism. We have solved the crystal structure of Osh6 in complex with PI4P and have been able to follow counterexchange of PI(4)P and PS in vitro. Concluding, our studies allow us to suggest a general mechanism for ORP/Osh-mediated counterexchange of PI4P for other lipids to maintain lipid gradients between the ER and late membranes of the secretory pathway
10
Cook, Neil James. „Le gmp cyclique et la phototransduction chez les vertebres“. Strasbourg 1, 1986. http://www.theses.fr/1986STR13147.
Der volle Inhalt der QuelleBücher zum Thema "Protein LMs"
1
Thomas, Pierre. Recherches biochimiques sur les protéiques de la levure. [Laval, Québec?: s.n.], 1997.
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2
Laborde, Christian. Danse avec les ours: OPA sur les Pyrénées. Paris: Editions R. Deforges, 1992.
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3
Domanick, Joe. To protect and to serve: The LAPD's century of war in the city of dreams. Los Angeles: Figueroa Press, 2003.
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4
To protect and to serve: The LAPD's century of war in the city of dreams. New York: Pocket Books, 1994.
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5
Dickmann, Nancy. La carne y las proteínas. Chicago, Ill: Heinemann Library, 2011.
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6
Nelson, Lim, Hrsg. To protect and to serve: Enhancing the efficiency of LAPD recruiting. Santa Monica, CA: RAND, 2009.
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7
Sébastien, Lernould, Hrsg. Les nouveaux militants. Paris: Petits matins, 2008.
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8
Tellería, Gabriel Loza. Adiós a las ideologías. La Paz: Plural Editores, 2008.
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10
Les recettes Dukan: Mon régime en 350 recettes. [Paris]: Flammarion, 2011.
Den vollen Inhalt der Quelle findenBuchteile zum Thema "Protein LMs"
1
Zhao, Hongyu, Baolin Wu und Ning Sun. „DNA-protein binding and gene expression patterns“. In Institute of Mathematical Statistics Lecture Notes - Monograph Series, 259–74. Beachwood, OH: Institute of Mathematical Statistics, 2003. http://dx.doi.org/10.1214/lnms/1215091147.
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Lapedes, Alan S., Bertrand Giraud, LonChang Liu und Gary D. Stormo. „Correlated mutations in models of protein sequences: phylogenetic and structural effects“. In Institute of Mathematical Statistics Lecture Notes - Monograph Series, 236–56. Hayward, CA: Institute of Mathematical Statistics, 1999. http://dx.doi.org/10.1214/lnms/1215455556.
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Edler, Lutz, und Janet Grassmann. „Protein fold class prediction is a new field for statistical classification and regression“. In Institute of Mathematical Statistics Lecture Notes - Monograph Series, 288–313. Hayward, CA: Institute of Mathematical Statistics, 1999. http://dx.doi.org/10.1214/lnms/1215455559.
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Lefèvre, G. „Le h-FABP (Heart Fatty Acid Binding Protein)“. In Les biomarqueurs en médecine d’urgence, 121–26. Paris: Springer Paris, 2012. http://dx.doi.org/10.1007/978-2-8178-0297-8_16.
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Arnold, Janine, Alexey Shapiguzov, Geoffrey Fucile, Jean-David Rochaix, Michel Goldschmidt-Clermont und Lutz Andreas Eichacker. „Separation of Membrane Protein Complexes by Native LDS-PAGE“. In Methods in Molecular Biology, 667–76. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-631-3_46.
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„Protein-based lms and coatings“. In Edible Coatings and Films to Improve Food Quality, 26–91. CRC Press, 2011. http://dx.doi.org/10.1201/b11082-6.
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7
Mohammed Ali Jassim, Marwa, Majid Mohammed Mahmood und Murtada Hafedh Hussein. „Human Herpetic Viruses and Immune Profiles“. In Innate Immunity in Health and Disease. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.96340.
