San Francisco, CA, United States

University of California at San Francisco
San Francisco, CA, United States

The University of California, San Francisco , is a center of health science research, patient care, and education; located in San Francisco, California, and is widely regarded as one of the world's leading universities in health science.Though one of the 10 campuses of the University of California, it is the only University of California campus dedicated solely to graduate education, and in health and biomedical science. Some of UCSF's treatment centers include kidney transplants and liver transplantation, radiology, neurosurgery, neurology, oncology, ophthalmology, gene therapy, women's health, fetal surgery, pediatrics, and internal medicine. With a work force of 22,800 people and annual economic impact of $2 billion, UCSF is San Francisco's second largest employer.Founded in 1873, the mission of UCSF is to serve as a "public university dedicated to saving lives and improving health." The UCSF Medical Center is consistently ranked among the top 10 hospitals in the United States by U.S. News & World Report, who also ranked UCSF's medical school as one of the top 10 in a number of specialties, including a specialty program in AIDS medical care ranked first in the country. Wikipedia.

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Papadopoulos M.C.,St George's, University of London | Verkman A.S.,University of California at San Francisco
Nature Reviews Neuroscience | Year: 2013

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage. © 2013 Macmillan Publishers Limited. All rights reserved.

Huganir R.L.,Johns Hopkins University | Nicoll R.A.,University of California at San Francisco
Neuron | Year: 2013

The study of synaptic plasticity and specifically LTP and LTD is one of the most active areas of research in neuroscience. In the last 25 years we have come a long way in our understanding of the mechanisms underlying synaptic plasticity. In 1988, AMPA and NMDA receptors were not even molecularly identified and we only had a simple model of the minimal requirements for the induction of plasticity. It is now clear that the modulation of the AMPA receptor function and membrane trafficking is critical for many forms of synaptic plasticity and a large number of proteins have been identified that regulate this complex process. Here we review the progress over the last two and a half decades and discuss the future challenges in the field

Davis G.,University of California at San Francisco
Neuron | Year: 2013

The brain is astonishing in its complexity and capacity for change. This has fascinated scientists for more than a century, filling the pages of this journal for the past 25 years. But a paradigm shift is underway. It seems likely that the plasticity that drives our ability to learn and remember can only be meaningful in the context of otherwise stable, reproducible, and predictable baseline neural function. Without the existence of potent mechanisms that stabilize neural function, our capacity to learn and remember would be lost in the chaos of daily experiential change. This underscores two great mysteries in neuroscience. How are the functional properties of individual neurons and neural circuits stably maintained throughout lifeα And, in the face of potent stabilizing mechanisms, how can neural circuitry be modified during neural development, learning, and memoryα Answers are emerging in the rapidly developing field of homeostatic plasticity

Nicoll R.A.,University of California at San Francisco
Neuron | Year: 2017

Since the discovery of long-term potentiation (LTP) in 1973, thousands of papers have been published on this intriguing phenomenon, which provides a compelling cellular model for learning and memory. Although LTP has suffered considerable growing pains over the years, LTP has finally come of age. Here the rich history of LTP is reviewed. These are exciting times and the pace of discovery is remarkable. © 2017

Sohal V.S.,University of California at San Francisco
Biological Psychiatry | Year: 2012

Cortical oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range have been hypothesized to play important roles in numerous cognitive processes and may be involved in psychiatric conditions including anxiety, schizophrenia, and autism. This review provides background information about these oscillations and their possible roles in psychiatric illness. Findings from recent studies that used optogenetic tools to demonstrate that 1) a particular class of inhibitory interneurons expressing the calcium binding protein parvalbumin plays a central role in gamma oscillations, 2) gamma oscillations can entrain rhythmic firing in pyramidal neurons, and 3) rhythmic firing at theta and gamma frequencies can enhance communication between neurons are described. Finally, how these findings may relate to the pathophysiology of psychiatric conditions, as well as questions for future studies, are discussed. © 2012 Society of Biological Psychiatry.

