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  1. Article ; Online: Depicting pseudotime-lagged causality across single-cell trajectories for accurate gene-regulatory inference.

    Reagor, Caleb C / Velez-Angel, Nicolas / Hudspeth, A J

    PNAS nexus

    2023  Volume 2, Issue 4, Page(s) pgad113

    Abstract: Identifying the causal interactions in gene-regulatory networks requires an accurate understanding of the time-lagged relationships between transcription factors and their target genes. Here we describe DELAY (short ... ...

    Abstract Identifying the causal interactions in gene-regulatory networks requires an accurate understanding of the time-lagged relationships between transcription factors and their target genes. Here we describe DELAY (short for
    Language English
    Publishing date 2023-03-30
    Publishing country England
    Document type Journal Article
    ISSN 2752-6542
    ISSN (online) 2752-6542
    DOI 10.1093/pnasnexus/pgad113
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  2. Article: Nanomechanics of wild-type and mutant dimers of the tip-link protein protocadherin 15.

    Villasante, Camila M / Deng, Xinyue / Cohen, Joel E / Hudspeth, A J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Mechanical force controls the opening and closing of mechanosensitive ion channels atop the hair bundles of the inner ear. The filamentous tip link connecting transduction channels to the tallest neighboring stereocilium modulates the force transmitted ... ...

    Abstract Mechanical force controls the opening and closing of mechanosensitive ion channels atop the hair bundles of the inner ear. The filamentous tip link connecting transduction channels to the tallest neighboring stereocilium modulates the force transmitted to the channels and thus changes their probability of opening. Each tip link comprises four molecules: a dimer of protocadherin 15 and a dimer of cadherin 23, all of which are stabilized by Ca
    Language English
    Publishing date 2023-10-19
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.17.562769
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  3. Article ; Online: Ultrasound-guided injection of the long head of the biceps tendon sheath with concomitant subacromial bursa injection through the same needlestick.

    Pujalte, George / Hudspeth, Loren J / Troyer, Wesley D / Shapiro, Shane A

    Clinical anatomy (New York, N.Y.)

    2022  Volume 36, Issue 3, Page(s) 400–405

    Abstract: Sonography and specific shoulder positions allow for injections into both the long head of the biceps tendon sheath (LHBTS) and the subacromial space (SS) with one needlestick. We validated this technique using cadavers. An experienced proceduralist ... ...

    Abstract Sonography and specific shoulder positions allow for injections into both the long head of the biceps tendon sheath (LHBTS) and the subacromial space (SS) with one needlestick. We validated this technique using cadavers. An experienced proceduralist injected latex solution into 12 unembalmed cadaveric shoulders, aiming for the LHBTS and SS, using an ultrasound-guided injection technique that employs a single-needle entry point. An experienced surgeon dissected each specimen and graded latex location as: (1) completely accurate (in both the SS and LHBTS); (2) partially accurate (in either the SS or LHBTS); (3) accurate with overflow (in both locations, but also elsewhere); (4) partially accurate with overflow (in either location, but also somewhere else); or (5) completely inaccurate (no latex in either location). All 12 ultrasound-guided injections using the technique accurately placed latex into both LHBTS and SS (100% accuracy). Latex was also found in adjacent regions after two (17%) injections: one within the shoulder joint and one within the deltoid musculature. This newly described technique allows highly accurate access to the LHBTS and SS with single-needle entry. This technique could become a favored alternative to subjecting patients to two needlesticks and preparing separate injections to address often concomitant pathologies.
    MeSH term(s) Humans ; Shoulder ; Needlestick Injuries ; Ultrasonography, Interventional/methods ; Injections, Intra-Articular/methods ; Tendons/diagnostic imaging
    Language English
    Publishing date 2022-10-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1025505-9
    ISSN 1098-2353 ; 0897-3806
    ISSN (online) 1098-2353
    ISSN 0897-3806
    DOI 10.1002/ca.23961
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  4. Article ; Online: Safety vs price in the generic drug market: metformin.

    Teasdale, Ben / Hudspeth, Amber / Kucera, Kaury / Light, David / Nailor, Jill / Williams, Shannon / Milstein, Arnold / Schulman, Kevin A

    The American journal of managed care

    2024  Volume 30, Issue 4, Page(s) 161–168

    Abstract: Objectives: Generic medications represent 90% of prescriptions in the US market and provide a tremendous financial benefit for patients. Recently, multiple generic drugs have been recalled due to the presence of carcinogens, predominantly N- ... ...

