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Article ; Online: High resolution seafloor thermometry for internal wave and upwelling monitoring using Distributed Acoustic Sensing.

Pelaez Quiñones, Julián David / Sladen, Anthony / Ponte, Aurelien / Lior, Itzhak / Ampuero, Jean-Paul / Rivet, Diane / Meulé, Samuel / Bouchette, Frédéric / Pairaud, Ivane / Coyle, Paschal

Scientific reports

2023 Volume 13, Issue 1, Page(s) 17459

Abstract: ... as well as for the understanding of the evolution of the ocean in a broad sense (e.g. physical and ...

Abstract	Temperature is an essential oceanographic variable (EOV) that still today remains coarsely resolved below the surface and near the seafloor. Here, we gather evidence to confirm that Distributed Acoustic Sensing (DAS) technology can convert tens of kilometer-long seafloor fiber-optic telecommunication cables into dense arrays of temperature anomaly sensors having millikelvin (mK) sensitivity, thus allowing to monitor oceanic processes such as internal waves and upwelling with unprecedented detail. Notably, we report high-resolution observations of highly coherent near-inertial and super-inertial internal waves in the NW Mediterranean sea, offshore of Toulon, France, having spatial extents of a few kilometers and producing maximum thermal anomalies of more than 5 K at maximum absolute rates of more than 1 K/h. We validate our observations with in-situ oceanographic sensors and an alternative optical fiber sensing technology. Currently, DAS only provides temperature changes estimates, however practical solutions are outlined to obtain continuous absolute temperature measurements with DAS at the seafloor. Our observations grant key advantages to DAS over established temperature sensors, showing its transformative potential for the description of seafloor temperature fluctuations over an extended range of spatial and temporal scales, as well as for the understanding of the evolution of the ocean in a broad sense (e.g. physical and ecological). Diverse ocean-oriented fields could benefit from the potential applications of this fast-developing technology.
Language	English
Publishing date	2023-10-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-44635-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Modelling autosomal dominant optic atrophy associated with OPA1 variants in iPSC-derived retinal ganglion cells.

Sladen, Paul E / Jovanovic, Katarina / Guarascio, Rosellina / Ottaviani, Daniele / Salsbury, Grace / Novoselova, Tatiana / Chapple, J Paul / Yu-Wai-Man, Patrick / Cheetham, Michael E

Human molecular genetics

2022 Volume 31, Issue 20, Page(s) 3478–3493

Abstract: Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterized by the preferential loss of retinal ganglion cells (RGCs), resulting in optic nerve degeneration and progressive bilateral central vision loss. More than ... ...

Abstract	Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, characterized by the preferential loss of retinal ganglion cells (RGCs), resulting in optic nerve degeneration and progressive bilateral central vision loss. More than 60% of genetically confirmed patients with DOA carry variants in the nuclear OPA1 gene, which encodes for a ubiquitously expressed, mitochondrial GTPase protein. OPA1 has diverse functions within the mitochondrial network, facilitating inner membrane fusion and cristae modelling, regulating mitochondrial DNA maintenance and coordinating mitochondrial bioenergetics. There are currently no licensed disease-modifying therapies for DOA and the disease mechanisms driving RGC degeneration are poorly understood. Here, we describe the generation of isogenic, heterozygous OPA1 null induced pluripotent stem cell (iPSC) (OPA1+/-) through clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing of a control cell line, in conjunction with the generation of DOA patient-derived iPSC carrying OPA1 variants, namely, the c.2708_2711delTTAG variant (DOA iPSC), and previously reported missense variant iPSC line (c.1334G>A, DOA plus [DOA]+ iPSC) and CRISPR/Cas9 corrected controls. A two-dimensional (2D) differentiation protocol was used to study the effect of OPA1 variants on iPSC-RGC differentiation and mitochondrial function. OPA1+/-, DOA and DOA+ iPSC showed no differentiation deficit compared to control iPSC lines, exhibiting comparable expression of all relevant markers at each stage of differentiation. OPA1+/- and OPA1 variant iPSC-RGCs exhibited impaired mitochondrial homeostasis, with reduced bioenergetic output and compromised mitochondrial DNA maintenance. These data highlight mitochondrial deficits associated with OPA1 dysfunction in human iPSC-RGCs, and establish a platform to study disease mechanisms that contribute to RGC loss in DOA, as well as potential therapeutic interventions.
MeSH term(s)	DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; GTP Phosphohydrolases/genetics ; GTP Phosphohydrolases/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Optic Atrophy, Autosomal Dominant/genetics ; Retinal Ganglion Cells/metabolism
Chemical Substances	DNA, Mitochondrial ; GTP Phosphohydrolases (EC 3.6.1.-) ; OPA1 protein, human (EC 3.6.1.-)
Language	English
Publishing date	2022-05-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddac128
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: CRISPR-Cas9 correction of

Sladen, Paul E / Perdigão, Pedro R L / Salsbury, Grace / Novoselova, Tatiana / van der Spuy, Jacqueline / Chapple, J Paul / Yu-Wai-Man, Patrick / Cheetham, Michael E

Molecular therapy. Nucleic acids

2021 Volume 26, Page(s) 432–443

Abstract: Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy in the United Kingdom. DOA has an insidious onset in early childhood, typically presenting with bilateral, central visual loss caused by the preferential loss of retinal ...

