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Article ; Online: Leukotriene A4 hydrolase inhibition improves age-related cognitive decline via modulation of synaptic function.

Adams, Julia M / Rege, Sanket V / Liu, Angela T / Vu, Ninh V / Raina, Sharda / Kirsher, Douglas Y / Nguyen, Amy L / Harish, Reema / Szoke, Balazs / Leone, Dino P / Czirr, Eva / Braithwaite, Steven / Kerrisk Campbell, Meghan

Science advances

2023 Volume 9, Issue 46, Page(s) eadf8764

Abstract: Leukotrienes, a class of inflammatory bioactive lipids, are well studied in the periphery, but less is known of their importance in the brain. We identified that the enzyme leukotriene A4 hydrolase (LTA4H) is expressed in healthy mouse neurons, and ... ...

Abstract	Leukotrienes, a class of inflammatory bioactive lipids, are well studied in the periphery, but less is known of their importance in the brain. We identified that the enzyme leukotriene A4 hydrolase (LTA4H) is expressed in healthy mouse neurons, and inhibition of LTA4H in aged mice improves hippocampal dependent memory. Single-cell nuclear RNA sequencing of hippocampal neurons after inhibition reveals major changes to genes important for synaptic organization, structure, and activity. We propose that LTA4H inhibition may act to improve cognition by directly inhibiting the enzymatic activity in neurons, leading to improved synaptic function. In addition, LTA4H plasma levels are increased in both aging and Alzheimer's disease and correlated with cognitive impairment. These results identify a role for LTA4H in the brain, and we propose that LTA4H inhibition may be a promising therapeutic strategy to treat cognitive decline in aging related diseases.
MeSH term(s)	Mice ; Animals ; Epoxide Hydrolases/chemistry ; Cognitive Dysfunction/drug therapy
Chemical Substances	leukotriene A4 hydrolase (V38765PUZ6) ; Epoxide Hydrolases (EC 3.3.2.-)
Language	English
Publishing date	2023-11-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adf8764
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Article ; Online: CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain.

Rege, Sanket V / Teichert, Arnaud / Masumi, Juliet / Dhande, Onkar S / Harish, Reema / Higgins, Brett W / Lopez, Yesenia / Akrapongpisak, Lily / Hackbart, Hannah / Caryotakis, Sofia / Leone, Dino P / Szoke, Balazs / Hannestad, Jonas / Nikolich, Karoly / Braithwaite, Steven P / Minami, S Sakura

Communications biology

2023 Volume 6, Issue 1, Page(s) 292

Abstract: Targeting immune-mediated, age-related, biology has the potential to be a transformative therapeutic strategy. However, the redundant nature of the multiple cytokines that change with aging requires identification of a master downstream regulator to ... ...

Abstract	Targeting immune-mediated, age-related, biology has the potential to be a transformative therapeutic strategy. However, the redundant nature of the multiple cytokines that change with aging requires identification of a master downstream regulator to successfully exert therapeutic efficacy. Here, we discovered CCR3 as a prime candidate, and inhibition of CCR3 has pro-cognitive benefits in mice, but these benefits are not driven by an obvious direct action on central nervous system (CNS)-resident cells. Instead, CCR3-expressing T cells in the periphery that are modulated in aging inhibit infiltration of these T cells across the blood-brain barrier and reduce neuroinflammation. The axis of CCR3-expressing T cells influencing crosstalk from periphery to brain provides a therapeutically tractable link. These findings indicate the broad therapeutic potential of CCR3 inhibition in a spectrum of neuroinflammatory diseases of aging.
MeSH term(s)	Animals ; Mice ; Brain/metabolism ; Central Nervous System ; Cognition ; Cytokines ; Receptors, CCR3/genetics ; Receptors, CCR3/metabolism ; T-Lymphocytes/metabolism ; Aging
Chemical Substances	Ccr3 protein, mouse ; Cytokines ; Receptors, CCR3
Language	English
Publishing date	2023-03-18
Publishing country	England
Document type	Journal Article
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-04665-w
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Article: The Assisi Think Tank Meeting Breast Large Database for Standardized Data Collection in Breast Cancer-ATTM.BLADE.

