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Article ; Online: Neurexin1⍺ differentially regulates synaptic efficacy within striatal circuits.

Davatolhagh, M Felicia / Fuccillo, Marc V

2021 Volume 34, Issue 8, Page(s) 108773

Abstract: Mutations in genes essential for synaptic function, such as the presynaptic adhesion molecule Neurexin1α (Nrxn1α), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse ... ...

Abstract	Mutations in genes essential for synaptic function, such as the presynaptic adhesion molecule Neurexin1α (Nrxn1α), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its impairment may represent a recurrent pathway to disease. Here, we test the functional relevance of Nrxn1α in striatal circuits by employing optogenetic-mediated afferent recruitment of dorsal prefrontal cortical (dPFC) and parafascicular thalamic connections onto dorsomedial striatal (DMS) spiny projection neurons (SPNs). For dPFC-DMS circuits, we find decreased synaptic strength specifically onto indirect pathway SPNs in both Nrxn1α
MeSH term(s)	Afferent Pathways/cytology ; Afferent Pathways/metabolism ; Animals ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/metabolism ; Corpus Striatum/cytology ; Corpus Striatum/metabolism ; Electrical Synapses/genetics ; Electrical Synapses/metabolism ; Excitatory Postsynaptic Potentials ; Glutamic Acid/metabolism ; Heterozygote ; Homozygote ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Neural Cell Adhesion Molecules/genetics ; Neural Cell Adhesion Molecules/metabolism ; Optogenetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synaptic Transmission ; Mice
Chemical Substances	Calcium-Binding Proteins ; Neural Cell Adhesion Molecules ; Nrxn1 protein, mouse ; Receptors, N-Methyl-D-Aspartate ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.108773
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Article ; Online: Brief report: Newborn adoption in a confined group of Japanese macaques.

Fuccillo, R / Scucchi, S / Troisi, A / D'Amato, F R

American journal of primatology

2020 Volume 5, Issue 3, Page(s) 257–260

Abstract: In a group of Japanese macaques, a multiparous high-ranking female gave birth to an infant and, two days later, adopted a neonate abandoned right after birth by a primiparous low-ranking female. Both infants were reared successfully. Whereas the "selfish" ...

Abstract	In a group of Japanese macaques, a multiparous high-ranking female gave birth to an infant and, two days later, adopted a neonate abandoned right after birth by a primiparous low-ranking female. Both infants were reared successfully. Whereas the "selfish" explanation does not accord with the evidence from the present case, the "altruistic" explanation cannot be discarded definitively. However, the context and the consequences of the adoption suggest reproductive error on the part of the adoptive mother as the most likely explanation.
Language	English
Publishing date	2020-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1495834-X
ISSN	1098-2345 ; 0275-2565
ISSN (online)	1098-2345
ISSN	0275-2565
DOI	10.1002/ajp.1350050310
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Article ; Online: Neurexin1⍺ differentially regulates synaptic efficacy within striatal circuits

M. Felicia Davatolhagh / Marc V. Fuccillo

Cell Reports, Vol 34, Iss 8, Pp 108773- (2021)

2021

Abstract: ... changes in synaptic N-methyl-D-aspartate receptor (NMDAR) content. These findings suggest ...

Abstract	Summary: Mutations in genes essential for synaptic function, such as the presynaptic adhesion molecule Neurexin1α (Nrxn1α), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its impairment may represent a recurrent pathway to disease. Here, we test the functional relevance of Nrxn1α in striatal circuits by employing optogenetic-mediated afferent recruitment of dorsal prefrontal cortical (dPFC) and parafascicular thalamic connections onto dorsomedial striatal (DMS) spiny projection neurons (SPNs). For dPFC-DMS circuits, we find decreased synaptic strength specifically onto indirect pathway SPNs in both Nrxn1α+/− and Nrxn1α−/− mice, driven by reductions in neurotransmitter release. In contrast, thalamic excitatory inputs to DMS exhibit relatively normal excitatory synaptic strength despite changes in synaptic N-methyl-D-aspartate receptor (NMDAR) content. These findings suggest that dysregulation of Nrxn1α modulates striatal function in an input- and target-specific manner.
Keywords	corticostriatal ; thalamostriatal ; synaptic transmission ; Neurexin1α ; prefrontal cortex ; striatum ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Coronary artery calcium score is a prognostic factor for mortality in idiopathic pulmonary fibrosis.