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Herpesviruses are large, spherical, enveloped viral particles with linear double-stranded DNA genome. Herpesvirus virion consists of an icosahedral capsid containing viral DNA, surrounded by a protein layer called tegument, and enclosed by an envelope consisting of a lipid bilayer with various glycoproteins. Herpesviruses persist lifelong in their hosts after primary infection by establishing a latent infection interrupted recurrently by reactivations. The Herpesviridae family is divided into three subfamilies; α-herpesviruses, β-herpesviruses, and γ-herpesviruses based on the genome organization, sequence homology, and biological properties. There are eight human herpes viruses: Herpes simplex virus type 1 and 2 (HSV-1, −2) andVaricella-zoster virus (VZV), which belong to the α-herpesvirus subfamily; Human cytomegalovirus (HCMV), and Human herpesvirus type 6 and 7 (HHV-6,HHV-7), which belong to the β-herpesvirus subfamily; and Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) or Human herpesvirus 8 (HHV-8), which belong to the γ-herpesvirus subfamily. Within this chapter, we summarize the current knowledge about EBV and CMV, regarding their genome organization, structural characteristics, mehanisms of latency, types of infections, mechanisms of immune escape and prevention. Epstein–Barr Virus (EBV) genome encodes over 100 proteins, of which only (30) proteins are well characterized, including the proteins expressed during latent infection and lytic cycle proteins. Based on major variation in the EBNA-2 gene sequence, two types of EBV are recognized, EBV type 1 and 2. Epstein–Barr virus types occur worldwide and differ in their geographic distribution depending on the type of virus. EBV spreads most commonly through bodily fluids, especially saliva. However, EBV can also spread through blood, blood transfusions, and organ transplantations. The EBV is associated with many malignant diseases such as lymphomas, carcinomas, and also more benign such as infectious mononucleosis, chronic active infection. The EBV has also been suggested as a trigger/cofactor for some autoimmune diseases. Overall, 1–1.5% of the cancer burden worldwide is estimated to be attributable to EBV The latently infected human cancer cells express the most powerful monogenic proteins, LMP-1 and LMP-2(Latent Membrane Protein-1,-2), as well as Epstein–Barr Nuclear Antigens (EBNA) and two small RNAs called Epstein–Barr Encoded Small RNAs (EBERs). The EBV can evade the immune system by its gene products that interfering with both innate and adaptive immunity, these include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. Currently no vaccine is available, although there are few candidates under evaluation. Human cytomegalovirus (HCMV) is a ubiquitous beta herpesvirus type 5 with seroprevalence ranges between 60 to 100% in developing countries. CMV is spread from one person to another, usually by direct and prolonged contact with bodily fluids, mainly saliva, but it can be transmitted by genital secretions, blood transfusion and organ transplantation. In addition, CMV can be transmitted vertically from mother to child. CMV infection can result in severe disease for babies, people who receive solid organ transplants or bone marrow/stem cell transplants and people with severe immune suppression such as advanced human immunodeficiency virus (HIV) infection. The HCMV has several mechanisms of immune system evasion. It interferes with the initiation of adaptive immune responses, as well as prevent CD8+ and CD4+ T cell recognition interfering with the normal cellular MHC Class I and MHC Class II processing and presentation pathways. Challenges in developing a vaccine include adeptness of CMV in evading the immune system. Though several vaccine candidates are under investigation.
8
Izuegbuna, Ogochukwu. „Inflammation-Based Markers of Nutrition in Cancer Patients“. In Malnutrition [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.104428.
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Malnutrition and cachexia are common findings in cancer patients, and they predict poorer clinical outcomes. Close to half of cancer patients regardless of cancer type have malnutrition and will require one form of nutritional support either before or during treatment. The early identification of malnutrition is thus important to physicians and caregivers. The role of inflammation in the development and progression of malnutrition and cachexia is being unravelled. Increasing evidence shows that systemic inflammatory response and nutritional status are involved in tumour development and influence the clinical prognosis. Serum proteins such as albumin and prealbumin have traditionally been used by physicians to determine patient nutritional status. More recently, inflammation-based prognostic scores including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS) have shown promise and have begun to be used in clinical practice to predict prognosis of cancer patients. This chapter highlights the role and pathophysiology of inflammation-based markers in assessing malnutrition and cachexia and their relationship to clinical screening tools.
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Swiderek, Kristine M., Michael L. Klein, Stanley A. Hefta und John E. Shively. „Strategies for the removal of ionic and non-ionic detergents from protein and peptide mixtures for on- and off-line liquid chromatography mass spectrometry (LCMS)“. In Techniques in Protein Chemistry, 267–75. Elsevier, 1995. http://dx.doi.org/10.1016/s1080-8914(06)80034-7.
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O'Cinneide, Colm. „Derechos sociales en Europa“. In Mecanismos de garantía de los derechos sociales, 44–61. The Global Initiative for Economic, Social and Cultural Rights, 2021. http://dx.doi.org/10.53110/ckwl8281.
