Search

Your search keyword '"Gossett, Daniel"' showing total 47 results
Start Over Author "Gossett, Daniel"
47 results on '"Gossett, Daniel"'

1. Longitudinal Plasma Metabolome Patterns and Relation to Kidney Function and Proteinuria in Pediatric CKD

Author

Lee, Arthur M., Xu, Yunwen, Hu, Jian, Xiao, Rui, Hooper, Stephen R., Hartung, Erum A., Coresh, Josef, Rhee, Eugene P., Vasan, Ramachandran S., Kimmel, Paul L., Warady, Bradley A., Furth, Susan L., Denburg, Michelle R., Abraham, Alison, Anderson, Amanda, Ballard, Shawn, Bonventre, Joseph, Clish, Clary, Collins, Heather, Coca, Steven, Coresh, Josef, Deo, Rajat, Denburg, Michelle, Dubin, Ruth, Feldman, Harold I., Ferket, Bart S., Foster, Meredith, Furth, Susan, Ganz, Peter, Gossett, Daniel, Grams, Morgan, Greenberg, Jason, Gutiérrez, Orlando M., Hostetter, Tom, Inker, Lesley A., Ix, Joachim, Kimmel, Paul L., Klein, Jon, Levey, Andrew S., Massaro, Joseph, McMahon, Gearoid, Mifflin, Theodore, Nadkarni, Girish N., Parikh, Chirag, Ramachandran, Vasan S., Rebholz, Casey, Rhee, Eugene, Rovin, Brad, Sarnak, Mark, Sabbisetti, Venkata, Schelling, Jeffrey, Seegmiller, Jesse, Shlipak, Michael G., Shou, Haochang, Tin, Adriene, Waikar, Sushrut, Warady, Bradley, Whitehead, Krista, and Xie, Dawei

Published
2024
Full Text
View/download PDF

2. Report of the Standardized Outcomes in Nephrology-transplant Consensus Workshop on Establishing a Core Outcome Measure for Infection in Kidney Transplant Recipients

Author

Chan, Samuel, Cazzolli, Rosanna, Jaure, Allison, Johnson, David W., Hawley, Carmel M., Craig, Jonathan C., Sautenet, Benedicte, van Zwieten, Anita, Cao, Christopher, Dobrijevic, Ellen, Wilson, Greg, Scholes-Robertson, Nicole, Carter, Simon, Vastani, Tom, Cho, Yeoungjee, Blumberg, Emily, Brennan, Daniel C., Huuskes, Brooke M., Knoll, Greg, Kotton, Camille, Mamode, Nizam, Muller, Elmi, Phan Ha, Hai An, Tedesco-Silva, Helio, White, David M., Viecelli, Andrea K., Martin, Adam, Tong, Allison, Gonzalez, Andrea Matus, Viecelli, Andrea, Demaine, Andrew, Wang, Angela, Zwieten, Anita van, Demaine, Ann, Preston, Anthony, Sautenet, Benedicte, De Coninck, Brenda, Huuskes, Brooke, Kotton, Camille, Hawley, Carmel, Guha, Chandana, Wanner, Christoph, Gossett, Daniel, Johnson, David, Purdy, Deb, Tarumbwa, Dorcas, Dobrijevic, Ellen, Muller, Elmi, Diekmann, Fritz, Tyson, Gene, Wong, Germaine, Mundy, Gillian, Wilson, Greg, Tesdesco-Silva, Helio, Craig, Jonathan, Manera, Karine, Abbott, Kevin, Lentine, Krista, Marson, Lorna, Frurian, Lucrezia, Hilbrands, Luuk, Naesens, Maarten, Bellini, Maria Irene, Hempstalk, Matty, Isbel, Nicole, Scholes-Robertson, Nicole, Ferrari, Paolo, Rossignol, Patrick, Henman, Paul, Reese, Peter, Oberbauer, Rainer, Pecoits-Filho, Roberto, Cazzolli, Rosanna, Chan, Samuel, Muthuramalingam, Shyamsundar, Carter, Simon, Al-Jabary, Tamara, Harris, Tess, Vastani, Tom, Parapiboon, Watanyu, van Biesen, Wim, and Cho, Yeoungjee

Published
2024
Full Text
View/download PDF

3. Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD

Author

Lee, Arthur M., Xu, Yunwen, Hooper, Stephen R., Abraham, Alison G., Hu, Jian, Xiao, Rui, Matheson, Matthew B., Brunson, Celina, Rhee, Eugene P., Coresh, Josef, Vasan, Ramachandran S., Schrauben, Sarah, Kimmel, Paul L., Warady, Bradley A., Furth, Susan L., Hartung, Erum A., Denburg, Michelle R., Abraham, Alison, Anderson, Amanda, Ballard, Shawn, Bonventre, Joseph, Clish, Clary, Collins, Heather, Coca, Steven, Coresh, Josef, Deo, Rajat, Denburg, Michelle, Dubin, Ruth, Feldman, Harold I., Ferket, Bart S., Foster, Meredith, Furth, Susan, Ganz, Peter, Gossett, Daniel, Grams, Morgan, Greenberg, Jason, Gutiérrez, Orlando M., Hostetter, Tom, Inker, Lesley A., Ix, Joachim, Kimmel, Paul L., Klein, Jon, Levey, Andrew S., Massaro, Joseph, McMahon, Gearoid, Mifflin, Theodore, Nadkarni, Girish N., Parikh, Chirag, Ramachandran, Vasan S., Rebholz, Casey, Rhee, Eugene, Rovin, Brad, Sarnak, M., Sabbisetti, Venkata, Schelling, Jeffrey, Seegmiller, Jesse, Shlipak, Michael G., Shou, Haochang, Tin, Adriene, Waikar, Sushrut, Warady, Bradley, Whitehead, Krista, and Xie, Dawei