Caminati, Antonella / Zompatori, Maurizio / Fuccillo, Nicoletta / Sonaglioni, Andrea / Elia, Davide / Cassandro, Roberto / Trevisan, Roberta / Rispoli, Anna / Pelosi, Giuseppe / Harari, Sergio

Minerva medica

2022 Volume 114, Issue 6, Page(s) 815–824

Abstract: Background: Cardiovascular diseases are frequent in idiopathic pulmonary fibrosis (IPF) and impact on survival. We investigated the association of coronary artery calcium (CAC) score at IPF diagnosis and during mid-term follow-up, with adverse ... ...

Abstract	Background: Cardiovascular diseases are frequent in idiopathic pulmonary fibrosis (IPF) and impact on survival. We investigated the association of coronary artery calcium (CAC) score at IPF diagnosis and during mid-term follow-up, with adverse cardiovascular events and all-cause mortality. Methods: Consecutive patients with IPF were retrospectively analyzed. Demographic data, smoking history, comorbidities and pulmonary function tests (PFTs) were recorded. All patients had at least two chest high resolution computed tomography (HRCT) performed 2 years apart. The total CAC score and visual fibrotic score were calculated, and all clinically significant cardiovascular events and deaths were reported. Results: The population consisted of 79 patients (57 males, mean age: 74.4±7.6 years); 67% of patients had a history of smoking, 48% of hypertension, 37% of dyslipidemia and 22.8% of diabetes. The visual score was 21.28±7.99% at T0 and 26.54±9.34% at T1, respectively (T1-T0 5.26±6.13%, P<0.001). CAC score at T0 and at T1 was 537.93±839.94 and 759.98±1027.6, respectively (T1-T0 224.66±406.87, P<0.001). Mean follow-up time was 2.47±1.1 years. On multivariate analysis, male sex (HR=3.58, 95% CI: 1.14-11.2) and CAC score at T0 (HR=1.04, 95% CI: 1.01-1.07) correlated with mortality and cardiovascular events. CAC score at T0≥405 showed 82% sensitivity and 100% specificity for predicting mortality and adverse cardiovascular events. Conclusions: IPF patients with a CAC score at diagnosis ≥405 have a poor prognosis over a mid-term follow-up. A higher CAC score is associated with mortality and cardiovascular events.
MeSH term(s)	Humans ; Male ; Aged ; Aged, 80 and over ; Coronary Artery Disease/complications ; Coronary Artery Disease/diagnostic imaging ; Calcium ; Prognosis ; Risk Factors ; Retrospective Studies ; Cardiovascular Diseases/etiology ; Idiopathic Pulmonary Fibrosis/diagnostic imaging ; Coronary Angiography/methods
Chemical Substances	Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-06-07
Publishing country	Italy
Document type	Journal Article
ZDB-ID	123586-2
ISSN	1827-1669 ; 0026-4806
ISSN (online)	1827-1669
ISSN	0026-4806
DOI	10.23736/S0026-4806.22.08018-1
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Article ; Online: Fede interdetta? L'esercizio della libertà religiosa collettiva durante l'emergenza COVID-19

FUCCILLO, Antonio / Abu, Salem / DECIMO, Ludovica

attualità e prospettive

2020

Abstract: ... provvedimenti restrittivi della libertà religiosa. Le ordinanze contingibili e urgenti e i D.L. hanno infatti ...

