Heterologous adenovirus-vector/messenger RNA regimen is associated with improved severe acute respiratory syndrome coronavirus 2 humoral response in liver transplant recipients

Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)-based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti-spike immunoglobulin G (IgG). In this prospective cohort study, SARS-CoV-2 anti-spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21–90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26-rAd5 (Sputnik V), inactivated BBIBP-CorV (Sinopharm), or the heterologous combination rAd26/mRNA-1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti-spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA-1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03–0.3; p < 0.001) and with increased BMI (OR, 0.4; 95% CI, 0.2–0.7; p = 0.005); and it was significantly higher in those immunized with rAd26/mRNA-1273 (OR, 13.1; 95% CI, 2.3–72.9; p = 0.003). In LTRs anti-spike IgG concentrations showed a very good correlation with NA titers (R2 = 0.949; 95% CI, 0.919–0.967; p < 0.001). No serious adverse events were reported in either group. Conclusion: In LTRs, rAd26/mRNA-1273 was independently associated with higher antibody response. Future studies are necessary to evaluate whether combining different vaccine platforms and MMF reduction may lead to a better booster response.Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Ducasa, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Benencio, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Cairo, Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Barbero, Manuel. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Etcheves, Patricia. No especifíca;Fil: Alter, Adriana. Hospital Italiano; ArgentinaFil: Scarton, Giampaolo. No especifíca;Fil: Abraldes, Juan G.. University of Alberta; CanadáFil: Biglione, Mirna Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Mauro, Ezequiel. Hospital Italiano; Argentin

Caffeine Prevents Transcription Inhibition and P-TEFb/7SK Dissociation Following UV-Induced DNA Damage

Background: The mechanisms by which DNA damage triggers suppression of transcription of a large number of genes are poorly understood. DNA damage rapidly induces a release of the positive transcription elongation factor b (P-TEFb) from the large inactive multisubunit 7SK snRNP complex. P-TEFb is required for transcription of most class II genes through stimulation of RNA polymerase II elongation and cotranscriptional pre-mRNA processing. Methodology/Principal Findings: We show here that caffeine prevents UV-induced dissociation of P-TEFb as well as transcription inhibition. The caffeine-effect does not involve PI3-kinase-related protein kinases, because inhibition of phosphatidylinositol 3-kinase family members (ATM, ATR and DNA-PK) neither prevents P-TEFb dissociation nor transcription inhibition. Finally, caffeine prevention of transcription inhibition is independent from DNA damage. Conclusion/Significance: Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibitio

Limited redundancy in genes regulated by Cyclin T2 and Cyclin T1

<p>Abstract</p> <p>Background</p> <p>The elongation phase, like other steps of transcription by RNA Polymerase II, is subject to regulation. The positive transcription elongation factor b (P-TEFb) complex allows for the transition of mRNA synthesis to the productive elongation phase. P-TEFb contains Cdk9 (Cyclin-dependent kinase 9) as its catalytic subunit and is regulated by its Cyclin partners, Cyclin T1 and Cyclin T2. The HIV-1 Tat transactivator protein enhances viral gene expression by exclusively recruiting the Cdk9-Cyclin T1 P-TEFb complex to a RNA element in nascent viral transcripts called TAR. The expression patterns of Cyclin T1 and Cyclin T2 in primary monocytes and CD4⁺T cells suggests that Cyclin T2 may be generally involved in expression of constitutively expressed genes in quiescent cells, while Cyclin T1 may be involved in expression of genes up-regulated during macrophage differentiation, T cell activation, and conditions of increased metabolic activity To investigate this issue, we wished to identify the sets of genes whose levels are regulated by either Cyclin T2 or Cyclin T1.</p> <p>Findings</p> <p>We used shRNA lentiviral vectors to stably deplete either Cyclin T2 or Cyclin T1 in HeLa cells. Total RNA extracted from these cells was subjected to cDNA microarray analysis. We found that 292 genes were down- regulated by depletion of Cyclin T2 and 631 genes were down-regulated by depletion of Cyclin T1 compared to cells transduced with a control lentivirus. Expression of 100 genes was commonly reduced in either knockdown. Additionally, 111 and 287 genes were up-regulated when either Cyclin T2 or Cyclin T1 was depleted, respectively, with 45 genes in common.</p> <p>Conclusions</p> <p>These results suggest that there is limited redundancy in genes regulated by Cyclin T1 or Cyclin T2.</p

The macroscopic yield behaviour of polymers

A yield criterion, not previously compared with the actual macroscopic behaviour of polymers, is herein compared with the pressure-modified octahedral shear stress criterion earlier suggested by others. This new relation, which is a version of the von Mises criterion, accommodates differences in tensile and compressive yield strengths and accounts for any dependence of yielding on the hydrostatic component of the applied stress state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44784/1/10853_2004_Article_BF00550671.pd

Fracture behaviour of unmodified and rubber-modified epoxies under hydrostatic pressure

The fracture toughness and uniaxial tensile yield strengths of unmodified and CTBN-rubber-modified epoxies were measured under hydrostatic pressure. The purpose of these experiments was to learn how suppressing cavitation in rubber particles affects the deformation mechanisms and the fracture toughness of rubber-modified epoxy. It was found that the cavitation of CTBN-rubber could be suppressed at a relatively low pressure (between 30 and 38 M Pa). With cavitation suppressed, the rubber particles are unable to induce massive shearyielding in the epoxy matrix, and the fracture toughness of the rubber-modified epoxy is no higher than that of the unmodified epoxy in the pressure range studied. Unmodified epoxy shows a brittle-to-ductile transition in fracture toughness test. The reason for this transition is the postponement of the cracking process by applied pressure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44734/1/10853_2005_Article_BF01154701.pd

Per la conservazione delle grandi coperture lignee del duomo di Vercelli

The great timber roof structures of the Cathedral of Vercelli offer an extraordinary path of knowledge, diagnosis and conservation, through a collaboration between the architects of the Cultural Heritage Office of the Diocese of Vercelli \u2013 responsible for the restoration process \u2013 and experts in the field of timber structures. The interest of the architectural complex is witnessed also by the contribution of renewed architects of Piedmont between the XVIth and XIXth centuries