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Article ; Online: Germline knockout of

Kolesnikov, Alexander V / Murphy, Daniel P / Corbo, Joseph C / Kefalov, Vladimir J

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

2024 Volume 121, Issue 11, Page(s) e2316118121

Abstract: Retinitis pigmentosa (RP) is a common form of retinal dystrophy that can be caused by mutations in any one of dozens of rod photoreceptor genes. The genetic heterogeneity of RP represents a significant challenge for the development of effective therapies. ...

Abstract	Retinitis pigmentosa (RP) is a common form of retinal dystrophy that can be caused by mutations in any one of dozens of rod photoreceptor genes. The genetic heterogeneity of RP represents a significant challenge for the development of effective therapies. Here, we present evidence for a potential gene-independent therapeutic strategy based on targeting
MeSH term(s)	Animals ; Mice ; Neuroprotective Agents ; Retinal Cone Photoreceptor Cells ; Retinitis Pigmentosa/genetics ; Retinal Dystrophies ; Disease Models, Animal ; Germ Cells ; Orphan Nuclear Receptors
Chemical Substances	Neuroprotective Agents ; Nr2e3 protein, mouse ; Orphan Nuclear Receptors
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2316118121
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Article ; Online: Transcription factor interactions explain the context-dependent activity of CRX binding sites.

Loell, Kaiser J / Friedman, Ryan Z / Myers, Connie A / Corbo, Joseph C / Cohen, Barak A / White, Michael A

PLoS computational biology

2024 Volume 20, Issue 1, Page(s) e1011802

Abstract: The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both ...

Abstract	The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both enhancers and silencers, but the sequence context that determines whether CRX binding sites contribute to activation or repression of transcription is not understood. To investigate the context-dependent activity of CRX sites, we fit neural network-based models to the activities of synthetic CREs composed of photoreceptor TFBSs. The models revealed that CRX binding sites consistently make positive, independent contributions to CRE activity, while negative homotypic interactions between sites cause CREs composed of multiple CRX sites to function as silencers. The effects of negative homotypic interactions can be overcome by the presence of other TFBSs that either interact cooperatively with CRX sites or make independent positive contributions to activity. The context-dependent activity of CRX sites is thus determined by the balance between positive heterotypic interactions, independent contributions of TFBSs, and negative homotypic interactions. Our findings explain observed patterns of activity among genomic CRX-bound enhancers and silencers, and suggest that enhancers may require diverse TFBSs to overcome negative homotypic interactions between TFBSs.
MeSH term(s)	Transcription Factors/metabolism ; Trans-Activators/metabolism ; Homeodomain Proteins/genetics ; Gene Expression Regulation ; Binding Sites/genetics ; Retina
Chemical Substances	Transcription Factors ; Trans-Activators ; Homeodomain Proteins
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1011802
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Article ; Online: Enzymatic vitamin A

Gerhards, Johanna / Volkov, Leo I / Corbo, Joseph C / Malan, Daniela / Sasse, Philipp

Pflugers Archiv : European journal of physiology

2023 Volume 475, Issue 12, Page(s) 1409–1419

Abstract: Optogenetics is a technology using light-sensitive proteins to control signaling pathways and physiological processes in cells and organs and has been applied in neuroscience, cardiovascular sciences, and many other research fields. Most commonly used ... ...

Abstract	Optogenetics is a technology using light-sensitive proteins to control signaling pathways and physiological processes in cells and organs and has been applied in neuroscience, cardiovascular sciences, and many other research fields. Most commonly used optogenetic actuators are sensitive to blue and green light, but red-light activation would allow better tissue penetration and less phototoxicity. Cyp27c1 is a recently deorphanized cytochrome P450 enzyme that converts vitamin A
MeSH term(s)	Humans ; Vitamin A/metabolism ; Optogenetics ; HEK293 Cells ; Heart ; Channelrhodopsins/genetics
Chemical Substances	vitamin A2 (104621892X) ; Vitamin A (11103-57-4) ; Channelrhodopsins
Language	English
Publishing date	2023-11-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-023-02880-2
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Article: Efficacy of Biologics on Refractory Eosinophilic Otitis Media Associated with Bronchial Asthma or Severe Uncontrolled CRSwNP.

De Corso, Eugenio / Montuori, Claudio / Settimi, Stefano / Mele, Dario Antonio / Cantiani, Alessandro / Corbò, Marco / Cantone, Elena / Paludetti, Gaetano / Galli, Jacopo

Journal of clinical medicine

2022 Volume 11, Issue 4

Abstract: Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic ... ...

Abstract	Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab:
Language	English
Publishing date	2022-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11040926
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Article ; Online: How to manage recurrences after surgery in CRSwNP patients in the biologic era: a narrative review.

De Corso, Eugenio / Settimi, Stefano / Montuori, Claudio / Cantiani, Alessandro / Corbò, Marco / Di Bella, Giuseppe Alberto / Sovardi, Fabio / Pagella, Fabio / Rigante, Mario / Passali, Giulio Cesare / Paludetti, Gaetano / Galli, Jacopo

Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale

2023 Volume 43, Issue Suppl. 1, Page(s) S3–S13

Abstract: Objective: This narrative review analyses factors affecting recurrence of Chronic rhinosinusitis with nasal polyps (CRSwNP) after surgery, such as type, extension and completeness of endoscopic sinus surgery (ESS). We also described new implications in ... ...

Abstract	Objective: This narrative review analyses factors affecting recurrence of Chronic rhinosinusitis with nasal polyps (CRSwNP) after surgery, such as type, extension and completeness of endoscopic sinus surgery (ESS). We also described new implications in the management of recurrences after the advent of biologics. Methods: We identified four topics: definition of disease state; factors linked to recurrence of polyps; evaluation and management of recurrence in clinical practice. Results: We analysed the differences between exacerbation and recurrence, as well as the concept of "controlled disease". We focused on potential predictors of recurrence after ESS, such as type 2 inflammation, asthma, aspirin-exacerbated respiratory disease, incomplete initial surgery and lack of adherence to long-term post-operative local corticosteroids. We discussed the new aspects of diagnosis and treatment of recurrences after surgery, summarising our suggestions in a detailed algorithm for practical management of patients with recurrent disease. Conclusions: The results emphasised the importance of accurate evaluation of patients with CRSwNP recurrence, focusing on the reasons of failure and risk of disease progression, in order to guide personalised interventions. It is crucial to define the concept of appropriate surgery, which affects the choice between starting a biologic or repeating surgery.
MeSH term(s)	Humans ; Nasal Polyps/complications ; Nasal Polyps/surgery ; Chronic Disease ; Sinusitis/complications ; Sinusitis/surgery ; Recurrence ; Biological Products/therapeutic use
Chemical Substances	Biological Products
Language	English
Publishing date	2023-09-11
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	604898-5
ISSN	1827-675X ; 0392-100X
ISSN (online)	1827-675X
ISSN	0392-100X
DOI	10.14639/0392-100X-suppl.1-43-2023-01
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Article ; Online: PRMT1, a Key Modulator of Unliganded Progesterone Receptor Signaling in Breast Cancer.

Malbeteau, Lucie / Jacquemetton, Julien / Languilaire, Cécile / Corbo, Laura / Le Romancer, Muriel / Poulard, Coralie

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: The progesterone receptor (PR) is a key player in major physiological and pathological responses in women, and the signaling pathways triggered following hormone binding have been extensively studied, particularly with respect to breast cancer ... ...

Abstract	The progesterone receptor (PR) is a key player in major physiological and pathological responses in women, and the signaling pathways triggered following hormone binding have been extensively studied, particularly with respect to breast cancer development and progression. Interestingly, growing evidence suggests a fundamental role for PR on breast cancer cell homeostasis in hormone-depleted conditions, with hormone-free or unliganded PR (uPR) involved in the silencing of relevant genes prior to hormonal stimulation. We herein identify the protein arginine methyltransferase PRMT1 as a novel actor in uPR signaling. In unstimulated T47D breast cancer cells, PRMT1 interacts and functions alongside uPR and its partners to target endogenous progesterone-responsive promoters. PRMT1 helps to finely tune the silencing of responsive genes, likely by promoting a proper BRCA1-mediated degradation and turnover of unliganded PR. As such, PRMT1 emerges as a key transcriptional coregulator of PR for a subset of relevant progestin-dependent genes before hormonal treatment. Since women experience periods of hormonal fluctuation throughout their lifetime, understanding how steroid receptor pathways in breast cancer cells are regulated when hormones decline may help to determine how to override treatment failure to hormonal therapy and improve patient outcome.
MeSH term(s)	Breast Neoplasms/metabolism ; Female ; Humans ; Progesterone/metabolism ; Progestins ; Protein-Arginine N-Methyltransferases/genetics ; Protein-Arginine N-Methyltransferases/metabolism ; Receptors, Progesterone/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Signal Transduction/physiology
Chemical Substances	Progestins ; Receptors, Progesterone ; Repressor Proteins ; Progesterone (4G7DS2Q64Y) ; PRMT1 protein, human (EC 2.1.1.319) ; Protein-Arginine N-Methyltransferases (EC 2.1.1.319)
Language	English
Publishing date	2022-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23179509
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Article: Use of the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) in Spinal Muscular Atrophy.

