Recursos de colección

Caltech Authors (163.728 recursos)

Repository of works by Caltech published authors.

Group = Heritage Medical Research Institute

Mostrando recursos 1 - 20 de 62

  1. Searching for the gut microbial contributing factors to social behavior in rodent models

    Needham, Brittany D.; Tang, Weiyi; Wu, Wei-Li
    Social impairment is one of the major symptoms in multiple psychiatric disorders, including autism spectrum disorder (ASD). Accumulated studies indicate a crucial role for the gut microbiota in social development, but these mechanisms remain unclear. This review focuses on two strategies adopted to elucidate the complicated relationship between gut bacteria and host social behavior. In a top-down approach, researchers have attempted to correlate behavioral abnormalities with altered gut microbial profiles in rodent models of ASD, including BTBR mice, maternal immune activation (MIA), maternal valproic acid (VPA) and maternal high-fat diet (MHFD) offspring. In a bottom-up approach, researchers use germ-free (GF)...

  2. Surface-Enhanced Raman Spectroscopy-Based Label-Free Insulin Detection at Physiological Concentrations for Analysis of Islet Performance

    Cho, Hyunjun; Kumar, Shailabh; Yang, Daejong; Vaidyanathan, Sagar; Woo, Kelly; Garcia, Ian; Shue, Hao J.; Yoon, Youngzoon; Ferreri, Kevin; Choo, Hyuck
    Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment; however, no existing method has met these criteria at physiological concentrations. Using spatially uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers. Label-free measurements of the islet secretions showed excellent correlation among the ambient glucose levels, secreted insulin concentrations, and measured Raman-emission intensities. When excited at 785 nm, plasmonic...

  3. Surface-Enhanced Raman Spectroscopy-Based Label-Free Insulin Detection at Physiological Concentrations for Analysis of Islet Performance

    Cho, Hyunjun; Kumar, Shailabh; Yang, Daejong; Vaidyanathan, Sagar; Woo, Kelly; Garcia, Ian; Shue, Hao J.; Yoon, Youngzoon; Ferreri, Kevin; Choo, Hyuck
    Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment; however, no existing method has met these criteria at physiological concentrations. Using spatially uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers. Label-free measurements of the islet secretions showed excellent correlation among the ambient glucose levels, secreted insulin concentrations, and measured Raman-emission intensities. When excited at 785 nm, plasmonic...

  4. Total Synthesis of (+)-Pleuromutilin

    Farney, Elliot P.; Feng, Sean S.; Schäfers, Felix; Reisman, Sarah E.
    An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps of the synthesis include a highly stereoselective SmI2-mediated cyclization to establish the eight-membered ring, and a stereospecific transannular [1,5]-hydrogen atom transfer to set the C10 stereocenter. This strategy was also used to prepare (+)-12-epi-pleuromutilin. The chemistry described here will enable efforts to prepare new mutilin antibiotics.

  5. Total Synthesis of (+)-Pleuromutilin

    Farney, Elliot P.; Feng, Sean S.; Schäfers, Felix; Reisman, Sarah E.
    An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps of the synthesis include a highly stereoselective SmI2-mediated cyclization to establish the eight-membered ring and a stereospecific transannular [1,5]-hydrogen atom transfer to set the C10 stereocenter. This strategy was also used to prepare (+)-12-epi-pleuromutilin. The chemistry described here will enable efforts to prepare new mutilin antibiotics.

  6. SERS-Based Label-Free Insulin Detection at Physiological Concentrations for Analysis of Islet Performance

    Cho, Hyunjun; Kumar, Shailabh; Yang, Daejong; Vaidyanathan, Sagar R.; Woo, Kelly; Garcia, Ian; Shue, Hao Jan; Yoon, Youngzoon; Ferreri, Kevin; Choo, Hyuck
    Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment, however no existing method has met these criteria at physiological concentrations. Using spatially-uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers. Label-free measurements of the islet secretions showed excellent correlation among the ambient glucose levels, secreted insulin concentrations, and measured Raman-emission intensities. When excited at 785 nm, plasmonic hotspots...

  7. Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits

    Szablowski, Jerzy O.; Lue, Brian; Lee-Gosselin, Audrey; Malounda, Dina; Shapiro, Mikhail G.
    Neurological and psychiatric diseases often involve the dysfunction of specific neural circuits in particular regions of the brain. Existing treatments, including drugs and implantable brain stimulators, aim to modulate the activity of these circuits, but are typically not cell type-specific, lack spatial targeting or require invasive procedures. Here, we introduce an approach to modulating neural circuits noninvasively with spatial, cell-type and temporal specificity. This approach, called acoustically targeted chemogenetics, or ATAC, uses transient ultrasonic opening of the blood brain barrier to transduce neurons at specific locations in the brain with virally-encoded engineered G-protein-coupled receptors, which subsequently respond to systemically administered...