    Abstract Objectives: Generic medications represent 90% of prescriptions in the US market and provide a tremendous financial benefit for patients. Recently, multiple generic drugs have been recalled due to the presence of carcinogens, predominantly N-nitrosodimethylamine (NDMA), including an extensive recall of extended-release (ER) metformin products in 2020.
    Study design: Primary pharmaceutical quality testing and database analysis.
    Methods: We tested marketed metformin immediate-release (IR) and ER tablets from a wide sample of generic manufacturers for the presence of carcinogenic impurities NDMA and N,N-dimethylformamide (DMF). We examined the association of level of impurity with drug price and the impact of the 2020 FDA recalls on unit price and prescription fill rate.
    Results: Postrecall NDMA levels were significantly lower in metformin ER samples (standardized mean difference = -2.0; P = .01); however, we found continued presence of carcinogens above the FDA threshold in 2 of 30 IR samples (6.67%). Overall, the presence of contaminant levels was not significantly associated with price for either IR (NDMA: R2 = 0.142; P = .981; DMF: R2 = 0.382; P = .436) or ER (NDMA: R2 = 0.124; P = .142; DMF: R2 = 0.199; P = .073) samples. Despite recalls, metformin ER prescription fills increased by 8.9% while unit price decreased by 19.61% (P < .05).
    Conclusions: Recalls of metformin ER medications were effective in lowering NDMA levels below the FDA threshold; however, some samples of generic metformin still contained carcinogens even after FDA-announced recalls. The absence of any correlation with price indicates that potentially safer products are available on the market for the same price as poorer-quality products.
    MeSH term(s) Humans ; Metformin/therapeutic use ; Drugs, Generic ; Prescriptions ; Dimethylnitrosamine/analysis ; Carcinogens
    Chemical Substances Metformin (9100L32L2N) ; Drugs, Generic ; Dimethylnitrosamine (M43H21IO8R) ; Carcinogens
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2035781-3
    ISSN 1936-2692 ; 1088-0224 ; 1096-1860
    ISSN (online) 1936-2692
    ISSN 1088-0224 ; 1096-1860
    DOI 10.37765/ajmc.2024.89450
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  5. Article ; Online: Integrating the active process of hair cells with cochlear function.

    Hudspeth, A J

    Nature reviews. Neuroscience

    2014  Volume 15, Issue 9, Page(s) 600–614

    Abstract: Uniquely among human senses, hearing is not simply a passive response to stimulation. Our auditory system is instead enhanced by an active process in cochlear hair cells that amplifies acoustic signals several hundred-fold, sharpens frequency selectivity ...

    Abstract Uniquely among human senses, hearing is not simply a passive response to stimulation. Our auditory system is instead enhanced by an active process in cochlear hair cells that amplifies acoustic signals several hundred-fold, sharpens frequency selectivity and broadens the ear's dynamic range. Active motility of the mechanoreceptive hair bundles underlies the active process in amphibians and some reptiles; in mammals, this mechanism operates in conjunction with prestin-based somatic motility. Both individual hair bundles and the cochlea as a whole operate near a dynamical instability, the Hopf bifurcation, which accounts for the cardinal features of the active process.
    MeSH term(s) Animals ; Auditory Pathways/physiology ; Cochlea/cytology ; Cochlea/physiology ; Hair Cells, Auditory/physiology ; Hair Cells, Auditory/ultrastructure ; Hearing ; Humans ; Mechanotransduction, Cellular/physiology
    Language English
    Publishing date 2014-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2034150-7
    ISSN 1471-0048 ; 1471-0048 ; 1471-003X
    ISSN (online) 1471-0048
    ISSN 1471-0048 ; 1471-003X
    DOI 10.1038/nrn3786
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    Zs.A 5473: Show issues Location:
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  6. Article ; Online: A New Twist on Tip Links.

    Bartsch, Tobias F / Hudspeth, A J

    Neuron

    2018  Volume 99, Issue 3, Page(s) 423–425

    Abstract: Auditory transduction is fast and sensitive owing to the direct detection of mechanical stimuli by hair cells, the sensory receptors of the internal ear. A study by Dionne et al. (2018) in this issue of Neuron suggests how signals propagate through tip ... ...

    Abstract Auditory transduction is fast and sensitive owing to the direct detection of mechanical stimuli by hair cells, the sensory receptors of the internal ear. A study by Dionne et al. (2018) in this issue of Neuron suggests how signals propagate through tip links, the cadherin-based strands that gate mechanically sensitive channels.
    MeSH term(s) Cadherins ; Hair Cells, Auditory ; Mechanotransduction, Cellular
    Chemical Substances Cadherins
    Language English
    Publishing date 2018-09-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2018.07.041
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    Zs.A 2496: Show issues Location:
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  7. Article ; Online: Volterra-series approach to stochastic nonlinear dynamics: Linear response of the Van der Pol oscillator driven by white noise.

    Belousov, Roman / Berger, Florian / Hudspeth, A J

    Physical review. E

    2020  Volume 102, Issue 3-1, Page(s) 32209

    Abstract: The Van der Pol equation is a paradigmatic model of relaxation oscillations. This remarkable nonlinear phenomenon of self-sustained oscillatory motion underlies important rhythmic processes in nature and electrical engineering. Relaxation oscillations in ...