Prusiner S.B.,University of California at San Francisco
Annual Review of Genetics | Year: 2013

Prions are proteins that acquire alternative conformations that become self-propagating. Transformation of proteins into prions is generally accompanied by an increase in β-sheet structure and a propensity to aggregate into oligomers. Some prions are beneficial and perform cellular functions, whereas others cause neurodegeneration. In mammals, more than a dozen proteins that become prions have been identified, and a similar number has been found in fungi. In both mammals and fungi, variations in the prion conformation encipher the biological properties of distinct prion strains. Increasing evidence argues that prions cause many neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's, Creutzfeldt-Jakob, and Lou Gehrig's diseases, as well as the tauopathies. The majority of NDs are sporadic, and 10% to 20% are inherited. The late onset of heritable NDs, like their sporadic counterparts, may reflect the stochastic nature of prion formation; the pathogenesis of such illnesses seems to require prion accumulation to exceed some critical threshold before neurological dysfunction manifests. © 2013 by Annual Reviews. All rights reserved.

The conserved transcriptional regulator heat shock factor 1 (Hsf1) is a key sensor of proteotoxic and other stress in the eukaryotic cytosol. We surveyed Hsf1 activity in a genome-wide loss-of-function library in Saccaromyces cerevisiae as well as ~78,000 double mutants and found Hsf1 activity to be modulated by highly diverse stresses. These included disruption of a ribosome-bound complex we named the Ribosome Quality Control Complex (RQC) comprising the Ltn1 E3 ubiquitin ligase, two highly conserved but poorly characterized proteins (Tae2 and Rqc1), and Cdc48 and its cofactors. Electron microscopy and biochemical analyses revealed that the RQC forms a stable complex with 60S ribosomal subunits containing stalled polypeptides and triggers their degradation. A negative feedback loop regulates the RQC, and Hsf1 senses an RQC-mediated translation-stress signal distinctly from other stresses. Our work reveals the range of stresses Hsf1 monitors and elucidates a conserved cotranslational protein quality control mechanism. Copyright © 2012 Elsevier Inc. All rights reserved.

Julius D.,University of California at San Francisco
Annual Review of Cell and Developmental Biology | Year: 2013

Nociception is the process whereby primary afferent nerve fibers of the somatosensory system detect noxious stimuli. Pungent irritants from pepper, mint, and mustard plants have served as powerful pharmacological tools for identifying molecules and mechanisms underlying this initial step of pain sensation. These natural products have revealed three members of the transient receptor potential (TRP) ion channel familymdashTRPV1, TRPM8, and TRPA1mdashas molecular detectors of thermal and chemical stimuli that activate sensory neurons to produce acute or persistent pain. Analysis of TRP channel function and expression has validated the existence of nociceptors as a specialized group of somatosensory neurons devoted to the detection of noxious stimuli. These studies are also providing insight into the coding logic of nociception and how specification of nociceptor subtypes underlies behavioral discrimination of noxious thermal, chemical, and mechanical stimuli. Biophysical and pharmacological characterization of these channels has provided the intellectual and technical foundation for developing new classes of analgesic drugs. © 2013 by Annual Reviews. All rights reserved.

Cheng Y.,University of California at San Francisco
Cell | Year: 2015

Until only a few years ago, single-particle electron cryo-microscopy (cryo-EM) was usually not the first choice for many structural biologists due to its limited resolution in the range of nanometer to subnanometer. Now, this method rivals X-ray crystallography in terms of resolution and can be used to determine atomic structures of macromolecules that are either refractory to crystallization or difficult to crystallize in specific functional states. In this review, I discuss the recent breakthroughs in both hardware and software that transformed cryo-microscopy, enabling understanding of complex biomolecules and their functions at atomic level. © 2015 Elsevier Inc.

Kenyon C.J.,University of California at San Francisco
Nature | Year: 2010

The nematode Caenorhabditis elegans ages and dies in a few weeks, but humans can live for 100 years or more. Assuming that the ancestor we share with nematodes aged rapidly, this means that over evolutionary time mutations have increased lifespan more than 2,000-fold. Which genes can extend lifespan? Can we augment their activities and live even longer? After centuries of wistful poetry and wild imagination, we are now getting answers, often unexpected ones, to these fundamental questions. © 2010 Macmillan Publishers Limited. All rights reserved.

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