The iso-Nazarov reaction

The construction of five-membered rings is essential in organic chemistry. In this context, pentannulation reactions that provide a straightforward access to cyclopentenones are of particular interest, as these structures are not only embedded in important molecules such as some prostaglandins, but also serve as versatile building blocks in organic synthesis. This review documents the acid-promoted cycloisomerization of conjugated dienals and linearly-conjugated dienones for the construction of cyclopentenones, a transformation that has been largely eclipsed by the well-known Nazarov reaction, i.e. the acid-promoted cycloisomerization of cross-conjugated ketones.Fil: Riveira, Martín Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Marsili, Lucía A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Mischne, Mirta Paulina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin

Crescimento de Araucaria angustifolia na reserva florestal Embrapa/Epagri, Caçador, SC.

Resumo

Relic wild grapevines in Extremadura (Spain)

Relic wild grapevine populations (Vitis vinifera L. subsp. sylvestris (C.C.Gmel.) Hegi), were surveyed in Extremadura region (Spain). Twenty-two populations were found along river bank forests in Badajoz and Cáceres provinces. The main ampelographical characteristics and phenology of vines and the incidence of parasites were evaluated. Supporting flora has been botanically characterized. Results confirmed the dioecious characteristic of this grapevine subspecies and showed that Colomerus vitis (Pagenstecher) (Acari, Eriophyiidae) mite and powdery and downy mildews are the main parasites affecting their populations

Chiral indolylarylsulfone non-nucleoside reverse transcriptase inhibitors as new potent and broad spectrum anti-HIV-1 agents

We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8–37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N–Y181C HIV-1 strains. Six racemic mixtures, 8, 23–25, 31, and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31, and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers. Compound 23 protected hippocampal neuronal cells from the excitotoxic insult, while efavirenz (EFV) did not contrast the neurotoxic effect of glutamate. The present results highlight the chiral IASs as new NNRTIs with improved resistance profile against the mutant HIV-1 strains and reduced neurotoxic effects

Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2

A Replication Study of the Association between Rheumatoid Arthritis and Deletion of the Late Cornified Envelope Genes LCE3B and LCE3C

OBJECTIVE: Two recent studies, in a Spanish and a Chinese population, point to an association between rheumatoid arthritis (RA) risk and the deletion of the Late Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor for psoriasis. We aimed to replicate these studies in a large Dutch cohort. METHODS: 1039 RA cases and 759 controls were genotyped for LCE3C_LCE3B-del. Association analysis was performed for the complete cohort and after stratification for the serologic markers anti-cyclic citrullinated peptide and rheumatoid factor. A meta-analysis was performed combining our data with the Spanish and Chinese datasets, resulting in an analysis including 2466 RA cases and 2438 controls. RESULTS: In the Dutch cohort we did not observe a significant association of LCE3C_LCE3B-del (p = 0.093) with RA risk. A stratified analysis for the serologic positive and negative group did not show an association between the genetic variant and disease risk, either. The meta-analysis, however, confirmed a significant association (p<0.0001, OR = 1.31, 95% confidence interval 1.16-1.47). CONCLUSION: Our meta-analysis confirms the association of the LCE3 deletion with RA, suggesting that LCE3C_LCE3B-del is a common risk factor for (auto)immune diseases

A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19

Background: current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. Methods: we conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. Results: the analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. Conclusions: postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)