  8. Ultrasonic Neuromodulation Causes Widespread Cortical Activation via an Indirect Auditory Mechanism

    Sato, Tomokazu; Shapiro, Mikhail G.; Tsao, Doris Y.
    Ultrasound has received widespread attention as an emerging technology for targeted, non-invasive neuromodulation based on its ability to evoke electrophysiological and motor responses in animals. However, little is known about the spatiotemporal pattern of ultrasound-induced brain activity that could drive these responses. Here, we address this question by combining focused ultrasound with wide-field optical imaging of calcium signals in transgenic mice. Surprisingly, we find cortical activity patterns consistent with indirect activation of auditory pathways rather than direct neuromodulation at the ultrasound focus. Ultrasound-induced activity is similar to that evoked by audible sound. Furthermore, both ultrasound and audible sound elicit motor...

  9. Black silicon as a multifunctional material for medical implants: First demonstrated use in in-vivo intraocular pressure sensing

    Narasimhan, Vinayak; Lee, Jeong Oen; Du, Juan; Ndjamen, Blaise; Sretavan, David; Choo, Hyuck
    We report the first in vivo demonstrated use of multifunctional black silicon (b-Si) on medical implants. B-Si is integrated onto the surface of a highly miniaturized sub-mm implantable intraocular pressure (IOP) sensor. This integration has significantly improved sensor signal-to-noise ratio (SNR) through the suppression of background noise as well as durability through minimized device biofouling. The incorporation of b-Si has enabled the use of a slit-lamp, the most widely used clinical ophthalmic microscope, for real-time IOP measurements on fully awake rabbits at a world-record 12-cm readout distance. Furthermore, b-Si has shown remarkable antifouling properties during a 6-month in vivo study...

  10. Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts

    Bourdeau, Raymond W.; Lee-Gosselin, Audrey; Lakshmanan, Anupama; Farhadi, Arash; Kumar, Sripriya Ravindra; Nety, Suchita P.; Shapiro, Mikhail G.
    The mammalian microbiome has many important roles in health and disease1,2, and genetic engineering is enabling the development of microbial therapeutics and diagnostics3,4,5,6,7. A key determinant of the activity of both natural and engineered microorganisms in vivo is their location within the host organism8,9. However, existing methods for imaging cellular location and function, primarily based on optical reporter genes, have limited deep tissue performance owing to light scattering or require radioactive tracers10,11,12. Here we introduce acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound, a widely available inexpensive technique with...

  11. Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light

    Ruan, Haowen; Brake, Joshua; Robinson, J. Elliott; Liu, Yan; Jang, Mooseok; Xiao, Cheng; Zhou, Chunyi; Gradinaru, Viviana; Yang, Changhuei
    Noninvasive light focusing deep inside living biological tissue has long been a goal in biomedical optics. However, the optical scattering of biological tissue prevents conventional optical systems from tightly focusing visible light beyond several hundred micrometers. The recently developed wavefront shaping technique time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light delivery to targeted locations beyond the optical diffusion limit. However, until now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We present the first example of TRUE focusing in 2-mm-thick living brain tissue and demonstrate its application for optogenetic modulation of neural activity in 800-μm-thick acute mouse brain...

  12. Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light

    Ruan, Haowen; Brake, Joshua; Robinson, J. Elliott; Liu, Yan; Jang, Mooseok; Xiao, Cheng; Zhou, Chunyi; Gradinaru, Viviana; Yang, Changhuei
    Noninvasive light focusing deep inside living biological tissue has long been a goal in biomedical optics. However, the optical scattering of biological tissue prevents conventional optical systems from tightly focusing visible light beyond several hundred micrometers. The recently developed wavefront shaping technique time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light delivery to targeted locations beyond the optical diffusion limit. However, until now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We present the first example of TRUE focusing in 2-mm-thick living brain tissue and demonstrate its application for optogenetic modulation of neural activity in 800-μm-thick acute mouse brain...

