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Article ; Online: A chromosome-scale assembly reveals chromosomal aberrations and exchanges generating genetic diversity in Coffea arabica germplasm.

Scalabrin, Simone / Magris, Gabriele / Liva, Mario / Vitulo, Nicola / Vidotto, Michele / Scaglione, Davide / Del Terra, Lorenzo / Ruosi, Manuela Rosanna / Navarini, Luciano / Pellegrino, Gloria / Berny Mier Y Teran, Jorge Carlos / Toniutti, Lucile / Suggi Liverani, Furio / Cerutti, Mario / Di Gaspero, Gabriele / Morgante, Michele

Nature communications

2024 Volume 15, Issue 1, Page(s) 463

Abstract: In order to better understand the mechanisms generating genetic diversity in the recent allotetraploid species Coffea arabica, here we present a chromosome-level assembly obtained with long read technology. Two genomic compartments with different ... ...

Abstract	In order to better understand the mechanisms generating genetic diversity in the recent allotetraploid species Coffea arabica, here we present a chromosome-level assembly obtained with long read technology. Two genomic compartments with different structural and functional properties are identified in the two homoeologous genomes. The resequencing data from a large set of accessions reveals low intraspecific diversity in the center of origin of the species. Across a limited number of genomic regions, diversity increases in some cultivated genotypes to levels similar to those observed within one of the progenitor species, Coffea canephora, presumably as a consequence of introgressions deriving from the so-called Timor hybrid. It also reveals that, in addition to few, early-occurring exchanges between homoeologous chromosomes, there are numerous recent chromosomal aberrations including aneuploidies, deletions, duplications and exchanges. These events are still polymorphic in the germplasm and could represent a fundamental source of genetic variation in such a lowly variable species.
MeSH term(s)	Coffea ; Chromosome Aberrations ; Aneuploidy ; Genomics ; Chromosomes
Language	English
Publishing date	2024-01-23
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/s41467-023-44449-8
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Article ; Online: Potential Cardiologic Protective Effects of Acetylcholinesterase Inhibitors in Patients With Mild to Moderate Dementia.

Rampa, Lorenzo / Santangelo, Roberto / Gaspardone, Carlo / Cerutti, Alice / Magnani, Giuseppe / Piscazzi, Francesco / Sgherzi, Giulia / Fiore, Giorgio / Filippi, Massimo / Agosta, Federica / Margonato, Alberto / Fragasso, Gabriele

The American journal of cardiology

2023 Volume 200, Page(s) 162–170

Abstract: In patients with mild to moderate dementia, acetylcholinesterase inhibitors (AChE-I) are used to improve cognitive functions, but bradycardia, conduction abnormalities, and hypotension are possible side effects because of the peripheral muscarinic M2 ... ...

Abstract	In patients with mild to moderate dementia, acetylcholinesterase inhibitors (AChE-I) are used to improve cognitive functions, but bradycardia, conduction abnormalities, and hypotension are possible side effects because of the peripheral muscarinic M2 receptor stimulation. This study aimed to evaluate the main cardiologic clinical outcomes in patients with dementia who are on AChE-I. In this retrospective, monocentric, observational cohort study, 2 groups were considered: (1) patients with dementia because of the typical and atypical forms of Alzheimer disease treated with AChE-I and (2) cognitively unimpaired, matched control group. The primary end point was a composite of cardiovascular death, nonfatal acute myocardial infarction, myocardial revascularization, occurrence of stroke and/or transient ischemic attacks, and hospitalization for heart failure occurring during a mean of 3.1 years of follow-up. The secondary end points were each individual component of the primary end point, total mortality, noncardiovascular death, and incidence of pacemaker implant. Each group included 221 patients who were homogeneous in terms of age, gender, and main cardiovascular risk factors. Major adverse cardiovascular events occurred in 24 patients with dementia (2.1 per 100 patient-years) compared with 56 in control group (5.0 per 100 patient-years), p = 0.036. Even if not significant, the difference was mainly driven by myocardial revascularization (3.2% vs 6.8%) and hospitalization for heart failure (4.5% vs 14.5%). As expected, noncardiovascular mortality was significantly higher in the treatment group (13.6% vs 2.7% p = 0.006). No significant difference between the groups was observed in terms of other secondary outcomes. In conclusion, in patients with dementia, the use of AChE-I may be protective for cardiovascular outcomes, especially in reducing heart failure hospitalization and myocardial revascularization.
MeSH term(s)	Humans ; Cholinesterase Inhibitors/therapeutic use ; Acetylcholinesterase ; Retrospective Studies ; Heart Failure/drug therapy ; Heart Failure/epidemiology ; Dementia/epidemiology
Chemical Substances	Cholinesterase Inhibitors ; Acetylcholinesterase (EC 3.1.1.7)
Language	English
Publishing date	2023-06-14
Publishing country	United States
Document type	Observational Study ; Journal Article
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2023.05.041
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Article ; Online: Structures of LRP2 reveal a molecular machine for endocytosis.

