Anti-HIV-1 Activity of Flavonoid Myricetin on HIV-1 Infection in a Dual-Chamber In Vitro Model

HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01–100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic), H9 and PBMC cells plus HIV-1 MN (X4 tropic), and the dual tropic (X4R5) HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.     

Seed predation and seedling recruitment in plants: the effect of the distance between parents

We present a graphic model that explores the effect of distance between parent plants on seed predation and seedling recruitment. Based on the assumption that distance between parents may affect the shape of the seed shadow, the model predicts that seed predators may affect seedling recruitment curves under isolated plants but they are unable to affect these curves under close parent plants. The predictions of the model are tested experimentally in Cryptocarya alba (Lauraceae), a common tree of the Mediterranean forest, Central Chile. Results show that predictions are not met under isolated parent plants. Although seed density decreases significantly away from parent plants, this effect is not relevant for seed predation and seedling recruitment. The biotic/abiotic contrast existing under the canopy vs outside the canopy, plus the shade-tolerance of this tree, better explains the seedling recruitment observed under isolated parent plants. Nevertheless, the predictions of the model are corroborated under close parent plants. Seed shadows overlap to the extent that they generate a homogeneous seed distribution, homogeneous seed predation and homogeneous seedling recruitment as well. We discuss the implications of the model in terms of the spatial pattern of seedlings and the benefits of dispersal from isolated and close parent plants.     

Diabetes Alters KIF1A and KIF5B Motor Proteins in the Hippocampus

Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose) for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal neurons, which may lead to changes in synaptic proteins, thus contributing to changes in hippocampal neurotransmission and to cognitive and memory impairments.     

Reproductive biology of Oreocereus fossulatus (Cactaceae), a long‐lived columnar cactus endemic to the tropical Andes

The geographic dichotomy hypothesis suggests that columnar cacti inhabiting the tropics depend on flower visitors (birds and bats) for their pollination, showing highly specialized animal‐pollinated systems. This pattern has been demonstrated for the northern hemisphere; however, our knowledge of the species of columnar cacti growing in the southern tropics is still scarce. In this study, we studied the reproductive biology of Oreocereus fossulatus (Cactaceae, Tribe Trichocereae), an endemic, columnar cactus of the tropical Andes, to determine if its pollination system tends to be more generalized (mixed systems of autogamy and xenogamy) than specialized (xenogamy) as a consequence of the geographic position of where it lives. Observations of the frequency of visits showed that Patagona gigas (Trochillidae) is its main pollinator. It visits the flowers when they are open, coinciding with the periods of greater floral reward (dusk and dawn of the first day of anthesis). The treatments of autogamy, xenogamy and geitonogamy produced fruits, showing that O. fossulatus exhibits a generalized pollination system, in the same way as its congeneric species O. celsianus, which is distributed farther south in the Prepuna biogeographical region. Our results suggest that species partially specializing in pollination by hummingbirds and, besides, capable of autopollination, could be common in the tropical and subtropical Andes, probably as a response to the unpredictable environments present in their ecosystems.     

Calpain restrains the stem cells compartment in breast cancer

CAPNS1 is essential for the stability and function of ubiquitous CAPN1 and CAPN2. Calpain modulates by proteolytic cleavage many cellular substrates and its activity is often deregulated in cancer cells, therefore calpain inhibition has been proposed as a therapeutical strategy for a number of malignancies. Here we show that CAPNS1 depletion is coupled to impairment of MCF7 and MCF10AT cell lines growth on plate and defective architecture of mammary acini derived from MCF10A cells. In soft agar CAPNS1 depletion leads to cell growth increase in MCF7, and decrease in MCF10AT cells. In both MCF7 and MCF10AT, CAPNS1 depletion leads to the enlargement of the stem cell compartment, as demonstrated by mammosphere formation assays and evaluation of stem cell markers by means of FACS and western blot analysis. Accordingly, activation of calpain by thapsigargin treatment leads to a decrease in the stem cell reservoir. The expansion of the cancer stem cell population in CAPNS1 depleted cells is coupled to a defective shift from symmetric to asymmetric division during mammosphere growth coupled to a decrease in NUMB protein level.     

