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Aging impairs the osteocytic regulation of collagen integrity and bone quality

Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna Bons Christina D.King Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck Institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly *** molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by *** hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material *** examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses *** control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)*** relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical *** effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

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Information-Theoretic Design for High-Dimensional Computational Imaging

Information-Theoretic Design for High-Dimensional Computatio...

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Computational Optical Sensing and Imaging, COSI 2024 - Part of Optica Imaging Congress

作者： Markley, Eric Kabuli, Leyla Chien, Tiffany Pinkard, Henry Waller, Laura UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley United States Department of Electrical Engineering and Computer Sciences University of California Berkeley United States

We present a technique for information-theoretic optimization of computational imaging systems demonstrated in snapshot 3D microscopy. By directly evaluating measurement quality and decoupling optimization from downst... 详细信息

关键词： Decoding

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TOWARDS SINGLE-CELL PROTEOFORM PROFILING: ON-CHIP ISOELECTRIC FOCUSING IN IMMOBILIZED PH GRADIENT GELS

TOWARDS SINGLE-CELL PROTEOFORM PROFILING: ON-CHIP ISOELECTRI...

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2022 Solid-State Sensors, Actuators and Microsystems Workshop, Hilton Head 2022

作者： Lomeli, Gabriela Herr, Amy E. UC Berkeley-UCSF Graduate Program in Bioengineering CA United States Department of Bioengineering University of California BerkeleyCA United States Chan Zuckerberg Biohub San FranciscoCA United States

ISBN: (纸本)9781940470047

Microfluidic tools are an essential capability in understanding cell-to-cell heterogeneity. Similarly, precision microanalytical tools can play an outsize role in measuring molecule-to-molecule heterogeneity, especially as protein post-translational modifications create proteoforms that execute regular and aberrant cellular functions. Although highly related, slight variations in protein charge contribute to proteoform heterogeneity. Electrophoretic methods, including immobilized pH gradient isoelectric focusing (IPG-IEF), provide the resolution to measure subtle protein-to-protein differences. However, conventional IPG-IEF can be low-throughput and requires large starting sample amounts, precluding single-cell analysis. Here, we present the first polydimethylsiloxane (PDMS)-based, immunoprobed, microfluidic IPG-IEF device to our knowledge. We demonstrate separation performance on par with our single-cell IEF device, including resolving analytes differing by only 0.1 pH. © 2022 TRF.

关键词： Electrophoresis

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Layered Diffusion Model for One-Shot High Resolution Text-to-Image Synthesis

arXiv

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arXiv 2024年

作者： Khwaja, Emaad Rashwan, Abdullah Chen, Ting Wang, Oliver Kothawade, Suraj Li, Yeqing UC Berkeley UCSF Joint Bioengineering Graduate Program United States Computer Science Division UC Berkeley United States Google United States Google Deepmind United Kingdom

We present a one-shot text-to-image diffusion model that can generate high-resolution images from natural language descriptions. Our model employs a layered U-Net architecture that simultaneously synthesizes images at multiple resolution scales. We show that this method outperforms the baseline of synthesizing images only at the target resolution, while reducing the computational cost per step. We demonstrate that higher resolution synthesis can be achieved by layering convolutions at additional resolution scales, in contrast to other methods which require additional models for super-resolution synthesis. © 2024, CC BY.

关键词： Diffusion

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OLIGONucLEOTIDE FUNCTIONALIZED POLYACRYLAMIDE BEADS FOR AMPLIFICATION BASED BIOMARKER DETECTION 25

OLIGONUCLEOTIDE FUNCTIONALIZED POLYACRYLAMIDE BEADS FOR AMPL...

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25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021

作者： Chaves, Rodrigo Cotrim Streets, Aaron University of California BerkeleyCA United States UC Berkeley UCSF Graduate Program in Bioengineering CA United States

ISBN: (纸本)9781733419031

Single-cell quantitative biomarker analysis is a powerful technique for studying tissue heterogeneity, but commonly used staining techniques cannot detect markers with lower than 100 target molecules per cell [1]. Here we report a droplet microfluidic platform for encapsulation of samples in Polyacrylamide (PA) hydrogel beads, and staining for fluorescence analysis. This is achieved by functionalizing the PA with oligonucleotides designed to capture biomarkers of interest, and amplifying targets through PCR, enabling sensitive detection of DNA, RNA or protein molecules with low copy number for quantification of cellular populations with traditional flow cytometry. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

关键词： Oligonucleotides

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MULTIPLEXED DNA-DIRECTED PATTERNING OF ANTIBODIES FOR SINGLE-CELL SURFACE MARKER ANALYSIS 25

MULTIPLEXED DNA-DIRECTED PATTERNING OF ANTIBODIES FOR SINGLE...