Brown, Laurey / Hoffman, Katie / Corbo-Galli, Chiara / Dong, Siyuan / Zumpf, Katelyn / Weigel, Christa / Blomgren, Colleen / Munson, Hannah / Bidwell, Jessa / Rao, Vamshi / Kuntz, Nancy L / Schwaede, Abigail / Krosschell, Kristin J

Journal of clinical medicine

2024 Volume 13, Issue 4

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13040921
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Article ; Online: Bivalirudin Compared to Heparin as the Primary Anticoagulant in Pediatric Berlin Heart Recipients.

Freniere, Victoria / Salerno, David M / Corbo, Heather / Law, Sabrina / McAllister, Jennie / Neunert, Cindy / Chen, Justin K

ASAIO journal (American Society for Artificial Internal Organs : 1992)

2023 Volume 69, Issue 5, Page(s) e205–e211

Abstract: Bivalirudin has been used in increasing frequency as an alternative to unfractionated heparin (UFH) in pediatric recipients of Berlin Heart EXCOR ventricular assist devices (VAD). This single-center, retrospective review characterizes anticoagulant ... ...

Abstract	Bivalirudin has been used in increasing frequency as an alternative to unfractionated heparin (UFH) in pediatric recipients of Berlin Heart EXCOR ventricular assist devices (VAD). This single-center, retrospective review characterizes anticoagulant trends and outcomes in pediatric Berlin Heart VAD recipients implanted between September 1, 2013, and August 31, 2021, anticoagulated with either bivalirudin or UFH. Thirty-one patients were included; 65% who received bivalirudin and 35% who received UFH. The median age was 2.9 years, included 64.5% females, with 61.3% of patients diagnosed with dilated cardiomyopathy and 25.8% of patients with congenital heart disease. Therapeutic anticoagulation was achieved sooner in the bivalirudin group compared to UFH via anti-Xa monitoring (median 5.7 and 69.5 hours, respectively, p < 0.001). Bivalirudin had a greater number of therapeutic values comparatively to UFH (52% and 24%, respectively; p < 0.001) and a superior number of hours in the therapeutic range (67% and 32%, respectively; p < 0.001). Secondary outcomes were similar among the two groups, apart from greater chest tube output (UFH), more frequent events of elevated plasma-free hemoglobin (bivalirudin), and more frequent elevated inflammatory markers postimplant (bivalirudin). Prevalence of pump replacements secondary to significant clot burden and prevalence of stroke was comparable. In this patient cohort, bivalirudin demonstrated greater anticoagulation stability comparatively to UFH. Multicenter collaboration would be necessary to identify whether this further translates into improved patient outcomes.
MeSH term(s)	Female ; Humans ; Child ; Child, Preschool ; Male ; Heparin/therapeutic use ; Anticoagulants/therapeutic use ; Treatment Outcome ; Hirudins ; Peptide Fragments/therapeutic use ; Retrospective Studies ; Recombinant Proteins ; Antithrombins/therapeutic use
Chemical Substances	Heparin (9005-49-6) ; Anticoagulants ; bivalirudin (TN9BEX005G) ; Hirudins ; Peptide Fragments ; Recombinant Proteins ; Antithrombins
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ZDB-ID	759982-1
ISSN	1538-943X ; 0162-1432 ; 1058-2916
ISSN (online)	1538-943X
ISSN	0162-1432 ; 1058-2916
DOI	10.1097/MAT.0000000000001921
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Uk I Zs.199: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.B 2435: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Regulation by the RNA-binding protein Unkempt at its effector interface.

