There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are ...still not completely understood. Here, a review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARS-CoV-2 interaction with the host. Some accessory proteins such as ORF3b, ORF6, ORF7a and ORF8 have been shown to be important IFN-I antagonists inducing an impairment in the host immune response. In addition, ORF3a is involved in apoptosis whereas others like ORF9b and ORF9c interact with cellular organelles leading to suppression of the antiviral response in infected cells. However, possible roles of ORF7b and ORF10 are still awaiting to be described. Also, ORF3d has been reassigned. Relevant information on the knowns and the unknowns in these proteins is analyzed, which could be crucial for further understanding of SARS-CoV-2 pathogenesis and to design strategies counteracting their actions evading immune responses in COVID-19.
In recent years, honeybees (Apis mellifera) have been strangely disappearing from their hives, and strong colonies have suddenly become weak and died. The precise aetiology underlying the ...disappearance of the bees remains a mystery. However, during the same period, Nosema ceranae, a microsporidium of the Asian bee Apis cerana, seems to have colonized A. mellifera, and it's now frequently detected all over the world in both healthy and weak honeybee colonies. For first time, we show that natural N. ceranae infection can cause the sudden collapse of bee colonies, establishing a direct correlation between N. ceranae infection and the death of honeybee colonies under field conditions. Signs of colony weakness were not evident until the queen could no longer replace the loss of the infected bees. The long asymptomatic incubation period can explain the absence of evident symptoms prior to colony collapse. Furthermore, our results demonstrate that healthy colonies near to an infected one can also become infected, and that N. ceranae infection can be controlled with a specific antibiotic, fumagillin. Moreover, the administration of 120 mg of fumagillin has proven to eliminate the infection, but it cannot avoid reinfection after 6 months. We provide Koch's postulates between N. ceranae infection and a syndrome with a long incubation period involving continuous death of adult bees, non-stop brood rearing by the bees and colony loss in winter or early spring despite the presence of sufficient remaining pollen and honey.
The present study investigated whether Spanish monolinguals and English learners of Spanish use grammatical gender information in articles and nouns to facilitate the processing of upcoming ...adjectives. Specifically, this study examined the role of noun transparency, the number of gender cues, and L2 proficiency. The results of an eye-tracking task revealed that Spanish monolinguals predicted the gender of upcoming adjectives much sooner than L2 learners. L2 learners used grammatical gender predictively, but their predictions were delayed compared to monolinguals. Advanced L2 learners predicted upcoming adjectives faster than intermediate learners. Notably, transparent nouns and a higher number of gender cues increased target fixations in all groups. Target fixations of advanced learners increased especially with transparent nouns, and target fixations of intermediate learners were higher with more gender cues present. The results showed that L2 learners can integrate L2 morphosyntactic information during rapid speech processing, and that transparently marked nouns and more gender cues aid gender processing.
In oncology, establishing the value of new cancer treatments is challenging. A clear definition of the different perspectives regarding the drivers of innovation in oncology is required to enable new ...cancer treatments to be properly rewarded for the value they create. The aim of this study was to analyze the views of oncologists, health care policy makers, patients, and the general population regarding the value of new cancer treatments.
An exploratory and qualitative study was conducted through structured interviews to assess participants' attitudes toward cost and outcomes of cancer drugs. First, the participants were asked to indicate the minimum survival benefit that a new treatment should have to be funded by the Spanish National Health System (NHS). Second, the participants were requested to state the highest cost that the NHS could afford for a medication that increases a patient's quality of life (QoL) by twofold with no changes in survival. The responses were used to calculate incremental cost-effectiveness ratios (ICERs).
The minimum improvement in patient survival means that justified inclusions into the NHS were 5.7, 8.2, 9.1, and 10.4 months, which implied different ICERs for oncologists (€106,000/quality-adjusted life year QALY), patients (€73,520/QALY), the general population (€66,074/QALY), and health care policy makers (€57,471/QALY), respectively. The costs stated in the QoL-enhancing scenario were €33,167, €30,200, €26,000, and €17,040, which resulted in ICERs of €82,917/QALY for patients, €75,500/QALY for the general population, €65,000/QALY for oncologists, and €42,600/QALY for health care policy makers, respectively.
All estimated ICER values were higher than the thresholds previously described in the literature. Oncologists most valued gains in survival, whereas patients assigned a higher monetary value to treatments that enhanced QoL. Health care policy makers were less likely to pay more for therapeutic improvements compared to the remaining participants.
Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary ...prevention of cardiovascular disease.
The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20–75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937.
From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 95% CI 27·9–28·3 in the Mediterranean diet group vs 37·7 37·5–37·9 in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541–0·957) to 0·753 (0·568–0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 95% CI 0·489–0·915, log-rank p=0·013), than in 175 women for whom no difference was found between groups.
In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention.
Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.
Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic ...taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer.
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•Synthesized taiwaniaquinoids display potent cytotoxicity against cancer cells.•C36 exhibits low toxicity in normal cells, suggesting therapeutic potential.•C36 acts by generating ROS, halting the cell cycle and inducing apoptosis.•In vivo studies confirm the safety and anticancer efficacy of C36.
Independent evolutionary lineages or species that lack phenotypic variation as an operative criterion for their delimitation are known as cryptic species. However, these have been delimited using ...other data sources and analysis. The aims of this study are: (1) to evaluate the divergence of the populations of the T. ionantha complex; and (2) to delimit the species using multilocus data, phylogenetic analysis and the coalescent model. Phylogenetic analyses, genetic diversity and population structure, and isolation by distance analysis were performed. A multispecies coalescent analysis to delimit the species was conducted. Phylogenetic analysis showed that T. ionantha is polyphyletic composed of eight evolutionary lineages. Haplotype distribution and genetic differentiation analysis detected strong population structure and high values of genetic differentiation among populations. The positive correlation between genetic differences with geographic distance indicate that the populations are evolving under the model of isolation by distance. The coalescent multispecies analysis performed with starBEAST supports the recognition of eight lineages as different species. Only three out of the eight species have morphological characters good enough to recognize them as different species, while five of them are cryptic species. Tillandsia scaposa and T. vanhyningii are corroborated as independent lineages, and T. ionantha var. stricta changed status to the species level.
Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and ...persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogen's ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infection.
Abstract
Agaves are major biotic resources in arid and semi-arid ecosystems. Despite their ecological, economical and cultural relevance, many aspects of the microbial communities associated with ...agaves are still unknown. Here, we investigated the bacterial communities associated with two Agave species by 16S rRNA- Denaturing gradient gel electrophoresis fingerprinting and sequencing. We also evaluated the effects of biotic and abiotic factors in the structure of the bacterial communities. In parallel, we isolated and characterized diazotrophic bacteria associated with agaves, as Agave soils are characterized by their low nitrogen content. Our results demonstrate that in Agave, the structure of prokaryotic assemblages was mostly influenced by the community group, where the soil, episphere, and endosphere were clearly distinct. Proteobacteria (γ and α), Actinobacteria, and Acidobacteria were the dominant phyla. Bacterial communities in the episphere of agaves were mainly influenced by the host species, whereas in the endosphere were affected by the season. Fifteen bacterial taxa were common and abundant in the endosphere of both Agave species during the dry season. Notably, some of the confirmed diazotrophic strains belonged to this group, suggesting a possible beneficial role in planta.
The structure of bacterial communities associated with Agave species is distinct among soil, episphere and endosphere, where diazotrophic bacteria may facilitate adaption of these crassulacean acid metabolism-plants to low-nutrient environments.
The structure of bacterial communities associated with Agave species is distinct among soil, episphere and endosphere, where diazotrophic bacteria may facilitate adaption of these crassulacean acid metabolism-plants to low-nutrient environments.
Aims/Objectives: The present study investigates whether lexical frequency can be increased experimentally, and whether an increase in lexical frequency facilitates L2 morphological processing. ...Design: English L2 learners of Spanish were randomly assigned to either a treatment or control group. Both groups completed a pre/post lexical decision task containing L2 words with either two or three morphemes, and a pre/post lexical frequency task. In addition, the treatment group completed four sessions in which they read texts containing low frequency words. Data/analysis: Linear mixed models and Bayes factors were used to analyze participants’ performance. Findings/Conclusions: Both groups took significantly longer to process morphologically complex words with three than with two morphemes at pretest. While this pattern was observed also at posttest for the control group, the treatment group took roughly the same to process both types of words following training. Taken together, the findings suggest that an increased exposure to low-frequency L2 words switches learners’ morphological computation strategies from decomposition to whole word processing. Originality: While previous cross-sectional studies have assessed the role of frequency on L2 morphological decomposition, this has not been confirmed by longitudinal data. Significance/Implications: The results support hybrid word recognition models claiming that frequency modulates morphological computation.
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