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25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021

作者： Kozminsky, Molly Scheideler, Olivia J. Li, Brian Liu, Nathaniel K. Sohn, Lydia L. California Institute of Quantitative Biosciences Berkeley United States UC Berkeley-UCSF Graduate Program in Bioengineering Berkeley and San Francisco United States UC Berkeley Department of Mechanical Engineering Berkeley United States

ISBN: (纸本)9781733419031

Cell surface marker expression is a ubiquitously measured property of single-cell phenotypes. However, measuring several markers with exogenous labels can be costly and complex. We applied a novel bioconjugation chemistry known as DNA-directed patterning to functionalize glass substrates with great specificity and flexibility. Combined with a newly-designed node-pore sensing device, we have developed a flexible and label-free platform for multiplexed surface-marker screening of single cells. In this work, we present our design and demonstrate our platform's capability to screen two example cell types for surface-marker expression. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

关键词： DNA

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DEVELOPING A DIGITAL TWIN FOR SINGLE-CELL MECHANICAL PHENOTYPING MICROFLUIDIC DEVICES 26

DEVELOPING A DIGITAL TWIN FOR SINGLE-CELL MECHANICAL PHENOTY...

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26th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2022

作者： Roychowdhury, Sayan Mahmud, Samreen T. Puleri, Daniel F. Lai, Andre Rex, Rachel Li, Brian Sohn, Lydia L. Randles, Amanda Department of Biomedical Engineering Duke University United States UC Berkeley-UC San Francisco Graduate Program in Bioengineering University of California Berkeley United States Department of Mechanical Engineering University of California Berkeley United States

ISBN: (纸本)9781733419048

Microfluidics can be used to characterize individual cells in a population based on their mechanical traits. In this work, we digitally replicate the microfluidic device developed by Li et al. [1] and perform simulations of a representative AP-1060 cell. We show that the numerical model is able to recover whole-cell deformability index, a metric used to quantify the resistance of cells to compressive deformation, within 3% of the experimental average. These results pave the way for future studies which utilize experimental and computational approaches to optimize geometric design parameters, complement signal analysis, and enhance the acquisition of mechanical information. © 2022 MicroTAS 2022 - 26th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

关键词： Fluid structure interaction

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Spectral DefocusCam: hyperspectral imaging using defocus and a spectral filter array

Spectral DefocusCam: hyperspectral imaging using defocus and...

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Computational Optical Sensing and Imaging, COSI 2022

作者： Foley, Christian Monakhova, Kristina Yanny, Kyrollos Waller, Laura Department of Electrical Engineering and Computer Sciences University of California Berkeley United States UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley United States

We propose a compact hyperspectral camera based on a focus-tunable lens and spectral filter array. The camera captures then fuses multiple defocused measurements to obtain a high-resolution hyperspectral volume. ©... 详细信息

ISBN: (纸本)9781557528209

关键词： Hyperspectral imaging

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FABRICATION OF STABLE GRADIENTS IN A HYDROGEL-FILLED MICROFLUIDIC DEVICE 25

FABRICATION OF STABLE GRADIENTS IN A HYDROGEL-FILLED MICROFL...

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25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021

ISBN: (纸本)9781733419031

Gradients play a key role in mimicking biological conditions in situ and in separating biological species for analysis. Current methods to generate microscale gradients typically require high reagent consumption and enclosed microfluidic devices. Here, we introduce a simple and controllable method to generate stable immobilized gradients in a hydrogel-filled PDMS channel using only 7 µL of reagent. The versatile fabrication technique forms gradients of compounds containing an abstractable hydrogen (C-H) bond. Moreover, the PDMS can be detached from the glass substrate for open access to the gradient gel. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

关键词： Hydrogels

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SAME-CELL, SINGLE-CELL DETECTION OF PROTEIN ISOFORMS AND NucLEIC ACIDS 25

SAME-CELL, SINGLE-CELL DETECTION OF PROTEIN ISOFORMS AND NUC...

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25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021

作者： Gomez Martinez, Ana E. Rosas-Canyelles, Elisabet Modzelewski, Andrew J. Geldert, Alisha Gopal, Anjali He, Lin Herr, Amy E. Department of Bioengineering University of California Berkeley BerkeleyCA United States UC Berkeley-UCSF Graduate Program in Bioengineering United States Division of Cellular and Developmental Biology Department of Molecular & Cell Biology University of California BerkeleyCA United States

ISBN: (纸本)9781733419031

Single-cell 'omics is advancing rapidly, but there are gaps in linking nucleic acids to proteins in their myriad forms. To surmount this gap, we describe a microfluidic device that reports information on nucleic acids and proteoforms, or proteins that arise from a variety of modifications to nucleic acids or proteins, which are detected by immunoblotting (triBlot). The triBlot fractionates nuclei from the cytoplasm, allowing analysis of cytoplasmic proteoforms. Then, nuclei-laden regions are laser excised to perform PCR/RT-qPCR. We correlate DNA, mRNA, and protein expression from the same few cells, a step forward in 'omics that measure diverse protein forms. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

关键词： Proteins

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