Regulation of Small RNA Accumulation in the Maize Shoot Apex

MicroRNAs (miRNAs) and trans-acting siRNAs (ta-siRNAs) are essential to the establishment of adaxial–abaxial (dorsoventral) leaf polarity. Tas3-derived ta-siRNAs define the adaxial side of the leaf by restricting the expression domain of miRNA miR166, which in turn demarcates the abaxial side of leaves by restricting the expression of adaxial determinants. To investigate the regulatory mechanisms that allow for the precise spatiotemporal accumulation of these polarizing small RNAs, we used laser-microdissection coupled to RT-PCR to determine the expression profiles of their precursor transcripts within the maize shoot apex. Our data reveal that the pattern of mature miR166 accumulation results, in part, from intricate transcriptional regulation of its precursor loci and that only a subset of mir166 family members contribute to the establishment of leaf polarity. We show that miR390, an upstream determinant in leaf polarity whose activity triggers tas3 ta-siRNA biogenesis, accumulates adaxially in leaves. The polar expression of miR390 is established and maintained independent of the ta-siRNA pathway. The comparison of small RNA localization data with the expression profiles of precursor transcripts suggests that miR166 and miR390 accumulation is also regulated at the level of biogenesis and/or stability. Furthermore, mir390 precursors accumulate exclusively within the epidermal layer of the incipient leaf, whereas mature miR390 accumulates in sub-epidermal layers as well. Regulation of miR390 biogenesis, stability, or even discrete trafficking of miR390 from the epidermis to underlying cell layers provide possible mechanisms that define the extent of miR390 accumulation within the incipient leaf, which patterns this small field of cells into adaxial and abaxial domains via the production of tas3-derived ta-siRNAs

Violacein Extracted from Chromobacterium violaceum Inhibits Plasmodium Growth in Vitro and in Vivo

Violacein is a violet pigment extracted from the gram-negative bacterium Chromobacterium violaceum. It presents bactericidal, tumoricidal, trypanocidal, and antileishmanial activities. We show that micromolar concentrations efficiently killed chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro; inhibited parasitemia in vivo, even after parasite establishment; and protected Plasmodium chabaudi chabaudi-infected mice from a lethal challenge.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Estadual Campinas, UNICAMP, Dept Parasitol, Inst Biol, BR-13083970 Campinas, SP, BrazilUniv Estadual Campinas, UNICAMP, Dept Microbiol & Imunol, Inst Biol, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Bioquim, BR-04044020 São Paulo, BrazilCEPEM, IPEPATRO, BR-78900970 Porto Velho, RO, BrazilUniv São Paulo, Dept Parasitol, ICB2, São Paulo, BrazilUniv Estadual Campinas, Dept Fisiol & Biofis, Inst Biol, BR-13083970 Campinas, SP, BrazilUniv Estadual Campinas, Lab Quim Biol, Inst Quim, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Bioquim, BR-04044020 São Paulo, BrazilFAPESP: 2004/00638-6CNPq: 470587/2006-7Web of Scienc

Leaf heteroblasty in Passiflora edulis as revealed by metabolic profiling and expression analyses of the microRNAs miR156 and miR172

Juvenile-to-adult phase transition is marked by changes in leaf morphology, mostly due to the temporal development of the shoot apical meristem, a phenomenon known as heteroblasty. Sugars and microRNA-controlled modules are components of the heteroblastic process in Arabidopsis thaliana leaves. However, our understanding about their roles during phase-changing in other species, such as Passiflora edulis, remains limited. Unlike Arabidopsis, P. edulis (a semi-woody perennial climbing vine) undergoes remarkable changes in leaf morphology throughout juvenile-to-adult transition. Nonetheless, the underlying molecular mechanisms are unknown.Here we evaluated the molecular mechanisms underlying the heteroblastic process by analysing the temporal expression of microRNAs and targets in leaves as well as the leaf metabolome during P. edulis development.Metabolic profiling revealed a unique composition of metabolites associated with leaf heteroblasty. Increasing levels of glucose and α-trehalose were observed during juvenile-to-adult phase transition. Accumulation of microRNA156 (miR156) correlated with juvenile leaf traits, whilst miR172 transcript accumulation was associated with leaf adult traits. Importantly, glucose may mediate adult leaf characteristics during de novo shoot organogenesis by modulating miR156-targeted PeSPL9 expression levels at early stages of shoot development.Altogether, our results suggest that specific sugars may act as co-regulators, along with two microRNAs, leading to leaf morphological modifications throughout juvenile-to-adult phase transition in P. edulis

Assessing the role of compound drought and heatwave events on unprecedented 2020 wildfires in the Pantanal

The year 2020 had the most catastrophic fire season over the last two decades in the Pantanal, which led to outstanding environmental impacts. Indeed, much of the Pantanal has been affected by severe dry conditions since 2019, with evidence of the 2020's drought being the most extreme and widespread ever recorded in the last 70 years. Although it is unquestionable that this mega-drought contributed significantly to the increase of fire risk, so far, the 2020's fire season has been analyzed at the univariate level of a single climate event, not considering the co-occurrence of extreme and persistent temperatures with soil dryness conditions. Here, we show that similarly to other areas of the globe, the influence of land-atmosphere feedbacks contributed decisively to the simultaneous occurrence of dry and hot spells (HPs), exacerbating fire risk. The ideal synoptic conditions for strong atmospheric heating and large evaporation rates were present, in particular during the HPs, when the maximum temperature was, on average, 6 °C above the normal. The short span of the period during those compound drought-heatwave (CDHW) events accounted for 55% of the burned area of 2020. The vulnerability in the northern forested areas was higher than in the other areas, revealing a synergistic effect between fuel availability and weather-hydrological conditions. Accordingly, where fuel is not a limiting factor, fire activity tends to be more modelled by CDHW events. Our work advances beyond an isolated event-level basis towards a compound and cascading natural hazards approach, simultaneously estimating the contribution of drought and heatwaves to fuelling extreme fire outbreaks in the Pantanal such as those in 2020. Thus, these findings are relevant within a broader context, as the driving mechanisms apply across other ecosystems, implying higher flammability conditions and further efforts for monitoring and predicting such extreme events

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease