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Article: Forgotten Fibrocytes: A Neglected, Supporting Cell Type of the Cochlea With the Potential to be an Alternative Therapeutic Target in Hearing Loss.

Furness, David N

2019 Volume 13, Page(s) 532

Abstract: Cochlear fibrocytes are a homeostatic supporting cell type embedded in the vascularized extracellular matrix of the spiral ligament, within the lateral wall. Here, they participate in the connective tissue syncytium that enables potassium recirculation ... ...

Abstract	Cochlear fibrocytes are a homeostatic supporting cell type embedded in the vascularized extracellular matrix of the spiral ligament, within the lateral wall. Here, they participate in the connective tissue syncytium that enables potassium recirculation into the
Language	English
Publishing date	2019-12-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2019.00532
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The conductance and organization of the TMC1-containing mechanotransducer channel complex in auditory hair cells.

Fettiplace, Robert / Furness, David N / Beurg, Maryline

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 41, Page(s) e2210849119

Abstract: Transmembrane channel-like protein 1 (TMC1) is thought to form the ion-conducting pore of the mechanoelectrical transducer (MET) channel in auditory hair cells. Using single-channel analysis and ionic permeability measurements, we characterized six ... ...

Abstract	Transmembrane channel-like protein 1 (TMC1) is thought to form the ion-conducting pore of the mechanoelectrical transducer (MET) channel in auditory hair cells. Using single-channel analysis and ionic permeability measurements, we characterized six missense mutations in the purported pore region of mouse TMC1. All mutations reduced the Ca
MeSH term(s)	Animals ; Hair Cells, Auditory, Outer/metabolism ; Hair Cells, Vestibular/metabolism ; Mechanotransduction, Cellular/genetics ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout ; Stereocilia/metabolism
Chemical Substances	Membrane Proteins ; TMC1 protein, mouse
Language	English
Publishing date	2022-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2210849119
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Article ; Online: Surgeon views regarding the adoption of a novel surgical innovation into clinical practice: systematic review.

Konda, Nagarjun N / Lewis, Thomas L / Furness, Hugh N / Miller, George W / Metcalfe, Andrew J / Ellard, David R

BJS open

2024 Volume 8, Issue 1

Abstract: Background: The haphazard adoption of new surgical technologies into practice has the potential to cause patient harm and there are many misconceptions in the decision-making behind the adoption of new innovations. The aim of this study was to ... ...

Abstract	Background: The haphazard adoption of new surgical technologies into practice has the potential to cause patient harm and there are many misconceptions in the decision-making behind the adoption of new innovations. The aim of this study was to synthesize factors affecting a surgeon's decision to adopt a novel surgical innovation into clinical practice. Methods: A systematic literature search was performed to obtain all studies where surgeon views on the adoption of a novel surgical innovation into clinical practice have been collected. The databases screened were MEDLINE, Embase, Science Direct, Scopus, the Web of Science, and the Cochrane Library of Systematic Reviews (last accessed October 2022). Innovations covered multiple specialties, including cardiac, general, urology, and orthopaedics. The quality of the papers was assessed using a 10-question Critical Appraisal Skills Programme (CASP) tool for qualitative research. Results: A total of 26 studies (including 1112 participants, of which 694 were surgeons) from nine countries satisfied the inclusion and exclusion criteria. Types of study included semi-structured interviews and focus groups, for example. Themes and sub-themes that emerged after a thematic synthesis were categorized using five causal factors (structural, organizational, patient-level, provider-level, and innovation-based). These themes were further split into facilitators and barriers. Key facilitators to adoption of an innovation include improved clinical outcomes, cost-effectiveness, and support from internal and external stakeholders. Barriers to adoption include lack of organizational support and views of senior surgeons. Conclusion: There are multiple complex factors that dynamically interact, affecting the adoption of a novel surgical innovation into clinical practice. There is a need to further investigate surgeon and other stakeholder views regarding the strength of clinical evidence required to support the widespread adoption of a surgical innovation into clinical practice.
MeSH term(s)	Humans ; Databases, Factual ; Focus Groups ; Surgeons
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article ; Systematic Review
ISSN	2474-9842
ISSN (online)	2474-9842
DOI	10.1093/bjsopen/zrad141
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Bakay, Warren M H / Cervantes, Blanca / Lao-Rodríguez, Ana B / Johannesen, Peter T / Lopez-Poveda, Enrique A / Furness, David N / Malmierca, Manuel S

Hearing research

2024 Volume 443, Page(s) 108963

Abstract: Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can ... ...

