Publications by authors named "Holly L Aaron"

4 Publications

  • Page 1 of 1

Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development.

JCI Insight 2019 Feb 7;4(3). Epub 2019 Feb 7.

Naomi Berrie Diabetes Center & Division of Molecular Genetics, Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, New York, USA.

Intronic polymorphisms in the α-ketoglutarate-dependent dioxygenase gene (FTO) that are highly associated with increased body weight have been implicated in the transcriptional control of a nearby ciliary gene, retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Previous studies have shown that congenital Rpgrip1l hypomorphism in murine proopiomelanocortin (Pomc) neurons causes obesity by increasing food intake. Here, we show by congenital and adult-onset Rpgrip1l deletion in Pomc-expressing neurons that the hyperphagia and obesity are likely due to neurodevelopmental effects that are characterized by a reduction in the Pomc/Neuropeptide Y (Npy) neuronal number ratio and marked increases in arcuate hypothalamic-paraventricular hypothalamic (ARH-PVH) axonal projections. Biallelic RPGRIP1L mutations result in fewer cilia-positive human induced pluripotent stem cell-derived (iPSC-derived) neurons and blunted responses to Sonic Hedgehog (SHH). Isogenic human ARH-like embryonic stem cell-derived (ESc-derived) neurons homozygous for the obesity-risk alleles at rs8050136 or rs1421085 have decreased RPGRIP1L expression and have lower numbers of POMC neurons. RPGRIP1L overexpression increases POMC cell number. These findings suggest that apparently functional intronic polymorphisms affect hypothalamic RPGRIP1L expression and impact development of POMC neurons and their derivatives, leading to hyperphagia and increased adiposity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.123337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413800PMC
February 2019

Aerosol droplet delivery of mesoporous silica nanoparticles: A strategy for respiratory-based therapeutics.

Nanomedicine 2015 Aug 25;11(6):1377-85. Epub 2015 Mar 25.

Center for Health and the Environment, University of California, Davis, USA. Electronic address:

Unlabelled: A highly versatile nanoplatform that couples mesoporous silica nanoparticles (MSNs) with an aerosol technology to achieve direct nanoscale delivery to the respiratory tract is described. This novel method can deposit MSN nanoparticles throughout the entire respiratory tract, including nasal, tracheobronchial and pulmonary regions using a water-based aerosol. This delivery method was successfully tested in mice by inhalation. The MSN nanoparticles used have the potential for carrying and delivering therapeutic agents to highly specific target sites of the respiratory tract. The approach provides a critical foundation for developing therapeutic treatment protocols for a wide range of diseases where aerosol delivery to the respiratory system would be desirable.

From The Clinical Editor: Delivery of drugs via the respiratory tract is an attractive route of administration. In this article, the authors described the design of mesoporous silica nanoparticles which could act as carriers for drugs. The underlying efficacy was successfully tested in a mouse model. This drug-carrier inhalation nanotechnology should potentially be useful in human clinical setting in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nano.2015.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494876PMC
August 2015

Optical lock-in detection imaging microscopy for contrast-enhanced imaging in living cells.

Proc Natl Acad Sci U S A 2008 Nov 12;105(46):17789-94. Epub 2008 Nov 12.

Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53705, USA.

One of the limitations on imaging fluorescent proteins within living cells is that they are usually present in small numbers and need to be detected over a large background. We have developed the means to isolate specific fluorescence signals from background by using lock-in detection of the modulated fluorescence of a class of optical probe termed "optical switches." This optical lock-in detection (OLID) approach involves modulating the fluorescence emission of the probe through deterministic, optical control of its fluorescent and nonfluorescent states, and subsequently applying a lock-in detection method to isolate the modulated signal of interest from nonmodulated background signals. Cross-correlation analysis provides a measure of correlation between the total fluorescence emission within single pixels of an image detected over several cycles of optical switching and a reference waveform detected within the same image over the same switching cycles. This approach to imaging provides a means to selectively detect the emission from optical switch probes among a larger population of conventional fluorescent probes and is compatible with conventional microscopes. OLID using nitrospirobenzopyran-based probes and the genetically encoded Dronpa fluorescent protein are shown to generate high-contrast images of specific structures and proteins in labeled cells in cultured and explanted neurons and in live Xenopus embryos and zebrafish larvae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.0808882105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2584753PMC
November 2008

Remote control of neuronal activity with a light-gated glutamate receptor.

Neuron 2007 May;54(4):535-45

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

The ability to stimulate select neurons in isolated tissue and in living animals is important for investigating their role in circuits and behavior. We show that the engineered light-gated ionotropic glutamate receptor (LiGluR), when introduced into neurons, enables remote control of their activity. Trains of action potentials are optimally evoked and extinguished by 380 nm and 500 nm light, respectively, while intermediate wavelengths provide graded control over the amplitude of depolarization. Light pulses of 1-5 ms in duration at approximately 380 nm trigger precisely timed action potentials and EPSP-like responses or can evoke sustained depolarizations that persist for minutes in the dark until extinguished by a short pulse of approximately 500 nm light. When introduced into sensory neurons in zebrafish larvae, activation of LiGluR reversibly blocks the escape response to touch. Our studies show that LiGluR provides robust control over neuronal activity, enabling the dissection and manipulation of neural circuitry in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2007.05.010DOI Listing
May 2007
-->