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Los derechos sociales suelen percibirse con recelo. Se les acusa de carecer de sustancia, de no ser justiciables, de reflejar la "inflación" del discurso de los derechos humanos en las últimas décadas; y, en última instancia, de ser una adición ajena e indeseada al restringido repertorio de derechos fundamentales "reales" que los sistemas constitucionales deben respetar y proteger. Hasta hace poco, este escepticismo ha dominado los debates sobre el estatus de los derechos sociales, en particular en el pensamiento jurisprudencial angloamericano. Aunque la aparición de sofisticados modelos de aplicación de los derechos socioeconómicos en Sudáfrica y en otros países durante las últimas décadas ha puesto en tela de juicio esta idea. No obstante, gran parte del discurso constitucional comparado sigue asumiendo que los derechos sociales son de algún modo problemáticos y que deberían recibir poco reconocimiento en cualquier marco constitucional. Esta creencia popular es errónea en muchos sentidos y uno de sus puntos débiles es que se ignora un aspecto comparativo importante del contexto europeo. Muchos sistemas jurídicos europeos han adoptado un enfoque muy diferente respecto a los derechos sociales.58 Es habitual que las constituciones europeas reconozcan la importancia fundamental de estos derechos y que los tribunales europeos los tengan en cuenta a la hora de interpretar y aplicar el derecho nacional.59 Además, los marcos jurídicos regionales europeos, concretamente la Carta Social Europea, la Convención Europea de Derechos Humanos y la legislación de la Unión Europea (EU), reconocen y protegen los derechos sociales de forma directa o indirecta. Dicha protección suele tener un alcance limitado, lo que resulta controvertido, tal como se analizará brevemente a continuación. Sin embargo, es una importante experiencia comparativa que debería tenerse en cuenta en cualquier debate sobre derechos sociales. En el contexto constitucional europeo, el carácter fundamental de estos derechos se afirma en textos constitucionales y se les da un grado de protección legal efectiva.
Konferenzberichte zum Thema "Protein LMs"
1
Jundt, Emily, Kaustav Majumder und Bijesh Maharjan. „Does Soil Nutrient Management with Nitrogen Fertilizer Increase Protein Content in Leguminous Plants“. In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/qgrx4847.
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Dry edible beans (Phaseolus vulgaris) are leguminous plants and are an excellent source of dietary proteins. Great Northern (GN) beans are a market class of dry edible beans and a major agricultural commodity in Nebraska. Soil nutrient management with nitrogen (N) fertilizer can enhance bean production by increasing N uptake, potentially improving protein quantity, and resulting in a potential economic benefit to bean farmers. Thus, this experiment aims to evaluate and optimize the effects of N treatment on yield, total protein, and soluble protein in GN beans. Seven treatments were tested, consisting of two controls and 5 treatments of urea at different rates. This field trial used a randomized complete block design (RCBD) structure, with four replications per treatment. GN beans were planted in May 2021, fertilized in June, and harvested in September 2021. Yield was calculated, total protein content was measured via the Dumas method, and soluble protein content was analyzed by Lowry’s protein estimation method. Bean yield linearly increased with fertilizer N rate. Bean yield ranged from 3260 lbs/ac at 0 lbs N/ac to 3710 lbs/ac at 125 lbs N/ac. Results also showed that both total and soluble protein content in GN beans linearly increased with applied N rate. The urea treatment at a rate of 100 and 125 lbs /ac increased the total protein content by 1.0 and 2.9%, respectively. Soluble protein content increased by 1.2 and 1.8% when urea was applied at rates of 100 and 125 lbs/ac, respectively. As the demand for plant-based protein continues to grow, it brings a large market for legume proteins that can be optimized with N management. The use of N management to enhance the bean quality by increasing total and soluble protein will add more economic value to the GN beans and benefit the bean growers.
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Kelleher, Stephen, Wayne Saunders und William Fielding. „Solubilized Proteins as a Fat Block in Production“. In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/xfuv8295.