Abstract	Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy in the United Kingdom. DOA has an insidious onset in early childhood, typically presenting with bilateral, central visual loss caused by the preferential loss of retinal ganglion cells. 60%-70% of genetically confirmed DOA cases are associated with variants in
Language	English
Publishing date	2021-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2021.08.015
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Article ; Online: Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models

Julio C. Corral-Serrano / Paul E. Sladen / Daniele Ottaviani / Olivia F. Rezek / Dimitra Athanasiou / Katarina Jovanovic / Jacqueline van der Spuy / Brian C. Mansfield / Michael E. Cheetham

Cells, Vol 12, Iss 1575, p

2023 Volume 1575

Abstract: ... G in CEP290 , there is a need for variant-independent approaches that could be applied to a broader ...

Abstract	The photoreceptor outer segment is a highly specialized primary cilium that is essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.2991+1655A>G in CEP290 , there is a need for variant-independent approaches that could be applied to a broader spectrum of ciliopathies. Here, we generated several distinct human models of CEP290 -related retinal disease and investigated the effects of the flavonoid eupatilin as a potential treatment. Eupatilin improved cilium formation and length in CEP290 LCA10 patient-derived fibroblasts, in gene-edited CEP290 knockout (CEP290 KO) RPE1 cells, and in both CEP290 LCA10 and CEP290 KO iPSCs-derived retinal organoids. Furthermore, eupatilin reduced rhodopsin retention in the outer nuclear layer of CEP290 LCA10 retinal organoids. Eupatilin altered gene transcription in retinal organoids by modulating the expression of rhodopsin and by targeting cilia and synaptic plasticity pathways. This work sheds light on the mechanism of action of eupatilin and supports its potential as a variant-independent approach for CEP290 -associated ciliopathies.
Keywords	CEP290 ; Leber congenital amaurosis (LCA) ; retina ; ciliopathy ; photoreceptor ; cilium ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High resolution seafloor thermometry for internal wave and upwelling monitoring using Distributed Acoustic Sensing

Julián David Pelaez Quiñones / Anthony Sladen / Aurelien Ponte / Itzhak Lior / Jean-Paul Ampuero / Diane Rivet / Samuel Meulé / Frédéric Bouchette / Ivane Pairaud / Paschal Coyle

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 16

Abstract: ... temporal scales, as well as for the understanding of the evolution of the ocean in a broad sense (e.g ...

Abstract	Abstract Temperature is an essential oceanographic variable (EOV) that still today remains coarsely resolved below the surface and near the seafloor. Here, we gather evidence to confirm that Distributed Acoustic Sensing (DAS) technology can convert tens of kilometer-long seafloor fiber-optic telecommunication cables into dense arrays of temperature anomaly sensors having millikelvin (mK) sensitivity, thus allowing to monitor oceanic processes such as internal waves and upwelling with unprecedented detail. Notably, we report high-resolution observations of highly coherent near-inertial and super-inertial internal waves in the NW Mediterranean sea, offshore of Toulon, France, having spatial extents of a few kilometers and producing maximum thermal anomalies of more than 5 K at maximum absolute rates of more than 1 K/h. We validate our observations with in-situ oceanographic sensors and an alternative optical fiber sensing technology. Currently, DAS only provides temperature changes estimates, however practical solutions are outlined to obtain continuous absolute temperature measurements with DAS at the seafloor. Our observations grant key advantages to DAS over established temperature sensors, showing its transformative potential for the description of seafloor temperature fluctuations over an extended range of spatial and temporal scales, as well as for the understanding of the evolution of the ocean in a broad sense (e.g. physical and ecological). Diverse ocean-oriented fields could benefit from the potential applications of this fast-developing technology.
Keywords	Medicine ; R ; Science ; Q
Subject code	551
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distributed sensing of earthquakes and ocean-solid Earth interactions on seafloor telecom cables.

Sladen, A / Rivet, D / Ampuero, J P / De Barros, L / Hello, Y / Calbris, G / Lamare, P

Nature communications

2019 Volume 10, Issue 1, Page(s) 5777

Abstract: ... interactions from the coast to the abyssal plain, in addition to regional seismicity (e.g., a magnitude 1.9 ...

Abstract	Two thirds of the surface of our planet are covered by water and are still poorly instrumented, which has prevented the earth science community from addressing numerous key scientific questions. The potential to leverage the existing fiber optic seafloor telecom cables that criss-cross the oceans, by using them as dense arrays of seismo-acoustic sensors, remains to be evaluated. Here, we report Distributed Acoustic Sensing measurements on a 41.5 km-long telecom cable that is deployed offshore Toulon, France. Our observations demonstrate the capability to monitor with unprecedented details the ocean-solid earth interactions from the coast to the abyssal plain, in addition to regional seismicity (e.g., a magnitude 1.9 micro-earthquake located 100 km away) with signal characteristics comparable to those of a coastal seismic station.
Language	English
Publishing date	2019-12-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-13793-z
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Article ; Online: Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema.