Journal of personalized medicine

2021 Volume 11, Issue 2

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-02-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm11020143
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Article ; Online: Compensatory Actions of Ldb Adaptor Proteins During Corticospinal Motor Neuron Differentiation.

Leone, Dino P / Panagiotakos, Georgia / Heavner, Whitney E / Joshi, Pushkar / Zhao, Yangu / Westphal, Heiner / McConnell, Susan K

Cerebral cortex (New York, N.Y. : 1991)

2017 Volume 27, Issue 2, Page(s) 1686–1699

Abstract: Although many genes that specify neocortical projection neuron subtypes have been identified, the downstream effectors that control differentiation of those subtypes remain largely unknown. Here, we demonstrate that the LIM domain-binding proteins Ldb1 ... ...

Abstract	Although many genes that specify neocortical projection neuron subtypes have been identified, the downstream effectors that control differentiation of those subtypes remain largely unknown. Here, we demonstrate that the LIM domain-binding proteins Ldb1 and Ldb2 exhibit dynamic and inversely correlated expression patterns during cerebral cortical development. Ldb1-deficient brains display severe defects in proliferation and changes in regionalization, phenotypes resembling those of Lhx mutants. Ldb2-deficient brains, on the other hand, exhibit striking phenotypes affecting layer 5 pyramidal neurons: Immature neurons have an impaired capacity to segregate into mature callosal and subcerebral projection neurons. The analysis of Ldb2 single-mutant mice reveals a compensatory role of Ldb1 for Ldb2 during corticospinal motor neuron (CSMN) differentiation. Animals lacking both Ldb1 and Ldb2 uncover the requirement for Ldb2 during CSMN differentiation, manifested as incomplete CSMN differentiation, and ultimately leading to a failure of the corticospinal tract.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cell Differentiation/physiology ; DNA-Binding Proteins/deficiency ; Gene Expression Regulation, Developmental/physiology ; LIM Domain Proteins/deficiency ; Mice, Transgenic ; Motor Neurons/metabolism ; Neurogenesis/physiology ; Pyramidal Tracts/metabolism ; Transcription Factors/deficiency ; Transcription Factors/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; DNA-Binding Proteins ; LIM Domain Proteins ; Ldb1 protein, mouse ; Ldb2 protein, mouse ; Transcription Factors
Language	English
Publishing date	2017--01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhw003
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Article ; Online: Improving Palivizumab Administration to High-Risk Infants with Heart Disease via a Communication-Based Quality Improvement Initiative.

Leone, David M / Rodriguez, Alexis / Cowenhoven, Kirsten / O'Connell, Matthew / Grossman, Matthew / Ferdman, Dina

Pediatric cardiology

2024

Abstract: ... during the final year of the project (p = 0.02). The percentage of infants who received 80% of eligible ... doses increased from 42.1 to 60% but was not statistically significant (p = 0.20). Interventions focused ...

Abstract	To improve palivizumab administration in high-risk infants with congenital heart disease to 80% over 2 years at an academic children's heart center. A multidisciplinary team at our institution implemented a series of interventions over a 2-year prior. Pediatric cardiac patients were identified for palivizumab eligibility, and a baseline rate of administration was obtained. A series of communication and documentation-based interventions were implemented over the course of the next 2 years. Palivizumab eligible infants (n = 114) were determined based on guidelines after review of diagnosis code, oxygen saturation, and medications. Doses of palivizumab were tracked via the electronic health record. The primary outcome measures were the rate of monthly palivizumab doses administered per the number of eligible months and the percentage of infants who received at least 80% of eligible doses during the respiratory syncytial virus season. The rate of monthly palivizumab doses increased from 57.6% during the baseline period to 78.4% during the final year of the project (p = 0.02). The percentage of infants who received 80% of eligible doses increased from 42.1 to 60% but was not statistically significant (p = 0.20). Interventions focused on properly identifying and tracking infants eligible for palivizumab treatment significantly increased the rates of administration.
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	800857-7
ISSN	1432-1971 ; 0172-0643
ISSN (online)	1432-1971
ISSN	0172-0643
DOI	10.1007/s00246-023-03388-3
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Article ; Online: The Assisi Think Tank Meeting Breast Large Database for Standardized Data Collection in Breast Cancer—ATTM.BLADE