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Fried foods are ubiquitous around the world with an estimated 83 billion pounds consumed in the Unites States and at least twice that value across the rest of the world. In application testing, solutions of myofibrillar and sarcoplasmic proteins at acidic pH from varying animal muscles have been shown to reduce fat and increase moisture in battered and breaded products when topically applied to the substrates just prior to deep fat frying. As an example, a previous benchtop result found a 17.7% reduction in fat and a 15.0% increase in moisture when chicken protein was applied to a battered and breaded four (4) oz chicken patty. Advancing the process from benchtop, full plant trials were performed at a run rate of 4500 lbs/hr with a two-pass batter/breading sequence. One full shift of approximately 40,000 lbs was run. A topical chicken protein solution with a 4.5% application rate resulted in a significant fat reduction of 33.64%, with a 9.61% increase in moisture on fully cooked tenders. Protein treated chicken boneless wings had 27.52% less fat and 8.22% increased moisture, compared to untreated controls. Piece count method estimation resulted in a minimum 7.32% yield increase for treated product. Improved coating adherence resulted in substantially less coating filtration. Free fatty acid values ranged from 0.02% (oleic) at the beginning of the trial with fresh oil to 0.07% after 4 hours of frying. One possible theory to explain efficacy is the protein created a micro barrier on the substrate’s surface, preventing moisture escape and oil absorption. Using solubilized muscle proteins as a topical spray suggests a method to lower production costs and improve nutrition.
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Caffrey, Martin. „Lipid Phase Behavior: Databases, Rational Design and Membrane Protein Crystallization“. In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192724.
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The relationship that exists between structure and function is a unifying theme in my varied biomembrane-based research activities. It applies equally well to the lipid as to the protein component of membranes. With a view to exploiting information that has been and that is currently being generated in my laboratory, as well as that which exists in the literature, a number of web-accessible, relational databases have been established over the years. These include databases dealing with lipids, detergents and membrane proteins. Those catering to lipids include i) LIPIDAT, a database of thermodynamic information on lipid phases and phase transitions, ii) LIPIDAG, a database of phase diagrams concerning lipid miscibility, and iii) LMSD, a lipid molecular structures database. CMCD is the detergent-based database. It houses critical micelle concentration information on a wide assortment of surfactants under different conditions. The membrane protein data bank (MPDB) was established to provide convenient access to the 3-D structure and related properties of membrane proteins and peptides. The utility and current status of these assorted databases will be described and recommendations will be made for extending their range and usefulness.
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Rivera Ocampo, Gloria, Diana Marcela Santos Cabrera, Gloria Emilse Buriticá Giraldo und Tatiana Castañeda López. „¿En el estado colombiano a las personas intersexuales se les protege su libertad sexual?“ In 6° Encuentro Nacional de Semilleros de Investigación Uniremington. Fondo Editorial Remington, 2017. http://dx.doi.org/10.22209/mensi.n6a25.
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Parola, Abraham H., Nurith Porat, Valeria R. Caiolfa, David Gill, Lutz A. Kiesow, Mathew Weisman, S. Nemschitz, Dahlia Yaron, Karen Singer und Ethel Solomon. „Membrane lipid-protein interactions modify the regulatory role of adenosine-deaminase complexing protein: a phase fluorometry study of a malignancy marker“. In OE/LASE '90, 14-19 Jan., Los Angeles, CA, herausgegeben von Joseph R. Lakowicz. SPIE, 1990. http://dx.doi.org/10.1117/12.17776.
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Small, Jeanne R., und Shane L. Larson. „Photoacoustic determination of fluorescent quantum yields of protein probes“. In OE/LASE '90, 14-19 Jan., Los Angeles, CA, herausgegeben von Joseph R. Lakowicz. SPIE, 1990. http://dx.doi.org/10.1117/12.17694.
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Nordlund, Thomas M. „Streak Camera Methods In Nucleic Acid And Protein Fluorescence Spectroscopy“. In 1988 Los Angeles Symposium--O-E/LASE '88, herausgegeben von Joseph R. Lakowicz. SPIE, 1988. http://dx.doi.org/10.1117/12.945367.
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Hudson, Bruce S., und Dan Harris. „T4 phage lysozyme: a protein designed for understanding tryptophan photophysics“. In OE/LASE '90, 14-19 Jan., Los Angeles, CA, herausgegeben von Joseph R. Lakowicz. SPIE, 1990. http://dx.doi.org/10.1117/12.17690.
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Lee, John W., Gary R. Holtom und Dennis J. O'Kane. „Picosecond resolution study of intramolecular energy transfer in lumazine protein“. In OE/LASE '90, 14-19 Jan., Los Angeles, CA, herausgegeben von Joseph R. Lakowicz. SPIE, 1990. http://dx.doi.org/10.1117/12.17750.
