First case of parthenogenesis in ladybirds (Coleoptera: Coccinellidae) suggests new mechanisms for the evolution of asexual reproduction

Parthenogenesis, the development of unfertilized eggs resulting in the exclusive production of female offspring, is rare in animals relative to sexual reproduction and is mainly reported in invertebrates. It has been hypothesized that polyploidy, hybridization and endosymbiont infections are its major causal events but the mechanisms triggering asexual reproduction remain unclear. Here, we study the proximate causes at the origin of parthenogenesis in the first reported case of asexuality in the Coccinellidae (Coleoptera). The asexual populations were found in the Azores and the Mascarene archipelagos, and were identified as Nephus voeltzkowi Weise, a bisexual species widespread in sub-Saharan Africa. The specimens from both populations are diploid but present different karyotypes and heterozygosities that evoke hybrid origins, commonly associated with parthenogenesis in Coleoptera. However, the close proximity of their genomes (99.8% homology for the complete mitochondrial genome and 99.9% for the complete nuclear ribosomal cluster) together with the congruence between the mtDNA tree and the nuclear tree, and the low heterozygosity levels, suggests that the two populations are not hybrid. We propose that they belong to a single chromosomally polymorphic species undergoing Robertsonian fusions. Furthermore, specimens from both populations are infected with Wolbachia (supergroup B strain), contrary to sympatric bisexual species of the same genus. Although Wolbachia has been shown to induce parthenogenesis in haplodiploid organisms, it has been recently suggested that it could also induce parthenogenesis in hosts with other sex determination systems. Whether chromosome rearrangements and/or Wolbachia infections are post-parthenogenetic events or are at the origin of parthenogenesis still needs to be determined.     

Decolorization of synthetic dyes and production of manganese-dependent peroxidase by new fungal isolates

Two yeasts, Debaryomyces polymorphus, Candida tropicalis, and two filamentous fungi, Umbelopsis isabellina, Penicillium geastrivorus, could completely decolorize 100 mg Reactive Black 5 (RB 5) l^–1 within 16–48 h. Manganese-dependent peroxidase (MnP) activities between 60 and 424 U l^–1 were detected in culture supernatants of three of these organisms indicating the color removal by enzymatic biodegradation but with P. geastrivorus there was no ligninolytic enzyme activity in its culture and the decolorization was mainly due to biosorption to mycelium. Extensive decolorization by D. polymorphus (69–94%) and C. tropicalis (30–97%) was obtained with five other azo dyes and one anthraquinone dye. Except for Reactive Brilliant Blue KNR and Reactive Yellow M-3R, the four azo dyes, Reactive Red M-3BE, Procion Scharlach H-E3G, Procion Marine H-EXL and Reactive Brilliant Red K-2BP, induced D. polymorphus to produce MnP (105–587 U l^–1). However, MnP activities of 198–329 U l^–1 were only detected in the culture of C. tropicalis containing Reactive Red M-3BE and Reactive Brilliant Red K-2BP, respectively.     

Early alterations of brain cellular energy homeostasis in Huntington disease models

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in Hdh(Q111/+) mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool.     

Synthesis of 4(3H)quinazolinimines with selective cytotoxic effect on human acute promyelocytic leukemia cells

We synthesized a new family of six 4(3H)quinazolinimines based on the reaction between (E)-N-(2-cyanophenyl)benzimidoyl chloride and substituted anilines reaching the formation of their corresponding C2, N3-substituted quinazoliniminium chlorides. This method provides novel, direct and flexible access to diverse substituted 4(3H)quinazolinimines.New compounds obtained following the proposed synthesis were fully characterized and, including the thirteen 4(3H)quinazolinimines synthesized by this method and previously reported by us, were used to study its cytotoxic effect on neoplastic cell lines. The mechanism involved in cell toxicity was also studied. Results showed that these compounds were highly cytotoxic, in particular on Human Promyelocytic Leukemia cells (HL60) and Chronic Myelogenous Leukemia cells (K562) when compared with conventional antineoplastic drugs such as etoposide and cisplatin. The mechanism associated to cytotoxic effect was mainly apoptosis, which not was decreased by antioxidant addition, thereby suggesting that the compounds exert apoptotic death through a mechanism unrelated with oxidative stress.     