Journal of Personalized Medicine, Vol 11, Iss 2, p

2021 Volume 143

Abstract: Background: During the 2016 Assisi Think Tank Meeting (ATTM) on breast cancer, the panel of experts proposed developing a validated system, based on rapid learning health care (RLHC) principles, to standardize inter-center data collection and promote ... ...

Abstract	Background: During the 2016 Assisi Think Tank Meeting (ATTM) on breast cancer, the panel of experts proposed developing a validated system, based on rapid learning health care (RLHC) principles, to standardize inter-center data collection and promote personalized treatments for breast cancer. Material and Methods: The seven-step Breast LArge DatabasE (BLADE) project included data collection, analysis, application, and evaluation on a data-sharing platform. The multidisciplinary team developed a consensus-based ontology of validated variables with over 80% agreement. This English-language ontology constituted a breast cancer library with seven knowledge domains: baseline, primary systemic therapy, surgery, adjuvant systemic therapies, radiation therapy, follow-up, and toxicity. The library was uploaded to the BLADE domain. The safety of data encryption and preservation was tested according to General Data Protection Regulation (GDPR) guidelines on data from 15 clinical charts. The system was validated on 64 patients who had undergone post-mastectomy radiation therapy. In October 2018, the BLADE system was approved by the Ethical Committee of Fondazione Policlinico Gemelli IRCCS, Rome, Italy (Protocol No. 0043996/18). Results: From June 2016 to July 2019, the multidisciplinary team completed the work plan. An ontology of 218 validated variables was uploaded to the BLADE domain. The GDPR safety test confirmed encryption and data preservation (on 5000 random cases). All validation benchmarks were met. Conclusion: BLADE is a support system for follow-up and assessment of breast cancer care. To successfully develop and validate it as the first standardized data collection system, multidisciplinary collaboration was crucial in selecting its ontology and knowledge domains. BLADE is suitable for multi-center uploading of retrospective and prospective clinical data, as it ensures anonymity and data privacy.
Keywords	breast cancer ; large database ; standardized data collection ; networks ; Medicine ; R
Subject code	616
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: TBADT-Mediated Photocatalytic Stereoselective Radical Alkylation of Chiral N-Sulfinyl Imines: Towards Efficient Synthesis of Diverse Chiral Amines.

Leone, Matteo / Milton, Joseph P / Gryko, Dorota / Neuville, Luc / Masson, Géraldine

Chemistry (Weinheim an der Bergstrasse, Germany)

2024 Volume 30, Issue 24, Page(s) e202400363

Abstract: Herein we describe a sustainable and efficient photocatalytic method for the stereoselective radical alkylation of chiral sulfinyl imines. By employing readily available non-prefunctionalized radical precursors and the cost-effective TBADT as a direct ... ...

Abstract	Herein we describe a sustainable and efficient photocatalytic method for the stereoselective radical alkylation of chiral sulfinyl imines. By employing readily available non-prefunctionalized radical precursors and the cost-effective TBADT as a direct HAT photocatalyst, we successfully obtain diverse chiral amines with high yields and excellent diastereoselectivity under mild conditions. This method provides an efficient approach for accessing a diverse array of medicinally relevant compounds, including both natural and synthetic α-amino acids, aryl ethyl amines, and other structural motifs commonly found in approved pharmaceuticals and natural product.
Language	English
Publishing date	2024-03-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202400363
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Article ; Online: Sorption of benzene derivatives onto a humic acid-zeolitic tuff adduct.