Published
2024
Full Text
View/download PDF

4. Association of Uremic Solutes With Cardiovascular Death in Diabetic Kidney Disease

Author

Massaro, Joseph, Clish, Clary, Denburg, Michelle, Furth, Susan, Warady, Bradley, Bonventre, Joseph, Waikar, Sushrut, McMahon, Gearoid, Sabbisetti, Venkata, Coresh, Josef, Grams, Morgan, Rebholz, Casey, Abraham, Alison, Tin, Adriene, Parikh, Chirag, Klein, Jon, Coca, Steven, Ferket, Bart S., Nadkarni, Girish N., Gossett, Daniel, Rovin, Brad, Levey, Andrew S., Inker, Lesley A., Foster, Meredith, Dubin, Ruth, Deo, Rajat, Anderson, Amanda, Mifflin, Theodore, Xie, Dawei, Shou, Haochang, Ballard, Shawn, Whitehead, Krista, Collins, Heather, Greenberg, Jason, Ganz, Peter, Sapa, Hima, Gutiérrez, Orlando M., Shlipak, Michael G., Katz, Ronit, Ix, Joachim H., Sarnak, Mark J., Cushman, Mary, Rhee, Eugene P., Kimmel, Paul L., Vasan, Ramachandran S., Schrauben, Sarah J., Feldman, Harold I., Seegmiller, Jesse C., Brunengraber, Henri, Hostetter, Thomas H., and Schelling, Jeffrey R.

Published
2022
Full Text
View/download PDF

5. Multiparameter mechanical and morphometric screening of cells.

Author

Masaeli, Mahdokht, Gupta, Dewal, O'Byrne, Sean, Tse, Henry TK, Gossett, Daniel R, Tseng, Peter, Utada, Andrew S, Jung, Hea-Jin, Young, Stephen, Clark, Amander T, and Di Carlo, Dino

Subjects
Fibroblasts, Animals, Humans, Mice, Microfluidic Analytical Techniques, Flow Cytometry, Cell Count, Rheology, Microfluidics, Biophysics, Phenotype, Embryonic Stem Cells, Hydrodynamics, Machine Learning
Abstract

We introduce a label-free method to rapidly phenotype and classify cells purely based on physical properties. We extract 15 biophysical parameters from cells as they deform in a microfluidic stretching flow field via high-speed microscopy and apply machine-learning approaches to discriminate different cell types and states. When employing the full 15 dimensional dataset, the technique robustly classifies individual cells based on their pluripotency, with accuracy above 95%. Rheological and morphological properties of cells while deforming were critical for this classification. We also show the application of this method in accurate classifying cells based on their viability, drug screening and detecting populations of malignant cells in mixed samples. We show that some of the extracted parameters are not linearly independent, and in fact we reach maximum classification accuracy by using only a subset of parameters. However, the informative subsets could vary depending on cell types in the sample. This work shows the utility of an assay purely based on intrinsic biophysical properties of cells to identify changes in cell state. In addition to a label-free alternative to flow cytometry in certain applications, this work, also can provide novel intracellular metrics that would not be feasible with labeled approaches (i.e. flow cytometry).

Published
2016

6. Digitally synthesized beat frequency multiplexing for sub-millisecond fluorescence microscopy

Author

Diebold, Eric D., Buckley, Brandon W., Gossett, Daniel R., and Jalali, Bahram

Subjects
Physics - Optics
Abstract

Fluorescence imaging is the most widely used method for unveiling the molecular composition of biological specimens. However, the weak optical emission of fluorescent probes and the tradeoff between imaging speed and sensitivity is problematic for acquiring blur-free images of fast phenomena, such as sub-millisecond biochemical dynamics in live cells and tissues, and cells flowing at high speed. We report a solution that achieves real-time pixel readout rates one order of magnitude faster than a modern electron multiplier charge coupled device (EMCCD) - the gold standard in high-speed fluorescence imaging technology. Deemed fluorescence imaging using radiofrequency-multiplexed excitation (FIRE), this approach maps the image into the radiofrequency spectrum using the beating of digitally synthesized optical fields. We demonstrate diffraction-limited confocal fluorescence imaging of stationary cells at a frame rate of 4.4 kHz, as well as fluorescence microscopy in flow at a throughput of approximately 50,000 cells per second., Comment: Main text, 4 figures, supplemental information

Published
2013
Full Text
View/download PDF

7. Rapid inertial solution exchange for enrichment and flow cytometric detection of microvesicles

Author

Dudani, Jaideep S, Gossett, Daniel R, Tse, Henry TK, Lamm, Robert J, Kulkarni, Rajan P, and Di Carlo, Dino

Subjects
Fluid Mechanics and Thermal Engineering, Engineering, Prevention, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Classical Physics, Interdisciplinary Engineering, Nanotechnology, Nanoscience & Nanotechnology, Fluid mechanics and thermal engineering
Abstract

Exosomes, nanosized membrane-bound vesicles released by cells, play roles in cell signaling, immunology, virology, and oncology. Their study, however, has been hampered by difficulty in isolation and quantification due to their size and the complexity of biological samples. Conventional approaches to improved isolation require specialized equipment and extensive sample preparation time. Therefore, isolation and detection methods of exosomes will benefit biological and clinical studies. Here, we report a microfluidic platform for inline exosome isolation and fluorescent detection using inertial manipulation of antibody-coated exosome capture beads from biological fluids.