  13. Synthesis of Enantioenriched Allylic Silanes via Nickel-Catalyzed Reductive Cross-Coupling

    Hofstra, Julie L.; Cherney, Alan H.; Ordner, Ciara M.; Reisman, Sarah E.
    An asymmetric Ni-catalyzed reductive cross-coupling has been developed to prepare enantioenriched allylic silanes. This enantioselective reductive alkenylation proceeds under mild conditions and exhibits good functional group tolerance. The chiral allylic silanes prepared here undergo a variety of stereospecific transformations, including intramolecular Hosomi-Sakurai reactions, to set vicinal stereogenic centers with excellent transfer of chirality.

  14. Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization

    Maranas, Costas D.; Bedbrook, Claire N.; Yang, Kevin K.; Rice, Austin J.; Gradinaru, Viviana; Arnold, Frances H.
    There is growing interest in studying and engineering integral membrane proteins (MPs) that play key roles in sensing and regulating cellular response to diverse external signals. A MP must be expressed, correctly inserted and folded in a lipid bilayer, and trafficked to the proper cellular location in order to function. The sequence and structural determinants of these processes are complex and highly constrained. Here we describe a predictive, machine-learning approach that captures this complexity to facilitate successful MP engineering and design. Machine learning on carefully-chosen training sequences made by structure-guided SCHEMA recombination has enabled us to accurately predict the rare...

  15. Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization

    Bedbrook, Claire N.; Yang, Kevin K.; Rice, Austin J.; Gradinaru, Viviana; Arnold, Frances H.
    There is growing interest in studying and engineering integral membrane proteins (MPs) that play key roles in sensing and regulating cellular response to diverse external signals. A MP must be expressed, correctly inserted and folded in a lipid bilayer, and trafficked to the proper cellular location in order to function. The sequence and structural determinants of these processes are complex and highly constrained. Here we describe a predictive, machine-learning approach that captures this complexity to facilitate successful MP engineering and design. Machine learning on carefully-chosen training sequences made by structure-guided SCHEMA recombination has enabled us to accurately predict the rare...

  16. Scanning confocal vibrometer microscope for vibration analysis of energy-harvesting MEMS in wearables

    Kowarsch, Robert; Janzen, Jürgen; Cho, Hyunjun; Choo, Hyuck; Rembe, Christian
    We present a scanning confocal laser-Doppler vibrometer microscope for sensitive, contactless measurement of microelectromechanical systems (MEMS). This systems enables the dynamic analysis up to 3.2 MHz with a lateral resolution of few micrometers. We show measurements on developed MEMS for vocal-energy harvesting in wearables and medical implants. For efficient harvesting a cantilever beam with a serpentine form was designed with a fundamental resonance at 200 Hz. We verified the simulated mode shapes with our vibration measurements. The observed deviations in resonance frequencies between simulation and measurement are due to modelling and manufacturing dissimilarities.

  17. Scanning confocal vibrometer microscope for vibration analysis of energy-harvesting MEMS in wearables

    Kowarsch, Robert; Janzen, Jürgen; Cho, Hyunjun; Choo, Hyuck; Rembe, Christian
    We present a scanning confocal laser-Doppler vibrometer microscope for sensitive, contactless measurement of microelectromechanical systems (MEMS). This systems enables the dynamic analysis up to 3.2 MHz with a lateral resolution of few micrometers. We show measurements on developed MEMS for vocal-energy harvesting in wearables and medical implants. For efficient harvesting a cantilever beam with a serpentine form was designed with a fundamental resonance at 200 Hz. We verified the simulated mode shapes with our vibration measurements. The observed deviations in resonance frequencies between simulation and measurement are due to modelling and manufacturing dissimilarities.

  18. Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

    Kim, Kun ho; Lee, Jeong Oen; Du, Juan; Sretavan, David; Choo, Hyuck
    Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo...

  19. Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

    Kim, Kun Ho; Lee, Jeong Oen; Du, Juan; Sretavan, David; Choo, Hyuck
    Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo...

  20. Q&A: How can advances in tissue clearing and optogenetics contribute to our understanding of normal and diseased biology?

    Greenbaum, Alon; Jang, Min J.; Challis, Collin; Gradinaru, Viviana
    Mammalian organs comprise a variety of cells that interact with each other and have distinct biological roles. Access to evaluate and perturb intact biological systems at the cellular and molecular levels is essential to fully understand their functioning in normal and diseased conditions, yet technical limitations have constrained most research to small pieces of tissue. Tissue clearing and optogenetics can help overcome this hurdle: tissue clearing affords optical interrogation of whole organs at the molecular level, and optogenetics enables the scalable control and measurement of cellular activity with light. In this Q&A, we delineate recent advances and practical challenges associated...

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