384 results on '"Banin E"'
Search Results
52. 53. Aluminum interferes with the control of synaptic transmission
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Banin, E., primary and Meiri, H., additional
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- 1987
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53. Multi-species biofilms: living with friendly neighbors.
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Elias, S. and Banin, E.
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- 2012
54. Blunt trauma in Best's vitelliform macular dystrophy
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Chowers, I., Zamir, E., Banin, E., Abdulrazik, M., and Hemo, Y.
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- 2000
55. Retinal Rod Photoreceptor–Specific Gene Mutation Perturbs Cone Pathway Development
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BANIN, E
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- 1999
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56. Toxic Effects of Aluminium on Nerve Cells and Synaptic Transmission
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Meiri, H., Banin, E., Roll, M., and Rousseau, A.
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- 1992
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57. Antibacterial, antibiofilm, and antiviral farnesol-containing nanoparticles prevent Staphylococcus aureus from drug resistance development
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Aleksandra Ivanova, Kristina Ivanova, Luisa Fiandra, Paride Mantecca, Tiziano Catelani, Michal Natan, Ehud Banin, Gila Jacobi, Tzanko Tzanov, Ivanova, A, Ivanova, K, Fiandra, L, Mantecca, P, Catelani, T, Natan, M, Banin, E, Jacobi, G, Tzanov, T, Universitat Politècnica de Catalunya. Departament d'Enginyeria Química, and Universitat Politècnica de Catalunya. GBMI - Grup de Biotecnologia Molecular i Industrial
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farnesol nanoparticle ,SARS-CoV-2 ,Organic Chemistry ,bacterial eradication ,Biocompatibilitat ,General Medicine ,COVID-19 (Malaltia) ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Farnesol nanoparticles ,biocompatibility ,farnesol nanoparticles ,biofilm prevention and elimination ,COVID-19 (Disease) ,Enginyeria química [Àrees temàtiques de la UPC] ,Biofilm prevention and elimination ,Biocompatibility ,Bacterial eradication ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development.
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- 2022
58. Ferric Uptake Regulator Fur Is Conditionally Essential in Pseudomonas aeruginosa
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Alessandra Lo Sciuto, Shirley Genah, Paolo Visca, Martina Pasqua, Francesco Imperi, Ehud Banin, Daniela Visaggio, Pasqua, M, Visaggio, D, Lo Sciuto, A, Genah, S, Banin, E, Visca, P, and Imperi, F
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0301 basic medicine ,Siderophore ,Mutant ,Pseudomonas syringae ,Siderophores ,Biofilm ,Colony formation ,Infection ,Iron uptake ,Oxidative stress ,Pseudomonas aeruginosa ,Pyochelin ,Bacterial Proteins ,Biofilms ,Culture Media ,Iron ,Mutagenesis ,Mutation ,Phenols ,Reactive Oxygen Species ,Repressor Proteins ,Thiazoles ,Virulence ,Gene Expression Regulation, Bacterial ,Microbiology ,Molecular Biology ,medicine.disease_cause ,biofilm ,integumentary system ,Bacterial ,Research Article ,inorganic chemicals ,030106 microbiology ,Biology ,colony formation ,03 medical and health sciences ,medicine ,oxidative stre ,iron uptake ,siderophores ,infection ,Deletion Mutagenesis ,pyochelin ,Regulon ,Gene Expression Regulation ,bacteria - Abstract
In Pseudomonas aeruginosa , the ferric uptake regulator (Fur) protein controls both metabolism and virulence in response to iron availability. Differently from other bacteria, attempts to obtain fur deletion mutants of P. aeruginosa failed, leading to the assumption that Fur is an essential protein in this bacterium. By investigating a P. aeruginosa conditional fur mutant, we demonstrate that Fur is not essential for P. aeruginosa growth in liquid media, biofilm formation, and pathogenicity in an insect model of infection. Conversely, Fur is essential for growth on solid media since Fur-depleted cells are severely impaired in colony formation. Transposon-mediated random mutagenesis experiments identified pyochelin siderophore biosynthesis as a major cause of the colony growth defect of the conditional fur mutant, and deletion mutagenesis confirmed this evidence. Impaired colony growth of pyochelin-proficient Fur-depleted cells does not depend on oxidative stress, since Fur-depleted cells do not accumulate higher levels of reactive oxygen species (ROS) and are not rescued by antioxidant agents or overexpression of ROS-detoxifying enzymes. Ectopic expression of pch genes revealed that pyochelin production has no inhibitory effects on a fur deletion mutant of Pseudomonas syringae pv. tabaci , suggesting that the toxicity of the pch locus in Fur-depleted cells involves a P. aeruginosa -specific pathway(s). IMPORTANCE Members of the ferric uptake regulator (Fur) protein family are bacterial transcriptional repressors that control iron uptake and storage in response to iron availability, thereby playing a crucial role in the maintenance of iron homeostasis. While fur null mutants of many bacteria have been obtained, Fur appears to be essential in Pseudomonas aeruginosa for still unknown reasons. We obtained Fur-depleted P. aeruginosa cells by conditional mutagenesis and showed that Fur is dispensable for planktonic growth, while it is required for colony formation. This is because Fur protects P. aeruginosa colonies from toxicity exerted by the pyochelin siderophore. This work provides a functional basis to the essentiality of Fur in P. aeruginosa and highlights unique properties of the Fur regulon in this species.
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- 2018
59. Advancing Therapeutic Strategies for Inherited Retinal Degeneration: Recommendations From the Monaciano Symposium
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Robin R. Ali, Thomas A. Reh, Alessandro Iannaccone, David M. Gamm, Debra A. Thompson, K. Thiran Jayasundera, Kari Branham, David N. Zacks, Eyal Banin, John R. Heckenlively, Richard G. Weleber, Naheed W. Khan, Mark E. Pennesi, Robert S. Molday, John G. Flannery, William W. Hauswirth, Thompson, D. A., Ali, R. R., Banin, E., Branham, K. E., Flannery, J. G., Gamm, D. M., Hauswirth, W. W., Heckenlively, J. R., Iannaccone, A., Thiran Jayasundera, K., Khan, N. W., Molday, R. S., Pennesi, M. E., Reh, T. A., Weleber, R. G., Zacks, D. N., and Auricchio, A.
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medicine.medical_specialty ,Blinding ,Population ,Translational research ,Eye ,Ophthalmology & Optometry ,Medical and Health Sciences ,Cell therapy ,outcome measures ,Cellular and Molecular Neuroscience ,Rare Diseases ,Gene therapy ,Ophthalmology ,Genetics ,medicine ,Humans ,retinal dystrophy ,Disease management (health) ,education ,Eye Disease and Disorders of Vision ,education.field_of_study ,business.industry ,Retinal Degeneration ,Neurosciences ,Retinal dystrophy ,Outcome Measure ,Disease Management ,Monaciano Consortium ,Articles ,Biological Sciences ,Congresses as Topic ,Disease phenotype ,gene therapy ,Sensory Systems ,Brain Disorders ,Transplantation ,Orphan Drug ,Transformative learning ,Practice Guidelines as Topic ,Position paper ,Engineering ethics ,cell therapy ,disease phenotypes ,business ,Retinal Dystrophies ,Human - Abstract
© 2015 The Association for Research in Vision and Ophthalmology, Inc. Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases.
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- 2015
60. Mutations in IMPG2, Encoding Interphotoreceptor Matrix Proteoglycan 2, Cause Autosomal-Recessive Retinitis Pigmentosa
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Ellen A.W. Blokland, Frans P.M. Cremers, Lina Zelinger, Dikla Bandah-Rozenfeld, Dirk J. Lefeber, Tim M. Strom, Karlien L.M. Coene, Francesco Testa, Inbar Erdinest, Caroline C W Klaver, Francesca Simonelli, Anneke I. den Hollander, Krysta Voesenek, L. Ingeborgh van den Born, Anna M. Siemiatkowska, Raheel Qamar, Rob W.J. Collin, Muhammad Imran Khan, Dror Sharon, Sandro Banfi, Eyal Banin, Hematology, Ophthalmology, Bandah Rozenfeld, D, Collin, Rw, Banin, E, Ingeborgh van den Born, L, Coene, Kl, Siemiatkowska, Am, Zelinger, L, Khan, Mi, Lefeber, Dj, Erdinest, I, Testa, Francesco, Simonelli, Francesca, Voesenek, K, Blokland, Ea, Strom, Tm, Klaver, Cc, Qamar, R, Banfi, Sandro, Cremers, Fp, Sharon, D, and den Hollander, Ai
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Adult ,Male ,Genetics and epigenetic pathways of disease [NCMLS 6] ,Fundus Oculi ,Genetic Linkage ,Nonsense mutation ,DNA Mutational Analysis ,Molecular Sequence Data ,Genes, Recessive ,Gene mutation ,Biology ,Interphotoreceptor matrix ,Neuroinformatics [DCN 3] ,medicine.disease_cause ,Article ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,Exon ,Chromosome Segregation ,Retinitis pigmentosa ,Chlorocebus aethiops ,medicine ,Genetics ,Missense mutation ,Animals ,Humans ,Genetics(clinical) ,Amino Acid Sequence ,Genetics (clinical) ,Aged ,Mutation ,Base Sequence ,Homozygote ,Chromosome Mapping ,Glycostation disorders [IGMD 4] ,Middle Aged ,medicine.disease ,Pedigree ,COS Cells ,Mutation testing ,Female ,Mutant Proteins ,Proteoglycans ,Retinitis Pigmentosa ,Subcellular Fractions - Abstract
Contains fulltext : 89392.pdf (Publisher’s version ) (Closed access) Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results in the absence of seven amino acids in a conserved SEA domain of the IMPG2 protein. Transient transfection of COS-1 cells showed that a construct expressing the wild-type SEA domain is properly targeted to the plasma membrane, whereas the mutant lacking the seven amino acids appears to be retained in the endoplasmic reticulum. Mutation analysis in ten additional index cases that were of Dutch, Israeli, Italian, and Pakistani origin and had homozygous regions encompassing IMPG2 revealed five additional mutations; four nonsense mutations and one missense mutation affecting a highly conserved phenylalanine residue. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The patient with the missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix. Our data therefore show that mutations in a structural component of the interphotoreceptor matrix can cause arRP.
