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101.
Using software‐modified smartphones to validate self‐reported mobile phone use in young people: A pilot study
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102.
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence
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Roberto Ferrari Amelie Montel‐Hagen Ben Van Handel Marc A Kerényi Rajkumar Sasidharan Liudmilla Rubbi Yuko Fujiwara Matteo Pellegrini Stuart H Orkin Siavash K Kurdistani Hanna KA Mikkola 《The EMBO journal》2015,34(6):759-777
Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre‐established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage‐specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated. 相似文献
103.
Mai H. Oushy Rebecca Palacios Alan E. C. Holden Amelie G. Ramirez Kipling J. Gallion Mary A. O’Connell 《PloS one》2015,10(9)
Background
Cancer health disparities research depends on access to biospecimens from diverse racial/ethnic populations. This multimethodological study, using mixed methods for quantitative and qualitative analysis of survey results, assessed barriers, concerns, and practices for sharing biospecimens/data among researchers working with biospecimens from minority populations in a 5 state region of the United States (Arizona, Colorado, New Mexico, Oklahoma, and Texas). The ultimate goals of this research were to understand data sharing barriers among biomedical researchers; guide strategies to increase participation in biospecimen research; and strengthen collaborative opportunities among researchers.Methods and Population
Email invitations to anonymous participants (n = 605 individuals identified by the NIH RePORT database), resulted in 112 responses. The survey assessed demographics, specimen collection data, and attitudes about virtual biorepositories. Respondents were primarily principal investigators at PhD granting institutions (91.1%) conducting basic (62.3%) research; most were non-Hispanic White (63.4%) and men (60.6%). The low response rate limited the statistical power of the analyses, further the number of respondents for each survey question was variable.Results
Findings from this study identified barriers to biospecimen research, including lack of access to sufficient biospecimens, and limited availability of diverse tissue samples. Many of these barriers can be attributed to poor annotation of biospecimens, and researchers’ unwillingness to share existing collections. Addressing these barriers to accessing biospecimens is essential to combating cancer in general and cancer health disparities in particular. This study confirmed researchers’ willingness to participate in a virtual biorepository (n = 50 respondents agreed). However, researchers in this region listed clear specifications for establishing and using such a biorepository: specifications related to standardized procedures, funding, and protections of human subjects and intellectual property. The results help guide strategies to increase data sharing behaviors and to increase participation of researchers with multiethnic biospecimen collections in collaborative research endeavorsConclusions
Data sharing by researchers is essential to leveraging knowledge and resources needed for the advancement of research on cancer health disparities. Although U.S. funding entities have guidelines for data and resource sharing, future efforts should address researcher preferences in order to promote collaboration to address cancer health disparities. 相似文献104.
In vivo evaluation of cysteine-based chelators for attachment of 99mTc to tumor-targeting Affibody molecules 总被引:1,自引:0,他引:1
Tran T Engfeldt T Orlova A Widström C Bruskin A Tolmachev V Karlström AE 《Bioconjugate chemistry》2007,18(2):549-558
Affibody molecules present a new class of affinity proteins, which utilizes a scaffold based on a 58-amino acid domain derived from protein A. The small (7 kDa) Affibody molecule can be selected to bind to cell-surface targets with high affinity. An Affibody molecule (ZHER2:342) with a dissociation constant (Kd) of 22 pM for binding to the HER2 receptor has been reported earlier. Preclinical and pilot clinical studies have demonstrated the utility of radiolabeled ZHER2:342 in imaging of HER2-expressing tumors. The small size and cysteine-free structure of Affibody molecules enable complete peptide synthesis and direct incorporation of radionuclide chelators. The goal of this study was to evaluate if incorporation of the natural peptide sequences cysteine-diglycine (CGG) and cysteine-triglycine (CGGG) sequences would enable labeling of Affibody molecules with 99mTc. In a model monomeric form, the chelating sequences were incorporated by peptide synthesis. The HER2-binding affinity was 280 and 250 pM for CGG-ZHER2:342 and CGGG-ZHER2:342, respectively. Conjugates were directly labeled with 99mTc with 90% efficiency and preserved the capacity to bind specifically to HER2-expressing cells. The biodistribution in normal mice showed a rapid clearance from the blood and the majority of organs (except kidneys). In the mice bearing SKOV-3 xenografts, tumor uptake of 99mTc-CGG-ZHER2:342 was HER2-specific and a tumor-to-blood ratio of 9.2 was obtained at 6 h postinjection. Gamma-camera imaging with 99mTc-CGG-ZHER2:342 clearly visualized tumors at 6 h postinjection. The results show that the use of a cysteine-based chelator enables 99mTc-labeling of Affibody molecules for imaging. 相似文献
105.
106.
Nishit Goradia Amelie Wißbrock Christoph Wiedemann Frank Bordusa Ramadurai Ramachandran Diana Imhof Oliver Ohlenschläger 《Biomolecular NMR assignments》2016,10(2):329-333
Interleukin-36α (IL-36α) is a recently characterised member of the interleukin-1 superfamily. It is involved in the pathogenesis of inflammatory arthritis in one third of psoriasis patients. By binding of IL-36α to its receptor IL-36R via the NF-κB pathway other cytokines involved in inflammatory and apoptotic cascade are activated. The efficacy of complex formation is controlled by N-terminal processing. To obtain a more detailed view on the structure function relationship we performed a heteronuclear multidimensional NMR investigation and here report the 1H, 13C, and 15N resonance assignments for the backbone and side chain nuclei of the pro-inflammatory cytokine interleukin-36α. 相似文献
107.