Abstract	Il Governo e le autonomie locali, per fronteggiare l’epidemia da Covid-19, hanno adottato provvedimenti restrittivi della libertà religiosa. Le ordinanze contingibili e urgenti e i D.L. hanno infatti disposto la sospensione dei riti e manifestazioni di culto e la limitazione all’accesso dei luoghi sacri, giustificati da una ragione di urgenza-emergenza per la tutela della salute pubblica. Tali provvedimenti che interdicono la fede sono del tutto legittimi? La libertà religiosa non è un diritto limitabile, ma è comprimibile in alcune sue manifestazioni nel rispetto delle regole dell’ordinamento costituzionale. Ciò è possibile con precisi vincoli temporali e sulla base di provvedimenti proporzionati e basati su reali esigenze di necessità ed urgenza a tutela di altrettanti valori costituzionalmente protetti come appunto la salute. Le misure adottate sono però avvertite come necessarie anche dalle confessioni che hanno collaborato con lo Stato. Le confessioni religiose non hanno contrastato i provvedimenti limitativi dei propri spazi di libertà e dell’esercizio del culto dei propri fedeli, ma hanno disposto autonomamente la chiusura di spazi ed edifici, invitando i fedeli a tenere atti di culto individuali. Ne discende una preziosa cooperazione tra Stato e religioni per contrastare l’emergenza sanitaria e tutelare la salute pubblica. La straordinaria emergenza sanitaria che sta vivendo il nostro paese deve però indurre il giurista a porsi alcune domande fondamentali. Potrà accadere di nuovo? Ci potranno essere altri eventi per i quali sarà necessario comprimere la libertà religiosa individuale e collettiva? È possibile ipotizzare che ciò avvenga con modalità concordate preventivamente con le stesse confessioni religiose, in ossequio al principio di bilateralità pattizia? A tali domande è necessario fornire prontamente delle risposte per salvaguardare il diritto di libertà religiosa e l’autonomia delle confessioni religiose da possibili prevaricazioni normative. In response to the Covid-19 epidemic, the government and local authorities have adopted measures which restrict religious freedom. The Italian authorities have imposed urgent and binding ordinances suspending all religious ceremonies, and have limited access to places of worship. These measures are justified by an emergency decree aimed at the protection of public health. Is such banning of religious practice entirely legitimate? The Italian Constitution stipulates that religious freedom can only be limited in certain manifestations and under specific conditions. Precise time constraints must be adhered to, and restrictions must be balanced against other constitutional rights including, of course, the right to health. The adopted measures taken by the government are applicable to religious denominations that have cooperated with the State. These denominations, in fact, have anticipated the needs of the State towards the protection of public health by closing places of worship and encouraging the faithful to practice autonomously. This state of emergency has ultimately strengthened the cooperation and understanding between State and denominations in important ways. The extraordinary health emergency that our country is experiencing, however, must lead the jurist to ask some fundamental questions. Will it happen again? Could there be other future events which will call for the limitation of individual and collective religious freedom? Might the State and religious denominations collaborate together in advance of such events in accordance with the principles of bi-laterality? These questions must be answered promptly in order to safeguard the right to religious freedom and the autonomy of religious denominations from possible regulatory circumvention.
Keywords	Libertà religiosa ; luogo di culto ; Covid-19 ; pandemia ; salute pubblica ; covid19
Language	Italian
Publishing country	it
Document type	Article ; Online
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Article ; Online: Temporal manipulation of Cdkl5 reveals essential postdevelopmental functions and reversible CDKL5 deficiency disorder-related deficits.

Terzic, Barbara / Davatolhagh, M Felicia / Ho, Yugong / Tang, Sheng / Liu, Yu-Ting / Xia, Zijie / Cui, Yue / Fuccillo, Marc V / Zhou, Zhaolan

The Journal of clinical investigation

2021 Volume 131, Issue 20

Abstract: CDKL5 deficiency disorder (CDD) is an early onset, neurodevelopmental syndrome associated with pathogenic variants in the X-linked gene encoding cyclin-dependent kinase-like 5 (CDKL5). CDKL5 has been implicated in neuronal synapse maturation, yet its ... ...