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- 2010
61. Characterising the refractive error in paediatric patients with congenital stationary night blindness: a multicentre study.
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Igelman AD, White E, Tayyib A, Everett L, Vincent A, Heon E, Zeitz C, Michaelides M, Mahroo OA, Katta M, Webster A, Preising M, Lorenz B, Khateb S, Banin E, Sharon D, Luski S, Van Den Broeck F, Leroy BP, De Baere E, Walraedt S, Stingl K, Kuehlewein L, Kohl S, Reith M, Fulton A, Raghuram A, Meunier I, Dollfus H, Aleman TS, Bedoukian EC, O'Neil EC, Krauss E, Vincent A, Jordan C, Iannaccone A, Sen P, Sundaramurthy S, Nagasamy S, Balikova I, Casteels I, Borooah S, Yassin S, Nagiel A, Schwartz H, Zanlonghi X, Gottlob I, McLean RJ, Munier FL, Stephenson A, Sisk R, Koenekoop R, Wilson LB, Fredrick D, Choi D, Yang P, and Pennesi ME
- Abstract
Background/aaims: Congenital stationary night blindness (CSNB) is an inherited retinal disease that is often associated with high myopia and can be caused by pathological variants in multiple genes, most commonly CACNA1F , NYX and TRPM1 . High myopia is associated with retinal degeneration and increased risk for retinal detachment. Slowing the progression of myopia in patients with CSNB would likely be beneficial in reducing risk, but before interventions can be considered, it is important to understand the natural history of myopic progression., Methods: This multicentre, retrospective study explored CSNB caused by variants in CACNA1F , NYX or TRPM1 in patients who had at least 6 measurements of their spherical equivalent of refraction (SER) before the age of 18. A mixed-effect model was used to predict progression of SER overtime and differences between genotypes were evaluated., Results: 78 individuals were included in this study. All genotypes showed a significant myopic predicted SER at birth (-3.076D, -5.511D and -5.386D) for CACNA1F , NYX and TRPM1 respectively. Additionally, significant progression of myopia per year (-0.254D, -0.257D and -0.326D) was observed for all three genotypes CACNA1F , NYX and TRPM1 , respectively., Conclusions: Patients with CSNB tend to be myopic from an early age and progress to become more myopic with age. Patients may benefit from long-term myopia slowing treatment in the future and further studies are indicated. Additionally, CSNB should be considered in the differential diagnosis for early-onset myopia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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62. KCNV2 -associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.
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de Guimaraes TAC, Georgiou M, Robson AG, Fujinami K, Vincent A, Nasser F, Khateb S, Mahroo OA, Pontikos N, Vargas ME, Thiadens AAHJ, Carvalho ER, Nguyen XT, Arno G, Fujinami-Yokokawa Y, Liu X, Tsunoda K, Hayashi T, Jiménez-Rolando B, Martin-Merida MI, Avila-Fernandez A, Salas EC, Garcia-Sandoval B, Ayuso C, Sharon D, Kohl S, Huckfeldt RM, Banin E, Pennesi ME, Khan AO, Wissinger B, Webster AR, Heon E, Boon CJF, Zrenner E, and Michaelides M
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- Child, Child, Preschool, Female, Humans, Male, DNA Mutational Analysis, Mutation, Missense, Potassium Channels, Voltage-Gated genetics, Retina physiopathology, Retinal Diseases genetics, Retinal Diseases physiopathology, Retinal Diseases diagnosis, Retrospective Studies, Tomography, Optical Coherence, Electroretinography, Genetic Association Studies, Visual Acuity physiology
- Abstract
Background/aims: To investigate genotype-phenotype associations in patients with KCNV2 retinopathy., Methods: Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants-two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)-and parameters were compared., Results: Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants., Conclusions: Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials., Competing Interests: Competing interests: MG and MM consult for MeiraGTx. KF consults for Astellas Pharma, Kubota Pharmaceutical Holdings, Acucela, Novartis AG and Janssen Pharmaceuticals. Ester Carreño consults for Active Biotech and Alimera. EZ consults for Acucela, IVERIC bi, Janssen Pharmaceuticals, ProQR Therapeutics N.V., Gyroscope Therapeutics and Biogen MA. AV consults for Adverum Biotechnologies. MEP consults for Spark Therapeutics. Susanne Kohl consults for Novartis AG. CA consults for Novartis AG, Janssen Pharmaceuticals and Santen. The rest of the authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
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- 2024
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63. Genetic Analysis of 252 Index Cases with Inherited Retinal Diseases Using a Panel of 351 Retinal Genes.
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Abu Elasal M, Mousa S, Salameh M, Blumenfeld A, Khateb S, Banin E, and Sharon D
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- Humans, Male, Female, ATP-Binding Cassette Transporters genetics, Eye Proteins genetics, Genetic Testing methods, Exome Sequencing methods, Extracellular Matrix Proteins genetics, Pedigree, Retinal Dystrophies genetics, Genetic Predisposition to Disease, Mutation, Retinal Diseases genetics
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Inherited retinal diseases (IRDs) are extremely heterogeneous with at least 350 causative genes, complicating the process of genetic diagnosis. We analyzed samples of 252 index cases with IRDs using the Blueprint Genetics panel for "Retinal Dystrophy" that includes 351 genes. The cause of disease could be identified in 55% of cases. A clear difference was obtained between newly recruited cases (74% solved) and cases that were previously analyzed by panels or whole exome sequencing (26% solved). As for the mode of inheritance, 75% of solved cases were autosomal recessive (AR), 10% were X-linked, 8% were autosomal dominant, and 7% were mitochondrial. Interestingly, in 12% of solved cases, structural variants (SVs) were identified as the cause of disease. The most commonly identified genes were ABCA4 , EYS and USH2A , and the most common mutations were MAK -c.1297_1298ins353 and FAM161A -c.1355_1356del. In line with our previous IRD carrier analysis, we identified heterozygous AR mutations that were not the cause of disease in 36% of cases. The studied IRD panel was found to be efficient in gene identification. Some variants were misinterpreted by the pipeline, and therefore, multiple analysis tools are recommended to obtain a more accurate annotation of potential disease-causing variants.
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- 2024
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64. Nationwide Prevalence of Inherited Retinal Diseases in the Israeli Population.
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Shalom S, Ben-Yosef T, Sher I, Zag A, Rotenstreich Y, Poleg T, Birk OS, Gradstein L, Ehrenberg M, Deitch I, Mezer E, Hecht I, Pras E, Ramon D, Khateb S, Zur D, Newman H, Kharouba R, Goldenberg-Cohen N, Leibu R, Soudry S, Perlman I, Banin E, and Sharon D
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- Humans, Israel epidemiology, Prevalence, Male, Female, Adult, Middle Aged, Phenotype, Adolescent, Young Adult, Aged, Child, Eye Diseases, Hereditary epidemiology, Eye Diseases, Hereditary genetics, Child, Preschool, Electroretinography, Retinal Diseases epidemiology, Retinal Diseases genetics, Retinal Diseases diagnosis
- Abstract
Importance: Data regarding the prevalence of various inherited retinal diseases (IRDs) are limited and vary across populations; moreover, nationwide prevalence studies may be limited to a specific IRD phenotype, potentially leading to inaccurate prevalence estimations. Therefore, nationwide prevalence data are needed., Objective: To determine the prevalence of 67 IRD phenotypes in the Israeli population., Design, Setting, and Participants: This cohort study collected nationwide data regarding the number of individuals affected with IRD phenotypes assessed in 10 clinical and academic centers in Israel as part of the research activity of the Israeli inherited retinal disease consortium. Data were collected in May 2023 on 9396 individuals residing in Israel who were diagnosed by an ophthalmologist with an IRD using either electroretinography or retinal imaging where included. Individuals with retinal diseases known to have a nonmendelian basis or without a clear genetic basis and those who were reported as deceased at the time of data collection were excluded from this study., Main Outcomes and Measures: Prevalence of 67 IRD phenotypes., Results: Among the 9396 participants in our cohort, the most common IRD in Israel was retinitis pigmentosa with a disease prevalence of approximately 1:2400 individuals, followed by cone-rod dystrophy (approximately 1:14 000), Stargardt disease (approximately 1:16 000), Usher syndrome (approximately 1:16,000), and congenital stationary night blindness (approximately 1:18 000). The prevalence of all IRDs combined was 1:1043 individuals., Conclusions and Relevance: The current study provides large prevalence dataset of 67 IRD phenotypes, some of which are extremely rare, with only a single identified case. This analysis highlights the potential importance of performing additional nationwide prevalence studies to potentially assist with determining the prevalence of IRDs worldwide.
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- 2024
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65. Current Status of Clinical Trials Design and Outcomes in Retinal Gene Therapy.
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Rosin B, Banin E, and Sahel JA
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- Humans, Retinal Diseases therapy, Treatment Outcome, Visual Acuity, Patient Safety, Retinal Degeneration therapy, Genetic Therapy methods, Clinical Trials as Topic, Research Design
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With the rapid expansion of methods encompassed by the term gene therapy, new trials exploring the safety and efficacy of these methods are initiated more frequently. As a result, important questions arise pertaining the design of these trials and patient participation. One of the most important aspects of any clinical trial is the ability to measure the trial's outcome in a manner that will reflect the effect of the treatment and allow its quantification, whether the trial is aimed at preservation or restoration of retinal cells (photoreceptors and others), vision, or both. Here we will review the existing methods for quantification of trial outcomes, stressing the importance of assessing the participant's visual function and not just visual acuity. We will also describe the key considerations in trial design. Finally, as patient safety remains the primary concern in any trial participation, we will outline the key principles in that regard., (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)
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- 2024
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66. Genetic and Clinical Analyses of the KIZ -c.226C>T Variant Resulting in a Dual Mutational Mechanism.