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Rousslang, Kenneth W., Steve K. Buratto, D. Haynes, P. Heath, D. Holloway, John C. Hulteen, Lisa Dick, K. Stevenson, C. O. Harding und J. B. Alexander Ross. „Time-resolved phosphorescence of proteins and polypeptides“. In OE/LASE '90, 14-19 Jan., Los Angeles, CA, herausgegeben von Joseph R. Lakowicz. SPIE, 1990. http://dx.doi.org/10.1117/12.17735.
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Shomer, Ilan, Louise Wicker, Uzi Merin und William L. Kerr. Interactions of Cloud Proteins, Pectins and Pectinesterases in Flocculation of Citrus Cloud. United States Department of Agriculture, Februar 2002. http://dx.doi.org/10.32747/2002.7580669.bard.
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The overall objective was to understand the cloud flocculation of citrus juice by characterization of the interactions between proteins and pectins, and to determine the role of PE isozymes in catalyzing this phenomenon. Specific objectives were to: 1. identify/characterize cloud-proteins in relation to their coagulable properties and affinity to pectins; 2. to determine structural changes of PME and other proteins induced by cation/pectin interactions; 3. localize cloud proteins, PME and bound protein/pectates in unheated and pasteurized juices; 4. to create "sensitized" pectins and determine their effect on clarification. The original objectives were not changed but the methods and approach were modified due to specific research requirements. Two i postulates were: 1. there is a specific interaction of cloud proteins with de-esterified regions of ! pectin and this contributes to cloud loss; 2. isozymes of pectin-methyl-esterase (PME) vary in efficiency to create sensitized pectins. The appearance of citrus fruit juice is an important quality factor and is determined by the color and turbidity that .are conferred by the suspended particles, i.e., by the cloud and its homogeneity. Under some circumstances the cloud tend to flocculate and the juice clarifies. The accepted approach to explain the clarification is based on pectin demethoxylation by PME that promotes formation of Ca-pectate. Therefore, the juice includes immediate heat-inactivation upon ~ squeezing. Protein coagulation also promotes cloud instability of citrus fruit extracts. However, the clarification mechanism is not fully understood. Information accumulated from several laboratories indicates that clarification is a more complex process than can be explained by a single mechanism. The increasing trend to consume natural-fresh juice emphasizing the importance of the knowledge to assure homogeneity of fresh juice. The research included complementary directions: Conditions that induce cloud-instability of natural- juice [IL]. Evaluate purification schemes of protein [USA]. Identifications of proteins, pectin and neutral sugars ([IL]; Structure of the cloud components using light and electron microscopy and immuno-labeling of PME, high-methoxyl-pectin (HMP) and low-methoxyl-pectin (LMP); Molecular weight of calcium sensitized pectins [US]; Evaluation of the products of PME activity [US]. Fractions and size distribution and cloud components [IL-US]. The optimal pH activity of PME is 7 and the flocculation pH of the cloud is 3-4. Thus, the c roles of PME, proteins and pectins in the cloud instability, were studied in pH ranges of 2- 7. The experiments led to establish firstly repeatable simulate conditions for cloud instability [IL]. Thermostable PME (TS-PE) known to induce cloud instability, but also thermolabile forms of PME (TL-PE) caused clarification, most likely due to the formation and dissolution of inactive :. PE-pectin complexes and displacement of a protective colloid from the cloud surface [US]. Furthermore, elimination of non-PME protein increases TS-PE activity, indicating that non-PME proteins moderate PME activity [US]. Other experiments Concomitantly with the study of the PME activity but promotes the association of cloud-proteins to pectin. Adjusting of the juice pH to f 7 retains the cloud stability and re-adjusting of the pH to 40% DE reacts to immuno-labeling in the cloud fragments, whereas
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Saunders, Alexander. Proton Radiography at Los Alamos. Office of Scientific and Technical Information (OSTI), Februar 2017. http://dx.doi.org/10.2172/1345179.
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Barash, Itamar, und Robert Rhoads. Translational Mechanisms Governing Milk Protein Levels and Composition. United States Department of Agriculture, 2006. http://dx.doi.org/10.32747/2006.7696526.bard.