Published
2015

8. RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS

Author

Dharmadhikari, Avinash V, primary, Abad, Maria Alba, additional, Khan, Sheraz, additional, Maroofian, Reza, additional, Sands, Tristan T, additional, Ullah, Farid, additional, Samejima, Itaru, additional, Wear, Martin A, additional, Moore, Kiara E, additional, Kondakova, Elena, additional, Mitina, Natalia, additional, Schaub, Theres, additional, Lee, Grace K, additional, Umandap, Christine H, additional, Berger, Sara M, additional, Iglesias, Alejandro D, additional, Popp, Bernt, additional, Jamra, Rami Abou, additional, Gabriel, Heinz, additional, Rentas, Stefan, additional, Rippert, Alyssa L, additional, Izumi, Kosuke, additional, Conlin, Laura K, additional, Koboldt, Daniel C, additional, Mihalic Mosher, Theresa, additional, Hickey, Scott E, additional, Albert, Dara VF, additional, Norwood, Haley, additional, Lewanda, Amy Feldman, additional, Dai, Hongzheng, additional, Liu, Pengfei, additional, Mitani, Tadahiro, additional, Marafi, Dana, additional, Pehlivan, Davut, additional, Posey, Jennifer E, additional, Lippa, Natalie, additional, Vena, Natalie, additional, Heinzen, Erin L, additional, Goldstein, David B, additional, Mignot, Cyril, additional, Agathe, Jean-Madeleine de Sainte, additional, Al-Sannaa, Nouriya Abbas, additional, Zamani, Mina, additional, Sadeghian, Saeid, additional, Seifia, Tahere, additional, Zaki, Maha S, additional, Abdel-Salam, Ghada MH, additional, Abdel-Hamid, Mohamed, additional, Alabdi, Lama, additional, Alkuraya, Fowzan Sami, additional, Dawoud, Heba, additional, Lofty, Aya, additional, Bauer, Peter, additional, Zifarelli, Giovanni, additional, Afzal, Erum, additional, Zafar, Faisal, additional, Efthymiou, Stephanie, additional, Gossett, Daniel, additional, Towne, Meghan C, additional, Yeneabat, Raey, additional, Wontakal, Sandeep N, additional, Aggarwal, Vimla S, additional, Rosenfeld, Jill A, additional, Tarabykin, Victor, additional, Ohta, Shinya, additional, Lupski, James R, additional, Houlden, Henry, additional, Earnshaw, William C, additional, Davis, Erica E, additional, Jeyaprakash, A Arockia, additional, and Liao, Jun, additional

Published
2024
Full Text
View/download PDF

9. Nomarski serial time-encoded amplified microscopy for high-speed contrast-enhanced imaging of transparent media

Author

Fard, Ali M, Mahjoubfar, Ata, Goda, Keisuke, Gossett, Daniel R, Di Carlo, Dino, and Jalali, Bahram

Subjects
Engineering, Biomedical Engineering, Bioengineering, (110.0180) Microscopy, (180.3170) Interference microscopy, (320.7160) Ultrafast technology, Optical Physics, Materials Engineering, Ophthalmology and optometry, Biomedical engineering, Atomic, molecular and optical physics
Abstract

High-speed high-contrast imaging modalities that enable image acquisition of transparent media without the need for chemical staining are essential tools for a broad range of applications; from semiconductor process monitoring to blood screening. Here we introduce a method for contrast-enhanced imaging of unstained transparent objects that is capable of high-throughput imaging. This method combines the Nomarski phase contrast capability with the ultrahigh frame rate and shutter speed of serial time-encoded amplified microscopy. As a proof of concept, we show imaging of a transparent test structure and white blood cells in flow at a shutter speed of 33 ps and a frame rate of 36.1 MHz using a single-pixel photo-detector. This method is expected to be a valuable tool for high-throughput screening of unstained cells.

Published
2011

10. Sequential Array Cytometry: Multi-Parameter Imaging with a Single Fluorescent Channel

Author

Gossett, Daniel R, Weaver, Westbrook M, Ahmed, Noor S, and Di Carlo, Dino

Subjects
Engineering, Biomedical Engineering, Bioengineering, Biotechnology, Genetics, Generic health relevance, Good Health and Well Being, Caco-2 Cells, Cell Separation, Flow Cytometry, Fluorescent Dyes, HeLa Cells, Humans, Microfluidic Analytical Techniques, Spectrometry, Fluorescence, Cytometry, Microfluidics, Single-cell, Immunocytochemistry, High content screening, Cellomics, Drug, discovery, Personalized medicine, Point-of-care, Hela Cells, Medical and Health Sciences, Biomedical engineering
Abstract

Heterogeneity within the human population and within diseased tissues necessitates a personalized medicine approach to diagnostics and the treatment of diseases. Functional assays at the single-cell level can contribute to uncovering heterogeneity and ultimately assist in improved treatment decisions based on the presence of outlier cells. We aim to develop a platform for high-throughput, single-cell-based assays using well-characterized hydrodynamic cell isolation arrays which allow for precise cell and fluid handling. Here, we demonstrate the ability to extract spatial and temporal information about several intracellular components using a single fluorescent channel, eliminating the problem of overlapping fluorescence emission spectra. Integrated with imaging technologies such as wide field-of-view lens-free fluorescent imaging, fiber-optic array scanning technology, and microlens arrays, use of a single fluorescent channel will reduce the cost of reagents and optical components. Specifically, we sequentially stain hydrodynamically trapped cells with three biochemical labels all sharing the same fluorescence excitation and emission spectrum. These markers allow us to analyze the amount of DNA, and compare nucleus-to-cytoplasm ratio, as well as glycosylation of surface proteins. By imaging cells in real-time we enable measurements of temporal localization of cellular components and intracellular reaction kinetics, the latter is used as a measurement of multi-drug resistance. Demonstrating the efficacy of this single-cell analysis platform is the first step in designing and implementing more complete assays, aimed toward improving diagnosis and personalized treatments to complex diseases.