Abstract	Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments. However, much of the neuronal research thus far has investigated how HHL affects the response characteristics of individual fibres in the auditory nerve, as opposed to higher stations in the auditory pathway. Human models show that the auditory nerve encodes sound stochastically. Therefore, a sufficient reduction in nerve fibres could result in lowering the sampling of the acoustic scene below the minimum rate necessary to fully encode the scene, thus reducing the efficacy of sound encoding. Here, we examine how HHL affects the responses to frequency and intensity of neurons in the inferior colliculus of rats, and the duration and firing rate of those responses. Finally, we examined how shorter stimuli are encoded less effectively by the auditory midbrain than longer stimuli, and how this could lead to a clinical test for HHL.
MeSH term(s)	Humans ; Rats ; Animals ; Hearing Loss, Noise-Induced ; Inferior Colliculi/physiology ; Noise/adverse effects ; Auditory Threshold/physiology ; Evoked Potentials, Auditory, Brain Stem/physiology ; Cochlea
Language	English
Publishing date	2024-01-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282629-x
ISSN	1878-5891 ; 0378-5955
ISSN (online)	1878-5891
ISSN	0378-5955
DOI	10.1016/j.heares.2024.108963
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Article ; Online: Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells.

Mahendrasingam, Shanthini / Furness, David N

Scientific reports

2019 Volume 9, Issue 1, Page(s) 1274

Abstract: Transmembrane channel like protein 1 (TMC1) is likely to be a pore-forming subunit of the transduction channel of cochlear hair cells that is mechanically gated by tension on tip links in the stereocilia bundle. To localise TMC1 precisely, we labelled ... ...

Abstract	Transmembrane channel like protein 1 (TMC1) is likely to be a pore-forming subunit of the transduction channel of cochlear hair cells that is mechanically gated by tension on tip links in the stereocilia bundle. To localise TMC1 precisely, we labelled mice cochleae of different ages using custom-made polyclonal antibodies to TMC1 for light and transmission electron microscopy (TEM). Immunofluorescence revealed stereocilia labelling at P9 but not at P3 in apical hair cells. Immunogold labelling for TEM confirmed that labelling was absent at P3, and showed weak labelling at P6 with no stereocilia tip labelling, increasing at P9, with specific tip labelling on shorter stereocilia and some throughout the bundle. At P12 and P21, labelling was refined mostly to stereocilia tips. Quantification showed that labelling overall reached maximum by P12, labelling per tip was relatively constant from P9 to P21, but percent tips labelled was reduced from 16% to 8%. Tmc1
MeSH term(s)	Animals ; Hair Cells, Auditory/cytology ; Hair Cells, Auditory/metabolism ; Mechanotransduction, Cellular ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout
Chemical Substances	LHFPL5 protein, mouse ; Membrane Proteins ; TMC1 protein, mouse
Language	English
Publishing date	2019-02-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-37563-x
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Article ; Online: Molecular basis of hair cell loss.

Furness, David N

Cell and tissue research

2015 Volume 361, Issue 1, Page(s) 387–399

Abstract: Mechanisms that lead to the death of hair cells are reviewed. Exposure to noise, the use of ototoxic drugs that damage the cochlea and old age are accompanied by hair cell death. Outer hair cells are often more susceptible than inner hair cells, partly ... ...

Abstract	Mechanisms that lead to the death of hair cells are reviewed. Exposure to noise, the use of ototoxic drugs that damage the cochlea and old age are accompanied by hair cell death. Outer hair cells are often more susceptible than inner hair cells, partly because of an intrinsically greater susceptibility; high frequency cells are also more vulnerable. A common factor in hair cell loss following age-related changes and exposure to ototoxic drugs or high noise levels is the generation of reactive oxygen species, which can trigger intrinsic apoptosis (the mitochondrial pathway). However, hair cell death is sometimes produced via an extracellular signal pathway triggering extrinsic apoptosis. Necrosis and necroptosis also play a role and, in various situations in which cochlear damage occurs, a balance exists between these possible routes of cell death, with no one mechanism being exclusively activated. Finally, the numerous studies on these mechanisms of hair cell death have led to the identification of many potential therapeutic agents, some of which have been used to attempt to treat people exposed to damaging events, although clinical trials are not yet conclusive. Continued work in this area is likely to lead to clinical treatments that could be used to prevent or ameliorate hearing loss.
MeSH term(s)	Apoptosis ; Cell Death ; Hair Cells, Auditory/cytology ; Hair Cells, Auditory/metabolism ; Hearing Loss/etiology ; Hearing Loss/pathology ; Humans ; Signal Transduction
Language	English
Publishing date	2015-07
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	125067-x
ISSN	1432-0878 ; 0302-766X
ISSN (online)	1432-0878
ISSN	0302-766X
DOI	10.1007/s00441-015-2113-z
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Article ; Online: Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells

Shanthini Mahendrasingam / David N. Furness

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 9

Abstract: Abstract Transmembrane channel like protein 1 (TMC1) is likely to be a pore-forming subunit of the transduction channel of cochlear hair cells that is mechanically gated by tension on tip links in the stereocilia bundle. To localise TMC1 precisely, we ... ...