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Sundaresan Y, Rivera A, Obolensky A, Gopalakrishnan P, Ohayon Hadad H, Shemesh A, Khateb S, Ross M, Ofri R, Durst S, Newman H, Leibu R, Soudry S, Zur D, Ben-Yosef T, Banin E, and Sharon D
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- Adolescent, Adult, Female, Humans, Male, Middle Aged, Exome Sequencing methods, Eye Proteins genetics, Jews genetics, Pedigree, Phenotype, Mutation, Retinitis Pigmentosa genetics, Retinitis Pigmentosa pathology
- Abstract
Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder. Mutations in KIZ cause autosomal recessive (AR) RP. We aimed to characterize the genotype, expression pattern, and phenotype in a large cohort of KIZ cases. Sanger and whole exome sequencing were used to identify the KIZ variants. Medical records were reviewed and analyzed. Thirty-one patients with biallelic KIZ mutations were identified: 28 homozygous for c.226C>T (p.R76*), 2 compound heterozygous for p.R76* and c.3G>A (p.M1?), and one homozygous for c.247C>T (p.R83*). c.226C>T is a founder mutation among patients of Jewish descent. The clinical parameters were less severe in KIZ compared to DHDDS and FAM161A cases. RT-PCR analysis in fibroblast cells revealed the presence of four different transcripts in both WT and mutant samples with a lower percentage of the WT transcript in patients. Sequence analysis identified an exonic sequence enhancer (ESE) that includes the c.226 position which is affected by the mutation. KIZ mutations are an uncommon cause of IRD worldwide but are not rare among Ashkenazi Jews. Our data indicate that p.R76* affect an ESE which in turn results in the pronounced skipping of exon 3. Therefore, RNA-based therapies might show low efficacy since the mutant transcripts are spliced.
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- 2024
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67. Loss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration.
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Han JH, Rodenburg K, Hayman T, Calzetti G, Kaminska K, Quinodoz M, Marra M, Wallerich S, Allon G, Nagy ZZ, Knézy K, Li Y, Chen R, Barboni MTS, Yang P, Pennesi ME, van den Born LI, Varsányi B, Szabó V, Sharon D, Banin E, Ben-Yosef T, Roosing S, Koenekoop RK, and Rivolta C
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- Humans, Male, Female, Adult, Middle Aged, Loss of Function Mutation, Genes, Recessive, Child, Adolescent, Cone-Rod Dystrophies genetics, Hungary, Young Adult, Genetic Predisposition to Disease, Pedigree, Retinal Degeneration genetics
- Abstract
Purpose: Inherited retinal diseases (IRDs) are a group of monogenic conditions that can lead to progressive blindness. Their missing heritability is still considerable, due in part to the presence of disease genes that await molecular identification. The purpose of this work was to identify novel genetic associations with IRDs., Methods: Patients underwent a comprehensive ophthalmological evaluation using standard-of-care tests, such as detailed retinal imaging (macular optical coherence tomography and short-wavelength fundus autofluorescence) and electrophysiological testing. Exome and genome sequencing, as well as computer-assisted data analysis were used for genotyping and detection of DNA variants. A minigene-driven splicing assay was performed to validate the deleterious effects of 1 of such variants., Results: We identified 8 unrelated families from Hungary, the United States, Israel, and The Netherlands with members presenting with a form of autosomal recessive and nonsyndromic retinal degeneration, predominantly described as rod-cone dystrophy but also including cases of cone/cone-rod dystrophy. Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later. Myopia greater than 5 diopters was present in 5 of 7 cases with available refractive data, and retinal detachment was reported in 2 cases. All ascertained patients carried biallelic loss-of-function variants in UBAP1L (HGNC: 40028), a gene with unknown function and with homologies to UBAP1, encoding a protein involved in ubiquitin metabolism. One of these pathogenic variants, the intronic NM_001163692.2:c.910-7G>A substitution, was identified in 5 unrelated families. Minigene-driven splicing assays in HEK293T cells confirmed that this DNA change is responsible for the creation of a new acceptor splice site, resulting in aberrant splicing., Conclusion: We identified UBAP1L as a novel IRD gene. Although its function is currently unknown, UBAP1L is almost exclusively expressed in photoreceptors and the retinal pigment epithelium, hence possibly explaining the link between pathogenic variants in this gene and an ocular phenotype., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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68. Simultaneous Detection of Common Founder Mutations Using a Cost-Effective Deep Sequencing Panel.
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Shalom S, Hanany M, Eilat A, Chowers I, Ben-Yosef T, Khateb S, Banin E, and Sharon D
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- Humans, Retinal Diseases genetics, Retinal Diseases diagnosis, Founder Effect, Male, Female, Genetic Testing methods, Genetic Testing economics, Cost-Benefit Analysis, Pedigree, High-Throughput Nucleotide Sequencing methods, High-Throughput Nucleotide Sequencing economics, Mutation
- Abstract
Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of diseases which cause visual loss due to Mendelian mutations in over 250 genes, making genetic diagnosis challenging and time-consuming. Here, we developed a new tool, CDIP (Cost-effective Deep-sequencing IRD Panel) in which a simultaneous sequencing of common mutations is performed. CDIP is based on simultaneous amplification of 47 amplicons harboring common mutations followed by next-generation sequencing (NGS). Following five rounds of calibration of NGS-based steps, CDIP was used in 740 IRD samples. The analysis revealed 151 mutations in 131 index cases. In 54 (7%) of these cases, CDIP identified the genetic cause of disease (the remaining were single-heterozygous recessive mutations). These include a patient that was clinically diagnosed with retinoschisis and found to be homozygous for NR2E3 -c.932G>A (p.R311Q), and a patient with RP who is hemizygous for an RPGR variant, c.292C>A (p.H98N), which was not included in the analysis but is located in proximity to one of these mutations. CDIP is a cost-effective deep sequencing panel for simultaneous detection of common founder mutations. This protocol can be implemented for additional populations as well as additional inherited diseases, and mainly in populations with strong founder effects.
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- 2024
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69. PemB, a type III secretion effector in Pseudomonas aeruginosa, affects Caenorhabditis elegans life span.
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Zelikman S, Dudkevich R, Korenfeld-Tzemach H, Shmidov E, Levi-Ferber M, Shoshani S, Ben-Aroya S, Henis-Korenblit S, and Banin E
- Abstract
Pseudomonas aeruginosa is one of the leading nosocomial opportunistic pathogens causing acute and chronic infections. Among its main virulent factors is the Type III secretion system (T3SS) which enhances disease severity by delivering effectors to the host in a highly regulated manner. Despite its importance for virulence, only six T3SS-dependent effectors have been discovered so far. Previously, we identified two new potential effectors using a machine-learning algorithm approach. Here we demonstrate that one of these effectors, PemB, is indeed virulent. Using a live Caenorhabditis elegans infection model, we demonstrate this effector damages the integrity of the intestine barrier leading to the death of the host. Implementing a high-throughput assay using Saccharomyces cerevisiae, we identified several candidate proteins that interact with PemB. One of them, EFT1, has an ortholog in C. elegans ( eef-2 ) and is also an essential gene and a well-known target utilized by different pathogens to induce toxicity to the worm. Accordingly, we found that by silencing the eef-2 gene in C. elegans , PemB could no longer induce its toxic effect. The current study further uncovers the complex machinery assisting P. aeruginosa virulence and may provide novel insight how to manage infection associated with this hard-to-treat pathogen., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)
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- 2024
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70. Development and Evaluation of a New Self-Administered Near Visual Acuity Chart: Accuracy and Feasibility of Usage.
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Ben-Eli H, Banin E, Levy J, Glik M, Afriat S, Magal Y, Harari R, Benyamin A, Shein S, and Chowers I
- Abstract
Background : Visual acuity (VA) assessments are crucial in ophthalmology but traditionally rely on in-clinic evaluations. The emergence of telemedicine has spurred interest in creating dependable self-administered VA tests for use beyond standard clinical environments. This study evaluated the practicality and validity of a self-administered near VA card test against traditional Snellen and Rosenbaum Pocket Vision Screener (RPVS) methods for home monitoring and enhancing clinical workflow. Methods : In a cross-sectional study, a near VA card (Hadassah Self-Visual Acuity Screener (HSVA)) was developed with written and videotaped instructions for self-use. Patients with a minimal best-corrected VA (BCVA) of 1.0 LogMAR in at least one eye were recruited from ophthalmology and optometry clinics. Outcomes included the mean BCVA difference between the self-administered values and those obtained by the examiner, and correlations between BCVA values obtained by the Snellen, RPVS, HSVA, and previous distance BCVA methods according to the patients' electronic medical records. Results : A total of 275 participants (mean age: 42.5 ± 19.4 years; range: 18-89 years; 47% female) were included. Test-retest reliability analysis of the HSVA demonstrated a very good correlation and repeatability (n = 38 patients; Rs = 1.0; p < 0.001). Accuracy analysis revealed the mean LogMAR BCVA values of an additional 237 patients obtained by the Snellen, RPVS, and HSVA methods were similar ( p = 0.10). The self-test BCVA results obtained by the HSVA agreed with the masked examiner-tested VA results (n = 67 patients; p = 0.17; Rs = 0.87; ICC = 0.96). Similar results were obtained when stratification by median age (42 years) was performed. Bland-Altman analysis of the HSVA and RPVS methods demonstrated a good agreement. To assess whether the HSVA could predict the VA results in the clinically used charts, multivariate analysis was used and revealed that the HSVA predicted the RPVS results (β = 0.91; p = 0.001; R
2 = 0.88), and the self-test HSVA predicted the Snellen VA results within two lines (β = 0.93; p = 0.01; R2 = 0.36). Conclusions : The home-based HSVA assessment exhibited high test-retest reliability, accuracy, and alignment with clinical-standard VA tests. Its efficacy in self-testing mirrored examiner-conducted VA assessments and accurately predicted Snellen VA outcomes, indicating the HSVA's suitability for self-monitoring in chronic ocular conditions or when access to conventional examinations is limited. The utility of self-administered VA tests may extend beyond ophthalmology and optometry, potentially benefiting primary care, emergency medicine, and neurology. Further research is needed to explore and validate the practical applications of remote VA testing.- Published
- 2024
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71. Retinal Disorders.
