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Cold Spring Harbor Perspectives in Medicine

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https://www.readbyqxmd.com/read/30323017/next-generation-sequencing-strategies
#1
Shawn E Levy, Braden E Boone
More than a decade ago, the term "next-generation" sequencing was coined to describe what was, at the time, revolutionary new methods to sequence RNA and DNA at a faster pace and cheaper cost than could be performed by standard bench-top protocols. Since then, the field of DNA sequencing has evolved at a rapid pace, with new breakthroughs allowing capacity to exponentially increase and cost to dramatically decrease. As genome-scale sequencing has become routine, a paradigm shift is occurring in genomics, which uses the power of high-throughput, rapid sequencing power with large-scale studies...
October 15, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30323016/toward-the-optical-cochlear-implant
#2
Tobias Dombrowski, Vladan Rankovic, Tobias Moser
When hearing fails, cochlear implants (CIs) provide open speech perception to most of the currently half a million CI users. CIs bypass the defective sensory organ and stimulate the auditory nerve electrically. The major bottleneck of current CIs is the poor coding of spectral information, which results from wide current spread from each electrode contact. As light can be more conveniently confined, optical stimulation of the auditory nerve presents a promising perspective for a fundamental advance of CIs. Moreover, given the improved frequency resolution of optical excitation and its versatility for arbitrary stimulation patterns the approach also bears potential for auditory research...
October 15, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30323015/active-biomechanics-of-sensory-hair-bundles
#3
Dolores Bozovic
During the detection of sound, hair bundles perform a crucial step by responding to mechanical deflections and converting them into changes in electrical potential that subsequently lead to the release of neurotransmitter. The sensory hair bundle response is characterized by an essential nonlinearity and an energy-consuming amplification of the incoming sound. The active response has been shown to enhance the hair bundle's sensitivity and frequency selectivity of detection. The biological phenomena shown by the bundle have been extensively studied in vitro, allowing comparisons to behaviors observed in vivo...
October 15, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30323014/cochlear-gene-therapy
#4
Lawrence Lustig, Omar Akil
Over 450 million people worldwide suffer from hearing loss, leading to an estimated economic burden of ∼$750 billion. The past decade has seen significant advances in the understanding of the molecular mechanisms that contribute to hearing, and the environmental and genetic factors that can go awry and lead to hearing loss. This in turn has sparked enormous interest in developing gene therapy approaches to treat this disorder. This review documents the most recent advances in cochlear gene therapy to restore hearing loss, and will cover viral vectors and construct designs, potential routes of delivery into the inner ear, and, lastly, the most promising genes of interest...
October 15, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30291150/function-and-dysfunction-of-tmc-channels-in-inner-ear-hair-cells
#5
David P Corey, Nurunisa Akyuz, Jeffrey R Holt
The TMC1 channel was identified as a protein essential for hearing in mouse and human, and recognized as one of a family of eight such proteins in mammals. The TMC family is part of a superfamily of seven branches, which includes the TMEM16s. Vertebrate hair cells express both TMC1 and TMC2. They are located at the tips of stereocilia and are required for hair cell mechanotransduction. TMC1 assembles as a dimer and its similarity to the TMEM16s has enabled a predicted tertiary structure with an ion conduction pore in each subunit of the dimer...
October 5, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30291149/age-related-hearing-loss
#6
Michael R Bowl, Sally J Dawson
Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive hearing impairment leads to social isolation and is also associated with comorbidities, such as frailty, falls, and late-onset depression. Moreover, there is a growing evidence linking it with cognitive decline and increased risk of dementia. Given the large social and welfare burden that results from ARHL, and because ARHL is potentially a modifiable risk factor for dementia, there is an urgent need for therapeutic interventions to ameliorate age-related auditory decline...
October 5, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30291148/prostate-stem-cells-and-cancer-stem-cells
#7
Jia J Li, Michael M Shen
Stem/progenitor cells play central roles in processes of organogenesis and tissue maintenance, whereas cancer stem cells (CSCs) are thought to drive tumor malignancy. Here, we review recent progress in the identification and analysis of normal prostate stem/progenitor cells as well as putative CSCs in both genetically engineered mouse models as well as in human tissue. We also discuss studies that have investigated the cell type of origin for prostate cancer. In addition, we provide a critical assessment of methodologies used in stem cell analyses and outline directions for future research...