Published
2011

11. Label-free cell separation and sorting in microfluidic systems

Author

Gossett, Daniel R., Weaver, Westbrook M., Mach, Albert J., Hur, Soojung Claire, Tse, Henry Tat, Lee, Wonhee, Amini, Hamed, and Di Carlo, Dino

Subjects
Chemistry, Food Science, Measurement Science and Instrumentation, Laboratory Medicine, Biochemistry, general, Analytical Chemistry, Environmental Monitoring/Analysis, Bioanalytical methods, Cell systems, Single cell analysis, Biochips, High-throughput screening, Microfluidics, Microfabrication, Separations, Instrumentation, Field-flow fractionation
Abstract

Cell separation and sorting are essential steps in cell biology research and in many diagnostic and therapeutic methods. Recently, there has been interest in methods which avoid the use of biochemical labels; numerous intrinsic biomarkers have been explored to identify cells including size, electrical polarizability, and hydrodynamic properties. This review highlights microfluidic techniques used for label-free discrimination and fractionation of cell populations. Microfluidic systems have been adopted to precisely handle single cells and interface with other tools for biochemical analysis. We analyzed many of these techniques, detailing their mode of separation, while concentrating on recent developments and evaluating their prospects for application. Furthermore, this was done from a perspective where inertial effects are considered important and general performance metrics were proposed which would ease comparison of reported technologies. Lastly, we assess the current state of these technologies and suggest directions which may make them more accessible. Figure A wide range of microfluidic technologies have been developed to separate and sort cells by taking advantage of differences in their intrinsic biophysical properties

Published
2010

12. Association of Integrated Proteomic and Metabolomic Modules with Risk of Kidney Disease Progression

Author

Schlosser, Pascal, Surapaneni, Aditya L., Borisov, Oleg, Schmidt, Insa M., Zhou, Linda, Anderson, Amanda, Deo, Rajat, Dubin, Ruth, Ganz, Peter, He, Jiang, Kimmel, Paul L., Li, Hongzhe, Nelson, Robert G., Porter, Anna C., Rahman, Mahboob, Rincon-Choles, Hernan, Shah, Vallabh, Unruh, Mark L., Vasan, Ramachandran S., Zheng, Zihe, Feldman, Harold I., Waikar, Sushrut S., Köttgen, Anna, Rhee, Eugene P., Coresh, Josef, Grams, Morgan E., Anderson, Amanda H., Appel, Lawrence J., Chen, Jing, Cohen, Debbie L., Dember, Laura M., Go, Alan S., Lash, James P., Rao, Panduranga S., Waikar, Sushrut, Schelling, Jeffrey, Denburg, Michelle, Furth, Susan, Warady, Bradley, Bonventre, Joseph, McMahon, Gearoid, Sabbisetti, Venkata, Coresh, Josef, Grams, Morgan, Rebholz, Casey, Abraham, Alison, Tin, Adriene, Parikh, Chirag, Klein, Jon, Coca, Steven, Ferket, Bart S., Nadkarni, Girish N., Rhee, Eugene, Kimmel, Paul L., Gossett, Daniel, Rovin, Brad, Shlipak, Michael G., Sarnak, M., Levey, Andrew S., Inker, Lesley A., Foster, Meredith, Gutiérrez, Orlando M., Ix, Joachim, Dubin, Ruth, Seegmiller, Jesse, Hostetter, Tom, Deo, Rajat, Li, Hongzhe, Ren, Yue, Schrauben, Sarah J., Feldman, Harold I., Anderson, Amanda, Mifflin, Theodore, Xie, Dawei, Shou, Haochang, Ballard, Shawn, Whitehead, Krista, Collins, Heather, Ramachandran, Vasan S., Greenberg, Jason, and Ganz, Peter

Published
2024
Full Text
View/download PDF

13. Association of Uremic Solutes With Cardiovascular Death in Diabetic Kidney Disease

Author

Sapa, Hima, primary, Gutiérrez, Orlando M., additional, Shlipak, Michael G., additional, Katz, Ronit, additional, Ix, Joachim H., additional, Sarnak, Mark J., additional, Cushman, Mary, additional, Rhee, Eugene P., additional, Kimmel, Paul L., additional, Vasan, Ramachandran S., additional, Schrauben, Sarah J., additional, Feldman, Harold I., additional, Seegmiller, Jesse C., additional, Brunengraber, Henri, additional, Hostetter, Thomas H., additional, Schelling, Jeffrey R., additional, Massaro, Joseph, additional, Clish, Clary, additional, Denburg, Michelle, additional, Furth, Susan, additional, Warady, Bradley, additional, Bonventre, Joseph, additional, Waikar, Sushrut, additional, McMahon, Gearoid, additional, Sabbisetti, Venkata, additional, Coresh, Josef, additional, Grams, Morgan, additional, Rebholz, Casey, additional, Abraham, Alison, additional, Tin, Adriene, additional, Parikh, Chirag, additional, Klein, Jon, additional, Coca, Steven, additional, Ferket, Bart S., additional, Nadkarni, Girish N., additional, Gossett, Daniel, additional, Rovin, Brad, additional, Levey, Andrew S., additional, Inker, Lesley A., additional, Foster, Meredith, additional, Dubin, Ruth, additional, Deo, Rajat, additional, Anderson, Amanda, additional, Mifflin, Theodore, additional, Xie, Dawei, additional, Shou, Haochang, additional, Ballard, Shawn, additional, Whitehead, Krista, additional, Collins, Heather, additional, Greenberg, Jason, additional, and Ganz, Peter, additional

Published
2022
Full Text
View/download PDF

14. High-throughput single-microparticle imaging flow analyzer

Author

Goda, Keisuke, Ayazi, Ali, Gossett, Daniel R., Sadasivam, Jagannath, Lonappan, Cejo K., Sollier, Elodie, Fard, Ali M., Hur, Soojung Claire, Adam, Jost, Murray, Coleman, Wang, Chao, Brackbill, Nora, Di Carlo, Dino, and Jalali, Bahram

Published
2012

17. Particle focusing mechanisms in curving confined flows

Author

Gossett, Daniel R. and Di Carlo, Dino

Subjects
Chemical equilibrium -- Research, Ion channels -- Research, Chemistry
Abstract