Beenken, Andrew / Cerutti, Gabriele / Brasch, Julia / Guo, Yicheng / Sheng, Zizhang / Erdjument-Bromage, Hediye / Aziz, Zainab / Robbins-Juarez, Shelief Y / Chavez, Estefania Y / Ahlsen, Goran / Katsamba, Phinikoula S / Neubert, Thomas A / Fitzpatrick, Anthony W P / Barasch, Jonathan / Shapiro, Lawrence

Cell

2023 Volume 186, Issue 4, Page(s) 821–836.e13

Abstract: The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the ... ...

Abstract	The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the kidney and brain. Here, we report high-resolution cryoelectron microscopy structures of LRP2 isolated from mouse kidney, at extracellular and endosomal pH. The structures reveal LRP2 to be a molecular machine that adopts a conformation for ligand binding at the cell surface and for ligand shedding in the endosome. LRP2 forms a homodimer, the conformational transformation of which is governed by pH-sensitive sites at both homodimer and intra-protomer interfaces. A subset of LRP2 deleterious missense variants in humans appears to impair homodimer assembly. These observations lay the foundation for further understanding the function and mechanism of LDL receptors and implicate homodimerization as a conserved feature of the LRP receptor subfamily.
MeSH term(s)	Animals ; Humans ; Mice ; Cryoelectron Microscopy ; Endocytosis ; Kidney/metabolism ; Ligands ; Low Density Lipoprotein Receptor-Related Protein-2/genetics ; Low Density Lipoprotein Receptor-Related Protein-2/metabolism
Chemical Substances	Ligands ; Low Density Lipoprotein Receptor-Related Protein-2 ; LRP2 protein, human ; Lrp2 protein, mouse
Language	English
Publishing date	2023-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.01.016
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Article ; Online: Cryo-EM structure of the SARS-CoV-2 Omicron spike.

Cerutti, Gabriele / Guo, Yicheng / Liu, Lihong / Liu, Liyuan / Zhang, Zhening / Luo, Yang / Huang, Yiming / Wang, Harris H / Ho, David D / Sheng, Zizhang / Shapiro, Lawrence

Cell reports

2022 Volume 38, Issue 9, Page(s) 110428

Abstract: The recently reported B.1.1.529 Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 34 mutations in the spike protein relative to the Wuhan strain, including 15 mutations in the receptor-binding domain (RBD). ... ...

Abstract	The recently reported B.1.1.529 Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 34 mutations in the spike protein relative to the Wuhan strain, including 15 mutations in the receptor-binding domain (RBD). Functional studies have shown Omicron to substantially escape the activity of many SARS-CoV-2-neutralizing antibodies. Here, we report a 3.1 Å-resolution cryoelectron microscopy (cryo-EM) structure of the Omicron spike protein ectodomain. The structure depicts a spike that is exclusively in the 1-RBD-up conformation with high mobility of RBD. Many mutations cause steric clashes and/or altered interactions at antibody-binding surfaces, whereas others mediate changes of the spike structure in local regions to interfere with antibody recognition. Overall, the structure of the Omicron spike reveals how mutations alter its conformation and explains its extraordinary ability to evade neutralizing antibodies.
MeSH term(s)	Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/metabolism ; Cryoelectron Microscopy ; Humans ; Immune Evasion/genetics ; Models, Molecular ; Mutation ; Neutralization Tests ; Protein Binding ; Protein Structure, Quaternary ; SARS-CoV-2/chemistry ; SARS-CoV-2/genetics ; SARS-CoV-2/ultrastructure ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics
Chemical Substances	Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Journal Article ; 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.2022.110428
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Article: Comparison of marginal fit of Lava CAD/CAM crown-copings with two finish lines.

