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Membraneless organelles restructured and built by pandemic viruses:HIV-1 and SARS-CoV-2

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Journal of Molecular Cell Biology 2021年第4期13卷 259-268页

作者： Viviana Scoca Francesca Di nunzio Advanced Molecular Virology and Retroviral Dynamics Group Department of VirologyPasteur InstituteParisFrance BioSPC Doctoral School Universite de ParisParisFrance

Viruses hijack host functions to invade their target cells and spread to new ***,viruses learned to usurp liquid-liquid phase separation(LLPS),a newly exploited mechanism,used by the cell to concentrate enzymes to accelerate and confine a wide variety of cellular *** gives rise to actual membraneless organelles(MLOs),which do not only increase reaction rates but also act as a filter to select molecules to be retained or to be excluded from the liquid *** is exactly what seems to happen with the condensation of SARS-CoV-2 nucleocapsid protein to favor the packaging of intact viral genomes,excluding viral subgenomic or host cellular *** older pandemic virus,HIV-1,also takes advantage of LLPS in the host cell during the viral *** discoveries highlighted that HIV-1 RNA genome condensates in nuclear MLOs accompanied by specific host and viral proteins,breaking the dogma of retroviruses that limited viral synthesis exclusively to the cytoplasmic *** fundamental properties of viral/host LLPS remain still *** studies will contribute to deeply understanding the role of pathogen-induced MLOs in the epidemic invasion of pandemic viruses.

关键词： LLPS MLO HIV-1 SARS-CoV-2

HIV-induced membraneless organelles orchestrate post-nuclear entry steps

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Journal of Molecular Cell Biology 2022年第11期14卷 9-23页

作者： Viviana Scoca Renaud Morin Maxence Collard Jean-Yves Tinevez Francesca Di nunzio Advanced Molecular Virology Unit Department of VirologyInstitut PasteurUniversitéParis Cité75015 ParisFrance Imactiv-3D 1 Place Pierre Potier31106 ToulouseFrance Image Analysis Hub/C2RT Institut PasteurUniversitéParis Cité75015 ParisFrance

HIV integration occurs in chromatin sites that favor the release of high levels of viral progeny;alternatively, the virus is alsoable to discreetly coexist with the host. The viral infection perturbs the cellular environment inducing the remodelling of thenuclear landscape. Indeed, HIV-1 triggers the nuclear clustering of the host factor CPSF6, but the underlying mechanism ispoorly understood. Our data indicate that HIV usurps a recently discovered biological phenomenon, called liquid–liquid phaseseparation, to hĳack the host cell. We observed CPSF6 clusters as part of HIV-induced membraneless organelles (HIV-1 MLOs) inmacrophages, one of the main HIV target cell types. We describe that HIV-1 MLOs follow phase-separation rules and representfunctional biomolecular condensates. We highlight HIV-1 MLOs as hubs of nuclear reverse transcription, while the double-strandedviral DNA, once formed, rapidly migrates outside these structures. Transcription-competent proviruses localize outside but nearHIV-1 MLOs in LEDGF-abundant regions, known to be active chromatin sites. Therefore, HIV-1 MLOs orchestrate viral events priorto the integration step and create a favorable environment for the viral replication. This study uncovers single functional host–viralcomplexes in their nuclear landscape, which is markedly restructured by HIV-1.

关键词： HIV nuclear condensates nuclear remodelling phase separation reverse transcription

Psychotic and nonpsychotic mood disorders in autoimmune encephalitis:diagnostic issues and research implications

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Neuroimmunology and Neuroinflammation 2015年第1期2卷 228-236页

作者： Giuseppe Quaranta nunzio Bucci Cristina Toni Giulio Perugi Department of Experimental and Clinic Medicine Section of PsychiatryUniversity of Pisa56100 PisaItaly Department of Mental Health Health District74100 TarantoItaly Institute of Behavioural Science G.De Lisio56100 PisaItaly