Leone, Vincenzo / Capasso, Sante / Chianese, Simone / Iovino, Pasquale / Musmarra, Dino

Environmental science and pollution research international

2018 Volume 25, Issue 27, Page(s) 26831–26836

Abstract: The sorption of some benzene derivatives: o-xylene, toluene, phenol, benzyl alcohol, resorcinol and hydroquinone onto a zeolitic tuff-humic acid adduct (PCT-ImHA) was analysed by batch technique at 25 °C and neutral pH. PCT-ImHA was prepared by binding ... ...

Abstract	The sorption of some benzene derivatives: o-xylene, toluene, phenol, benzyl alcohol, resorcinol and hydroquinone onto a zeolitic tuff-humic acid adduct (PCT-ImHA) was analysed by batch technique at 25 °C and neutral pH. PCT-ImHA was prepared by binding leonardite-extracted humic acids (HA) to a zeolitic tuff sample rich in phillipsite and chabazite and enriched with Ca
MeSH term(s)	Adsorption ; Benzene Derivatives/chemistry ; Humic Substances ; Hydrogen-Ion Concentration ; Minerals ; Phenol ; Phenols ; Toluene ; Water Purification/methods ; Xylenes ; Zeolites/chemistry
Chemical Substances	Benzene Derivatives ; Humic Substances ; Minerals ; Phenols ; Xylenes ; chabazite ; leonardite ; phillipsite (12174-18-4) ; Zeolites (1318-02-1) ; Phenol (339NCG44TV) ; Toluene (3FPU23BG52) ; 2-xylene (Z2474E14QP)
Language	English
Publishing date	2018-02-21
Publishing country	Germany
Document type	Evaluation Studies ; Journal Article
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-018-1540-2
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Article ; Online: The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrain.

Leone, Dino P / Srinivasan, Karpagam / Brakebusch, Cord / McConnell, Susan K

Developmental neurobiology

2010 Volume 70, Issue 9, Page(s) 659–678

Abstract: Progenitor cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing forebrain give rise to neurons and glial cells, and are characterized by distinct morphologies and proliferative behaviors. The mechanisms that distinguish VZ ... ...

Abstract	Progenitor cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing forebrain give rise to neurons and glial cells, and are characterized by distinct morphologies and proliferative behaviors. The mechanisms that distinguish VZ and SVZ progenitors are not well understood, although the homeodomain transcription factor Cux2 and Cyclin D2, a core component of the cell cycle machinery, are specifically involved in controlling SVZ cell proliferation. Rho GTPases have been implicated in regulating the proliferation, differentiation, and migration of many cell types, and one family member, Cdc42, affects the polarity and proliferation of radial glial cells in the VZ. Here, we show that another family member, Rac1, is required for the normal proliferation and differentiation of SVZ progenitors and for survival of both VZ and SVZ progenitors. A forebrain-specific loss of Rac1 leads to an SVZ-specific reduction in proliferation, a concomitant increase in cell cycle exit, and premature differentiation. In Rac1 mutants, the SVZ and VZ can no longer be delineated, but rather fuse to become a single compact zone of intermingled cells. Cyclin D2 expression, which is normally expressed by both VZ and SVZ progenitors, is reduced in Rac1 mutants, suggesting that the mutant cells differentiate precociously. Rac1-deficient mice can still generate SVZ-derived upper layer neurons, indicating that Rac1 is not required for the acquisition of upper layer neuronal fates, but instead is needed for the normal regulation of proliferation by progenitor cells in the SVZ.
MeSH term(s)	Animals ; Apoptosis/physiology ; Cell Differentiation/physiology ; Cell Movement/physiology ; Cell Proliferation ; Cell Survival/physiology ; Cerebral Cortex/embryology ; Cerebral Cortex/pathology ; Cerebral Cortex/physiology ; Cyclin D1/metabolism ; Cyclin D2/metabolism ; Immunohistochemistry ; In Situ Hybridization ; Mice ; Mice, Knockout ; Neurogenesis/physiology ; Neurons/physiology ; Neuropeptides/deficiency ; Neuropeptides/genetics ; Neuropeptides/metabolism ; Prosencephalon/embryology ; Prosencephalon/pathology ; Prosencephalon/physiology ; Stem Cell Niche/embryology ; Stem Cell Niche/pathology ; Stem Cell Niche/physiology ; Stem Cells/physiology ; rac GTP-Binding Proteins/deficiency ; rac GTP-Binding Proteins/genetics ; rac GTP-Binding Proteins/metabolism ; rac1 GTP-Binding Protein
Chemical Substances	Ccnd1 protein, mouse ; Ccnd2 protein, mouse ; Cyclin D2 ; Neuropeptides ; Rac1 protein, mouse ; Cyclin D1 (136601-57-5) ; rac GTP-Binding Proteins (EC 3.6.5.2) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2010-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2256184-5
ISSN	1932-846X ; 1097-4695 ; 1932-8451 ; 0022-3034
ISSN (online)	1932-846X ; 1097-4695
ISSN	1932-8451 ; 0022-3034
DOI	10.1002/dneu.20804
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Zs.A 853: Show issues