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Sahel JA, Banin E, Bennett J, Duncan JL, and Roska B
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Retinal disorders caused by genetic or environmental factors cause severe visual impairment and often result in blindness. The past ten years have seen rapid progress in our understanding of the biological basis of these conditions, as well as significant advances towards gene and cell-based therapies. Regulatory challenges remain, but there is reason to hope that creative approaches will lead to safe and effective breakthrough treatments for these conditions in the near future., (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)
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- 2024
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72. Fine-tuning FAM161A gene augmentation therapy to restore retinal function.
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Arsenijevic Y, Chang N, Mercey O, El Fersioui Y, Koskiniemi-Kuendig H, Joubert C, Bemelmans AP, Rivolta C, Banin E, Sharon D, Guichard P, Hamel V, and Kostic C
- Subjects
- Animals, Mice, Humans, Retina metabolism, Exons, Protein Isoforms genetics, Protein Isoforms metabolism, Genetic Therapy, Eye Proteins genetics, Eye Proteins chemistry, Eye Proteins metabolism, Retinitis Pigmentosa genetics, Retinitis Pigmentosa therapy, Retinitis Pigmentosa metabolism
- Abstract
For 15 years, gene therapy has been viewed as a beacon of hope for inherited retinal diseases. Many preclinical investigations have centered around vectors with maximal gene expression capabilities, yet despite efficient gene transfer, minimal physiological improvements have been observed in various ciliopathies. Retinitis pigmentosa-type 28 (RP28) is the consequence of bi-allelic null mutations in the FAM161A, an essential protein for the structure of the photoreceptor connecting cilium (CC). In its absence, cilia become disorganized, leading to outer segment collapses and vision impairment. Within the human retina, FAM161A has two isoforms: the long one with exon 4, and the short one without it. To restore CC in Fam161a-deficient mice shortly after the onset of cilium disorganization, we compared AAV vectors with varying promoter activities, doses, and human isoforms. While all vectors improved cell survival, only the combination of both isoforms using the weak FCBR1-F0.4 promoter enabled precise FAM161A expression in the CC and enhanced retinal function. Our investigation into FAM161A gene replacement for RP28 emphasizes the importance of precise therapeutic gene regulation, appropriate vector dosing, and delivery of both isoforms. This precision is pivotal for secure gene therapy involving structural proteins like FAM161A., (© 2024. The Author(s).)
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- 2024
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73. Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.
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Hitti-Malin RJ, Panneman DM, Corradi Z, Boonen EGM, Astuti G, Dhaenens CM, Stöhr H, Weber BHF, Sharon D, Banin E, Karali M, Banfi S, Ben-Yosef T, Glavač D, Farrar GJ, Ayuso C, Liskova P, Dudakova L, Vajter M, Ołdak M, Szaflik JP, Matynia A, Gorin MB, Kämpjärvi K, Bauwens M, De Baere E, Hoyng CB, Li CHZ, Klaver CCW, Inglehearn CF, Fujinami K, Rivolta C, Allikmets R, Zernant J, Lee W, Podhajcer OL, Fakin A, Sajovic J, AlTalbishi A, Valeina S, Taurina G, Vincent AL, Roberts L, Ramesar R, Sartor G, Luppi E, Downes SM, van den Born LI, McLaren TL, De Roach JN, Lamey TM, Thompson JA, Chen FK, Tracewska AM, Kamakari S, Sallum JMF, Bolz HJ, Kayserili H, Roosing S, and Cremers FPM
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- Humans, Mutation, Penetrance, Pedigree, Retina, Phenotype, ATP-Binding Cassette Transporters genetics, Eye Proteins, Cadherin Related Proteins, Nerve Tissue Proteins genetics, Macular Degeneration genetics
- Abstract
Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1 :c.783G>A and CNGB3 :c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.
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- 2024
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74. Whole exome sequencing of 491 individuals with inherited retinal diseases reveals a large spectrum of variants and identification of novel candidate genes.
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Hayman T, Millo T, Hendler K, Chowers I, Gross M, Banin E, and Sharon D
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- Humans, Exome Sequencing, Sequence Analysis, DNA methods, DNA, DNA Copy Number Variations genetics, Retinal Diseases genetics
- Abstract
Background: Inherited retinal diseases (IRDs) include a range of vision loss conditions caused by variants in different genes. The clinical and genetic heterogeneity make identification of the genetic cause challenging. Here, a cohort of 491 unsolved cases from our cohort of Israeli and Palestinian families with IRDs underwent whole exome sequencing (WES), including detection of CNVs as well as single nucleotide variants (SNVs)., Methods: All participants underwent clinical examinations. Following WES on DNA samples by 3 billion, initial SNV analysis was performed by 3 billion and SNV and CNV analysis by Franklin Genoox. The CNVs indicated by the programme were confirmed by PCR followed by gel electrophoresis., Results: WES of 491 IRD cases revealed the genetic cause of disease in 51% of cases, of which 11% were due wholly or in part to CNVs. In two cases, we clarified previously incorrect or unclear clinical diagnoses. This analysis also identified ESRRB and DNM1 as potential novel genes., Conclusion: This analysis is the most extensive one to include CNVs to examine IRD causing genes in the Israeli and Palestinian populations. It has allowed us to identify the causative variant of many patients with IRDs including ones with unclear diagnoses and potential novel genes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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75. Protecting the Antibacterial Coating of Urinal Catheters for Improving Safety.
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Perelshtein I, Shoshani S, Jacobi G, Natan M, Dudchenko N, Perkas N, Tkachev M, Bengalli R, Fiandra L, Mantecca P, Ivanova K, Tzanov T, Banin E, and Gedanken A
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- Humans, Silicon Dioxide pharmacology, Biofilms, Anti-Bacterial Agents pharmacology, Catheters, Carbon, Zinc Oxide pharmacology, Bathroom Equipment
- Abstract
Catheter-associated urinary tract infections (CAUTI) are among the most common bacterial infections associated with prolonged hospitalization and increased healthcare expenditures. Despite recent advances in the prevention and treatment of these infections, there are still many challenges remaining, among them the creation of a durable catheter coating, which prevents bacterial biofilm formation. The current work reports on a method of protecting medical tubing endowed with antibiofilm properties. Silicone catheters coated sonochemically with ZnO nanoparticles (NPs) demonstrated excellent antibiofilm effects. Toward approval by the European Medicines Agency, it was realized that the ZnO coating would not withstand the regulatory requirements of avoiding dissolution for 14 days in artificial urine examination. Namely, after exposure to urine for 14 days, the coating amount was reduced by 90%. Additional coatings with either carbon or silica maintained antibiofilm activity against Staphylococcus aureus while resisting dissolution in artificial urine for 14 days (C- or SiO
2 -protected catheters exhibited only 29% reduction). HR-SEM images of the protected catheters indicate the presence of the ZnO coating as well as the protective layer. Antibiofilm activity of all catheters was evaluated both before and after exposure to artificial urine. It was shown that before artificial urine exposure, all coated catheters showed high antibiofilm properties compared to the uncoated control. Exposure of ZnO-coated catheters, without the protective layer, to artificial urine had a significant effect exhibited by the decrease in antibiofilm activity by almost 2 orders of magnitude, compared to unexposed catheters. Toxicity studies performed using a reconstructed human epidermis demonstrated the safety of the improved coating. Exposure of the epidermis to ZnO catheter extracts in artificial urine affects tissue viability compared with control samples, which was not observed in the case of ZnO NPs coating with SiO2 or C. We suggest that silica and carbon coatings confer some protection against zinc ions release, improving ZnO coating safety.- Published
- 2024
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76. Best Disease: Global Mutations Review, Genotype-Phenotype Correlation, and Prevalence Analysis in the Israeli Population.
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Beryozkin A, Sher I, Ehrenberg M, Zur D, Newman H, Gradstein L, Simaan F, Rotenstreich Y, Goldenberg-Cohen N, Bahar I, Blumenfeld A, Rivera A, Rosin B, Deitch-Harel I, Perlman I, Mechoulam H, Chowers I, Leibu R, Ben-Yosef T, Pras E, Banin E, Sharon D, and Khateb S
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- Humans, Israel epidemiology, Prevalence, Mutation, Genetic Association Studies, Bestrophins, Vitelliform Macular Dystrophy
- Abstract
Purpose: To review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population., Methods: Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources., Results: A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein., Conclusions: This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.
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- 2024
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77. A pipeline for identifying guide RNA sequences that promote RNA editing of nonsense mutations that cause inherited retinal diseases.
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Schneider N, Steinberg R, Ben-David A, Valensi J, David-Kadoch G, Rosenwasser Z, Banin E, Levanon EY, Sharon D, and Ben-Aroya S
- Abstract
Adenosine deaminases acting on RNA (ADARs) are endogenous enzymes catalyzing the deamination of adenosines to inosines, which are then read as guanosines during translation. This ability to recode makes ADAR an attractive therapeutic tool to edit genetic mutations and reprogram genetic information at the mRNA level. Using the endogenous ADARs and guiding them to a selected target has promising therapeutic potential. Indeed, different studies have reported several site-directed RNA-editing approaches for making targeted base changes in RNA molecules. The basic strategy has been to use guide RNAs (gRNAs) that hybridize and form a double-stranded RNA (dsRNA) structure with the desired RNA target because of ADAR activity in regions of dsRNA formation. Here we report on a novel pipeline for identifying disease-causing variants as candidates for RNA editing, using a yeast-based screening system to select efficient gRNAs for editing of nonsense mutations, and test them in a human cell line reporter system. We have used this pipeline to modify the sequence of transcripts carrying nonsense mutations that cause inherited retinal diseases in the FAM161A , KIZ , TRPM1 , and USH2A genes. Our approach can serve as a basis for gene therapy intervention in knockin mouse models and ultimately in human patients., Competing Interests: S.B.-A. and E.Y.L. are inventors of a filed patent based on the work published here: “Composition and Methods for Identifying Antisense Guide RNA for RNA Editing” (7632-PCT | PCT/IL2021/050800, Bar-Ilan University)., (© 2024 The Author(s).)