    Abstract The Van der Pol equation is a paradigmatic model of relaxation oscillations. This remarkable nonlinear phenomenon of self-sustained oscillatory motion underlies important rhythmic processes in nature and electrical engineering. Relaxation oscillations in a real system are usually coupled to environmental noise, which further enriches their dynamics, but makes theoretical analysis of such systems and determination of the equation parameter values a difficult task. In a companion paper we have proposed an analytic approach to a similar problem for another classical nonlinear model-the bistable Duffing oscillator. Here we extend our techniques to the case of the Van der Pol equation driven by white noise. We analyze the statistics of solutions and propose a method to estimate parameter values from the oscillator's time series. We use experimental data of active oscillations in a biophysical system to demonstrate how our method applies to real observations and can be generalized for more complex models.
    Language English
    Publishing date 2020-10-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2844562-4
    ISSN 2470-0053 ; 2470-0045
    ISSN (online) 2470-0053
    ISSN 2470-0045
    DOI 10.1103/PhysRevE.102.032209
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  8. Article ; Online: Association Between Personality Types and Predilection to Chronic Pain.

    Hudspeth, MaKenzie / Rash, Ashley / Guffey, J Stephen

    Journal of allied health

    2020  Volume 49, Issue 1, Page(s) e69–e72

    Abstract: Chronic pain is a problem that has become common across communities. Currently there is no uniform approach for treating chronic pain. The purpose of this study was to explore whether an association exists between personality type and the predisposition ... ...

    Abstract Chronic pain is a problem that has become common across communities. Currently there is no uniform approach for treating chronic pain. The purpose of this study was to explore whether an association exists between personality type and the predisposition to developing chronic pain. Using a personality profile tool, we surveyed 29 subjects suffering from chronic pain and found that 25 of the 29 approached their pain experience from a "feeling" or subjective perspective. Emotion, rather than logic, was more likely to drive these subjects' understanding of their chronic pain state. Considering this predilection toward emotion should be part of treating patients with chronic pain states. Educators who prepare future health professionals and those professionals currently in practice should appreciate the psychosocial nature of chronic pain and direct treatment, at least in part, toward the psychosocial component of the lived pain experience.
    MeSH term(s) Attitude to Health ; Chronic Pain/psychology ; Humans ; Personality
    Language English
    Publishing date 2020-02-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 197884-6
    ISSN 1945-404X ; 0090-7421
    ISSN (online) 1945-404X
    ISSN 0090-7421
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  9. Article ; Online: SnapShot: Auditory transduction.

    Hudspeth, A J

    Neuron

    2013  Volume 80, Issue 2, Page(s) 536.e1

    MeSH term(s) Auditory Pathways/anatomy & histology ; Auditory Pathways/physiology ; Cochlea/anatomy & histology ; Cochlea/physiology ; Hair Cells, Auditory/cytology ; Hair Cells, Auditory/physiology ; Humans ; Models, Neurological
    Language English
    Publishing date 2013-10-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2013.10.003
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  10. Article ; Online: Rapid mechanical stimulation of inner-ear hair cells by photonic pressure.

    Abeytunge, Sanjeewa / Gianoli, Francesco / Hudspeth, A J / Kozlov, Andrei S

    eLife

    2021  Volume 10

    Abstract: Hair cells, the receptors of the inner ear, detect sounds by transducing mechanical vibrations into electrical signals. From the top surface of each hair cell protrudes a mechanical antenna, the hair bundle, which the cell uses to detect and amplify ... ...

    Abstract Hair cells, the receptors of the inner ear, detect sounds by transducing mechanical vibrations into electrical signals. From the top surface of each hair cell protrudes a mechanical antenna, the hair bundle, which the cell uses to detect and amplify auditory stimuli, thus sharpening frequency selectivity and providing a broad dynamic range. Current methods for mechanically stimulating hair bundles are too slow to encompass the frequency range of mammalian hearing and are plagued by inconsistencies. To overcome these challenges, we have developed a method to move individual hair bundles with photonic force. This technique uses an optical fiber whose tip is tapered to a diameter of a few micrometers and endowed with a ball lens to minimize divergence of the light beam. Here we describe the fabrication, characterization, and application of this optical system and demonstrate the rapid application of photonic force to vestibular and cochlear hair cells.
    MeSH term(s) Animals ; Ear, Inner ; Hair ; Hair Cells, Auditory/physiology ; Hair Cells, Auditory, Inner/physiology ; Hearing/physiology ; Mechanical Phenomena ; Optical Fibers ; Rana catesbeiana ; Rats ; Stereocilia ; Vibration
    Language English
    Publishing date 2021-07-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.65930
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