Particles in finite-inertia confined channel flows are known to segregate and focus to equilibrium positions whose number corresponds with the fold of symmetry of the channel's cross section. The addition of curvature into channels presumably modifies these equilibrium inertial focusing positions, because of the secondary flow induced in curved channels. Here, we identify the critical interaction of the secondary flow field with inertial lift forces to create complex sets of particle focusing positions that vary with the channel Reynolds number ([Re.sub.c]) and the inertial force ratio, which is a new dimensionless parameter that is based on the ratio of inertial lift to drag forces from the secondary flow. We use these results to identify microfluidic channel geometries to focus particles at rates an order of magnitude higher than previously shown (channel Reynolds number, [Re.sub.c] = 270) and develop design criteria for the focusing of potentially arbitrary-sized particles. In addition, our results indicate that channel curvature can lead to microfluidic designs with reduced fluidic resistance, useful for lower power inertial focusing or separation. These results will enable design of practical particle/ cell separation, filtration, and focusing systems for critical applications in biomedicine and environmental cleanup. 10.1021/ac901306y

Published
2009

18. High-Speed Manipulation of Cells and Particles for Single-Cell Analysis and Mechanophenotyping

Author

Gossett, Daniel Robert

Subjects
Biomedical engineering, Biophysics, Biomechanics, Cytometry, Diagnostics, Inertial Focusing, Mechanophenotyping, Microfluidics, Single Cell Analysis
Abstract

Due to the heterogeneity of cellular populations it is important to assay individual cells to garner an accurate representation of the system of interest, and oftentimes the cells which are most critical to detect are in a minority. High-throughput single-cell analysis methods, especially flow cytometry, possess this ability and have had a significant impact on the way many diseases are diagnosed and monitored and the way research in biology is performed. The frontiers of single-cell analysis lie in extending the accessibility of these methods to the point-of-care, where the cell manipulation strategies of traditional flow cytometry are ill-suited, and expanding upon the number and type of biomarkers which can be measured. This dissertation reports the development of new strategies for manipulating cells and particles in high-speed flows, a critical step toward meeting the needs of next-generation cytometric technologies. These strategies employ inertial phenomena present in finite Reynolds number confined flows to transfer cells and particles across laminar streamlines and perform operations on cells. Specifically, this dissertation reports the development of (1) a theoretical background and design criteria for inertial focusing at high Reynolds number, (2) a method for performing continuous rapid solution exchange around cells, and (3) a tool for assaying the mechanical properties of cells at a throughput comparable to flow cytometry (`deformability cytometry'). Generalized design rules, developed in the earlier work, were employed to develop tools for automated cellular sample preparation (`rapid inertial solution exchange') and to focus cells to ensure uniform hydrodynamic stretching in the deformability cytometry method and will be applicable to many future applications of inertial focusing for cytometry, imaging, and bead-based tools. Rapid inertial solution exchange will increase the accessibility of complicated assays to the point-of-care by increasing repeatability of cell-based protocols and minimizing labor-associated time and cost requirements while the label-free metrics provided by deformability cytometry stand in contrast to the variability and cost associated with label-based methods, and potentially extend the use of cytometric methods to new arenas and for more frequent and accurate monitoring of disease.

Published
2012

20. Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D

Author

Chen, Teresa K., Coca, Steven G., Estrella, Michelle M., Appel, Lawrence J., Coresh, Josef, Thiessen Philbrook, Heather, Obeid, Wassim, Fried, Linda F., Heerspink, Hiddo J.L., Ix, Joachim H., Shlipak, Michael G., Kimmel, Paul L., Parikh, Chirag R., Grams, Morgan E., Ramachandran, Vasan S., Massaro, Joseph, Clish, Clary, Schelling, Jeffrey, Denburg, Michelle, Furth, Susan, Warady, Bradley, Bonventre, Joseph, Waikar, Sushrut, McMahon, Gearoid, Sabbisetti, Venkata, Coresh, Josef, Grams, Morgan, Rebholz, Casey, Abraham, Alison, Tin, Adrienne, Parikh, Chirag, Klein, Jon, Coca, Steven, Ferket, Bart S, Nadkarni, Girish N., Rhee, Eugene, Kimmel, Paul L., Gossett, Daniel, Rovin, Brad, Shlipak, Michael G., Sarnak, M, Levey, Andrew S., Inker, Lesley A., Foster, Meredith, Guti?rrez, Orlando M., Ix, Joachim, Dubin, Ruth, Seegmiller, Jesse, Hostetter, Tom, Deo, Rajat, Feldman, Harold I., Anderson, Amanda, Mifflin, Theodore, Xie, Dawei, Shou, Haochang, Ballard, Shawn, Whitehead, Krista, Collins, Heather, Greenberg, Jason, and Ganz, Peter

Abstract

Recent research suggests that biomarkers of the TNF pathway (TNFR1 and TNFR2) are associated with worse kidney outcomes. Most of these studies, however, evaluated baseline levels rather than longitudinal changes. In two cohorts (AASK, which enrolled Black people with CKD attributed to hypertension, and VA NEPHRON-D, which enrolled veterans with albuminuric CKD and type 2 diabetes), greater longitudinal increases in serum or plasma TNFR1 and TNFR2 were associated with higher risks of ESKD in AASK and subsequent kidney function decline in VA NEPHRON-D. These associations were independent of baseline biomarker level and kidney function. Longitudinal trajectories in TNFR1 and TNFR2 may ultimately allow improved risk assessment for kidney failure in persons with CKD.