Contrasting effects of fire frequency on plant traits of three dominant perennial herbs from Chaco Serrano

Fire frequencies are currently increasing in many regions across the world as a result of anthropic activities, affecting ecological processes and plant population dynamics. Fire can generate important changes in soil properties, altering nutrient dynamics and thereby plant growth. Here we analyse fire frequency effects on soil quality and plant traits of three native perennial herbaceous plants (Cologania broussonetii, Desmodium uncinatum and Rhynchosia edulis; Fabaceae) with the capacity for biological N₂ fixation that resprouts and are abundant after fire in Chaco Serrano forests. Based on 22‐year fire history, we assessed plant traits in sites with low and high fire frequencies along with unburned scenarios. We found significantly lower water content, nitrates and electrical conductivity in frequently burned soils. As a result, the three species showed consistently lower leaf area and specific leaf area in both fire frequencies, implying lower growth rates in comparison to unburned sites. However, total leaf biomass was not affected by fire, leaf phosphorus concentration was higher in R. edulis in high fire frequency and leaf N concentration was twice as large in plants growing in sites of high fire frequency in C. broussonetii and R. edulis. Such an increase in N and phosphorus concentrations is likely a result of both their conservative use of resources and their biological N₂ fixation capacity. To our knowledge, this is the first record of such contrasting fire effects observed consistently in three co‐occurring species: while plant growth decreased with fire frequency, leaf nutritional traits remain unchanged or increased in frequently burned sites. Quality‐depleted and drier soils that result from increased fire frequencies may not only affect trait variation at the intraspecific level but can also drive to a homogenization of the plant community, selecting species with particular combinations of morphological and functional traits.     

Environmental and genetic interactions reveal FLOWERING LOCUS C as a modulator of the natural variation for the plasticity of flowering in Arabidopsis

The timing of flowering initiation depends strongly on the environment, a property termed as the plasticity of flowering. Such plasticity determines the adaptive potential of plants because it provides phenotypic buffer against environmental changes, and its natural variation contributes to evolutionary adaptation. We addressed the genetic mechanisms of the natural variation for this plasticity in Arabidopsis thaliana by analysing a population of recombinant inbred lines derived from Don‐0 and Ler accessions collected from distinct climates. Quantitative trait locus (QTL) mapping in four environmental conditions differing in photoperiod, vernalization treatment and ambient temperature detected the folllowing: (i) FLOWERING LOCUS C (FLC) as a large effect QTL affecting flowering time differentially in all environments; (ii) numerous QTL displaying smaller effects specifically in some conditions; and (iii) significant genetic interactions between FLC and other loci. Hence, the variation for the plasticity of flowering is determined by a combination of environmentally sensitive and specific QTL, and epistasis. Analysis of FLC from Don identified a new and more active allele likely caused by a cis‐regulatory deletion covering the non‐coding RNA COLDAIR. Further characterization of four FLC natural alleles showed different environmental and genetic interactions. Thus, FLC appears as a major modulator of the natural variation for the plasticity of flowering to multiple environmental factors.     

Improvement of photovoltaic performance by substituent effect of donor and acceptor structure of TPA-based dye-sensitized solar cells

We report a computational study of a series of organic dyes built with triphenylamine (TPA) as an electron donor group. We designed a set of six dyes called (TPA-n, where n?=?0–5). In order to enhance the electron-injection process, the electron-donor effect of some specific substituent was studied. Thus, we gave insights into the rational design of organic TPA-based chromophores for use in dye-sensitized solar cells (DSSCs). In addition, we report the HOMO, LUMO, the calculated excited state oxidized potential E^dye*(eV) and the free energy change for electron-injection ΔG_inject(eV), and the UV-visible absorption bands for TPA-n dyes by a time-dependent density functional theory (TDDFT) procedure at the B3LYP and CAM-B3LYP levels with solvent effect. The results demonstrate that the introduction of the electron-acceptor groups produces an intramolecular charge transfer showing a shift of the absorption wavelengths of TPA-n under studies.

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Graphical Abstract Several organic dyes TPA-n with different donors and acceptors are modeled. A strong conjugation acrros the donor and anchoring groips (TPA-n) bas been studied. Candidate TPA-3 shows a promising results.