Recent research on autoimmune disorders suggests additional links between systemic and central nervous system(CNS)pathophysiology,among which the identification of antibody-induced limbic encephalitis provided the strongest evidence for the potential involvement of autoimmunity in the pathogenesis of severe mood and psychotic *** these illnesses,psychiatric symptoms predominate in the initial phase of the disorder in up to 70%of the cases,and they often lead patients to early psychiatric *** this reason,it is very important to increase the limited knowledge among psychiatrists about these autoimmune neuropsychiatric diseases,which can mimic psychiatric syndromes,in particular,those typically presented in severe mood disorders and *** the other hand,similarities in clinical presentation suggest that neuroinflammation and systemic immune dysregulation may play a role in the pathophysiology of severe mood and psychotic disorders.A complex interaction between periphery and immune cells of the CNS may result in cellular damage through mechanisms involving excitotoxicity,oxidative stress,and mitochondrial *** pathways are possibly shared between comorbid medical disorders and severe mood and psychotic disorders and may reflect common underlying vulnerability.

关键词： Autoimmune encephalitis mood disorders psychosis

Optic nerve compression:the role of the lamina cribrosa and translaminar pressure

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International Journal of Ophthalmology(English edition) 2017年第12期10卷 1883-1888页

作者： mario r romano gilda cennamo maria angelica breve michela piedepalumbo claudio iovino nunzio velotti giovanni cennamo department of biomedical sciences humanitas universityMilan 20089Ital department of public health university of naples federicoⅡNaples 80131Italy department of neurosciences reproductive sciences and dentistryuniversity of naples federicoⅡNaples 80100Italy

AIM： To describe the morphological changes of the lamina cribrosa （LC） in patients with optic nerve compression. METHODS： Cross-sectional study. Twenty eyes with optic nerve compression, affected by Graves＇ ophthalmopathy （GO） were compared with 18 refractive error-matched healthy eyes. The following examinations were performed： best-corrected visual acuity （BCVA）, intraocular pressure, optic nerve echography, visual field, SD-OCT including the retinal nerve fiber layer （RNFL）, ganglion cell complex （GCC）, and LC thickness and extent. RESULTS： A-scan revealed significant differences in the subarachnoid space （SAS） between the affected and control groups. LC thickness and LC area were 233 pm （SD 23） and 0.41 mm2 （SD 0.19）, respectively. Average GCC thickness （P=-0.0005）, LC thickness （P=-0.001）, MD （P=-0.001） and PSD （P=-0.001） differed significantly between the two groups; whereas LC area （P=-0.2） and average RFNL （P=-0.1） did not. CONCLUSION： Optic nerve compression reduces the SAS thereby altering the morphology of LC thickness and causing GCC damage.

关键词： optic nerve compression lamina cribrosa translaminar pressure

The Rise and Fall of the Secular Trend in Body Height in Sardinia:An Age-Period-Cohort Analysis

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Biomedical and Environmental Sciences 2020年第3期33卷 183-190页

作者： Giovanni Mario PES Roberta SALIS Alessandra ERRIGO Marco SATURNO Stefano BIBBO’ Bianca Maria QUARTA COLOSSO nunzio Pio LONGO Maria Pina DORE Department of Medical Surgical and Experimental SciencesUniversity of SassariI-07100 SassariItaly

Objective Over the last century, a progressive rise in stature, known as the ‘secular trend’, was documented worldwide, and especially in Sardinia, it has reached a peak in Europe. However, this situation recently ceased in several populations. In this study, we tested the hypothesis that the stature secular trend has significantly leveled off in the Sardinian younger *** Height measurements were retrieved from a database of patients undergoing digestive endoscopy, spanning generations between 1920 and 1990. Sex-specific principal component regression models were fitted to decompose stature variation into the contribution of age, period, and birth *** A steady increase in stature was observed in generations born after 1920, with an upward surge in those born after 1950. However, a significant leveling off was observed among cohorts born after 1970 among both sexes, as mean heights stabilized at 171.1 cm with a standard error(SE) of 0.9 cm among men and a mean of 160.1 cm(SE = 0.9 cm) among *** Our findings support a significant slowdown in the secular trend of stature among the latest Sardinian generations. Several factors, including the consumption of low-quality food, lack of physical activity, and late motherhood, among others, may explain the decline in the secular trend.