Abstract	CDKL5 deficiency disorder (CDD) is an early onset, neurodevelopmental syndrome associated with pathogenic variants in the X-linked gene encoding cyclin-dependent kinase-like 5 (CDKL5). CDKL5 has been implicated in neuronal synapse maturation, yet its postdevelopmental necessity and the reversibility of CDD-associated impairments remain unknown. We temporally manipulated endogenous Cdkl5 expression in male mice and found that postdevelopmental loss of CDKL5 disrupts numerous behavioral domains, hippocampal circuit communication, and dendritic spine morphology, demonstrating an indispensable role for CDKL5 in the adult brain. Accordingly, restoration of Cdkl5 after the early stages of brain development using a conditional rescue mouse model ameliorated CDD-related behavioral impairments and aberrant NMDA receptor signaling. These findings highlight the requirement of CDKL5 beyond early development, underscore the potential for disease reversal in CDD, and suggest that a broad therapeutic time window exists for potential treatment of CDD-related deficits.
MeSH term(s)	Animals ; Dendrites/pathology ; Epileptic Syndromes/psychology ; Evoked Potentials/physiology ; Mice ; Mice, Inbred C57BL ; Protein Serine-Threonine Kinases/physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Spasms, Infantile/psychology
Chemical Substances	Receptors, N-Methyl-D-Aspartate ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; CDKL5 protein, mouse (EC 2.7.11.22)
Language	English
Publishing date	2021-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI143655
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Article ; Online: Evidence of SARS-CoV-2 in nasal brushings and olfactory mucosa biopsies of COVID-19 patients.

Pipolo, Carlotta / Bottai, Daniele / Fuccillo, Emanuela / Aronica, Eleonora / Bruschi, Fabio / Bulfamante, Antonio Mario / Castellani, Luca / Canevini, Maria Paola / Chiumello, Davide / Ferrari, Sergio / Martinelli, Carla / Muttini, Stefano / Priori, Alberto / Saibene, Alberto Maria / Spoldi, Chiara / Tosi, Delfina / Zanusso, Gianluigi / Bulfamante, Gaetano Pietro / Felisati, Giovanni

PloS one

2022 Volume 17, Issue 4, Page(s) e0266740

Abstract: The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a ... ...

Abstract	The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.
MeSH term(s)	Biopsy ; COVID-19/diagnosis ; Humans ; Olfactory Mucosa/pathology ; SARS-CoV-2
Language	English
Publishing date	2022-04-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0266740
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Article: Brain-wide neuronal circuit connectome of human glioblastoma.

Sun, Yusha / Wang, Xin / Zhang, Daniel Y / Zhang, Zhijian / Bhattarai, Janardhan P / Wang, Yingqi / Dong, Weifan / Zhang, Feng / Park, Kristen H / Galanaugh, Jamie / Sambangi, Abhijeet / Yang, Qian / Kim, Sang Hoon / Wheeler, Garrett / Goncalves, Tiago / Wang, Qing / Geschwind, Daniel / Kawaguchi, Riki / Wang, Huadong /

Xu, Fuqiang / Binder, Zev A / Chen, Isaac H / Pai, Emily Ling-Lin / Stone, Sara / Nasrallah, MacLean / Christian, Kimberly M / Fuccillo, Marc / O'Rourke, Donald M / Ma, Minghong / Ming, Guo-Li / Song, Hongjun

bioRxiv : the preprint server for biology

2024

Abstract: Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor ... ...

Abstract	Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.01.583047
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Article ; Online: Gold-gold bonding: the key to stabilizing the 19-electron ternary phases LnAuSb (Ln = La-Nd and Sm).