Published
2022
Full Text
View/download PDF

21. Statistical methods for building better biomarkers of chronic kidney disease

Author

Pencina, Michael J., primary, Parikh, Chirag R., additional, Kimmel, Paul L., additional, Cook, Nancy R., additional, Coresh, Josef, additional, Feldman, Harold I., additional, Foulkes, Andrea, additional, Gimotty, Phyllis A., additional, Hsu, Chi‐yuan, additional, Lemley, Kevin, additional, Song, Peter, additional, Wilkins, Kenneth, additional, Gossett, Daniel R., additional, Xie, Yining, additional, and Star, Robert A., additional

Published
2019
Full Text
View/download PDF

23. Overcoming Translational Barriers in Acute Kidney Injury

Author

Zuk, Anna, primary, Palevsky, Paul M., additional, Fried, Linda, additional, Harrell, Frank E., additional, Khan, Samina, additional, McKay, Dianne B., additional, Devey, Luke, additional, Chawla, Lakhmir, additional, de Caestecker, Mark, additional, Kaufman, James S., additional, Thompson, B. Taylor, additional, Agarwal, Anupam, additional, Greene, Tom, additional, Okusa, Mark Douglas, additional, Bonventre, Joseph V., additional, Dember, Laura M., additional, Liu, Kathleen D., additional, Humphreys, Benjamin D., additional, Gossett, Daniel, additional, Xie, Yining, additional, Norton, Jenna M., additional, Kimmel, Paul L., additional, and Star, Robert A., additional

Published
2018
Full Text
View/download PDF

24. Metabolite Biomarkers of CKD Progression in Children

Author

Denburg, Michelle R., Xu, Yunwen, Abraham, Alison G., Coresh, Josef, Chen, Jingsha, Grams, Morgan E., Feldman, Harold I., Kimmel, Paul L., Rebholz, Casey M., Rhee, Eugene P., Vasan, Ramachandran S., Warady, Bradley A., Furth, Susan L., Ramachandran, Vasan S., Massaro, Joseph, Clish, Clary, Schelling, Jeffrey, Denburg, Michelle, Furth, Susan, Warady, Bradley, Bonventre, Joseph, Waikar, Sushrut, McMahon, Gearoid, Sabbisetti, Venkata, Coresh, Josef, Grams, Morgan, Rebholz, Casey, Abraham, Alison, Tin, Adriene, Parikh, Chirag, Klein, Jon, Coca, Steven, Ferket, Bart S, Nadkarni, Girish N., Rhee, Eugene, Kimmel, Paul L., Gossett, Daniel, Rovin, Brad, Shlipak, Michael G., Sarnak, M, Levey, Andrew S., Inker, Lesley A., Foster, Meredith, Gutiérrez, Orlando M., Ix, Joachim, Dubin, Ruth, Seegmiller, Jesse, Hostetter, Tom, Deo, Rajat, Feldman, Harold I., Anderson, Amanda, Mifflin, Theodore, Xie, Dawei, Shou, Haochang, Ballard, Shawn, Whitehead, Krista, Collins, Heather, Greenberg, Jason, and Ganz, Peter

Published
2021
Full Text
View/download PDF

26. (Re)Building a Kidney

Author

Oxburgh, Leif, primary, Carroll, Thomas J., additional, Cleaver, Ondine, additional, Gossett, Daniel R., additional, Hoshizaki, Deborah K., additional, Hubbell, Jeffrey A., additional, Humphreys, Benjamin D., additional, Jain, Sanjay, additional, Jensen, Jan, additional, Kaplan, David L., additional, Kesselman, Carl, additional, Ketchum, Christian J., additional, Little, Melissa H., additional, McMahon, Andrew P., additional, Shankland, Stuart J., additional, Spence, Jason R., additional, Valerius, M. Todd, additional, Wertheim, Jason A., additional, Wessely, Oliver, additional, Zheng, Ying, additional, and Drummond, Iain A., additional

Published
2017
Full Text
View/download PDF

27. 3D ultrafast laser scanner

Author

Heisterkamp, Alexander, Mahjoubfar, A., Goda, Keisuke, Wang, Chao, Fard, Ali M., Adam, Jost, Gossett, Daniel R., Ayazi, Ali, Sollier, Elodie, Malik, Omer, Chen, E., Liu, Y., Brown, Rupert, Sarkhosh, N., Di Carlo, Dino, Jalali, Bahram, Herman, Peter R., Meunier, Michel, Nolte, Stefan, Heisterkamp, Alexander, Mahjoubfar, A., Goda, Keisuke, Wang, Chao, Fard, Ali M., Adam, Jost, Gossett, Daniel R., Ayazi, Ali, Sollier, Elodie, Malik, Omer, Chen, E., Liu, Y., Brown, Rupert, Sarkhosh, N., Di Carlo, Dino, Jalali, Bahram, Herman, Peter R., Meunier, Michel, and Nolte, Stefan

Abstract

Laser scanners are essential for scientific research, manufacturing, defense, and medical practice. Unfortunately, often times the speed of conventional laser scanners (e.g., galvanometric mirrors and acousto-optic deflectors) falls short for many applications, resulting in motion blur and failure to capture fast transient information. Here, we present a novel type of laser scanner that offers roughly three orders of magnitude higher scan rates than conventional methods. Our laser scanner, which we refer to as the hybrid dispersion laser scanner, performs inertia-free laser scanning by dispersing a train of broadband pulses both temporally and spatially. More specifically, each broadband pulse is temporally processed by time stretch dispersive Fourier transform and further dispersed into space by one or more diffractive elements such as prisms and gratings. As a proof-of-principle demonstration, we perform 1D line scans at a record high scan rate of 91 MHz and 2D raster scans and 3D volumetric scans at an unprecedented scan rate of 105 kHz. The method holds promise for a broad range of scientific, industrial, and biomedical applications. To show the utility of our method, we demonstrate imaging, nanometer-resolved surface vibrometry, and high-precision flow cytometry with real-time throughput that conventional laser scanners cannot offer due to their low scan rates. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Published
2013

28. Real-time image processor for detection of rare cells and particles in flow at 37 MHz line scans per second

Author

Farkas, Daniel L., Ayazi, Ali, Goda, Keisuke, Sadasivam, Jagannath, Lonappan, Cejo K., Gossett, Daniel R., Sollier, Elodie, Fard, Ali M., Hur, Soojung Claire, Kim, Sujin, Adam, Jost, Murray, Coleman, Wang, Chao, Brackbill, Nora, Di Carlo, Dino, Jalali, Bahram, Nicolau, Dan V., Leif, Robert C., Farkas, Daniel L., Ayazi, Ali, Goda, Keisuke, Sadasivam, Jagannath, Lonappan, Cejo K., Gossett, Daniel R., Sollier, Elodie, Fard, Ali M., Hur, Soojung Claire, Kim, Sujin, Adam, Jost, Murray, Coleman, Wang, Chao, Brackbill, Nora, Di Carlo, Dino, Jalali, Bahram, Nicolau, Dan V., and Leif, Robert C.