Abstract	Abstract Transmembrane channel like protein 1 (TMC1) is likely to be a pore-forming subunit of the transduction channel of cochlear hair cells that is mechanically gated by tension on tip links in the stereocilia bundle. To localise TMC1 precisely, we labelled mice cochleae of different ages using custom-made polyclonal antibodies to TMC1 for light and transmission electron microscopy (TEM). Immunofluorescence revealed stereocilia labelling at P9 but not at P3 in apical hair cells. Immunogold labelling for TEM confirmed that labelling was absent at P3, and showed weak labelling at P6 with no stereocilia tip labelling, increasing at P9, with specific tip labelling on shorter stereocilia and some throughout the bundle. At P12 and P21, labelling was refined mostly to stereocilia tips. Quantification showed that labelling overall reached maximum by P12, labelling per tip was relatively constant from P9 to P21, but percent tips labelled was reduced from 16% to 8%. Tmc1 −/− showed no labelling. Thus TMC1 occurs at the lower end of the tip link, supporting its presence in the MET complex and likely the channel. Tip localisation from P9 onwards coincides with lipoma HMGIC fusion partner-like 5 (LHFPL5), a protein that may be involved in acquiring/maintaining TMC1 localisation.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Repeated independent origins of the placenta reveal convergent and divergent organ evolution within a single fish family (Poeciliidae).

Safian, Diego / Ahmed, Marwa / van Kruistum, Henri / Furness, Andrew I / Reznick, David N / Wiegertjes, Geert F / Pollux, Bart J A

Science advances

2023 Volume 9, Issue 34, Page(s) eadf3915

Abstract: An outstanding question in biology is to what extent convergent evolution produces similar, but not necessarily identical, complex phenotypic solutions. The placenta is a complex organ that repeatedly evolved in the livebearing fish family Poeciliidae. ... ...

Abstract	An outstanding question in biology is to what extent convergent evolution produces similar, but not necessarily identical, complex phenotypic solutions. The placenta is a complex organ that repeatedly evolved in the livebearing fish family Poeciliidae. Here, we apply comparative approaches to test whether evolution has produced similar or different placental phenotypes in the Poeciliidae and to what extent these phenotypes correlate with convergence at the molecular level. We show the existence of two placental phenotypes characterized by distinctly different anatomical adaptations (divergent evolution). Furthermore, each placental phenotype independently evolved multiple times across the family, providing evidence for repeated convergence. Moreover, our comparative genomic analysis revealed that the genomes of species with different placentas are evolving at a different pace. Last, we show that the two placental phenotypes correlate with two previously described contrasting life-history optima. Our results argue for high evolvability (both divergent and convergent) of the placenta within a group of closely related species in a single family.
MeSH term(s)	Female ; Pregnancy ; Animals ; Placenta ; Acclimatization ; Fishes/genetics ; Phenotype
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adf3915
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Article ; Online: The evolution of the placenta in poeciliid fishes.

Furness, Andrew I / Avise, John C / Pollux, Bart J A / Reynoso, Yuridia / Reznick, David N

Current biology : CB

2021 Volume 31, Issue 9, Page(s) 2004–2011.e5

Abstract: How and why complex organs evolve is generally lost to history. The mammalian placenta, for example, was derived from a single common ancestor that lived over 100 million years ago. ...

Abstract	How and why complex organs evolve is generally lost to history. The mammalian placenta, for example, was derived from a single common ancestor that lived over 100 million years ago.
MeSH term(s)	Animals ; Biological Evolution ; Body Size ; Cyprinodontiformes ; Female ; Phylogeny ; Placenta ; Pregnancy ; Reproduction
Language	English
Publishing date	2021-03-02
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2021.02.008
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Article: A benchtop brain injury model using resected donor tissue from patients with Chiari malformation.

Tickle, Jacqueline A / Sen, Jon / Adams, Christopher / Furness, David N / Price, Rupert / Kandula, Viswapathi / Tzerakis, Nikolaos / Chari, Divya M

Neural regeneration research

2022 Volume 18, Issue 5, Page(s) 1057–1061

Abstract: The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative ... ...

Abstract	The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative models that replicate the 3D architecture of the central nervous system have prompted the development of organotypic neural injury models. However, the lack of reliable means to access normal human neural tissue has driven reliance on pathological or post-mortem tissue which limits their biological utility. We have established a protocol to use donor cerebellar tonsillar tissue surgically resected from patients with Chiari malformation (cerebellar herniation towards the foramen magnum, with ectopic rather than diseased tissue) to develop an in vitro organotypic model of traumatic brain injury. Viable tissue was maintained for approximately 2 weeks with all the major neural cell types detected. Traumatic injuries could be introduced into the slices with some cardinal features of post-injury pathology evident. Biomaterial placement was also feasible within the in vitro lesions. Accordingly, this 'proof-of-concept' study demonstrates that the model offers potential as an alternative to the use of animal tissue for preclinical testing in neural tissue engineering. To our knowledge, this is the first demonstration that donor tissue from patients with Chiari malformation can be used to develop a benchtop model of traumatic brain injury. However, significant challenges in relation to the clinical availability of tissue were encountered, and we discuss logistical issues that must be considered for model scale-up.
Language	English
Publishing date	2022-10-18
Publishing country	India
Document type	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.355761
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