Shah, Kriti / He, Shiyang / Turner, David J / Corbo, Joshua / Rebbani, Khadija / Dominguez, Daniel / Bateman, Joseph M / Cheloufi, Sihem / Igreja, Cátia / Valkov, Eugene / Murn, Jernej

Nature communications

2024 Volume 15, Issue 1, Page(s) 3159

Abstract: How RNA-binding proteins (RBPs) convey regulatory instructions to the core effectors of RNA processing is unclear. Here, we document the existence and functions of a multivalent RBP-effector interface. We show that the effector interface of a conserved ... ...

Abstract	How RNA-binding proteins (RBPs) convey regulatory instructions to the core effectors of RNA processing is unclear. Here, we document the existence and functions of a multivalent RBP-effector interface. We show that the effector interface of a conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of 'dual-purpose' peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by Unkempt. Systems analyses reveal that multivalent RBP-effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for the reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP-effector interface.
MeSH term(s)	Animals ; RNA-Binding Proteins/metabolism ; RNA/metabolism ; RNA Processing, Post-Transcriptional ; Peptides/metabolism
Chemical Substances	RNA-Binding Proteins ; RNA (63231-63-0) ; Peptides
Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47449-4
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Article ; Online: Axenic interspecies and intraclonal hybrid formation in Leishmania: Successful crossings between visceral and cutaneous strains.

Gutiérrez-Corbo, Camino / Domínguez-Asenjo, Bárbara / Pérez-Pertejo, Yolanda / García-Estrada, Carlos / Bello, Felio J / Balaña-Fouce, Rafael / Reguera, Rosa M

PLoS neglected tropical diseases

2022 Volume 16, Issue 2, Page(s) e0010170

Abstract: Diseases caused by trypanosomatids are serious public health concerns in low-income endemic countries. Leishmaniasis is presented in two main clinical forms, visceral leishmaniasis-caused by L. infantum and L. donovani-and cutaneous leishmaniasis-caused ... ...

Abstract	Diseases caused by trypanosomatids are serious public health concerns in low-income endemic countries. Leishmaniasis is presented in two main clinical forms, visceral leishmaniasis-caused by L. infantum and L. donovani-and cutaneous leishmaniasis-caused by many species, including L. major, L. tropica and L. braziliensis. As for certain other trypanosomatids, sexual reproduction has been confirmed in these parasites, and formation of hybrids can contribute to virulence, drug resistance or adaptation to the host immune system. In the present work, the capability of intraclonal and interspecies genetic exchange has been investigated using three parental strains: L. donovani, L. tropica and L. major, which have been engineered to express different fluorescent proteins and antibiotic resistance markers in order to facilitate the phenotypic selection of hybrid parasites after mating events. Stationary and exponential-phase promastigotes of each species were used, in in vitro experiments, some of them containing LULO cells (an embryonic cell line derived from Lutzomyia longipalpis). Several intraclonal hybrids were obtained with L. tropica as crossing progenitor, but not with L. donovani or L. major. In interspecies crossings, three L. donovani x L. major hybrids and two L. donovani x L. tropica hybrids were isolated, thereby demonstrating the feasibility to obtain in vitro hybrids of parental lines causing different tropism of leishmaniasis. Ploidy analysis revealed an increase in DNA content in all hybrids compared to the parental strains, and nuclear analysis showed that interspecies hybrids are complete hybrids, i.e. each of them showing at least one chromosomal set from each parental. Regarding kDNA inheritance, discrepancies were observed between maxi and minicircle heritage. Finally, phenotypic studies showed either intermediate phenotypes in terms of growth profiles, or a decreased in vitro infection capacity compared to the parental cells. To the best of our knowledge, this is the first time that in vitro interspecies outcrossing has been demonstrated between Leishmania species with different tropism, thus contributing to shed light on the mechanisms underlying sexual reproduction in these parasites.
MeSH term(s)	Animals ; Cell Line ; Hybridization, Genetic ; Leishmania donovani/genetics ; Leishmania major/genetics ; Leishmania tropica/genetics ; Leishmaniasis, Cutaneous/parasitology ; Leishmaniasis, Visceral/parasitology ; Psychodidae
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0010170
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