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Roni F Rayes, Simon Milette, Maria Celia Fernandez, Boram Ham, Ni Wang, France Bourdeau, Stephanie Perrino, Shoshana Yakar, Pnina Brodt
The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls...
March 20, 2018: Oncotarget
Lorena Benedetti, Andrew E S Barentine, Mirko Messa, Heather Wheeler, Joerg Bewersdorf, Pietro De Camilli
Methods to acutely manipulate protein interactions at the subcellular level are powerful tools in cell biology. Several blue-light-dependent optical dimerization tools have been developed. In these systems one protein component of the dimer (the bait) is directed to a specific subcellular location, while the other component (the prey) is fused to the protein of interest. Upon illumination, binding of the prey to the bait results in its subcellular redistribution. Here, we compared and quantified the extent of light-dependent dimer occurrence in small, subcellular volumes controlled by three such tools: Cry2/CIB1, iLID, and Magnets...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Soha Rostaminia, Addison Mayberry, Deepak Ganesan, Benjamin Marlin, Jeremy Gummeson
The ability to monitor eye closures and blink patterns has long been known to enable accurate assessment of fatigue and drowsiness in individuals. Many measures of the eye are known to be correlated with fatigue including coarse-grained measures like the rate of blinks as well as fine-grained measures like the duration of blinks and the extent of eye closures. Despite a plethora of research validating these measures, we lack wearable devices that can continually and reliably monitor them in the natural environment...
June 2017: Proceedings of the ACM on interactive, mobile, wearable and ubiquitous technologies
S M Bartelt, E Chervyachkova, J Steinkühler, J Ricken, R Wieneke, R Tampé, R Dimova, S V Wegner
The blue light-dependent interaction between the proteins iLID and Nano allows recruiting and patterning proteins on GUV membranes, which thereby capture key features of patterns observed in nature. This photoswitchable protein interaction provides non-invasive, reversible and dynamic control over protein patterns of different sizes with high specificity and spatiotemporal resolution.
January 23, 2018: Chemical Communications: Chem Comm
Rebecca C Adikes, Ryan A Hallett, Brian F Saway, Brian Kuhlman, Kevin C Slep
We developed a novel optogenetic tool, SxIP-improved light-inducible dimer (iLID), to facilitate the reversible recruitment of factors to microtubule (MT) plus ends in an end-binding protein-dependent manner using blue light. We show that SxIP-iLID can track MT plus ends and recruit tgRFP-SspB upon blue light activation. We used this system to investigate the effects of cross-linking MT plus ends and F-actin in Drosophila melanogaster S2 cells to gain insight into spectraplakin function and mechanism. We show that SxIP-iLID can be used to temporally recruit an F-actin binding domain to MT plus ends and cross-link the MT and F-actin networks...
February 5, 2018: Journal of Cell Biology
Fan Shi, Fuun Kawano, Seon-Hye Emily Park, Shinji Komazaki, Yusuke Hirabayashi, Franck Polleux, Masayuki Yazawa
The organelle interface emerges as a dynamic platform for a variety of biological responses. However, their study has been limited by the lack of tools to manipulate their occurrence in live cells spatiotemporally. Here, we report the development of a genetically encoded light-inducible tethering (LIT) system allowing the induction of contacts between endoplasmic reticulum (ER) and mitochondria, taking advantage of a pair of light-dependent heterodimerization called an iLID system. We demonstrate that the iLID-based LIT approach enables control of ER-mitochondria tethering with high spatiotemporal precision in various cell types including primary neurons, which will facilitate the functional study of ER-mitochondrial contacts...
January 19, 2018: ACS Synthetic Biology
Seth P Zimmerman, Ryan A Hallett, Ashley M Bourke, James E Bear, Matthew J Kennedy, Brian Kuhlman
Inducible dimers are powerful tools for controlling biological processes through colocalizing signaling molecules. To be effective, an inducible system should have a dissociation constant in the "off" state that is greater (i.e., weaker affinity) than the concentrations of the molecules that are being controlled, and in the "on" state a dissociation constant that is less (i.e., stronger affinity) than the relevant protein concentrations. Here, we reengineer the interaction between the light inducible dimer, iLID, and its binding partner SspB, to better control proteins present at high effective concentrations (5-100 μM)...
September 20, 2016: Biochemistry
Taiqing Wang, Shaogang Gong, Xiatian Zhu, Shengjin Wang
Current person re-identification (ReID) methods typically rely on single-frame imagery features, whilst ignoring space-time information from image sequences often available in the practical surveillance scenarios. Single-frame (single-shot) based visual appearance matching is inherently limited for person ReID in public spaces due to the challenging visual ambiguity and uncertainty arising from non-overlapping camera views where viewing condition changes can cause significant people appearance variations. In this work, we present a novel model to automatically select the most discriminative video fragments from noisy/incomplete image sequences of people from which reliable space-time and appearance features can be computed, whilst simultaneously learning a video ranking function for person ReID...
December 2016: IEEE Transactions on Pattern Analysis and Machine Intelligence
Ryan A Hallett, Seth P Zimmerman, Hayretin Yumerefendi, James E Bear, Brian Kuhlman
Light-inducible dimers are powerful tools for cellular optogenetics, as they can be used to control the localization and activity of proteins with high spatial and temporal resolution. Despite the generality of the approach, application of light-inducible dimers is not always straightforward, as it is frequently necessary to test alternative dimer systems and fusion strategies before the desired biological activity is achieved. This process is further hindered by an incomplete understanding of the biophysical/biochemical mechanisms by which available dimers behave and how this correlates to in vivo function...