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- 2024
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78. The biofilm community resurfaces: new findings and post-pandemic progress.
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Greenwich JL, Fleming D, Banin E, Häussler S, Kjellerup BV, Sauer K, Visick KL, and Fuqua C
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- Humans, United States, Biofilms, Pandemics, Societies, Scientific
- Abstract
The ninth American Society for Microbiology Conference on Biofilms was convened in-person on 13-17 November 2022 in Charlotte, NC. As the first of these conferences since prior to the start of the COVID-19 pandemic, the energy among the participants of the conference was clear, and the meeting was a tremendous success. The mixture of >330 oral and poster presentations resoundingly embodied the vitality of biofilm research across a wide range of topics and multiple scientific disciplines. Special activities, including a pre-conference symposium for early career researchers, further enhanced the attendee experience. As a general theme, the conference was deliberately structured to provide high levels of participation and engagement among early career scientists., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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79. ZnO Quantum Photoinitiators as an All-in-One Solution for Multifunctional Photopolymer Nanocomposites.
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Naor T, Gigi S, Waiskopf N, Jacobi G, Shoshani S, Kam D, Magdassi S, Banin E, and Banin U
- Abstract
Nanocomposites are constructed from a matrix material combined with dispersed nanosized filler particles. Such a combination yields a powerful ability to tailor the desired mechanical, optical, electrical, thermodynamic, and antimicrobial material properties. Colloidal semiconductor nanocrystals (SCNCs) are exciting potential fillers, as they display size-, shape-, and composition-controlled properties and are easily embedded in diverse matrices. Here we present their role as quantum photoinitiators (QPIs) in acrylate-based polymer, where they act as a catalytic radical initiator and endow the system with mechanical, photocatalytic, and antimicrobial properties. By utilizing ZnO nanorods (NRs) as QPIs, we were able to increase the tensile strength and elongation at break of poly(ethylene glycol) diacrylate (PEGDA) hydrogels by up to 85%, unlike the use of the same ZnO NRs acting merely as fillers. Simultaneously, we endowed the PEGDA hydrogels with post-polymerization photocatalytic and antimicrobial activities and showed their ability to decompose methylene blue and significantly eradicate antibiotic-resistant bacteria and viral pathogens. Moreover, we demonstrate two fabrication showcase methods, traditional molding and digital light processing printing, that can yield hydrogels with complex architectures. These results position SCNC-based systems as promising candidates to act as all-in-one photoinitiators and fillers in nanocomposites for diverse biomedical applications, where specific and purpose-oriented characteristics are required.
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- 2023
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80. Corrigendum: Comparative genomics of Bacillus cereus sensu lato spp. biocontrol strains in correlation to in-vitro phenotypes and plant pathogen antagonistic capacity.
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Moshe M, Gupta CL, Jain RM, Sela N, Minz D, Banin E, Frenkel O, and Cytryn E
- Abstract
[This corrects the article DOI: 10.3389/fmicb.2023.996287.]., (Copyright © 2023 Moshe, Gupta, Jain, Sela, Minz, Banin, Frenkel and Cytryn.)
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- 2023
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81. Synthesis and Characterization of Durable Antibiofilm and Antiviral Silane-Phosphonium Thin Coatings for Medical and Agricultural Applications.
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Nissim M, Lline-Vul T, Shoshani S, Jacobi G, Malka E, Dombrovsky A, Banin E, and Margel S
- Abstract
Pathogens such as bacteria and viruses cause disease in a range of hosts, from humans to plants. Bacterial biofilms, communities of bacteria, e.g., Staphylococcus aureus and Escherichia coli , attached to the surface, create a protective layer that enhances their survival in harsh environments and resistance to antibiotics and the host's immune system. Biofilms are commonly associated with food spoilage and chronic infections, posing challenges for treatment and prevention. Tomato brown rugose fruit virus (ToBRFV), a newly discovered tobamovirus, infects tomato plants, causing unique symptoms on the fruit, posing a risk for tomato production. The present study focuses on the effectiveness of silane-phosphonium thin coatings on polymeric films, e.g., polypropylene. Phosphonium has significant antibacterial activity and is less susceptible to antibacterial resistance, making it a safer alternative with a reduced environmental impact. We successfully synthesized silane-phosphonium monomers as confirmed by
31 P NMR and mass spectrometry. The chemical composition, thickness, morphology, and wetting properties of the coatings were tested by Fourier-transform infrared spectroscopy with attenuated total reflectance, focused ion beam, atomic force microscopy, environmental scanning electron microscope, and contact angle (CA) measurements. The antibiofilm and antibacterial activities of the coatings were tested against S. aureus and E. coli , while the antiviral activity was evaluated against ToBRFV. The significant antibiofilm and antiviral activity suggests applications in various fields including medicine, agriculture, and the food industry., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)- Published
- 2023
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82. Gene augmentation therapy attenuates retinal degeneration in a knockout mouse model of Fam161a retinitis pigmentosa.
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Matsevich C, Gopalakrishnan P, Chang N, Obolensky A, Beryozkin A, Salameh M, Kostic C, Sharon D, Arsenijevic Y, and Banin E
- Subjects
- Mice, Animals, Humans, Mice, Knockout, Eye Proteins genetics, Eye Proteins metabolism, Retina metabolism, Electroretinography, Retinal Degeneration genetics, Retinal Degeneration therapy, Retinal Degeneration pathology, Retinitis Pigmentosa genetics, Retinitis Pigmentosa therapy, Retinitis Pigmentosa metabolism
- Abstract
Photoreceptor cell degeneration and death is the major hallmark of a wide group of human blinding diseases including age-related macular degeneration and inherited retinal diseases such as retinitis pigmentosa. In recent years, inherited retinal diseases have become the "testing ground" for novel therapeutic modalities, including gene and cell-based therapies. Currently there is no available treatment for retinitis pigmentosa caused by FAM161A biallelic pathogenic variants. In this study, we injected an adeno-associated virus encoding for the longer transcript of mFam161a into the subretinal space of P24-P29 Fam161a knockout mice to characterize the safety and efficacy of gene augmentation therapy. Serial in vivo assessment of retinal function and structure at 3, 6, and 8 months of age using the optomotor response test, full-field electroretinography, fundus autofluorescence, and optical coherence tomography imaging as well as ex vivo quantitative histology and immunohistochemical studies revealed a significant structural and functional rescue effect in treated eyes accompanied by expression of the FAM161A protein in photoreceptors. The results of this study may serve as an important step toward future application of gene augmentation therapy in FAM161A-deficient patients by identifying a promising isoform to rescue photoreceptors and their function., Competing Interests: Declaration of interests Y.A., C.K., N.C., D.S., and E.B. have filed a provisional application for FAM161A gene therapy on behalf of The Fondation Asile des aveugles, the Hebrew University, and the University of Lausanne., (Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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83. Achromatopsia-Visual Cortex Stability and Plasticity in the Absence of Functional Cones.
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Molz B, Herbik A, Baseler HA, de Best P, Raz N, Gouws A, Ahmadi K, Lowndes R, McLean RJ, Gottlob I, Kohl S, Choritz L, Maguire J, Kanowski M, Käsmann-Kellner B, Wieland I, Banin E, Levin N, Morland AB, and Hoffmann MB
- Subjects
- Humans, Retinal Cone Photoreceptor Cells pathology, Cyclic Nucleotide-Gated Cation Channels genetics, Mutation, Color Vision Defects, Visual Cortex
- Abstract
Purpose: Achromatopsia is a rare inherited disorder rendering retinal cone photoreceptors nonfunctional. As a consequence, the sizable foveal representation in the visual cortex is congenitally deprived of visual input, which prompts a fundamental question: is the cortical representation of the central visual field in patients with achromatopsia remapped to take up processing of paracentral inputs? Such remapping might interfere with gene therapeutic treatments aimed at restoring cone function., Methods: We conducted a multicenter study to explore the nature and plasticity of vision in the absence of functional cones in a cohort of 17 individuals affected by autosomal recessive achromatopsia and confirmed biallelic disease-causing CNGA3 or CNGB3 mutations. Specifically, we tested the hypothesis of foveal remapping in human achromatopsia. For this purpose, we applied two independent functional magnetic resonance imaging (fMRI)-based mapping approaches, i.e. conventional phase-encoded eccentricity and population receptive field mapping, to separate data sets., Results: Both fMRI approaches produced the same result in the group comparison of achromatopsia versus healthy controls: sizable remapping of the representation of the central visual field in the primary visual cortex was not apparent., Conclusions: Remapping of the cortical representation of the central visual field is not a general feature in achromatopsia. It is concluded that plasticity of the human primary visual cortex is less pronounced than previously assumed. A pretherapeutic imaging workup is proposed to optimize interventions.
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- 2023
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84. Seeing color following gene augmentation therapy in achromatopsia.