Re, Dino / Cerutti, Francesca / Augusti, Gabriele / Cerutti, Antonio / Augusti, Davide

The international journal of esthetic dentistry

2014 Volume 9, Issue 3, Page(s) 426–435

Abstract: Purpose: Marginal fit is valued as one of the most important criteria for the clinical quality and success of all-ceramic crowns. The aim of this in vitro study was to investigate the marginal fit of Lava Zirconia crown-copings on chamfer and shoulder ... ...

Abstract	Purpose: Marginal fit is valued as one of the most important criteria for the clinical quality and success of all-ceramic crowns. The aim of this in vitro study was to investigate the marginal fit of Lava Zirconia crown-copings on chamfer and shoulder preparations. Methods: Two acrylic model teeth were selected to simulate the clinical preparations: one molar was prepared with a chamfer finish line (C) and one premolar was prepared with a rounded shoulder finish line (RS). Each resin model was duplicated 10 times using silicon-based impression material and poured in type IV dental stone for the fabrication of working dies. A total of 20 copings were divided into two groups (n = 10 for each finish line). Fifty measuring locations were chosen randomly along the margin on the dies and the gap width - vertical marginal discrepancy - was measured under a light microscope with a magnification of x100. Measurements were made without cementation. The mean marginal gap widths and standard deviations were calculated and a one-way analysis of variance (ANOVA) was performed for different types of preparations in order to detect differences (α = 0.05). Results: The mean marginal gap was 30 ± 3 μm for the C group and 28 ± 4 μm for the RS group. The one-way ANOVA showed no statistical significant difference between the two groups (P = 0.23). Conclusions: Within the limitations of this study, the marginal discrepancies were all within the clinical acceptable standard set at 120 μm. Chamfer and shoulder preparations did not show differences regarding the gap dimension. Clinical significance: Bur design is an easily selected parameter before natural tooth preparation. Both tested finish lines are able to help clinicians in obtaining acceptable marginal fit values for the investigated zirconia copings.
MeSH term(s)	Bicuspid ; Ceramics/chemistry ; Computer-Aided Design ; Crowns ; Dental Marginal Adaptation ; Dental Materials/chemistry ; Dental Prosthesis Design ; Humans ; Molar ; Surface Properties ; Tooth Preparation, Prosthodontic/methods ; Zirconium/chemistry
Chemical Substances	Dental Materials ; Zirconium (C6V6S92N3C) ; zirconium oxide (S38N85C5G0)
Language	English
Publishing date	2014-08-12
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ISSN	2198-591X
ISSN	2198-591X
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Article: Modelling, assessing, and ranking public procurement options for a climate-friendly catering service

Cerutti, AlessandroK / Fulvio Ardente / Simone Contu / Dario Donno / Gabriele L. Beccaro

international journal of life cycle assessment. 2018 Jan., v. 23, no. 1

2018

Abstract: PURPOSE: Several scientific papers and technical reports have discussed the role of green public procurement in the food sector. Different strategies for the restoration sector have been identified. However, there is not yet a common understanding of ... ...