Zurek, Magdalena / Sladen, Louise / Johansson, Edvin / Olsson, Marita / Jackson, Sonya / Zhang, Hui / Mayer, Gaell / Hockings, Paul D

PloS one

2016 Volume 11, Issue 3, Page(s) e0151211

Abstract: Purpose: A magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung ...

Abstract	Purpose: A magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function. Method: Nine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts. Principal findings: PPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups. Conclusions: The proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting heterogeneous lung disorders was found. This indicated that the technique has potential for early detection of lung dysfunction-before global changes occur.
MeSH term(s)	Animals ; Disease Models, Animal ; Female ; Lung/pathology ; Lung/physiopathology ; Magnetic Resonance Imaging/methods ; Mice ; Mice, Inbred C57BL ; Oxygen ; Pancreatic Elastase ; Pulmonary Emphysema/chemically induced ; Pulmonary Emphysema/pathology ; Pulmonary Emphysema/physiopathology ; Respiratory Function Tests
Chemical Substances	Pancreatic Elastase (EC 3.4.21.36) ; Oxygen (S88TT14065)
Language	English
Publishing date	2016-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0151211
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Membership of the BSG 1937-1987. British Society of Gastroenterology.

Sladen, G E

Gut

1987 Volume 28 Suppl, Page(s) 16–17

MeSH term(s)	Gastroenterology/history ; History, 20th Century ; Societies, Medical/history ; United Kingdom
Language	English
Publishing date	1987-09
Publishing country	England
Document type	Historical Article ; Journal Article
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Inorganic approaches for radiolabelling biomolecules with fluorine-18 for imaging with positron emission tomography.

Smith, Gareth E / Sladen, Helen L / Biagini, Stefano C G / Blower, Philip J

Dalton transactions (Cambridge, England : 2003)

2011 Volume 40, Issue 23, Page(s) 6196–6205

Abstract: ... elements form strong bonds (i.e. with high bond enthalpy) with fluorine, but with lower activation energy ...

Abstract	Conventional methods for radiolabelling biomolecules such as proteins and peptides with fluorine-18 for PET imaging rely on carbon-fluorine bond formation and are complex and inefficient. Several non-carbon elements form strong bonds (i.e. with high bond enthalpy) with fluorine, but with lower activation energy for their formation compared to carbon-fluorine bonds, whilst preserving a relatively high kinetic stability. In particular, by incorporating boron-, aluminium- and silicon-containing prosthetic groups into biomolecules, promising results have recently been achieved in the radiolabelling with F-18-fluoride under mild aqueous conditions, affording a level of convenience, efficiency and specific activity potentially superior to those offered by conventional C-F bond formation methods. The promise already shown by these early studies heralds a new branch of bioconjugate radiochemistry involving a wider range of "fluoridephilic" elements for synthesis of PET molecular imaging agents.
MeSH term(s)	Aluminum/chemistry ; Animals ; Boron/chemistry ; Chelating Agents/chemistry ; Fluorine Radioisotopes/chemistry ; Isotope Labeling ; Mice ; Positron-Emission Tomography ; Radiopharmaceuticals/chemistry ; Radiopharmaceuticals/pharmacokinetics ; Silicon/chemistry ; Tissue Distribution
Chemical Substances	Chelating Agents ; Fluorine Radioisotopes ; Radiopharmaceuticals ; Aluminum (CPD4NFA903) ; Boron (N9E3X5056Q) ; Silicon (Z4152N8IUI)
Language	English
Publishing date	2011-06-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/c0dt01594f
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Article: The pathogenesis of cholera and some wider implications.

Sladen, G E

Gut

1973 Volume 14, Issue 8, Page(s) 671–680

MeSH term(s)	Acetazolamide/pharmacology ; Amphotericin B/pharmacology ; Animals ; Cholera/physiopathology ; Cyclic AMP/physiology ; Diarrhea/etiology ; Dogs ; Duodenum/metabolism ; Escherichia coli/pathogenicity ; Ethacrynic Acid/pharmacology ; Fluorescent Antibody Technique ; Gastrins/blood ; Humans ; Intestinal Absorption ; Intestinal Mucosa/metabolism ; Jejunum/metabolism ; Models, Biological ; Peptides ; Rabbits ; Rats ; Sodium/metabolism ; Toxins, Biological ; Ultrafiltration ; Zollinger-Ellison Syndrome/complications
Chemical Substances	Gastrins ; Peptides ; Toxins, Biological ; Amphotericin B (7XU7A7DROE) ; Sodium (9NEZ333N27) ; Cyclic AMP (E0399OZS9N) ; Ethacrynic Acid (M5DP350VZV) ; Acetazolamide (O3FX965V0I)
Language	English
Publishing date	1973-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gut.14.8.671
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