关键词： Body height Secular trend Socioeconomic status Sardinia

Biochemical sensing exploiting plasmonic sensors based on gold nanogratings and polymer optical fibers

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Photonics Research 2021年第7期9卷 1397-1408页

作者： FRANCESCO ARCADIO LUIGI ZENI DOMENICO MONTEMURRO CATERINA ERAMO STEFANIA DI RONZA CHIARA PERRI GIROLAMO D’AGOSTINO GUIDO CHIARETTI GIOVANNI PORTO nunzio CENNAMO Department of Engineering University of Campania Luigi VanvitelliAversa 81031Italy Department of Physics E.Pancini University of Naples Federico IINaples 80126Italy Moresense Srl Filarete FoundationMilan 20139Italy

In this work,we present a novel biochemical sensing approach based on a plasmonic sensor chip,combined with a specific receptor,excited and interrogated via a custom 3D-printed holder through a transmission-based experimental setup,exploiting polymer optical fibers. The setup is designed to measure a disposable plasmonic chip based on a gold nanograting fabricated on a polymethylmethacrylate substrate. The examined sensor configurations here presented are simulated,realized,and experimentally tested. More specifically,first,a numerical analysis is carried out by changing several sensor parameters,then an experimental optical characterization of different sensor configurations is reported. Finally,to test the biosensing capabilities of the proposed method,as a proof of concept,we deposit on the best sensor configuration a biomimetic receptor specific for bovine serum albumin detection. The experimental results demonstrate that the proposed sensor shows an ultra-low limit of detection,equal to about 37 pmol/L.

关键词： exploit optical polymer

Optical coherence tomography-angiography of juxtapapillary hamartoma

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International Journal of Ophthalmology(English edition) 2017年第8期10卷 1328-1330页

作者： Gilda Cennamo Mario R Romano Maria Angelica Breve nunzio Velotti Giuseppe de Crecchio Giovanni Cennamo Department of Neurosciences Reproductive Sciences and Dentistry Eye Clinic University of Naples Federico II Via S.Pansini 5 Naples 80133 Italy

Dear Editor,I＇m Dr. Gilda Cennamo from the Eye Clinic of Department of Neurosciences, Reproductive Sciences and Dentistry,University of Naples Federico II, Naples, Italy. I write to present four cases ofjuxtapapillar... 详细信息

关键词： In show Optical coherence tomography-angiography of juxtapapillary hamartoma Figure

Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions

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World Journal of Gastroenterology 2017年第32期23卷 5875-5886页

作者： Guido Giordano Massimo Pancione nunzio Olivieri Pietro Parcesepe Marianna Velocci Tania Di Raimo Luigi Coppola Giuseppe Toffoli Mario Rosario D’Andrea Medical Oncology Unit San Filippo Neri Hospital CRO Aviano National Cancer Institute Department of Sciences and Technologies University of Sannio Department of Biochemistry and Molecular Biology II Faculty of PharmacyComplutense University Department of Biology University of Naples Department of Pathology and Diagnostics University of Verona Strada Anatomic Pathology Unit San Filippo Neri00135 RomaItaly Experimental and Clinical Pharmacology Unit CRO-National Cancer Institute Via F

Pancreatic cancer(PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase Ⅲ study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.

关键词： Nano 白朊 bound-paclitaxel 胰腺的癌症变形疾病 Gemcitabine Folfirinox

Polyphenol and Biogenic Amine Profiles of Albana and Lambrusco Grape Berries and Wines Obtained Following Different Agricultural and Oenological Practices

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Food and Nutrition Sciences 2014年第1期5卷 8-16页

作者： Annalisa Tassoni nunzio Tango Maura Ferri Department of Biological Geological and Environmental Sciences University of Bologna Bologna Italy.

The levels of polyphenols, anthocyanins, antioxidant activity and of biogenic amines, were measured in white (Albana) and red (Lambrusco) grape berries and wines from the Emilia-Romagna region (Italy) obtained following conventional, organic and biodynamic agricultural and oenological practices. No significant difference was shown among the samples coming from different agricultural and winemaking practices, with few exceptions of single compounds. Biogenic amine amounts were higher in red than in white berries and wines. Putrescine and histamine were the most abundant biogenic amines respectively in berries and wines of both cultivars. Red grapes and wines were richer in anthocyanins and showed higher antioxidant activity than white ones. The total level of polyphenols was similar in red and white berries and wines, but with different metabolite profiles depending on the grape variety.

关键词： Antioxidant Activity Biogenic Amines Polyphenols Polyamines Vitis Vinifera