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Article: A Guide to Single-Cell Transcriptomics in Adult Rodent Brain: The Medium Spiny Neuron Transcriptome Revisited.

Ho, Hanson / Both, Matt De / Siniard, Ashley / Sharma, Sasha / Notwell, James H / Wallace, Michelle / Leone, Dino P / Nguyen, Amy / Zhao, Eric / Lee, Hannah / Zwilling, Daniel / Thompson, Kimberly R / Braithwaite, Steven P / Huentelman, Matthew / Portmann, Thomas

Frontiers in cellular neuroscience

2018 Volume 12, Page(s) 159

Abstract: Recent advances in single-cell technologies are paving the way to a comprehensive understanding of the cellular complexity in the brain. Protocols for single-cell transcriptomics combine a variety of sophisticated methods for the purpose of isolating the ...

Abstract	Recent advances in single-cell technologies are paving the way to a comprehensive understanding of the cellular complexity in the brain. Protocols for single-cell transcriptomics combine a variety of sophisticated methods for the purpose of isolating the heavily interconnected and heterogeneous neuronal cell types in a relatively intact and healthy state. The emphasis of single-cell transcriptome studies has thus far been on comparing library generation and sequencing techniques that enable measurement of the minute amounts of starting material from a single cell. However, in order for data to be comparable, standardized cell isolation techniques are essential. Here, we analyzed and simplified methods for the different steps critically involved in single-cell isolation from brain. These include enzymatic digestion, tissue trituration, improved methods for efficient fluorescence-activated cell sorting in samples containing high degree of debris from the neuropil, and finally, highly region-specific cellular labeling compatible with use of stereotaxic coordinates. The methods are exemplified using medium spiny neurons (MSN) from dorsomedial striatum, a cell type that is clinically relevant for disorders of the basal ganglia, including psychiatric and neurodegenerative diseases. We present single-cell RNA sequencing (scRNA-Seq) data from D1 and D2 dopamine receptor expressing MSN subtypes. We illustrate the need for single-cell resolution by comparing to available population-based gene expression data of striatal MSN subtypes. Our findings contribute toward standardizing important steps of single-cell isolation from adult brain tissue to increase comparability of data. Furthermore, our data redefine the transcriptome of MSNs at unprecedented resolution by confirming established marker genes, resolving inconsistencies from previous gene expression studies, and identifying novel subtype-specific marker genes in this important cell type.
Language	English
Publishing date	2018-06-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2018.00159
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