Future projections for Mexican faunas under global climate change scenarios

Global climates are changing rapidly, with unexpected consequences. Because elements of biodiversity respond intimately to climate as an important driving force of distributional limitation, distributional shifts and biodiversity losses are expected. Nevertheless, in spite of modelling efforts focused on single species or entire ecosystems, a few preliminary surveys of fauna-wide effects, and evidence of climate change-mediated shifts in several species, the likely effects of climate change on species' distributions remain little known, and fauna-wide or community-level effects are almost completely unexplored. Here, using a genetic algorithm and museum specimen occurrence data, we develop ecological niche models for 1,870 species occurring in Mexico and project them onto two climate surfaces modelled for 2055. Although extinctions and drastic range reductions are predicted to be relatively few, species turnover in some local communities is predicted to be high (>40% of species), suggesting that severe ecological perturbations may result.     

RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels

Therapeutics that discriminate between the genetic makeup of normal cells and tumour cells are valuable for treating and understanding cancer. Small molecules with oncogene-selective lethality may reveal novel functions of oncoproteins and enable the creation of more selective drugs. Here we describe the mechanism of action of the selective anti-tumour agent erastin, involving the RAS-RAF-MEK signalling pathway functioning in cell proliferation, differentiation and survival. Erastin exhibits greater lethality in human tumour cells harbouring mutations in the oncogenes HRAS, KRAS or BRAF. Using affinity purification and mass spectrometry, we discovered that erastin acts through mitochondrial voltage-dependent anion channels (VDACs)--a novel target for anti-cancer drugs. We show that erastin treatment of cells harbouring oncogenic RAS causes the appearance of oxidative species and subsequent death through an oxidative, non-apoptotic mechanism. RNA-interference-mediated knockdown of VDAC2 or VDAC3 caused resistance to erastin, implicating these two VDAC isoforms in the mechanism of action of erastin. Moreover, using purified mitochondria expressing a single VDAC isoform, we found that erastin alters the permeability of the outer mitochondrial membrane. Finally, using a radiolabelled analogue and a filter-binding assay, we show that erastin binds directly to VDAC2. These results demonstrate that ligands to VDAC proteins can induce non-apoptotic cell death selectively in some tumour cells harbouring activating mutations in the RAS-RAF-MEK pathway.     

Melanism in endangered Mohave tui chub Siphateles bicolor mohavensis Snyder 1918 (Cypriniformes: Cyprinidae)

Although melanism has been reported in a wide variety of taxa, the presence of melanic individuals is relatively rare in fishes. Melanism in Mohave tui chub ( Siphateles bicolor mohavensis ), an endangered endemic of the Mojave Desert in California, is reported from 2 of 4 surveyed populations. The typical body color varies from dark brown to olive brown dorsally and is whitish ventrally; sides are silvery or golden, and fins are pale yellow to dusky red. While conducting population censuses in 2007–2008, we found 4 melanic Mohave tui chubs from 2 of 4 surveyed habitats. Two of 1049 fish (0.19%) handled from Lake Tuendae (Mojave National Preserve) and 2 of 1516 fish (0.13%) handled from Bud’s Pond (Camp Cady Wildlife Area) were melanic. Melanic individuals were dorsally black, gradually fading into blackish brown on the sides; the sides had a golden or silvery sheen, and fins were blackish brown. Though the occurrence of melanism is very rare, it may reflect underlying genetic variation, which is of particular interest to the conservation of rare and endangered species. Aunque se han reportado casos de melanismo en varios taxa, son relativamente poco frecuentes los individuos melánicos entre los peces. Se reporta la presencia de melanismo en 2 de las 4 poblaciones estudiadas de la carpa tui del Mohave ( Siphateles bicolor mohavensis ), una especie endémica en peligro de extinción del Desierto de Mojave en California. El color típico de su cuerpo varía entre café oscuro y café olivo en el dorso, con el abdomen blancuzco, los costados dorados o plateados y las aletas entre amarillo claro y rojo violáceo. Encontramos 4 carpas tui del Mohave melánicas en 2 de los 4 hábitats estudiados al hacer censos poblacionales entre 2007 y 2008. Fueron melánicos 2 de los 1049 peces (0.19%) y 2 de los 1516 peces (0.13%) examinados en el lago Tuendae (Mojave National Preserve) y en el estanque de Bud (Camp Cady Wildlife Area), respectivamente. Los individuos melánicos tenían el dorso de color negro que gradualmente se convertía en café negruzco hacia los costados, los cuales tenían un brillo dorado o plateado. Las aletas eran color café negruzco. Aunque el melanismo es relativamente poco común, podría reflejar la variación genética subyacente, la cual es de especial interés para la conservación de especies raras y en peligro de extinción.     

Life history variation in recently established populations of western mosquitofish ( Gambusia affinis )

We report life history characteristics for 4 recently established populations of western mosquitofish ( Gambusia affinis ). Mosquitofish from thermally stable habitats, Bonham and Garrett, were characterized by maturity at large sizes, high fat reserves, and large embryos. In contrast, females from a thermally unstable habitat, Wabuska, matured at small sizes and had low fat reserves and small embryos. Females from Parker, a site with no appreciable thermal input, matured at intermediate sizes and had low fat reserves as well as large embryos. These populations shared a common ancestor in 1937; therefore, these results suggest either phenotypic plasticity or rapid evolution.     

Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure

Ferroptosis is a recently recognized caspase-independent form of regulated cell death that is characterized by the accumulation of lethal lipid ROS produced through iron-dependent lipid peroxidation. Considering that regulation of fatty acid metabolism is responsible for the membrane-resident pool of oxidizable fatty acids that undergo lipid peroxidation in ferroptotic processes, we examined the contribution of the key fatty acid metabolism enzyme, acyl-CoA synthetase long-chain family member 4 (ACSL4), in regulating ferroptosis. By using CRISPR/Cas9 technology, we found that knockout of Acsl4 in ferroptosis-sensitive murine and human cells conferred protection from erastin- and RSL3-induced cell death. In the same cell types, deletion of mixed lineage kinase domain-like (Mlkl) blocked susceptibility to necroptosis, as expected. Surprisingly, these studies also revealed ferroptosis and necroptosis are alternative, in that resistance to one pathway sensitized cells to death via the other pathway. These data suggest a mechanism by which one regulated necrosis pathway compensates for another when either ferroptosis or necroptosis is compromised. We verified the synergistic contributions of ferroptosis and necroptosis to tissue damage during acute organ failure in vivo. Interestingly, in the course of pathophysiological acute ischemic kidney injury, ACSL4 was initially upregulated and its expression level correlated with the severity of tissue damage. Together, our findings reveal ACSL4 to be a reliable biomarker of the emerging cell death modality of ferroptosis, which may also serve as a novel therapeutic target in preventing pathological cell death processes.     

Exploring biology with small organic molecules

Small organic molecules have proven to be invaluable tools for investigating biological systems, but there is still much to learn from their use. To discover and to use more effectively new chemical tools to understand biology, strategies are needed that allow us to systematically explore 'biological-activity space'. Such strategies involve analysing both protein binding of, and phenotypic responses to, small organic molecules. The mapping of biological-activity space using small molecules is akin to mapping the stars--uncharted territory is explored using a system of coordinates that describes where each new feature lies.