Abstract

We describe a real-time image processor that has enabled a new automated flow through microscope to screen cells in flow at 100,000 cells/s and a record false positive rate of one in a million. This unit is integrated with an ultrafast optical imaging modality known as serial time-encoded amplified microscopy (STEAM) for blur-free imaging of particles in high-speed flow. We show real-time image-based identification and screening of budding yeast cells and rare breast cancer cells in blood. The system generates E-slides (an electronic version of glass slides) on which particles of interest are digitally analyzed.

Published
2013

31. Size-selective collection of circulating tumor cells using Vortex technology

Author

Sollier, Elodie, primary, Go, Derek E., additional, Che, James, additional, Gossett, Daniel R., additional, O'Byrne, Sean, additional, Weaver, Westbrook M., additional, Kummer, Nicolas, additional, Rettig, Matthew, additional, Goldman, Jonathan, additional, Nickols, Nicholas, additional, McCloskey, Susan, additional, Kulkarni, Rajan P., additional, and Di Carlo, Dino, additional

Published
2014
Full Text
View/download PDF

44. Hexanucleotide repeat expansions in C9ORF72in the spectrum of motor neuron diseases

Author

van Rheenen, Wouter, van Blitterswijk, Marka, Huisman, Mark H.B., Vlam, Lotte, Doormaal, Perry T.C. van, Seelen, Meinie, Medic, Jelena, Dooijes, Dennis, de Visser, Marianne, Kooi, Anneke J. van der, Raaphorst, Joost, Schelhaas, Helenius J., Pol, W. Ludo van der, Veldink, Jan H., Berg, Leonard H. van den, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Clifford, R. Jack, Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Beckett, Laurel, Harvey, Danielle, Gamst, Anthony, Donohue, Michael, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Cairns, Nigel J., Taylor-Reinwald, Lisa, Shaw, Les, Lee, Virginia M.Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M., Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Johnson, Kris, S. Doody, Rachelle, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, Leon, Mony J de, Glodzik, Lidia, Doraiswamy, P. Murali, Petrella, Jeffrey R., Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Apostolova, Liana, Graff-Radford, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., Dyck, Christopher H. van, Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Frey, Meghan, Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Obisesan, Thomas O., Wolday, Saba, Bwayo, Salome K., Lerner, Alan, Hudson, Leon, Ogrocki, Paula, DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Saykin, Andrew J., Santulli, Robert B., Schwartz, Eben S., Williamson, Jeff D., Sink, Kaycee M., Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Kwon, Sun-Uck, Kim, Joon-Tae, Cho, Ki-Hyun, Shin, Dong-Ick, Ko, Yungchai, Lee, Soo Joo, Cha, Jae-Kwan, Kim, Yong-Jae, Shin, Dong-Jin, Jang, Hyuk, Choi, Nack-Cheon, Hong, Seok-Chang, Rha, Joung-Ho, Hong, Keun-Sik, Kim, Eung-Gyu, Choi, Jay Chol, Sohn, Sung-Il, Shin, Won Chul, HyukHeo, Sung, Chung, Kyung Cheon, Park, Jong-Ho, Lee, Jun Hong, Park, Jong-Moo, Park, Tai Hwan, Bae, Hee-Joon, Han, Moon-Ku, Kwon, Hyung-Min, Lee, Kyung Bok, Lee, Tae-Kyeong, Jeong, Dushin, Lee, Jun, Ashwal, Steve, deVeber, Gabrielle, Ferriero, Donna, Fullerton, Heather, Ichord, Rebecca, Kirkham, Fenella, Lynch, John K., O'Callaghan, Finbar, Pavlakis, Steve, Sebire, Guillaume, Willan, Andrew, Willan, Andrew, Sofronas, Marianne, Dlamini, Noma, Elbers, Jorina, Nowak-Göttl, Ulrike, Düring, Christine, Krümpel, Anne, Plumb, Patricia, Journeycake, Janna, van de Bruinhorst, Katrina, Gossett, Daniel, Chavez, Marta Isabel Hernandez, Monagle, Paul, MacKay, Mark, Barnes, Chris, Furmedge, Janine, Gordon, Anne, Benedict, Susan L., Bale, James F., Nielson, Denise, Abdalla, Abdalla, Chadehumbe, Madeline, Kabbouche, Marielle, Karti, Pooja, Phillips, Tonya, Friedman, Neil, Rizkallah, Elie, Zamel, Khaled, Wiznitzer, Max, Lidsky, Karen, Bernard, Timothy, Goldenberg, Neil A., Armstrong-Wells, Jennifer, Booth, Frances, Nash, Monica, Beslow, Lauren, Carpenter, Jessica, Chang, Taeun, Weinstein, Steven, Kan, Li, Smith, Robin, Maytal, Joseph, Sy-Kho, Rosemarie, Yager, Jerome Y., Massicotte, Patti, Ashwal, Steve, McClure, Chalmer, Bjornson, Bruce, Hukin, Juliet, Bucevska, Marija, Kent, Sheila, Riviello, James, Rivkin, Michael, Trenor, Cameron, Amlie-Lefond, Catherine, Whelan, Harry T., Ferriero, Donna, Fullerton, Heather, Fox, Christine, Pavlakis, Steve, Goodman, Sharon, Levinson, Kim, Kolk, Anneli, Laugesaar, Rael, Talvik, Tiina, Imam, Hussain, Thomas, Terrence, Golomb, Meredith, Kirton, Adam, Heyer, Geoffrey, Ganesan, Vijeya, Saengpattrachai, Montri, Crosswell, Hal, Mancuso, Ann, Tatishvili, Nana, Yeh, Ann, Humpherys, Peter, Abraham, Lisa, Alveal, Lucila Andrade, Ortiz, Manuel Arriaza, Altuna, Diana, Maxit, Clarisa, Gonzalez, Veronica, Alam, Muhammad, Buckley, David, Penney, Sharon, Jordan, Lori, Grabowski, Eric, Chan, Anthony, Deray, Marcel, Khatib, Zaid, Kovacevic, Gordana, Kosofsky, Barry, Leifer, Dana, Nass, Ruth, Wong, Virginia, Catsman, Coriene, El-Hakam, Lisa, Sebire, Guillaume, Cholette, Jill M., Narang, Shalu, Lerner, Norma B., Carpenter, Shannon, Bischoff, Kurt, Frei-Jones, Melissa, Masur, David, Epstein, Leon G, Bagiella, Emilia, Hinton, Veronica J., Gallentine, William, Rende, Elizabeth, Provenzale, James, Voyvodic, James, Song, Allen, Conklin, Terrie, O'Hara, Kathryn, Seinfeld, Syndi, Conry, Joan, Glauser, Tracy, Ayala, Jennifer, Facchini, Ronda, Sigalova, Maryana, Hannigan, James, Weiss, Erica, Mancini, Ann, Curran, John, Ahlm, Sarah, Renaldi, Julie, Umanzour, Diana K, Kim, Andrew, Hamidullah, Aaliyah, Litherland, Claire, Bonner, Melanie, Xu, Yuan, Van de Water, Virginia, Grasso, Susan, Kushner, David, Culbert, James, Bush, Brian J, Chandrasekaran, Sreedevi, Davis, Lori L, Rogers, Christiane, Sabo, Cynthia Shier, Wang, Helen, and Noebels, Jeffrey L