Abstract	PURPOSE: Several scientific papers and technical reports have discussed the role of green public procurement in the food sector. Different strategies for the restoration sector have been identified. However, there is not yet a common understanding of which policies could be the most efficient in reducing the global warming potential of the public restoration service. This paper assesses a set of procurement policies, ranking them according to their potential to reduce the greenhouse gas emissions of public catering. METHODS: Eleven relevant green public procurement policies were identified from the literature. These are discussed in the context of a case study of the school catering service in the city of Turin (Italy). Initially, a life cycle approach is applied to a baseline scenario of the collective restoration system of the city, to quantify the quantity of greenhouse gases produced by the entire catering service (including all stages from the production of food to the management of waste from kitchens and canteens). Afterwards, the 11 policies were applied to the baseline scenario so that the potential improvement achieved by each policy could be quantified. RESULTS AND DISCUSSION: The baseline scenario resulted in 1.67 kgCO₂eq per average meal. The production of food dominates the global warming potential of the full service, being responsible for about 78% of the greenhouse gas emissions. Among the selected policies, a change in diet was the most effective (leading to a 32% reduction of the CO₂eq emissions), followed by the adoption of improved food production practices (11% reduction) and the purchasing of certified green electricity (6% reduction). CONCLUSIONS: The proposed method allows the assessment of procurement policies in the catering service by applying a simplified life cycle approach that considers all the stages of the process. Public authorities and other stakeholders could benefit from basing their decisions upon scientific evidence and avoiding the prioritisation of policies based on personal opinions or weak evidence. Uncertainties and areas for improvement in the method have been also identified for future investigation.
Keywords	attitudes and opinions ; case studies ; catering ; diet ; food production ; global warming potential ; greenhouse gas emissions ; greenhouse gases ; issues and policy ; kitchens ; models ; prioritization ; purchasing ; renewable energy sources ; stakeholders ; uncertainty ; wastes ; Italy
Language	English
Dates of publication	2018-01
Size	p. 95-115.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	2009386-X
ISSN	1614-7502 ; 0948-3349
ISSN (online)	1614-7502
ISSN	0948-3349
DOI	10.1007/s11367-017-1306-y
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Article ; Online: Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization.

Glögl, Matthias / Friedrich, Nikolas / Cerutti, Gabriele / Lemmin, Thomas / Kwon, Young D / Gorman, Jason / Maliqi, Liridona / Mittl, Peer R E / Hesselman, Maria C / Schmidt, Daniel / Weber, Jacqueline / Foulkes, Caio / Dingens, Adam S / Bylund, Tatsiana / Olia, Adam S / Verardi, Raffaello / Reinberg, Thomas / Baumann, Nicolas S / Rusert, Peter /

Dreier, Birgit / Shapiro, Lawrence / Kwong, Peter D / Plückthun, Andreas / Trkola, Alexandra

Nature structural & molecular biology

2023 Volume 30, Issue 9, Page(s) 1323–1336

Abstract: The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows efficient neutralization via V3 only by rare, broadly ... ...

Abstract	The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows efficient neutralization via V3 only by rare, broadly neutralizing glycan-dependent antibodies targeting the closed prefusion trimer but not by abundant antibodies that access the V3 crown on open trimers after CD4 attachment. Here, we report on a distinct category of V3-specific inhibitors based on designed ankyrin repeat protein (DARPin) technology that reinstitute the CD4-bound state as a key neutralization target with up to >90% breadth. Broadly neutralizing DARPins (bnDs) bound V3 solely on open envelope and recognized a four-turn amphipathic α-helix in the carboxy-terminal half of V3 (amino acids 314-324), which we termed 'αV3C'. The bnD contact surface on αV3C was as conserved as the CD4 binding site. Molecular dynamics and escape mutation analyses underscored the functional relevance of αV3C, highlighting the potential of αV3C-based inhibitors and, more generally, of postattachment inhibition of HIV-1.
MeSH term(s)	Humans ; HIV-1 ; Amino Acids ; Antibodies ; Binding Sites ; Molecular Conformation
Chemical Substances	Amino Acids ; Antibodies
Language	English
Publishing date	2023-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/s41594-023-01062-z
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Article: Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization.

Wang, Pengfei / Casner, Ryan G / Nair, Manoj S / Wang, Maple / Yu, Jian / Cerutti, Gabriele / Liu, Lihong / Kwong, Peter D / Huang, Yaoxing / Shapiro, Lawrence / Ho, David D

bioRxiv : the preprint server for biology

2021

Abstract: The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been described recently. We now report that another emergent variant from Brazil, P.1, is not only refractory to multiple neutralizing monoclonal antibodies, ...

Abstract	The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been described recently. We now report that another emergent variant from Brazil, P.1, is not only refractory to multiple neutralizing monoclonal antibodies, but also more resistant to neutralization by convalescent plasma (3.4 fold) and vaccinee sera (3.8-4.8 fold). The cryo-electron microscopy structure of a soluble prefusion-stabilized spike reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the "up" position, with the functional impact of mutations appearing to arise from local changes instead of global conformational alterations. The P.1 variant threatens current antibody therapies but less so the protective efficacy of our vaccines.
Language	English
Publishing date	2021-04-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.01.433466
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Article: Biomolecules and Natural Medicine Preparations: Analysis of New Sources of Bioactive Compounds from Ribes and Rubus spp. Buds.