A Model for the Spread of an Invasive Weed, <Emphasis Type="Italic">Tradescantia fluminensis</Emphasis>

Tradescantia fluminensis is an invasive weed and a serious threat to native forests in eastern Australia and New Zealand. Current methods of eradication are often ineffective, so understanding the growth mechanisms of Tradescantia is important in formulating better control strategies. We present a partial differential equation (PDE) model for Tradescantia growth and spatial proliferation that accounts for Tradescantia’s particular creeping and branching morphology, and the impact of self-shading on plant growth. This is the first PDE model to represent a weed that spreads via a creeping growth habit rather than by seed dispersal. We use a travelling wave analysis to investigate how Tradescantia extends to colonise new territory. Numerical simulations and analysis show that the model provides a good qualitative representation of the behaviour of this plant. This model provides a foundation for assessing different control and eradication strategies for Tradescantia.     

In Silico,In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH<Subscript>2</Subscript>, A Vasoactive Proline-Rich Oligopeptide from <Emphasis Type="Italic">Brachycephalus ephippium</Emphasis>

BPP-BrachyNH₂ is a proline-rich oligopeptide (PRO) firstly identified in skin secretion of the frog Brachycephalus ephippium, which possess in vitro inhibitory activity of angiotensin-I converting enzyme (ACE) and endothelium-dependent vasorelaxant activity. Considering its potential application in the treatment of cardiovascular diseases, the present work assessed the toxicological profile of the BPP-BrachyNH₂. The in silico toxicity prediction was performed from the best model obtained through the optimization of the FASTA query peptide. This prediction study revealed that BPP-BrachyNH₂ induced high predicted LD₅₀ values for both humans and rats, and then is well-tolerated in the recommended range. The MTT assay was applied for the in vitro cytotoxic evaluation in murine macrophages. In this assay, a decrease of cell viability was not observed. The in vivo acute toxicological study was performed after the intraperitoneal administration of BPP-BrachyNH₂ at doses of 5 and 50 mg/kg. After intraperitoneal administration, no death, alterations in behavioral parameters or weight gain curve was observed, as well as none in the serum biochemical parameters, and gross pathological and histopathological analyses. These observations demonstrates an acceptable safety profile for BPP-BrachyNH₂, leading towards further studies focused on investigation of pharmacological and therapeutical applications for this peptide.     

NEIL3-Dependent Regulation of Cardiac Fibroblast Proliferation Prevents Myocardial Rupture

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Protein release from galactoglucomannan hydrogels: influence of substitutions and enzymatic hydrolysis by beta-mannanase

O-Acetyl-galactoglucomannan (AcGGM) is the major soft-wood hemicellulose. Structurally modified AcGGM and hydrogels of AcGGM were prepared. The degree of substitution (DS) of AcGGM was modified enzymatically with alpha-galactosidase, and chemically with an acrylate derivative, 2-hydroxyethylmethacrylate (HEMA). The hydrolysis of AcGGM with beta-mannanase was shown to increase with decreasing DS. AcGGM hydrogels were prepared from chemically modified AcGGM with varying DS of HEMA. Bovine serum albumin (BSA) was encapsulated in hydrogels. A spontaneous burst release of BSA was decreased with increased DS of HEMA. The addition of beta-mannanase significantly enhanced the BSA release from hydrogels with a DS of 0.36, reaching a maximum of 95% released BSA after eight hours compared to 60% without enzyme. Thus, both the pendant group composition and the enzyme action are valuable tools in the tailoring of hydrogel release profiles of potential interest for intestine drug delivery.