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Original objectives: The long-term goal of the research is to achieve higher protein content in the milk of ruminants by modulating the translational apparatus of the mammary gland genetically, nutritionally, or pharmacologically. The short-term objectives are to obtain a better understanding of 1) the role of amino acids (AA) as regulators of translation in bovine and mouse mammary epithelial cells and 2) the mechanism responsible for the synergistic enhancement of milk-protein mRNA polyadenylation by insulin and prolactin. Background of the topic: In many cell types and tissues, individual AA affect a signaling pathway which parallels the insulin pathway to modulate rates and levels of protein synthesis. Diverse nutritional and hormonal conditions are funneled to mTOR, a multidomain serine/threonine kinase that regulates a number of components in the initiation and elongation stages of translation. The mechanism by which AA signal mTOR is largely unknown. During the current grant period, we have studied the effect of essential AA on mechanisms involved in protein synthesis in differentiated mammary epithelial cells cultured under lactogenic conditions. We also studied lactogenic hormone regulation of milk protein synthesis in differentiated mammary epithelial cells. In the first BARD grant (2000-03), we discovered a novel mechanism for mRNA-specific hormone-regulated translation, namely, that the combination of insulin plus prolactin causes cytoplasmic polyadenylation of milk protein mRNAs, which leads to their efficient translation. In the current BARD grant, we have pursued the signaling pathways of this novel hormone action. Major conclusions/solutions/achievements: The positive and negative signaling from AA to the mTOR pathway, combined with modulation of insulin sensitization, mediates the synthesis rates of total and specific milk proteins in mammary epithelial cells. The current in vitro study revealed cryptic negative effects of Lys, His, and Thr on cellular mechanisms regulating translation initiation and protein synthesis in mammary epithelial cells that could not be detected by conventional in vivo analyses. We also showed that a signaling pathway involving Jak2 and Stat5, previously shown to lead from the prolactin receptor to transcription of milk protein genes, is also used for cytoplasmic polyadenylation of milk protein mRNAs, thereby stabilizing these mRNAs and activating them for translation. Implications: In vivo, plasma AA levels are affected by nutritional and hormonal effects as well as by conditions of exercise and stress. The amplitude in plasma AA levels resembles that applied in the current in vitro study. Thus, by changing plasma AA levels in the epithelial cell microenvironment or by sensitizing the mTOR pathway to their presence, it should be possible to modulate the rate of milk protein synthesis. Furthermore, knowledge that phosphorylation of Stat5 is required for enhanced milk protein synthesis in response to lactogenic opens the possibility for pharmacologic approaches to increase the phosphorylation of Stat5 and, thereby, milk protein production.
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Carrillo Cruz, Yudy Andrea. La protección del agua y los derechos humanos de las futuras generaciones. Ediciones Universidad Cooperativa de Colombia, Dezember 2022. http://dx.doi.org/10.16925/wpai.12.
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El derecho constitucional al agua está ligado de manera profunda con los derechos humanos de las generaciones venideras; la importancia del agua no solo se debe entender desde un enfoque científico, sino también es necesario comprender la relación jurídica que tiene con la efectividad de otros derechos, al tratarse de un líquido vital para la supervivencia del ser humano. En el presente avance de investigación, se hace una relación de las teorías jurídicas que se han ido implementando tanto a nivel internacional como en Colombia, respecto a la protección del agua y de las generaciones futuras, teniendo como punto de partida en común que ninguno de estos derechos se encuentra consagrado de manera expresa en la Constitución Política de 1991. Así las cosas, su desarrollo y protección se evidencia tanto en la doctrina como en la jurisprudencia de cortes constitucionales y de derechos humanos, como es el caso de la Corte Interamericana de Derechos Humanos en el continente americano. En este texto se analiza, teniendo en cuenta un enfoque cualitativo, la responsabilidad que tiene el Estado frente a la protección de estos dos derechos y se realiza una exploración de literatura sobre la temática. La evolución del derecho constitucional y de los derechos humanos ha llevado a que se protejan los derechos de quienes aún no nacen a través de declaraciones, sentencias y normatividad que amparan a las futuras generaciones. Conservar las fuentes hídricas es una responsabilidad de la generación actual que envuelve la protección de los derechos humanos de las generaciones futuras.
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Del Pozo, Claudia May, Ana Victoria Martín del Campo Alcocer und Mariana Róo Rubí. Aprendizaje en línea seguro: políticas y gobernanza para la protección de datos de los estudiantes en América Latina. Inter-American Development Bank, September 2021. http://dx.doi.org/10.18235/0003675.