Seibel, Elizabeth M / Schoop, Leslie M / Xie, Weiwei / Gibson, Quinn D / Webb, James B / Fuccillo, Michael K / Krizan, Jason W / Cava, Robert J

Journal of the American Chemical Society

2015 Volume 137, Issue 3, Page(s) 1282–1289

Abstract: We report a new family of ternary 111 hexagonal LnAuSb (Ln = La-Nd, Sm) compounds that, with a 19 valence electron count, has one extra electron compared to all other known LnAuZ compounds. LaAuSb, CeAuSb, PrAuSb, NdAuSb, and SmAuSb crystallize in the ... ...

Abstract	We report a new family of ternary 111 hexagonal LnAuSb (Ln = La-Nd, Sm) compounds that, with a 19 valence electron count, has one extra electron compared to all other known LnAuZ compounds. LaAuSb, CeAuSb, PrAuSb, NdAuSb, and SmAuSb crystallize in the YPtAs-type structure, and have a doubled unit cell compared to other LnAuZ phases as a result of the buckling of the Au-Sb honeycomb layers to create interlayer Au-Au dimers. The dimers accommodate the one excess electron per Au and thus these new phases can be considered Ln2(3+)(Au-Au)(0)Sb2(3-). Band structure, density of states, and crystal orbital calculations confirm this picture, which results in a nearly complete band gap between full and empty electronic states and stable compounds; we can thus present a structural stability phase diagram for the LnAuZ (Z = Ge, As, Sn, Sb, Pb, Bi) family of phases. Those calculations also show that LaAuSb has a bulk Dirac cone below the Fermi level. The YPtAs-type LnAuSb family reported here is an example of the uniqueness of gold chemistry applied to a rigidly closed shell system in an unconventional way.
Language	English
Publishing date	2015-01-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/ja511394q
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Article: Nasal cytology in children: scraping or swabbing?

Pipolo, C / Bianchini, S / Barberi, S / Landi, M / D'Auria, E / Fuccillo, E / Gaffuri, M / Marchisio, P / Rosazza, C / Saibene, A M / Gelardi, M / Torretta, S

Rhinology

2017 Volume 55, Issue 3, Page(s) 242–250

Abstract: Nasal cytology has become a valuable tool in the assessment of a multitude of nasal pathologies in children. Collection methods differ significantly and even though the use of the nasal curette is regarded as the most reliable in adults, most ... ...

Abstract	Nasal cytology has become a valuable tool in the assessment of a multitude of nasal pathologies in children. Collection methods differ significantly and even though the use of the nasal curette is regarded as the most reliable in adults, most practitioners use the nasal swab in children. However, no studies have validated the reliability and supposed better tolerability of the latter. We have compared these two sampling methods regarding their tolerability and analysed the diagnostic accuracy of the cotton nasal swab (NSW) to identify nasal cytotypes and rhinitis phenotypes, using nasal scraping (NSC) for comparison. In a multicentric prospective study we recruited 208 children and performed nasal cytology by means of NSW and NSC. Microscopic evaluating of the nasal cytotypes was performed and tolerability of NSW and NSC was tested. Our data revealed a significantly inferior diagnostic accuracy of NSW compared to NSC regarding reliability and cell counts. Our study is the first to shed light on the role of the sampling tools for pediatric nasal cytology. We documented a poor diagnostic accuracy of NSW, thus suggesting using only the nasal curette in clinical practice. Furthermore, tolerability did not differ between the two, refuting the common thesis that swabs are to be preferred when doing nasal cytology in children.
MeSH term(s)	Cell Count/methods ; Child, Preschool ; Cytodiagnosis/methods ; Humans ; Nasal Mucosa/cytology ; Nasal Mucosa/pathology ; Prospective Studies ; Reproducibility of Results ; Rhinitis/diagnosis
Language	English
Publishing date	2017-09-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80336-4
ISSN	0300-0729
ISSN	0300-0729
DOI	10.4193/Rhin16.287
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