Hiroki Mutoh Amelie Perron Dimitar Dimitrov Yuka Iwamoto Walther Akemann Dmitriy M. Chudakov Thomas Kn?pfel 《PloS one》2009,4(2)
Genetically-encoded optical probes for membrane potential hold the promise of monitoring electrical signaling of electrically active cells such as specific neuronal populations in intact brain tissue. The most advanced class of these probes was generated by molecular fusion of the voltage sensing domain (VSD) of Ci-VSP with a fluorescent protein (FP) pair. We quantitatively compared the three most advanced versions of these probes (two previously reported and one new variant), each involving a spectrally distinct tandem of FPs. Despite these different FP tandems and dissimilarities within the amino acid sequence linking the VSD to the FPs, the amplitude and kinetics of voltage dependent fluorescence changes were surprisingly similar. However, each of these fluorescent probes has specific merits when considering different potential applications. 相似文献
108.
Lindgren J Wahlström A Danielsson J Markova N Ekblad C Gräslund A Abrahmsén L Karlström AE Wärmländer SK 《Protein science : a publication of the Protein Society》2010,19(12):2319-2329
The aggregation of amyloid-β (Aβ) peptides is believed to be a major factor in the onset and progression of Alzheimer's disease. Molecules binding with high affinity and selectivity to Aβ-peptides are important tools for investigating the aggregation process. An Aβ-binding Affibody molecule, ZAβ3 , has earlier been selected by phage display and shown to bind Aβ(1-40) with nanomolar affinity and to inhibit Aβ-peptide aggregation. In this study, we create truncated functional versions of the ZAβ3 Affibody molecule better suited for chemical synthesis production. Engineered Affibody molecules of different length were produced by solid phase peptide synthesis and allowed to form covalently linked homodimers by S-S-bridges. The N-terminally truncated Affibody molecules ZAβ3 (12-58), ZAβ3 (15-58), and ZAβ3 (18-58) were produced in considerably higher synthetic yield than the corresponding full-length molecule ZAβ3 (1-58). Circular dichroism spectroscopy and surface plasmon resonance-based biosensor analysis showed that the shortest Affibody molecule, ZAβ3 (18-58), exhibited complete loss of binding to the Aβ(1-40)-peptide, while the ZAβ3 (12-58) and ZAβ3 (15-58) Affibody molecules both displayed approximately one order of magnitude higher binding affinity to the Aβ(1-40)-peptide compared to the full-length Affibody molecule. Nuclear magnetic resonance spectroscopy showed that the structure of Aβ(1-40) in complex with the truncated Affibody dimers is very similar to the previously published solution structure of the Aβ(1-40)-peptide in complex with the full-length ZAβ3 Affibody molecule. This indicates that the N-terminally truncated Affibody molecules ZAβ3 (12-58) and ZAβ3 (15-58) are highly promising for further engineering and future use as binding agents to monomeric Aβ(1-40). 相似文献
109.
Amelie Fassbender Peter Simsa Cleophas M Kyama Etienne Waelkens Attila Mihalyi Christel Meuleman Olivier Gevaert Raf Van de Plas Bart de Moor Thomas M D'Hooghe 《Reproductive biology and endocrinology : RB&E》2010,8(1):123
Background
According to mRNA microarray, proteomics and other studies, biological abnormalities of eutopic endometrium (EM) are involved in the pathogenesis of endometriosis, but the relationship between mRNA and protein expression in EM is not clear. We tested for the first time the hypothesis that EM TRIzol extraction allows proteomic Surface Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (SELDI-TOF MS) analysis and that these proteomic data can be related to mRNA (microarray) data obtained from the same EM sample from women with and without endometriosis. 相似文献110.
High-level expression of nonglycosylated human pancreatic lipase-related protein 2 in Pichia pastoris 总被引:3,自引:0,他引:3
Sebban-Kreuzer C Deprez-Beauclair P Berton A Crenon I 《Protein expression and purification》2006,49(2):284-291
The human pancreatic lipase-related protein 2 (HPLRP2) was produced in the methylotrophic yeast Pichia pastoris. The HPLRP2 cDNA corresponding to the protein coding sequence including the native signal sequence, was cloned into the pPIC9K vector and integrated into the genome of P. pastoris. P. pastoris transformants secreting high-level rHPLRP2 were obtained and the expression level into the liquid culture medium reached about 40mg/L after 4 days of culture. rHPLRP2 was purified by a single anion-exchange step after an overnight dialysis. N-terminal sequence analysis showed that the purified rHPLRP2 mature protein possessed a correct N-terminal amino acid sequence indicating that its signal peptide was properly processed. Mass spectrometry analysis showed that the recombinant HPLRP2 molecular weight was 52,532Da which was 2451Da greater than the mass calculated from the sequence of the protein (50,081Da) and 1536Da greater than the mass of the native human protein (50,996Da). In vitro deglycosylation experiments by peptide:N-glycosidase F (PNGase F) indicated that rHPLRP2 secreted from P. pastoris was N-glycosylated. Specific conditions were setup in order to obtain a recombinant protein free of glycan chain. We observed that blocking glycosylation in vivo by addition of tunicamycin in the culture medium during the production resulted in a correct processing of the rHPLRP2 mature protein. The lipase activity of glycosylated or nonglycosylated rHPLRP2, which was about 800U/mg on tributyrin, was inhibited by the presence of bile salts and not restored by adding colipase. In conclusion, the experimental procedure which we have developed will allow us to get a high-level production in P. pastoris of glycosylated and nonglycosylated rHPLRP2, suitable for subsequent biophysical and structural studies. 相似文献