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McKyton A, Marks Ohana D, Nahmany E, Banin E, and Levin N
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- Humans, Cyclic Nucleotide-Gated Cation Channels metabolism, Vision, Ocular, Retinal Cone Photoreceptor Cells metabolism, Color Vision Defects genetics, Color Vision Defects therapy
- Abstract
How will people who spent their visual lives with only rods respond to cone function restoration? Will they be able suddenly see the colors of the rainbow? CNGA3-achromatopsia is a congenital hereditary disease in which cone dysfunction leads patients to have rod photoreceptor-driven vision only in daylight,
1 , 2 , 3 , 4 seeing the world in blurry shades of gray.5 , 6 We studied color perception in four CNGA3-achromatopsia patients following monocular retinal gene augmentation therapy.7 , 8 , 9 Following treatment, although some cortical changes were reported,3 , 4 patients did not report a dramatic change in their vision.3 , 9 However, in accordance with the fact that sensitivity of rods and cones is most different at long wavelengths, they consistently reported seeing red objects on dark backgrounds differently than they did before surgery.3 Because clinical color assessments failed to find any indication of color vision, we conducted a gamut of tailored tests to better define patients' descriptions. We evaluated patients' perceived lightness of different colors, color detection, and saliency, comparing their treated with their untreated eyes. Although the perceived lightness of different colors was generally similar between the eyes and matched a rod-input model, patients could detect a colored stimulus only in their treated eyes. In a search task, long response times, which were further extended with array size, suggested low saliency. We suggest that treated CNGA3-achromatopsia patients can perceive a stimulus's color attribute, although in a manner that is different and very limited compared with sighted individuals. We discuss the retinal and cortical obstacles that might explain this perceptual gap., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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85. A green formulation for superhydrophobic coatings based on Pickering emulsion templating for anti-biofilm applications.
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Cohen R, Mani KA, Pirmatova M, Jacobi G, Zelinger E, Belausov E, Fallik E, Banin E, and Mechrez G
- Subjects
- Emulsions chemistry, Hydrophobic and Hydrophilic Interactions, Water, Biofilms, Staphylococcus aureus
- Abstract
This study reports significant steps toward developing anti-biofilm surfaces based on superhydrophobic properties that meet the complex demands of today's food and medical regulations. It presents inverse Pickering emulsions of water in dimethyl carbonate (DMC) stabilized by hydrophobic silica (R202) as a possible food-grade coating formulation and describes its significant passive anti-biofilm properties. The final coatings are formed by applying the emulsions on the target surface, followed by evaporation to form a rough layer. Analysis shows that the final coatings exhibited a Contact Angle (CA) of up to 155° and a Roll-off Angle (RA) lower than 1° on the polypropylene (PP) surface, along with a relatively high light transition. Dissolving polycaprolactone (PCL) into the continuous phase enhanced the average CA and coating uniformity but hindered the anti-biofilm activity and light transmission. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed a uniform coating by a "Swiss-cheese" like structure with high nanoscale and microscale roughness. Biofilm experiments confirm the coating's anti-biofilm abilities that led to the reduction in survival rates of S.aureus and E.coli, by 90-95% respectively, compared to uncoated PP surfaces., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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86. Survival of Neural Progenitors Derived from Human Embryonic Stem Cells Following Subretinal Transplantation in Rodents.
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Aweidah H, Matsevich C, Khaner H, Idelson M, Ejzenberg A, Reubinoff B, Banin E, and Obolensky A
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- Mice, Humans, Rats, Animals, Rodentia, Retina metabolism, Cell Differentiation, Stem Cell Transplantation, Cell Survival, Human Embryonic Stem Cells
- Abstract
Purpose: To examine the survival of neural progenitors (NPs) cells derived from human embryonic stem cells (hESCs) following subretinal (SR) transplantation in rodents. Methods: hESCs engineered to express enhanced green fluorescent protein (eGFP) were differentiated in vitro toward an NP fate using a 4-week protocol. State of differentiation was characterized by quantitative-PCR. NPs in suspension (75,000/μl) were transplanted to the SR-space of Royal College of Surgeons (RCS) rats ( n = 66), nude-RCS rats ( n = 18), and NOD scid gamma (NSG) mice ( n = 53). Success of engraftment was determined at 4 weeks post-transplant by in vivo visualization of GFP-expression using a properly filtered rodent fundus camera. Transplanted eyes were examined in vivo at set time points using the fundus camera, and in select cases, by optical coherence tomography imaging, and after enucleation, by retinal histology and immunohistochemistry. Results: In RCS rats, cell rejection was observed in 29% of eyes at 6 weeks, rising to 92% at 8 weeks. In the more immunodeficient nude-RCS rats, the rejection rate was still high reaching 62% of eyes at 6 weeks post-transplant. Following transplantation in highly immunodeficient NSG mice, survival of the hESC-derived NPs was much improved, with 100% survival at 9 weeks and 72% at 20 weeks. A small number of eyes that were followed past 20 weeks showed survival also at 22 weeks. Conclusions: Immune status of recipient animals influences transplant survival. Highly immunodeficient NSG mice provide a better model for studying long-term survival, differentiation, and possible integration of hESC-derived NPs. Clinical Trial Registration numbers: NCT02286089, NCT05626114.
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- 2023
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87. Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.
- Author
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Ben Yosef T, Banin E, Chervinsky E, Shalev SA, Leibu R, Mezer E, Rotenstreich Y, Goldenberg-Cohen N, Weiss S, Khan MI, Panneman DM, Hitti-Malin RJ, Weiner C, Roosing S, Cremers FPM, Pras E, Zur D, Newman H, Deitch I, Sharon D, and Ehrenberg M
- Subjects
- Female, Humans, Male, Jews genetics, Israel epidemiology, Pedigree, Retina, Mutation genetics, DNA Mutational Analysis, ATP-Binding Cassette Transporters genetics, Retinitis Pigmentosa epidemiology, Retinitis Pigmentosa genetics, Retinal Diseases
- Abstract
Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry., Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing)., Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4 . Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4 -c.6077delT, is likely a founder mutation among the studied population., Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future., (Copyright © 2023 Molecular Vision.)
- Published
- 2023
88. Homozygous Knockout of Cep250 Leads to a Relatively Late-Onset Retinal Degeneration and Sensorineural Hearing Loss in Mice.
- Author
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Abu-Diab A, Gopalakrishnan P, Matsevich C, de Jong M, Obolensky A, Khalaileh A, Salameh M, Ejzenberg A, Gross M, Banin E, Sharon D, and Khateb S
- Subjects
- Animals, Mice, Iran, Mice, Knockout, Autoantigens genetics, Hearing Loss, Sensorineural genetics, Retinal Degeneration genetics, Cell Cycle Proteins genetics
- Abstract
Purpose: Usher syndrome (USH) is the most common syndromic inherited retinal disease, causing retinitis pigmentosa and sensorineural hearing loss. We reported previously that a nonsense mutation in the centrosome-associated protein CEP250 gene (encoding C-Nap1) causes atypical USH in patients of Iranian Jewish origin. To better characterize CEP250, we aimed to generate and study a knockout (KO) mouse model for Cep250., Methods: Mice heterozygous for a "knockout-first" Cep250 construct were generated and bred with Cre recombinase mice to generate the null allele and produce homozygous Cep250 KO mice. Retinal function was evaluated by full-field electroretinography (ffERG) at variable ages, and retinal structure changes were examined using histological analysis. Hearing thresholds were detected using auditory brainstem response (ABR) at the age of 20 months., Results: The Cep250 KO mouse model was generated by activating a construct harboring a deletion of exons 6 and 7. At 6 months, the ffERG was normal, but it decreased gradually with age. For both photopic and scotopic ffERG responses, very low amplitudes were evident at 20 months. Histological analysis confirmed late-onset retinal degeneration. ABR tests illustrated that hearing threshold significantly increased at the age of 20 months., Conclusions: Although most USH animal models have normal retinal function and structure, the Cep250 KO mouse model shows both retinal degeneration and hearing loss with a relatively late age of onset. This model may shed more light on CEP250-associated retinal and hearing deficits and represents an efficient platform for the development of treatment modalities for USH., Translational Relevance: Our study demonstrates better understanding of Cep250-associated retinal and hearing disease in a mouse model and may help in developing more efficient gene therapy modalities.
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- 2023
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89. Comparative genomics of Bacillus cereus sensu lato spp. biocontrol strains in correlation to in-vitro phenotypes and plant pathogen antagonistic capacity.
- Author
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Moshe M, Gupta CL, Sela N, Minz D, Banin E, Frenkel O, and Cytryn E
- Abstract
Bacillus cereus sensu lato (Bcsl) strains are widely explored due to their capacity to antagonize a broad range of plant pathogens. These include B. cereus sp. UW85, whose antagonistic capacity is attributed to the secondary metabolite Zwittermicin A (ZwA). We recently isolated four soil and root-associated Bcsl strains (MO2, S-10, S-25, LSTW-24) that displayed different growth profiles and in-vitro antagonistic effects against three soilborne plant pathogens models: Pythium aphanidermatum (oomycete) Rhizoctonia solani (basidiomycete), and Fusarium oxysporum (ascomycete). To identify genetic mechanisms potentially responsible for the differences in growth and antagonistic phenotypes of these Bcsl strains, we sequenced and compared their genomes, and that of strain UW85 using a hybrid sequencing pipeline. Despite similarities, specific Bcsl strains had unique secondary metabolite and chitinase-encoding genes that could potentially explain observed differences in in-vitro chitinolytic potential and anti-fungal activity. Strains UW85, S-10 and S-25 contained a (~500 Kbp) mega-plasmid that harbored the ZwA biosynthetic gene cluster. The UW85 mega-plasmid contained more ABC transporters than the other two strains, whereas the S-25 mega-plasmid carried a unique cluster containing cellulose and chitin degrading genes. Collectively, comparative genomics revealed several mechanisms that can potentially explain differences in in-vitro antagonism of Bcsl strains toward fungal plant pathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Moshe, Gupta, Sela, Minz, Banin, Frenkel and Cytryn.)
- Published
- 2023
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90. Enhanced S-Cone Syndrome Masquerading as TORCH in an Infant and a Toddler.