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Desde principios de 2020 y hasta la fecha de publicación de este reporte, algunas de las escuelas donde estudian más de 168 millones de niños y niñas del mundo llevan más de un año entero cerradas debido a la pandemia del Covid-19. Como respuesta de emergencia, millones de estudiantes, docentes y directores tuvieron que migrar de manera masiva a plataformas digitales para no interrumpir su aprendizaje y enseñanza. Aún cuando el uso de la tecnología es fundamental para la educación en momentos de distanciamiento social, y su importancia sólo seguirá creciendo en el futuro, el uso de estas plataformas pone a los niños y las niñas en un estado de vulnerabilidad si los datos que se recolectan y guardan de ellos y ellas no son gestionados de manera que protejan su privacidad y seguridad. Es importante que los países de Latinoamérica impulsen una gobernanza de datos de sistemas educativos centrada en los derechos de los estudiantes. Esta gobernanza requeriría un conjunto de iniciativas y procedimientos que prescriban la manera correcta de recopilar, mantener, utilizar y distribuir los datos sensibles, concretamente la información personal de estudiantes y docentes. Este reporte busca servir como insumo para que las Secretarías y Ministerios de Educación de la región sigan desarrollando políticas, procedimientos y responsabilidades que proporcionen claridad en torno a los datos de los estudiantes, preparando el camino para que la información proteja los derechos de privacidad, confidencialidad y seguridad del estudiante.
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Meijer, William. Dark Field Proton Radiography Los Alamos LDRD Report. Office of Scientific and Technical Information (OSTI), März 2023. http://dx.doi.org/10.2172/1961360.
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Kolski, Jeffrey S., Robert J. Macek und Rodney C. McCrady. Orbit Response Matrix (ORM) Analysis in the Los Alamos Proton Storage Ring. Office of Scientific and Technical Information (OSTI), Januar 2011. http://dx.doi.org/10.2172/1009114.
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Thiessen, H. A., F. Neri, K. Rust und D. B. Redd. Multi-pulse extraction from Los Alamos Proton Storage Ring for radiographic applications. Office of Scientific and Technical Information (OSTI), August 1997. http://dx.doi.org/10.2172/521645.
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Barefoot, Susan F., Bonita A. Glatz, Nathan Gollop und Thomas A. Hughes. Bacteriocin Markers for Propionibacteria Gene Transfer Systems. United States Department of Agriculture, Juni 2000. http://dx.doi.org/10.32747/2000.7573993.bard.
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The antibotulinal baceriocins, propionicin PLG-1 and jenseniin G., were the first to be identified, purified and characterized for the dairy propionibaceria and are produced by Propionibacterium thoenii P127 and P. thoenii/jensenii P126, respectively. Objectives of this project were to (a) produce polyclonal antibodies for detection, comparison and monitoring of propionicin PLG-1; (b) identify, clone and characterize the propionicin PLG-1 (plg-1) and jenseniin G (jnG) genes; and (3) develop gene transfer systems for dairy propionibacteria using them as models. Polyclonal antibodies for detection, comparison and monitoring of propionicin PLG-1 were produced in rabbits. Anti-PLG-1 antiserum had high titers (256,000 to 512,000), neutralized PLG-1 activity, and detected purified PLG-1 at 0.10 mg/ml (indirect ELISA) and 0.033 mg/ml (competitive indirect ELISA). Thirty-nine of 158 strains (most P. thoenii or P. jensenii) yielded cross-reacting material; four strains of P. thoenii, including two previously unidentified bacteriocin producers, showed biological activity. Eight propionicin-negative P127 mutants produced neither ELISA response nor biological activity. Western blot analyses of supernates detected a PLG-1 band at 9.1 kDa and two additional protein bands with apparent molecular weights of 16.2 and 27.5 kDa. PLG-1 polyclonal antibodies were used for detection of jenseniin G. PLG-1 antibodies neutralized jenseniin G activity and detected a jenseniin G-sized, 3.5 kDa peptide. Preliminary immunoprecipitation of crude preparations with PLG-1 antibodies yielded three proteins including an active 3-4 kDa band. Propionicin PLG-1 antibodies were used to screen a P. jensenii/thoenii P126 genomic expression library. Complete sequencing of a cloned insert identified by PLG-1 antibodies revealed a putative response regulator, transport protein, transmembrane protein and an open reading frame (ORF) potentially encoding jenseniin G. PCR cloning of the putative plg-1 gene yielded a 1,100 bp fragment with a 355 bp ORF encoding 118 amino acids; the