October 5, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30291147/technobiology-s-enabler-the-magnetoelectric-nanoparticle
#8
Sakhrat Khizroev
To enable patient- and disease-specific diagnostic and treatment at the intracellular level in real time, it is imperative to engineer a perfect way to locally stimulate selected individual neurons, navigate and dispense a cargo of biomolecules into damaged cells or image sites with relatively high efficacy and with adequate spatial and temporal resolutions. Significant progress has been made using biotechnology; especially with the development of bioinformatics, there are endless molecular databases to identify biomolecules to target almost any disease-specific biomarker...
October 5, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30291146/optogenetic-medicine-synthetic-therapeutic-solutions-precision-guided-by-light
#9
Haifeng Ye, Martin Fussenegger
Gene- and cell-based therapies are well recognized as central pillars of next-generation medicine, but controllability remains a critical issue for clinical applications. In this context, optogenetics is opening up exciting new opportunities for precision-guided medicine by using illumination with light of appropriate intensity and wavelength as a trigger signal to achieve pinpoint spatiotemporal control of cellular activities, such as transgene expression. In this review, we highlight recent advances in optogenetics, focusing on devices for biomedical applications...
October 5, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30291145/electrical-impedance-methods-in-neuromuscular-assessment-an-overview
#10
Seward B Rutkove, Benjamin Sanchez
Electrical impedance methods have been used as evaluation tools in biological and medical science for well over 100 years. However, only recently have these techniques been applied specifically to the evaluation of conditions affecting nerve and muscle. This specific application, termed electrical impedance myography (EIM), is finding wide application as it can provide a quantitative index of muscle condition that can assist with diagnosis, track disease progression, and assess the beneficial impact of therapy...
October 5, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30249602/small-heat-shock-proteins-amyloid-fibrils-and-nicotine-stimulate-a-common-immune-suppressive-pathway-with-implications-for-future-therapies
#11
Jonathan B Rothbard, Michael P Kurnellas, Shalina S Ousman, Sara Brownell, Jesse J Rothbard, Lawrence Steinman
The α7 nicotinic acetylcholine receptor (α7nAChR) is central to the anti-inflammatory function of the vagus nerve in a physiological mechanism termed the inflammatory reflex. Studies on the inflammatory reflex have been instrumental for the current development of the field of bioelectronic medicine. An independent investigation of the biological role of αB-crystallin (HspB5), the most abundant gene transcript present in active multiple sclerosis lesions in human brains, also led to α7nAChR. Induction of experimental autoimmune encephalomyelitis (EAE) in HspB5-/- mice results in greater paralytic signs, increased levels of proinflammatory cytokines, and T-lymphocyte activation relative to wild-type animals...
September 24, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30249601/electromagnetic-regulation-of-cell-activity
#12
Sarah A Stanley, Jeffrey M Friedman
The ability to observe the effects of rapidly and reversibly regulating cell activity in targeted cell populations has provided numerous physiologic insights. Over the last decade, a wide range of technologies have emerged for regulating cellular activity using optical, chemical, and, more recently, electromagnetic modalities. Electromagnetic fields can freely penetrate cells and tissue and their energy can be absorbed by metal particles. When released, the absorbed energy can in turn gate endogenous or engineered receptors and ion channels to regulate cell activity...
September 24, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30249600/use-of-bioelectronics-in-the-gastrointestinal-tract
#13
Larry Miller, Aydin Farajidavar, Anil Vegesna
Gastrointestinal (GI) motility disorders are major contributing factors to functional GI diseases that account for >40% of patients seen in gastroenterology clinics and affect >20% of the general population. The autonomic and enteric nervous systems and the muscles within the luminal GI tract have key roles in motility. In health, this complex integrated system works seamlessly to transport liquid, solid, and gas through the GI tract. However, major and minor motility disorders occur when these systems fail...