- Author
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Navarrete A, Matanis-Suidan M, Hemo I, Mechoulam H, Banin E, and Amer R
- Subjects
- Male, Humans, Bevacizumab therapeutic use, Angiogenesis Inhibitors therapeutic use, Fluorescein Angiography, Intravitreal Injections, Tomography, Optical Coherence, Hyperopia complications, Hyperopia drug therapy, Choroidal Neovascularization diagnosis
- Abstract
Purpose: To report two cases masquerading as TORCH but eventually diagnosed with Enhanced S-cone Syndrome (ESCS)., Methods: Descriptive case report., Results: Case 1 : A ten-month-old boy presented with high hypermetropia, strabismus and bilateral chorioretinal pigmented scars with a history of cat scratch of his mother during pregnancy. He was treated for suspected toxoplasma retinitis. Choroidal neovascular membranes (CNV) were diagnosed bilaterally and treated with intravitreal bevacizumab. Genetic testing showed homozygote mutation in NR2E3 gene. Case 2 : A two-year old girl presented with bilateral high hypermetropia and strabismus. Funduscopy revealed extrafoveal chorioretinal lesions and surrounding subretinal fibrosis. An elevated titer of anti-toxocara IgG antibodies was detected and managed accordingly. LE CNV was diagnosed and treated with intravitreal bevacizumab. Genetic testing disclosed homozygote mutation in NR2E3., Conclusion: Ocular manifestations in ESCS can be reminiscent to TORCH. CNV may develop with an incidence of 15%. We report the youngest patient with ESCS-associated CNV.
- Published
- 2023
- Full Text
- View/download PDF
91. Ultrasonic-assisted synthesis of lignin-capped Cu 2 O nanocomposite with antibiofilm properties.
- Author
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Maruthapandi M, Gupta A, Saravanan A, Jacobi G, Banin E, Luong JHT, and Gedanken A
- Subjects
- Staphylococcus aureus, Lignin pharmacology, Escherichia coli, Ultrasonics, Bacteria, Biofilms, Microbial Sensitivity Tests, Anti-Bacterial Agents chemistry, Nanocomposites chemistry
- Abstract
Under ultrasonication, cuprous oxide (Cu
2 O) microparticles (<5 µm) were fragmented into nanoparticles (NPs, ranging from 10 to 30 nm in diameter), and interacted strongly with alkali lignin (Mw = 10 kDa) to form a nanocomposite. The ultrasonic wave generates strong binding interaction between lignin and Cu2 O. The L-Cu nanocomposite exhibited synergistic effects with enhanced antibiofilm activities against E. coli, multidrug-resistant (MDR) E. coli, S. aureus (SA), methicillin-resistant SA, and P. aeruginosa (PA). The lignin-Cu2 O (L-Cu) nanocomposite also imparted notable eradication of such bacterial biofilms. Experimental evidence unraveled the destruction of bacterial cell walls by L-Cu, which interacted strongly with the bacterial membrane. After exposure to L-Cu, the bacterial cells lost the integrated structural morphology. The estimated MIC for biofilm inhibition for the five tested pathogens was 1 mg/mL L-Cu (92 % lignin and 8 % Cu2 ONPs, w/w %). The MIC for bacterial eradication was noticeably lower; 0.3 mg/mL (87 % lignin + 13 % Cu2 ONPs, w/w %) for PA and SA, whereas this value was appreciably higher for MDR E. coli (0.56 mg/mL, 86 % lignin and 14 % Cu2 O NPs). Such results highlighted the potential of L-Cu as an alternative to neutralize MDR pathogens., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)- Published
- 2023
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92. Exonic Variants that Affect Splicing - An Opportunity for "Hidden" Mutations Causing Inherited Retinal Diseases.
- Author
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Sundaresan Y, Banin E, and Sharon D
- Subjects
- Humans, Mutation, Exons genetics, Retina, Alternative Splicing, RNA Splicing genetics, Retinal Diseases genetics
- Abstract
Inherited retinal diseases (IRDs) are an extremely diverse group of ocular disorders characterized by progressive loss of photoreceptors leading to blindness. So far, pathogenic variants in over 300 genes are reported to structurally and functionally affect the retina resulting in visual impairment. Around 15% of all IRD mutations are known to affect an essential regulatory mechanism, pre-mRNA splicing, which contributes to the transcriptomic diversity. These variants disrupt potential donor and acceptor splice sites as well as other crucial cis-acting elements resulting in aberrant splicing. One group of these elements, the exonic splicing enhancers (ESEs), are involved in promoting exon definition and are likely to harbor "hidden" mutations since sequence-analyzing pipelines cannot identify them efficiently. The main focus of this review is to discuss the molecular mechanisms behind various exonic variants affecting splice sites and ESEs that lead to impaired splicing which in turn result in an IRD pathology., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2023
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93. Factors Affecting Readthrough of Natural Versus Premature Termination Codons.
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Beryozkin A, Nagel-Wolfum K, Banin E, and Sharon D
- Subjects
- Amino Acids, RNA, Messenger genetics, Codon, Nonsense genetics, Protein Biosynthesis genetics
- Abstract
Nonsense mutations occur within the open-reading frame of a gene resulting in a premature termination codon (PTC). PTC-containing mRNAs can either be degeraded or cause premature translation termination producing a truncated protein that can be either nonfunctional or toxic. Translational readthrough inducing drugs (TRIDs) are small molecules that are able to induce readthrough, resulting in the restoration of full-length protein expression. The re-expressed proteins usually harbor a missense change. The effciency of individual TRIDs is variable and varies between different genes and even different nonsense mutations in the same gene. This review summarizes factors, including the sequences located upstream and downstream the disease-causing mutation and the type of PTC, affecting the translational readthrough process by modulating the type of amino acid insertion and the efficiency of the process during readthrough following TRIDs treatments., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
- Published
- 2023
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94. Morphological and Functional Comparison of Mice Models for Retinitis Pigmentosa.
- Author
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Gopalakrishnan P, Beryozkin A, Banin E, and Sharon D
- Subjects
- Mice, Animals, Eye Proteins genetics, Eye Proteins chemistry, Retina, Mice, Knockout, Disease Models, Animal, Orphan Nuclear Receptors, Retinitis Pigmentosa genetics, Retinitis Pigmentosa therapy, Retinal Degeneration genetics
- Abstract
Retinitis pigmentosa (RP) is the predominant form of inherited retinal degenerations (IRDs) caused by abnormalities and loss of photoreceptor cells ensuing diminishment of vision. RP is a heterogenous genetic disorder associated with mutations in over 80 genes, showing various inheritance patterns. Laboratory mouse models are important for our understanding of disease mechanisms, modifier effects, and development of therapeutic modalities. In this review, we have summarized a comprehensive comparison of our previously reported Fam161a knockout (KO) mouse model with other well-studied RP mouse models, Fam161a
GT/GT , Pde6brd1 , Nr2e3rd7 , Rpgrrd9 , and Pde6brd10 using structural and functional analysis of the retina. Fam161atm1b/tm1b mouse models are important for developing novel therapies and mainly AAV-based gene therapy and translational read-through-inducing drugs., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)- Published
- 2023
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95. Ultra-widefield fundus autofluorescence imaging in patients with autosomal recessive retinitis pigmentosa reveals a genotype-phenotype correlation.
- Author
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Patal R, Banin E, Batash T, Sharon D, and Levy J
- Subjects
- Humans, Fluorescein Angiography methods, Retrospective Studies, Visual Acuity, Genetic Association Studies, Vision Disorders, Optical Imaging, Fundus Oculi, Tomography, Optical Coherence methods, Retinitis Pigmentosa diagnosis, Retinitis Pigmentosa genetics
- Abstract
Purpose: To analyze the genotype-phenotype correlation in patients with retinitis pigmentosa (RP) caused by mutations in the FAM161A, DHDDS, or MAK genes using ultra-widefield fundus autofluorescence (UWF-FAF) imaging., Methods: Retrospective case series of patients with autosomal recessive RP (ARRP) with confirmed causative genetic mutations and available UWF-FAF imaging data. The UWF-FAF data were graded in a blinded fashion using the following criteria: the pattern of macular abnormalities on FAF, the presence or absence of horizontal linear hyperautofluorescence, the extent of decreased autofluorescence (DAF), the shape of DAF, and the presence of hyperautofluorescence at the optic disk., Results: A total of 43 patients (mean age of 47 ± 16 years, ranging from 17 to 79 years) with ARRP (86 eyes) were included in our analysis. Genotyping data revealed biallelic mutations in the FAM161A, DHDDS, and MAK genes in 20, 12, and 11 patients, respectively. We found significant differences between the three groups with respect to the pattern of macular abnormalities on FAF (p = 0.001), DAF configuration (p = 0.007), and extent of DAF (p = 0.037). The largest difference between groups was found for macular abnormalities on FAF, with DHDDS patients differing significantly from the MAK and FAM161A groups (p = 0.001). Specifically, DHDDS patients had a more abnormal macular FAF pattern and more widespread decrease in peripheral autofluorescence. No other parameters differed significantly between the three groups., Conclusions: Patients with ARRP can present with specific UWF-FAF patterns based on the underlying causative gene. Future studies are warranted in order to expand this analysis to include additional genes, mutations, and patients as well as assessment of disease progression by following patients over longer periods of time., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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96. Prevalence and associated factors of cystoid macular edema in children with early onset inherited retinal dystrophies.
