| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
- 2023
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 8:81, s. eade0958-
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Tidskriftsartikel (refereegranskat)abstract
- Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2′ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
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| 7. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
- 2023
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 8:81, s. eade0958-
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Tidskriftsartikel (refereegranskat)abstract
- Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2′ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
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| 8. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2
- 2022
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the fourgenera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2’ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive withOrthocoronavirinae, including SARS-CoV-2 variants.Broadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery.
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| 10. |
- Farina, R., et al.
(författare)
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Change in the Gingival Margin Profile After the Single Flap Approach in Periodontal Intraosseous Defects
- 2015
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Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 86:9, s. 1038-1046
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study is to evaluate the association of patient-related and site-specific factors, as well as the adopted treatment modality, with the change in buccal (bREC) and interdental (iREC) gingival recession observed at 6 months after treatment of periodontal intraosseous defects with the single flap approach (SFA). Methods: Sixty-six patients contributing 74 intraosseous defects accessed with a buccal SFA and treated with different modalities were selected retrospectively. A two-level (patient and site) model was constructed, with the 6-month changes in bREC and iREC as the dependent variables. Results: 1) Significant 6-month increases in bREC (-0.6 +/- 0.7 mm) and iREC (-0.9 +/- -1.1 mm) were observed. 2) bREC change was significantly predicted by presurgery interproximal probing depth (PD) and depth of osseous dehiscence at the buccal aspect. 3) iREC change was significantly predicted by presurgery interproximal PD and the treatment modality, with defects treated with SFA in combination with a graft material and a bioactive agent being less prone to iREC increase compared to defects treated with SFA alone. Conclusions: After buccal SFA, greater post-surgery increase in bREC must be expected for deep intraosseous defects associated with a buccal dehiscence. The combination of a graft material and a bioactive agent in adjunct to the SFA may limit the postoperative increase in iREC.
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| 13. |
- Simonelli, A., et al.
(författare)
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Prognostic value of a composite outcome measure for periodontal stability following periodontal regenerative treatment: A retrospective analysis at 4 years
- 2023
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Ingår i: Journal of Periodontology. - 0022-3492. ; 94:9, s. 1090-1099
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecently, a composite outcome measure (COM) was proposed to describe the short-term results of periodontal regenerative treatment. The present retrospective study aimed at evaluating the prognostic value of COM on clinical attachment level (CAL) change over a 4-year period of supportive periodontal care (SPC). MethodsSeventy-four intraosseous defects in 59 patients were evaluated at 6 months and 4 years following regenerative treatment. Based on 6-month CAL change and probing depth (PD), defects were classified as: COM1 (CAL gain & GE;3 mm, PD & LE;4 mm); COM2 (CAL gain <3 mm, PD & LE;4 mm); COM3 (CAL gain & GE;3 mm, PD >4 mm); or COM4 (CAL gain <3 mm, PD >4 mm). COM groups were compared for "stability" (i.e., CAL gain, no change in CAL or CAL loss <1 mm) at 4 years. Also, groups were compared for mean change in PD and CAL, need for surgical retreatment, and tooth survival. ResultsAt 4 years, the proportion of stable defects in COM1, COM2, COM3, and COM4 group was 69.2%, 75%, 50%, and 28.6%, respectively, with a substantially higher probability for a defect to show stability for COM1, COM2, and COM3 compared with COM4 (odds ratio 4.6, 9.1, and 2.4, respectively). Although higher prevalence of surgical reinterventions and lower tooth survival were observed in COM4, no significant differences were detected among COM groups. ConclusionsCOM may be of value in predicting CAL change at sites undergoing SPC following periodontal regenerative surgery. Studies on larger cohorts, however, are needed to substantiate the present findings.
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| 14. |
- Simonelli, L., et al.
(författare)
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The CLEAR X-ray emission spectrometer available at the CLAESS beamline of ALBA synchrotron
- 2023
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 30, s. 235-241
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Tidskriftsartikel (refereegranskat)abstract
- The CLEAR X-ray emission spectrometer installed at the CLAESS beamline of the ALBA synchrotron is described. It is an energy-dispersive spectrometer based on Rowland circle geometry with 1 m-diameter circle. The energy dispersion is achieved by the combination of a diced analyzer crystal and a unidimensional detector. A single unconventional dynamically bent analyzer crystal (Si 111) permits a wide energy range to be covered, just by exploiting its different reflections (333, 444, 555, 777, 888): 6-22 keV, with a spectrometer efficiency that decreases above 11 keV because of the Si detector thickness (Mythen, 350 μm), while the relative scattering intensities for the Si 333, 444, 555, 777 and 888 reflections correspond to 36, 40, 21, 13 and 15, respectively. The provided energy resolution is typically below 1-2 eV and depends on the beam size, working Bragg angle and reflection exploited. In most cases the energy dispersion ranges from 10 to 20 eV and can be enlarged by working in the out-of-Rowland geometry up to 40 eV. The spectrometer works in full backscattering geometry with the beam passing through the two halves of the analyzer. The vacuum beam path and the particular geometry allow a typical average noise of only 0.5 counts per second per pixel. The spectrometer is mainly used for measuring emission lines and high-resolution absorption spectra, with a typical scanning time for highly concentrated systems of around half an hour, including several repeats. The intrinsic energy dispersion allows systematic collection of resonant X-ray emission maps by measuring high-resolution absorption spectra. Moreover, it allows spectra to be measured on a single-shot basis. Resonant inelastic X-ray scattering experiments to probe electronic excitations are feasible, although the spectrometer is not optimized for this purpose due to the limited energy resolution and scattering geometry provided. In that case, to minimize the quasi-elastic line, the spectrometer is able to rotate along the beam path. Advantages and disadvantages with respect to other existing spectrometers are highlighted.
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| 16. |
- Colombo, GI, et al.
(författare)
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The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study
- 2021
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMTmax; cIMTmean–max of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMTmax and cIMTmean–max, but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMTmax or cIMTmean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMTmax and cIMTmean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMTmax and cIMTmean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMTmax. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMTmax. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMTmax. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.
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| 20. |
- Zheng, W., et al.
(författare)
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Extracellular albumin covalently sequesters selenocompounds and determines cytotoxicity
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:19
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Tidskriftsartikel (refereegranskat)abstract
- Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of action is not fully understood. Several SeCs have been reported to have albumin-binding ability, which is an important factor in determining the treatment efficacy of drugs. In the present investigation, we hypothesized that extracellular albumin might orchestrate SeCs efficacy. Four SeCs representing distinct categories were selected to investigate their cytotoxicity, cellular uptake, and species transformation. Concomitant treatment of albumin greatly decreased cytotoxicity and cellular uptake of SeCs. Using both X-ray absorption spectroscopy and hyphenated mass spectrometry, we confirmed the formation of macromolecular conjugates between SeCs and albumin. Although the conjugate was still internalized, possibly via albumin scavenger receptors expressed on the cell surface, the uptake was strongly inhibited by excess albumin. In summary, the present investigation established the importance of extracellular albumin binding in determining SeCs cytotoxicity. Due to the fact that albumin content is higher in humans and animals than in cell cultures, and varies among many patient categories, our results are believed to have high translational impact and clinical implications.
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