Mitostemness

Unraveling the key mechanisms governing the retention versus loss of the cancer stem cell (CSC) state would open new therapeutic avenues to eradicate cancer. Mitochondria are increasingly recognized key drivers in the origin and development of CSC functional traits. We here propose the new term “mitostemness” to designate the mitochondria-dependent signaling functions that, evolutionary rooted in the bacterial origin of mitochondria, regulate the maintenance of CSC self-renewal and resistance to differentiation. Mitostemness traits, namely mitonuclear communication, mitoproteome components, and mitochondrial fission/fusion dynamics, can be therapeutically exploited to target the CSC state. We briefly review the pre-clinical evidence of action of investigational compounds on mitostemness traits and discuss ongoing strategies to accelerate the clinical translation of new mitostemness drugs. The recognition that the bacterial origin of present-day mitochondria can drive decision-making signaling phenomena may open up a new therapeutic dimension against life-threatening CSCs. New therapeutics aimed to target mitochondria not only as biochemical but also as biophysical and morpho-physiological hallmarks of CSC might certainly guide improvements to cancer treatment.     

Oxidative mutagenesis of doxorubicin-Fe(III) complex

Doxorubicin has a high affinity for inorganic iron, Fe(III), and has potential to form doxorubicin-Fe(III) complexes in biological systems. Indirect involvement of iron has been substantiated in the oxidative mutagenicity of doxorubicin. In this study, however, direct involvement of Fe(III) was evaluated in mutagenicity studies with the doxorubicin-Fe(III) complex. The Salmonella mutagenicity assay with strain TA102 was used with a pre-incubation step. The highest mutagenicity of doxorubicin-Fe(III) complex was observed at the dose of 2.5 nmol/plate of the complex. The S9-mix decreased this highest mutagenicity but increased the number of revertants at a higher dose of 10 nmol/plate of the complex. On the other hand, the mutagenicity of the doxorubicin-Fe(III) complex at the doses of 0.25, 0.5, 1 and 2 nmol/plate was enhanced about twice by the addition of glutathione plus H₂O₂. This enhanced mutagenicity as well as of the complex itself, the complex plus glutathione, and the complex plus H₂O₂ were reduced by the addition of ADR-529, an Fe(III) chelator, and potassium iodide, a hydroxyl radical scavenger. These results indicate that doxorubicin-Fe(III) complex exert the mutagenicity through oxidative DNA damage and that Fe(III) is a required element in the mutagenesis of doxorubicin.     

High stability hybrids producing monoclonal antibodies against human C-reactive protein

This report shows how high stability hybrids producing monoclonal antibodies against human C-reactive protein were raised and selected. Monoclonal antibodies can be produced in large enough quantities through this method, to allow for the design and use of quantitative C-reactive protein determination on a clinical scale. This novel strategy consisted of the following: growing the hybrids and freezing them before cloning in order to assure stability and selecting the hybrids from those producing high titres in mouse ascite induction. Two monoclonal antibodies of high stability and great potential for large scale production have been developed in this manner. Production on a large scale of these monoclonal antibodies against human C-reactive protein can be useful both in clinical quantification and in physiological studies concerning its still unknown in vivo function.     

Sex differences in mutational rate and mutational mechanism in the NF1 gene in neurofibromatosis type 1 patients

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a prevalence of around 1 in 3500, affecting all ethnic groups. The clinical manifestations of the disease are variable, even among members of the same family, and affect a variety of tissues and cell types, including skin, iris, central and peripheral nervous systems and skeletal system. It has been reported that the majority of sporadic mutations in NF1 arise in paternally inherited alleles. We present here a collaborative study of the parental origin and type of mutation in individuals with de novo NF1, who account for up to a half of all cases of clinically diagnosed NF1. We have studied intragenic and extragenic markers in 470 NF1 families. In 32 of these families it was possible to assess the parental origin of a de novo NF1 mutation either by linkage analysis (in families with three generations) or by the detection of an intragenic deletion in a sporadic NF1 case. Eleven of these 32 families have three generations (the second and third generation being affected), with the mutation (not a large deletion) being of paternal origin in 82% of them (P < 0.05). In the other 21 families an intragenic deletion was detected, in 76% being in the maternal chromosome and in 24% in the paternal one (P < 0.05). Our results suggest that in NF1 the majority of deletions occur in oogenesis, while other types of mutations should account for the paternally derived NF1 mutations. Received: 26 June 1996 / Revised: 1 August 1996     

Making protected areas effective for biodiversity,climate and food

The spatial extent of marine and terrestrial protected areas (PAs) was among the most intensely debated issues prior to the decision about the post-2020 Global Biodiversity Framework (GBF) of the Convention on Biological Diversity. Positive impacts of PAs on habitats, species diversity and abundance are well documented. Yet, biodiversity loss continues unabated despite efforts to protect 17% of land and 10% of the oceans by 2020. This casts doubt on whether extending PAs to 30%, the agreed target in the Kunming-Montreal GBF, will indeed achieve meaningful biodiversity benefits. Critically, the focus on area coverage obscures the importance of PA effectiveness and overlooks concerns about the impact of PAs on other sustainability objectives. We propose a simple means of assessing and visualising the complex relationships between PA area coverage and effectiveness and their effects on biodiversity conservation, nature-based climate mitigation and food production. Our analysis illustrates how achieving a 30% PA global target could be beneficial for biodiversity and climate. It also highlights important caveats: (i) achieving lofty area coverage objectives alone will be of little benefit without concomitant improvements in effectiveness, (ii) trade-offs with food production particularly for high levels of coverage and effectiveness are likely and (iii) important differences in terrestrial and marine systems need to be recognized when setting and implementing PA targets. The CBD's call for a significant increase in PA will need to be accompanied by clear PA effectiveness goals to reduce and revert dangerous anthropogenic impacts on socio-ecological systems and biodiversity.     

Geographic isolation and long-distance gene flow influence the genetic structure of the blue fan palm Brahea armata (Arecaceae)

Journal of Plant Research - The formation of the Baja California Peninsula (BCP) has impacted the microevolutionary dynamics of different species in ways that depend on biological traits such as...     

Nutrient‐specific foraging leads to Allee effects and dynamic functional responses

Most animals forage in nutritionally complicated environments in which the densities of complementary foods vary in space and time. Locally rare foods can lead to nutritional deficiencies in consumers, yet there has been little consideration of the influence of nutritional deficits, and consumers’ efforts to redress these deficits, on population and community dynamics. A taxonomically and trophically diverse group of animals can redress accumulated deficits using nutrient‐specific foraging, defined here as the ability of an animal to bias its foraging effort towards certain foods on the basis of its own nutritional state. We focus on the true omnivores, because they feed on vastly different nutrient sources, animals and plants. We use an ordinary differential equation model to show that nutrient‐specific foraging may destabilize omnivore–prey population dynamics, depending on the degree to which the omnivore alters its foraging in an attempt to balance its nutritional state. In particular, a high behavioral sensitivity to nutritional imbalances led to a novel type of Allee effect driven by the interaction between prey density and nutritional deficiencies in the omnivore. Our model overall is characterized by a causal loop between the omnivore's nutritional state, food preferences and population dynamics. Consequently, the omnivore exhibited a dynamic functional response, in which the relationship between prey density and omnivore per capita consumption of prey was influenced by the current nutritional state of the omnivore. With regards to omnivory in general, our results reinforce the idea that statements about the effects of omnivory on population or community stability are not possible without a consideration of the behavioral mechanisms of diet mixing.