Donno, Dario / Mellano, Maria Gabriella / Cerutti, Alessandro Kim / Beccaro, Gabriele Loris

Pharmaceuticals (Basel, Switzerland)

2016 Volume 9, Issue 1

Abstract: It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring ... ...

Abstract	It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring groups of phytochemicals. Some endemic species may be used for the production of herbal preparations containing phytochemicals with significant bioactivity, as antioxidant activity and anti-inflammatory capacities, and health benefits. Blackberry sprouts and blackcurrant buds are known to contain appreciable levels of bioactive compounds, including flavonols, phenolic acids, monoterpenes, vitamin C, and catechins, with several clinical effects. The aim of this research was to perform an analytical study of blackcurrant and blackberry bud-preparations, in order to identify and quantify the main biomarkers, obtaining a specific phytochemical fingerprint to evaluate the single botanical class contribution to total phytocomplex and relative bioactivity, using a High Performance Liquid Chromatograph-Diode Array Detector; the same analyses were performed both on the University laboratory and commercial preparations. Different chromatographic methods were used to determine concentrations of biomolecules in the preparations, allowing for quantification of statistically significant differences in their bioactive compound content both in the case of Ribes nigrum and Rubus cultivated varieties at different harvest stages. In blackcurrant bud-extracts the most important class was organic acids (50.98%) followed by monoterpenes (14.05%), while in blackberry preparations the main bioactive classes were catechins (50.06%) and organic acids (27.34%). Chemical, pharmaceutical and agronomic-environmental knowledge could be important for obtaining label certifications for the valorization of specific genotypes, with high clinical and pharmaceutical value: this study allowed to develop an effective tool for the natural preparation quality control and bioactivity evaluation through the chemical fingerprinting of bud preparations.
Language	English
Publishing date	2016-02-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph9010007
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Article ; Online: Probing the Role of Murine Neuroglobin CDloop-D-Helix Unit in CO Ligand Binding and Structural Dynamics.

Exertier, Cécile / Sebastiani, Federico / Freda, Ida / Gugole, Elena / Cerutti, Gabriele / Parisi, Giacomo / Montemiglio, Linda Celeste / Becucci, Maurizio / Viappiani, Cristiano / Bruno, Stefano / Savino, Carmelinda / Zamparelli, Carlotta / Anselmi, Massimiliano / Abbruzzetti, Stefania / Smulevich, Giulietta / Vallone, Beatrice

ACS chemical biology

2022 Volume 17, Issue 8, Page(s) 2099–2108

Abstract: We produced a neuroglobin variant, namely, Ngb CDless, with the excised CDloop- and D-helix, directly joining the C- and E-helices. The CDless variant retained bis-His hexacoordination, and we investigated the role of the CDloop-D-helix unit in ... ...

Abstract	We produced a neuroglobin variant, namely, Ngb CDless, with the excised CDloop- and D-helix, directly joining the C- and E-helices. The CDless variant retained bis-His hexacoordination, and we investigated the role of the CDloop-D-helix unit in controlling the CO binding and structural dynamics by an integrative approach based on X-ray crystallography, rapid mixing, laser flash photolysis, resonance Raman spectroscopy, and molecular dynamics simulations. Rapid mixing and laser flash photolysis showed that ligand affinity was unchanged with respect to the wild-type protein, albeit with increased on and off constants for rate-limiting heme iron hexacoordination by the distal His64. Accordingly, resonance Raman spectroscopy highlighted a more open distal pocket in the CO complex that, in agreement with MD simulations, likely involves His64 swinging inward and outward of the distal heme pocket. Ngb CDless displays a more rigid overall structure with respect to the wild type, abolishing the structural dynamics of the CDloop-D-helix hypothesized to mediate its signaling role, and it retains ligand binding control by distal His64. In conclusion, this mutant may represent a tool to investigate the involvement of CDloop-D-helix in neuroprotective signaling in a cellular or animal model.
MeSH term(s)	Animals ; Heme/chemistry ; Ligands ; Mice ; Neuroglobin/chemistry ; Neuroglobin/metabolism
Chemical Substances	Ligands ; Neuroglobin ; Ngb protein, mouse ; Heme (42VZT0U6YR)
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.2c00172
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