deduced N-terminus was similar to the known PLG-1 N-terminus. The 118 amino acid sequence deduced from the putative plg-1 gene was larger than PLG-1 possibly due to post-translational processing. The product of the putative plg-1 gene had a calculated molecular weight of 12.8 kDa, a pI of 11.7, 14 negatively charged residues (Asp+Glu) and 24 positively charged residues (Arg+Lys). The putative plg-1 gene was expressed as an inducible fusion protein with a six-histidine residue tag. Metal affinity chromatography of the fused protein yielded a homogeneous product. The fused purified protein sequence matched the deduced putative plg-1 gene sequence. The data preliminarily suggest that both the plg-1 and jnG genes have been identified and cloned. Demonstrating that antibodies can be produced for propionicin PLG-1 and that those antibodies can be used to detect, monitor and compare activity throughout growth and purification was an important step towards monitoring PLG-1 concentrations in food systems. The unexpected but fortunate cross-reactivity of PLG-1 antibodies with jenseniin G led to selective recovery of jenseniin G by immunoprecipitation. Further refinement of this separation technique could lead to powerful affinity methods for rapid, specific separation of the two bacteriocins and thus facilitate their availability for industrial or pharmaceutical uses. Preliminary identification of genes encoding the two dairy propionibacteria bacteriocins must be confirmed; further analysis will provide means for understanding how they work, for increasing their production and for manipulating the peptides to increase their target species. Further development of these systems would contribute to basic knowledge about dairy propionibacteria and has potential for improving other industrially significant characteristics.
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Aguerrevere, Gabriela, und Maria Victoria Fazio. 'E-lancing' en América Latina y el Caribe: ¿cómo conectar el talento digital con oportunidades globales? Inter-American Development Bank, August 2021. http://dx.doi.org/10.18235/0003590.
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Las plataformas digitales han revolucionado los mercados laborales en todo el mundo, transformando la manera de trabajar y ofreciendo oportunidades para trabajadores con perfiles muy diversos. Las plataformas de trabajo remoto o plataformas de 'e-lancing', en particular, conectan a las personas con clientes que pueden estar en cualquier parte del mundo. Así, surgen nuevos mecanismos de generación de ingresos que pueden ser especialmente atractivos para grupos que suelen enfrentar barreras para encontrar un empleo tradicional. Esta publicación recoge las lecciones aprendidas de un programa piloto desarrollado por el BID en El Salvador en 2020 para entender cómo conectar a los jóvenes de América Latina y el Caribe con este tipo de oportunidades. Como parte de este programa, los participantes tuvieron acceso a contenidos teóricos y ejercicios prácticos diseñados para desarrollar las habilidades requeridas para trabajar en estas plataformas, incluyendo la creación de perfiles, preparación de propuestas y gerencia de proyectos. También tuvieron acceso a tutores que monitoreaban su progreso y les apoyaban con la preparación de las propuestas, lo que resultó ser un elemento clave para el éxito del programa. En total, los participantes presentaron más de mil propuestas entre todos, trabajando con clientes en países como Alemania, Estados Unidos y Vietnam. Cómo se posicionará la región en esta nueva dinámica de oportunidades laborales dependerá de las políticas que se tomen en torno al trabajo en estas plataformas de 'e-lancing'. Al respecto, la publicación comparte algunas acciones que se pueden tomar en este ámbito. En primer lugar, para mejorar las oportunidades de los trabajadores en este ecosistema, los gobiernos deben incrementar el acceso a las tecnologías de la información y comunicación y expandir la formación en habilidades digitales. Además, es necesario implementar estrategias de diseminación para que individuos y empresas conozcan las potencialidades de estas plataformas. A su vez, estas estrategias deben estar acompañadas de programas de capacitación que ayuden a que las personas desarrollen las habilidades requeridas para triunfar en este universo. También es importante aumentar la inclusión financiera, y modernizar las regulaciones laborales para asegurar que protegen a los 'e-lancers' o en general, a trabajadores en nuevas ocupaciones generadas por la tecnología. Para acompañar el diseño de esas políticas, será necesario encaminar más investigaciones que permitan seguir dimensionando el impacto de estas plataformas de cara al futuro del desarrollo productivo en la región.