- Author
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Ben-Avi R, Rivera A, Hendler K, Sharon D, Banin E, Khateb S, and Yahalom C
- Abstract
Purpose: To assess the prevalence of Cystoid macular edema (CME) in children with early onset retinal dystrophies (EORD) and to evaluate if there are associated factors and/or response to early treatment., Methods: Consecutive, retrospective case series. Medical records of patients, 18 years or younger, diagnosed with EORD were included in the study. Optic coherence tomography (OCT) scans, clinical and genetic characteristics as well as other associated factors were analyzed. Main outcome was the presence of CME on OCT scans ., Results: One hundred and two children with EORD (aged 1-18 years, mean 9.7 ± 4.2) were recruited. OCT was performed in 60/102 and among them, 19/60 had CME (31.7%). The disease-causing gene was identified in 13 children with CME; autosomal-recessive inheritance was found in 88.3% of those with an identified genotype. Children with Usher syndrome had CME in 44.4% of the cases. Early treatment of CME resulted in variable response., Conclusions: Our results show that 31.7% of children with EORD who underwent OCT have macular edema. CME prevalence was found to be relatively higher in children with Usher syndrome. Autosomal recessive was the most prevalent inheritance identified in the EORD group as well as in the CME group. Additional prospective research is needed to assess the efficacy of early CME treatment in pediatric EORD patients.
- Published
- 2022
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- View/download PDF
97. Autosomal dominant retinitis pigmentosa with incomplete penetrance due to an intronic mutation of the PRPF31 gene.
- Author
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Ali-Nasser T, Zayit-Soudry S, Banin E, Sharon D, and Ben-Yosef T
- Subjects
- Male, Humans, Child, Pedigree, Mutation genetics, RNA, Genes, Dominant, Transcription Factors genetics, Eye Proteins genetics, Eye Proteins metabolism, Retinitis Pigmentosa diagnosis
- Abstract
Purpose: To identify the molecular mechanisms of the development of autosomal dominant retinitis pigmentosa (adRP) with incomplete penetrance in an Israeli Muslim Arab family., Methods: Two patients with adRP underwent a detailed ophthalmic evaluation, including funduscopic examination, visual field testing, optical coherence tomography, and electroretinography. Genetic analysis was performed using a combination of whole exome sequencing (WES) and Sanger sequencing. The pathogenicity of the identified intronic variant was evaluated in silico using several web-based tools, in vitro using a minigene-based assay, and in vivo using reverse transcription PCR analysis of lymphocyte-derived RNA. The relative abundance of alternatively spliced transcripts was evaluated using amplicon-based next-generation sequencing. The relative expression levels of PRPF31 and CNOT3 were measured using quantitative PCR (qPCR) analysis., Results: The two patients recruited in this study had childhood-onset RP, with night blindness as the initial symptom, followed by concentric restriction of the visual field. The funduscopic findings included narrowed retinal blood vessels and peripheral bone spicule pigmentation. By the third decade of life, the full-field electroretinography findings had been remarkably attenuated. In these patients, we identified a novel heterozygous intronic variant at position +5 of PRPF31 intron 11 (c.1146+5G>T). The same variant was also detected in one asymptomatic family member. Through in silico analysis, the variant was predicted to alter the splicing of intron 11. An in vitro splicing assay and a reverse transcription PCR analysis of lymphocyte-derived RNA revealed that the mutant allele yielded mainly a shorter transcript in which exon 11 was skipped. The skipping of exon 11 was expected to cause a frameshift and an aberrant truncated protein (p.Tyr359Ser fs *29). The qPCR analysis revealed reduced PRPF31 expression levels in the mutation carriers, without a significant difference between the affected patient and his asymptomatic brother. We evaluated several factors that have been suggested to correlate with non-penetrance of PRPF31 mutations, including the number of cis-acting MSR1 elements adjacent to the PRPF31 core promoter, CNOT3 expression level, and CNOT3 rs4806718 single-nucleotide polymorphism. None of these factors correlated with non-penetrance in the family in this study., Conclusions: We report a novel intronic mutation in PRPF31 underlying adRP. This report expands the spectrum of pathogenic mutations in PRPF31 and further demonstrates the importance of intronic mutations. Moreover, it demonstrates the phenomenon of incomplete penetrance previously associated with PRPF31 mutations. The fact that the non-penetrance in the family in this study could not be explained by any of the known mechanisms suggests the possible contribution of a novel modifier of PRPF31 penetrance., (Copyright © 2022 Molecular Vision.)
- Published
- 2022
98. Retinal Structure and Function in a Knock-in Mouse Model for the FAM161A- p.Arg523∗ Human Nonsense Pathogenic Variant.
- Author
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Matsevich C, Gopalakrishnan P, Obolensky A, Banin E, Sharon D, and Beryozkin A
- Abstract
Purpose: Pathogenic variants in FAM161A are the most common cause of retinitis pigmentosa in Israel. Two founder pathogenic variants explain the vast majority of cases of Jewish origin, 1 being a nonsense variant (p.Arg523∗). The aim of this study was to generate a knock-in (KI) mouse model harboring the corresponding p.Arg512∗ pathogenic variant and characterize the course of retinal disease., Design: Experimental study of a mouse animal model., Subjects/participants/controls: A total of 106 Fam161a knock-in mice and 29 wild-type mice with C57BL/6J background particiapted in this study., Methods: Homozygous Fam161a p.Arg512∗ KI mice were generated by Cyagen Biosciences. Visual acuity (VA) was evaluated using optomotor tracking response and retinal function was assessed by electroretinography (ERG). Retinal structure was examined in vivo using OCT and fundus autofluorescence imaging. Retinal morphometry was evaluated by histologic and immunohistochemical (IHC) analyses., Main Outcome Measures: Visual and retinal function assessments, clinical imaging examinations, quantitative histology, and IHC studies of KI as compared with wild-type (WT) mice retinas., Results: The KI model was generated by replacing 3 bp, resulting in p.Arg512∗. Homozygous KI mice that had progressive loss of VA and ERG responses until the age of 18 months, with no detectable response at 21 months. OCT showed complete loss of the outer nuclear layer at 21 months. Fundus autofluorescence imaging revealed progressive narrowing of blood vessels and formation of patchy hyper-autofluorescent and hypo-autofluorescent spots. Histologic analysis showed progressive loss of photoreceptor nuclei. Immunohistochemistry staining showed Fam161a expression mainly in photoreceptors cilia and the outer plexiform layer (OPL) in WT mice retinas, whereas faint expression was evident mainly in the cilia and OPL of KI mice., Conclusions: The Fam161a - p.Arg512∗ KI mouse model is characterized by widespread retinal degeneration with relatively slow progression. Surprisingly, disease onset is delayed and progression is slower compared with the previously reported knock-out model. The common human null mutation in the KI mouse model is potentially amenable for correction by translational read-through-inducing drugs and by gene augmentation therapy and RNA editing, and can serve to test these treatments as a first step toward possible application in patients., Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article., (© 2022 by the American Academy of Ophthalmology.)
- Published
- 2022
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- View/download PDF
99. Antibacterial Properties and Mechanisms of Action of Sonoenzymatically Synthesized Lignin-Based Nanoparticles.
- Author
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Morena AG, Bassegoda A, Natan M, Jacobi G, Banin E, and Tzanov T
- Subjects
- Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Bacteria, Laccase chemistry, Lignin chemistry, Lignin pharmacology, Anti-Infective Agents chemistry, Metal Nanoparticles chemistry, Nanoparticles chemistry
- Abstract
In recent years, lignin has drawn increasing attention for different applications due to its intrinsic antibacterial and antioxidant properties, coupled with biodegradability and biocompatibility. However, chemical modification or combination with metals is usually required to increase its antimicrobial functionality and produce biobased added-value materials for applications wherein bacterial growth should be avoided, such as biomedical and food industries. In this work, a sonoenzymatic approach for the simultaneous functionalization and nanotransformation of lignin to prepare metal-free antibacterial phenolated lignin nanoparticles (PheLigNPs) is developed. The grafting of tannic acid, a natural phenolic compound, onto lignin was achieved by an environmentally friendly approach using laccase oxidation upon the application of high-intensity ultrasound to rearrange lignin into NPs. PheLigNPs presented higher antibacterial activity than nonfunctionalized LigNPs and phenolated lignin in the bulk form, indicating the contribution of both the phenolic content and the nanosize to the antibacterial activity. Studies on the antibacterial mode of action showed that bacteria in contact with the functionalized NPs presented decreased metabolic activity and high levels of reactive oxygen species (ROS). Moreover, PheLigNPs demonstrated affinity to the bacterial surface and the ability to cause membrane destabilization. Antimicrobial resistance studies showed that the NPs did not induce resistance in pathogenic bacteria, unlike traditional antibiotics.
- Published
- 2022
- Full Text
- View/download PDF
100. Cuprous Oxide Nanoparticles Decorated Fabric Materials with Anti-biofilm Properties.
- Author
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Gupta A, Maruthapandi M, Das P, Saravanan A, Jacobi G, Natan M, Banin E, Luong JHT, and Gedanken A
- Abstract
Considering the global spread of bacterial infections, the development of anti-biofilm surfaces with high antimicrobial activities is highly desired. This work unraveled a simple, sonochemical method for coating Cu
2 O nanoparticles (NPs) on three different flexible substrates: polyester (PE), nylon 2 (N2), and polyethylene (PEL). The introduction of Cu2 O NPs on these substrates enhanced their surface hydrophobicity, induced ROS generation, and completely inhibited the growth of sensitive ( Escherichia coli and Staphyloccocus aureus ) and drug-resistant (MDR E. coli and MRSA) planktonic and biofilm. The experimental results confirmed that Cu2 O-PE exhibited complete biofilm mass reduction ability for all four strains, whereas Cu2 O-N2 showed more than 99% biomass inhibition against both drug-resistant and sensitive pathogens in 6 h. Moreover, Cu2 O-PEL also indicated a 99.95, 97.73, 98.00, and 99.20% biomass reduction of MRSA, MDR E. coli , E. coli , and S. aureus , respectively. All substrates were investigated for time-dependent inhibitions, and the associated biofilm mass and log reduction were evaluated. The mechanisms of Cu2 O NP action against the mature biofilms include the generation of reactive oxygen species (ROS) as well as electrostatic interaction between Cu2 O NPs and bacterial membranes. The current study could pave the way for the commercialization of sonochemically coated Cu2 O NP flexible substrates for the prevention of microbial contamination in hospitals and industrial environments.- Published
- 2022
- Full Text
- View/download PDF
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