January 15, 2016: ACS Synthetic Biology
Gurkan Guntas, Ryan A Hallett, Seth P Zimmerman, Tishan Williams, Hayretin Yumerefendi, James E Bear, Brian Kuhlman
The discovery of light-inducible protein-protein interactions has allowed for the spatial and temporal control of a variety of biological processes. To be effective, a photodimerizer should have several characteristics: it should show a large change in binding affinity upon light stimulation, it should not cross-react with other molecules in the cell, and it should be easily used in a variety of organisms to recruit proteins of interest to each other. To create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2 (LOV2) domain from Avena sativa...
January 6, 2015: Proceedings of the National Academy of Sciences of the United States of America
Zhenwei Gong, Oran Kennedy, Hui Sun, YingJie Wu, Garry A Williams, Laura Klein, Luis Cardoso, Ronald W Matheny, Gene B Hubbard, Yuji Ikeno, Roger P Farrar, Mitchell B Schaffler, Martin L Adamo, Radhika H Muzumdar, Shoshana Yakar
In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF-1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging...
June 2014: Aging Cell
Huanhuan Shen, Sébastien Coëtmellec, Gérard Gréhan, Marc Brunel
We report the development of an interferometric laser imaging for droplet sizing (ILIDS) numerical simulator. It is based on the use of generalized Huygens-Fresnel integrals associated to transfer matrices that describe the whole imaging setup. This simulator allows easy simulation of any kind of ILIDS setup. Simulations are shown to be in good agreement with experimental results. This simulator offers important perspectives in the design, realization, and calibration of ILIDS instruments, as airborne instruments, or in situ measurements in flows...
August 1, 2012: Applied Optics
Hayden-William Courtland, Sebastien Elis, Yingjie Wu, Hui Sun, Clifford J Rosen, Karl J Jepsen, Shoshana Yakar
Insulin-like growth factor-1 (IGF-1) plays a critical role in the development of the growing skeleton by establishing both longitudinal and transverse bone accrual. IGF-1 has also been implicated in the maintenance of bone mass during late adulthood and aging, as decreases in serum IGF-1 levels appear to correlate with decreases in bone mineral density (BMD). Although informative, mouse models to date have been unable to separate the temporal effects of IGF-1 depletion on skeletal development. To address this problem, we performed a skeletal characterization of the inducible LID mouse (iLID), in which serum IGF-1 levels are depleted at selected ages...
2011: PloS One
Yingjie Wu, Pnina Brodt, Hui Sun, Wilson Mejia, Ruslan Novosyadlyy, Nomeli Nunez, Xiaoli Chen, Arnulfo Mendoza, Sung-Hyeok Hong, Chand Khanna, Shoshana Yakar
Among the mechanisms implicated in the tumor-promoting effects of obesity, signaling by insulin-like growth factor-I (IGF-I) and insulin has received considerable attention. However, the emerging realization that obesity is associated with chronic inflammation has prompted other consideration of how the IGF-I axis may participate in cancer progression. In the present study, we used two mouse models of chronic (LID) and inducible (iLID) igf-1 gene deficiency in the liver to investigate the role of IGF-I in regulating the host microenvironment and colorectal carcinoma growth and metastasis in obese mice...
January 1, 2010: Cancer Research
No abstract text is available yet for this article.
January 1965: Medicinski Arhiv
R Klinck, E Westhof, S Walker, M Afshar, A Collier, F Aboul-Ela
Subdomain IlId from the hepatitis C virus (HCV) internal ribosome entry site (IRES) has been shown to be essential for cap-independent translation. We have conducted a structural study of a 27-nt fragment, identical in sequence to IlId, to explore the structural features of this subdomain. The proposed secondary structure of IlId is comprised of two 3 bp helical regions separated by an internal loop and closed at one end by a 6-nt terminal loop. NMR and molecular modeling were used interactively to formulate a validated model of the three-dimensional structure of IlId...
October 2000: RNA
Y Tsuda, K Wanaka, M Tada, S Okamoto, A Hijikata-Okunomiya, Y Okada
The synthetic plasma kallikrein (PK) inhibitor trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527) consists of three parts. Each part was replaced by analogues in an attempt to improve the potency and the selectivity of PKSI-527. Among the peptides examined, trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide 16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being as potent as PKSI-527.
March 1998: Chemical & Pharmaceutical Bulletin
V I Bunik, V S Gomazkova
The protective effect of alpha-ketoglutarate dehydrogenase substrate and its analogs on the enzyme inactivation by diethylpyrocarbonate was studied. The values of true rate constants for diethylpyrocarbonate-induced inactivation and the Kd values for the enzyme complexes with ligands were determined. A comparison of Kd values for a number of ligands suggests that the histidine residue of the enzyme active center interacts with the alpha-keto group of the substrate. A mechanism of this histidine residue involvement in the catalytic act is proposed...
August 1987: Biokhimii︠a︡
M Caproşu, M Ungureanu, G Grosu, M Petrovanu
Continuing the investigations on the synthesis and pharmacodynamic action of some pyridaziniu-ilides, this paper presents the results of the preliminary investigations on the antimicrobial activity of the synthetized products. Their action against Staphylococcus aureus Oxford and the anti-yeast action of the cycloimonium salts is underlined.
January 1991: Revista Medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti Din Iaş̧i
M Caproşu, M Ungureanu, G Grosu, M Petrovanu
Our investigation for obtaining carbon-nitrogen stable ilides continued by the synthesis of new phthalazinic derivatives by the action of ethyl brompyruvate. The structure of the obtained products was confirmed by chemical and spectral analyses. The results regarding their antimicrobial action are also presented.
January 1992: Revista Medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti Din Iaş̧i
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