Abstract

To assess the frequency and phenotype of hexanucleotide repeat expansions in C9ORF72in a large cohort of patients of Dutch descent with familial (fALS) and sporadic (sALS) amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS).

Published
2012
Full Text
View/download PDF

45. Ed Marston remembered.

Author

Ring, Ray, Saiff, Edward, Richmond, Charlie, Jones, Lisa, Farrell, Sean Patrick, Hanscom, Greg, Storer, Liz, Propst, Luther, Sibley, George, Fulkerson, Bob, Gossett, Daniel, Christensen, Jon, Wiessner, Andy, Jenkins, Matt, Hamilton, Bruce, Hamilton, Joan, and Williams, Florence

Published
2018

46. RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS.

Author

Dharmadhikari AV, Abad MA, Khan S, Maroofian R, Sands TT, Ullah F, Samejima I, Wear MA, Moore KE, Kondakova E, Mitina N, Schaub T, Lee GK, Umandap CH, Berger SM, Iglesias AD, Popp B, Jamra RA, Gabriel H, Rentas S, Rippert AL, Izumi K, Conlin LK, Koboldt DC, Mosher TM, Hickey SE, Albert DVF, Norwood H, Lewanda AF, Dai H, Liu P, Mitani T, Marafi D, Pehlivan D, Posey JE, Lippa N, Vena N, Heinzen EL, Goldstein DB, Mignot C, de Sainte Agathe JM, Al-Sannaa NA, Zamani M, Sadeghian S, Azizimalamiri R, Seifia T, Zaki MS, Abdel-Salam GMH, Abdel-Hamid M, Alabdi L, Alkuraya FS, Dawoud H, Lofty A, Bauer P, Zifarelli G, Afzal E, Zafar F, Efthymiou S, Gossett D, Towne MC, Yeneabat R, Wontakal SN, Aggarwal VS, Rosenfeld JA, Tarabykin V, Ohta S, Lupski JR, Houlden H, Earnshaw WC, Davis EE, Jeyaprakash AA, and Liao J

Abstract

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, we identified 24 individuals with neurodevelopmental delays from 18 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants showed reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicated that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 revealed that most disease-associated missense variants mapped to the catalytic domain. Additionally, SPOUT1/CENP-32 recurrent missense variants had reduced methyltransferase activity in vitro and compromised centrosome tethering to the spindle poles in human cells. Thus, SPOUT1/CENP-32 pathogenic variants cause an autosomal recessive neurodevelopmental disorder: SpADMiSS ( SPOUT1 Associated Development delay Microcephaly Seizures Short stature) underpinned by mitotic spindle organization defects and consequent chromosome segregation errors.

Published
2024
Full Text
View/download PDF

47. Introduction: why analyze single cells?

Author

Di Carlo D, Tse HT, and Gossett DR

Subjects
Animals, Gene Expression Profiling instrumentation, Gene Expression Profiling methods, Humans, Microfluidic Analytical Techniques instrumentation, Microtechnology, Single-Cell Analysis instrumentation, Microfluidic Analytical Techniques methods, Single-Cell Analysis methods
Abstract

Powerful methods in molecular biology are abundant; however, in many fields including hematology, stem cell biology, tissue engineering, and cancer biology, data from tools and assays that analyze the average signals from many cells may not yield the desired result because the cells of interest may be in the minority-their behavior masked by the majority-or because the dynamics of the populations of interest are offset in time. Accurate characterization of samples with high cellular heterogeneity may only be achieved by analyzing single cells. In this chapter, we discuss the rationale for performing analyses on individual cells in more depth, cover the fields of study in which single-cell behavior is yielding new insights into biological and clinical questions, and speculate on how single-cell analysis will be critical in the future.

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results