Efecto del bioestimulante Enerplant® en la aclimatización ex vitro de plantas propagadas in vitro de caña de azúcar cv. C97-445

Las plantas in vitro de caña de azúcar (Saccharum spp.) son susceptibles a los cambios ambientales en la fase de aclimatización lo cual afecta su crecimiento y desarrollo. El presente trabajo tuvo como objetivo evaluar el efecto del bioestimulante Enerplant® en el la supervivencia y el crecimiento de plantas in vitro de caña de azúcar cv. C97-445  en la aclimatización ex vitro. Se evaluaron tres disoluciones (0.6, 0.8 y 1.0 ml l-1) de Enerplant® y se comparó con el bioestimulante VIUSID Agro® 0.8 ml l-1. Se realizaron dos aplicaciones diarias, los primeros tres días y posteriormente una vez por semana. Los experimentos se llevaron a cabo en época de seca. Las variables evaluadas fueron la supervivencia a los 15 días y las morfo-fisiológicas a los 55 días después del trasplante. Se comprobó que la aplicación de Enerplant® incrementa la supervivencia de las plantas in vitro de caña de azúcar y mejora su crecimiento. El tratamiento con 0.8 ml l-1 de este bioestimulante tuvo el mayor efecto en el crecimiento de las plantas in vitro en condiciones de aclimatización ex vitro.Las plantas in vitro de caña de azúcar (Saccharum spp.) son susceptibles a los cambios ambientales en la fase de aclimatización lo cual afecta su crecimiento y desarrollo. El presente trabajo tuvo como objetivo evaluar el efecto del bioestimulante Enerplant® en la supervivencia y el crecimiento de plantas in vitro de caña de azúcar cv. C97-445 en la aclimatización ex vitro. Se evaluaron tres disoluciones (0.6, 0.8 y 1.0 ml l-1) de Enerplant® y se comparó con el bioestimulante VIUSID-Agro® 0.8 ml l-1. Se realizaron dos aplicaciones diarias, los primeros tres días y posteriormente una vez por semana. Los experimentos se llevaron a cabo en época de seca. Las variables evaluadas fueron la supervivencia a los 15 días y las morfofisiológicas a los 55 días después del trasplante. Se comprobó que la aplicación de Enerplant® incrementa la supervivencia de las plantas in vitro de caña de azúcar y mejora su crecimiento. El tratamiento con 0.8 ml l-1 de este bioestimulante tuvo el mayor efecto en el crecimiento de las plantas in vitro en condiciones de aclimatización ex vitro

Effect of Enerplant® biostimulant on ex vitro acclimatization of in vitro propagated sugarcane plants cv. C97-4450

In vitro sugarcane plants (Saccharum spp.) are susceptible to environmental changes in theacclimatization phase, which affects their growth and development. The objective of thiswork was to evaluate the effect of the biostimulant Enerplant® on the survival and growth ofin vitro plants of sugarcane cv. C97-445 inex vitro acclimatization. Three solutions (0.6, 0.8and 1.0 ml l-1) of Enerplant® were evaluated and compared with the biostimulant VIUSID Agro®0.8 ml l-1. Two daily applications were made, the first three days after transplant and thenonce a week. The experiments were carried out in the dry season. The variables evaluatedwere survival at 15 days and morphophysiological at 55 days after transplantation. It wasverified that the application of Enerplant® increases the survival of sugarcanein vitroplantsand improves their growth. Treatment with 0.8 ml l-1 of this biostimulant had the greatest effect onin vitroplant growth underex vitro acclimatization conditions

Safety and efficacy of vanzacaftor–tezacaftor–deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials

Background Elexacaftor–tezacaftor–ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing. Methods We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor–tezacaftor–deutivacaftor in participants with cystic fibrosis who were aged 18 years or older. A phase 2 randomised, double-blind, active-controlled study (VX18-561-101; April 17, 2019, to Aug 20, 2020) was carried out to compare deutivacaftor monotherapy with ivacaftor monotherapy in participants with CFTR gating mutations, following a 4-week ivacaftor monotherapy run-in period. Participants were randomly assigned to receive either ivacaftor 150 mg every 12 h, deutivacaftor 25 mg once daily, deutivacaftor 50 mg once daily, deutivacaftor 150 mg once daily, or deutivacaftor 250 mg once daily in a 1:1:2:2:2 ratio. The primary endpoint was absolute change in ppFEV1 from baseline at week 12. A phase 2 randomised, double-blind, controlled, proof-of-concept study of vanzacaftor–tezacaftor–deutivacaftor (VX18-121-101; April 30, 2019, to Dec 10, 2019) was conducted in participants with cystic fibrosis and heterozygous for F508del and a minimal function mutation (F/MF genotypes) or homozygous for F508del (F/F genotype). Participants with F/MF genotypes were randomly assigned 1:2:2:1 to receive either 5 mg, 10 mg, or 20 mg of vanzacaftor in combination with tezacaftor–deutivacaftor or a triple placebo for 4 weeks, and participants with the F/F genotype were randomly assigned 2:1 to receive either vanzacaftor (20 mg)–tezacaftor–deutivacaftor or tezacaftor–ivacaftor active control for 4 weeks, following a 4-week tezacaftor–ivacaftor run-in period. Primary endpoints for part 1 and part 2 were safety and tolerability and absolute change in ppFEV1 from baseline to day 29. Secondary efficacy endpoints were absolute change from baseline at day 29 in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. These clinical trials are registered with ClinicalTrials.gov, NCT03911713 and NCT03912233, and are complete. Findings In study VX18-561-101, participants treated with deutivacaftor 150 mg once daily (n=23) or deutivacaftor 250 mg once daily (n=24) had mean absolute changes in ppFEV1 of 3·1 percentage points (95% CI –0·8 to 7·0) and 2·7 percentage points (–1·0 to 6·5) from baseline at week 12, respectively, versus –0·8 percentage points (–6·2 to 4·7) with ivacaftor 150 mg every 12 h (n=11); the deutivacaftor safety profile was consistent with the established safety profile of ivacaftor 150 mg every 12 h. In study VX18-121-101, participants with F/MF genotypes treated with vanzacaftor (5 mg)–tezacaftor–deutivacaftor (n=9), vanzacaftor (10 mg)–tezacaftor–deutivacaftor (n=19), vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=20), and placebo (n=10) had mean changes relative to baseline at day 29 in ppFEV1 of 4·6 percentage points (−1·3 to 10·6), 14·2 percentage points (10·0 to 18·4), 9·8 percentage points (5·7 to 13·8), and 1·9 percentage points (−4·1 to 8·0), respectively, in sweat chloride concentration of −42·8 mmol/L (–51·7 to –34·0), −45·8 mmol/L (95% CI –51·9 to –39·7), −49·5 mmol/L (–55·9 to –43·1), and 2·3 mmol/L (−7·0 to 11·6), respectively, and in CFQ-R respiratory domain score of 17·6 points (3·5 to 31·6), 21·2 points (11·9 to 30·6), 29·8 points (21·0 to 38·7), and 3·3 points (−10·1 to 16·6), respectively. Participants with the F/F genotype treated with vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=18) and tezacaftor–ivacaftor (n=10) had mean changes relative to baseline (taking tezacaftor–ivacaftor) at day 29 in ppFEV1 of 15·9 percentage points (11·3 to 20·6) and −0·1 percentage points (−6·4 to 6·1), respectively, in sweat chloride concentration of −45·5 mmol/L (−49·7 to −41·3) and −2·6 mmol/L (−8·2 to 3·1), respectively, and in CFQ-R respiratory domain score of 19·4 points (95% CI 10·5 to 28·3) and −5·0 points (−16·9 to 7·0), respectively. The most common adverse events overall were cough, increased sputum, and headache. One participant in the vanzacaftor–tezacaftor–deutivacaftor group had a serious adverse event of infective pulmonary exacerbation and another participant had a serious rash event that led to treatment discontinuation. For most participants, adverse events were mild or moderate in severity. Interpretation Once-daily dosing with vanzacaftor–tezacaftor–deutivacaftor was safe and well tolerated and improved lung function, respiratory symptoms, and CFTR function. These results support the continued investigation of vanzacaftor–tezacaftor–deutivacaftor in phase 3 clinical trials compared with elexacaftor–tezacaftor–ivacaftor. Funding Vertex Pharmaceuticals

Differential Effects of Tra2ß Isoforms on HIV-1 RNA Processing and Expression

<div><p>Balanced processing of HIV-1 RNA is critical to virus replication and is regulated by host factors. In this report, we demonstrate that overexpression of either Tra2α or Tra2β results in a marked reduction in HIV-1 Gag/ Env expression, an effect associated with changes in HIV-1 RNA accumulation, altered viral splice site usage, and a block to export of HIV-1 genomic RNA. A natural isoform of Tra2β (Tra2ß3), lacking the N-terminal RS domain, also suppressed HIV-1 expression but had different effects on viral RNA processing. The functional differences between the Tra2β isoforms were also observed in the context of another RNA substrate indicating that these factors have distinct functions within the cell. Finally, we demonstrate that Tra2ß depletion results in a selective reduction in HIV-1 Env expression as well as an increase in multiply spliced viral RNA. Together, the findings indicate that Tra2α/β can play important roles in regulating HIV-1 RNA metabolism and expression.</p></div