September 24, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30249599/stem-cells-and-the-bird-cochlea-where-is-everybody
#14
Amanda S Janesick, Stefan Heller
In sharp contrast to the adult mammalian cochlea, which lacks regenerative ability, the mature avian cochlea, or basilar papilla (BP) is capable of complete recovery from hearing loss after damage. Avian sensory hair cell regeneration relies on rousing quiescent supporting cells to proliferate or transdifferentiate after hair cell death. Unlike mammalian cochlear supporting cells, which have clearly defined subtypes, avian BP supporting cells are deceptively indistinguishable and molecular markers have yet to be identified...
September 24, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30249598/the-epidemiology-of-deafness
#15
Abraham M Sheffield, Richard J H Smith
Hearing loss is the most common sensory deficit worldwide. It affects ∼5% of the world population, impacts people of all ages, and exacts a significant personal and societal cost. This review presents epidemiological data on hearing loss. We discuss hereditary hearing loss, complex hearing loss with genetic and environmental factors, and hearing loss that is more clearly related to environment. We also discuss the disparity in hearing loss across the world, with more economically developed countries having overall lower rates of hearing loss compared with developing countries, and the opportunity to improve diagnosis, prevention, and treatment of this disorder...
September 24, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30201789/sequencing-in-high-definition-drives-a-changing-worldview-of-the-epigenome
#16
Emily Hodges
Single-molecule sequencing approaches have transformed the study of the human epigenome, accelerating efforts to describe genome function beyond the sequences that encode proteins. The post-genome era has ignited strong interest in the noncoding genome and profiling epigenetic signatures genome-wide have been critical for the identification and characterization of noncoding gene-regulatory sequences in various cellular and developmental contexts. These technologies enable quantification of epigenetic marks through digital assessment of DNA fragments...
September 10, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30201788/vagus-nerve-stimulation-at-the-interface-of-brain-gut-interactions
#17
Bruno Bonaz, Valérie Sinniger, Sonia Pellissier
The vagus nerve, a key component of the cross-communication between the gut and the brain, is a major element of homeostasis sensing the "milieu intérieur" and boosting the nervous and endocrine responses to maintain the gastrointestinal health status. This nerve has anti-inflammatory properties regulating the gut through the activation of the hypothalamic-pituitary-adrenal axis and the release of cortisol and through a vagovagal reflex, which has an anti-tumor necrosis factor (TNF) effect called the cholinergic anti-inflammatory pathway...
September 10, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30201787/immunotherapy-for-prostate-cancer
#18
Nicholas J Venturini, Charles G Drake
Immunotherapy with agents that block immune checkpoints is a mainstay of therapy for several common tumor types; so far, prostate cancer is not among those treated using this method. The observed lack of activity in prostate cancer is not due to a lack of testing; several agents have been evaluated both alone and in combination. Although several combination strategies show some promise, it appears likely that a greater understanding of the prostate cancer tumor microenvironment and baseline immune response will be required to optimize future treatment strategies...
September 10, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30181356/empirically-based-guidelines-for-selecting-vagus-nerve-stimulation-parameters-in-epilepsy-and-heart-failure
#19
Eric D Musselman, Nicole A Pelot, Warren M Grill
Vagus nerve stimulation (VNS) is a promising therapy to treat patients with epilepsy and heart failure. Outcomes of preclinical studies and clinical trials indicate that the selection of stimulation parameters has a direct impact on therapeutic efficacy and patient tolerability, suggesting that both the efficacy and tolerability of VNS could potentially be improved with a change in stimulation parameters. In this review, the success of translating stimulation parameters for epilepsy and heart failure from preclinical studies in animal models to human use in the clinic is evaluated on the basis of patient outcomes and stimulation-induced side effects...
September 4, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/30181355/outer-hair-cells-and-electromotility
#20
Jonathan Ashmore
Outer hair cells (OHCs) of the mammalian cochlea behave like actuators: they feed energy into the cochlear partition and determine the overall mechanics of hearing. They do this by generating voltage-dependent axial forces. The resulting change in the cell length, observed by microscopy, has been termed "electromotility." The mechanism of force generation OHCs can be traced to a specific protein, prestin, a member of a superfamily SLC26 of transporters. This short review will identify some of the more recent findings on prestin...
September 4, 2018: Cold Spring Harbor Perspectives in Medicine
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