Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation

In a wide variety of animal species, oocyte maturation is arrested temporarily at prophase of meiosis I (ref. 1). Resumption of meiosis requires activation of cyclin-dependent kinase-1 (CDK1, p34cdc2), one component of maturation-promoting factor (MPF). The dual specificity phosphatases Cdc25a, Cdc25b and Cdc25c are activators of cyclin-dependent kinases; consequently, they are postulated to regulate cell-cycle progression in meiosis and mitosis as well as the DNA-damage response. We generated Cdc25b-deficient (Cdc25b-/-) mice and found that they are viable. As compared with wildtype cells, fibroblasts from Cdc25b-/- mice grew vigorously in culture and arrested normally in response to DNA damage. Female Cdc25b-/- mice were sterile, and Cdc25b-/- oocytes remained arrested at prophase with low MPF activity. Microinjection of wildtype Cdc25b mRNA into Cdc25b-/- oocytes caused activation of MPF and resumption of meiosis. Thus, Cdc25b-/- female mice are sterile because of permanent meiotic arrest resulting from the inability to activate MPF. Cdc25b is therefore essential for meiotic resumption in female mice. Mice lacking Cdc25b provide the first genetic model for studying the mechanisms regulating prophase arrest in vertebrates.     

Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity

Expression of oncogenic Ras in primary human cells activates p53, thereby protecting cells from transformation. We show that in Ras-expressing IMR-90 cells, p53 is phosphorylated at Ser33 and Ser46 by the p38 mitogen-activated protein kinase (MAPK). Activity of p38 MAPK is regulated by the p53-inducible phosphatase PPM1D, creating a potential feedback loop. Expression of oncogenic Ras suppresses PPM1D mRNA induction, leaving p53 phosphorylated at Ser33 and Ser46 and in an active state. Retrovirus-mediated overexpression of PPM1D reduced p53 phosphorylation at these sites, abrogated Ras-induced apoptosis and partially rescued cells from cell-cycle arrest. Inactivation of p38 MAPK (the product of Mapk14) in vivo by gene targeting or by PPM1D overexpression expedited tumor formation after injection of mouse embryo fibroblasts (MEFs) expressing E1A+Ras into nude mice. The gene encoding PPM1D (PPM1D, at 17q22/q23) is amplified in human breast-tumor cell lines and in approximately 11% of primary breast tumors, most of which harbor wildtype p53. These findings suggest that inactivation of the p38 MAPK through PPM1D overexpression resulting from PPM1D amplification contributes to the development of human cancers by suppressing p53 activation.     

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.     

Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis

Individuals with hereditary hemochromatosis suffer from systemic iron overload due to duodenal hyperabsorption. Most cases arise from a founder mutation in HFE (845G-->A; ref. 2) that results in the amino-acid substitution C282Y and prevents the association of HFE with beta2-microglobulin. Mice homozygous with respect to a null allele of Hfe (Hfe-/-) or homozygous with respect to the orthologous 882G-->A mutation (Hfe(845A/845A)) develop iron overload that recapitulates hereditary hemochromatosis in humans, confirming that hereditary hemochromatosis arises from loss of HFE function. Much work has focused on an exclusive role for the intestine in hereditary hemochromatosis. HFE deficiency in intestinal crypt cells is thought to cause intestinal iron deficiency and greater expression of iron transporters such as SLC11A2 (also called DMT1, DCT1 and NRAMP2) and SLC11A3 (also called IREG1, ferroportin and MTP1; ref. 3). Published data on the expression of these transporters in the duodenum of HFE-deficient mice and humans are contradictory. In this report, we used a custom microarray to assay changes in duodenal and hepatic gene expression in Hfe-deficient mice. We found unexpected alterations in the expression of Slc39a1 (mouse ortholog of SLC11A3) and Cybrd1, which encode key iron transport proteins, and Hamp (hepcidin antimicrobial peptide), a hepatic regulator of iron transport. We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1.     

Preadult lethality in four populations of Drosophila melanogaster treated with formaldehyde

Samples from 4 populations of D. melanogaster were treated with formaldehyde by the larval feeding method, and induced lethality was scored. The results showed relevant differences among the populations analyzed.     

Tumour biology: senescence in premalignant tumours

Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer.     

Induced pluripotent stem cell (iPS) technology: promises and challenges

In 2006, an article published in Cell by Shinya Yamanaka took by surprise the stem cell research community. By performing systematic retroviral transduction of factors enriched in embryonic stem (ES) cells, the authors demonstrated the reprogramming of mouse fibroblasts into an ES cell-like state. These cells, baptized iPS (induced pluripotent stem) cells, were immediately recognized as a ground-breaking discovery. Subsequently, the same authors and other groups reported a similar achievement with human fibroblasts. Two years later, the number of top quality papers on iPS is astonishing, and interest in the scientific community has risen to a fever pitch. But although iPS has the potential to revolutionize Regenerative Medicine, important questions still remain unanswered. Work from multiple laboratories worldwide including ours is focused on deciphering the molecular mechanisms of iPS, and trying to improve the technique to make it suitable for the clinic. In this review article we briefly discuss the past, present and future of iPS, with emphasis on urgent issues to be solved. Supported by the National Nature Science Foundation of China (Grant Nos. 30725012, 30630039 and 90813033), Knowledge Innovation Project of Chinese Academy of Sciences (Grant No. KSCX2-YW-R-48), National Key Basic Research and Development Program of China (Grant Nos. 2006CB701504, 2006CB943600, 2007CB948002, 2007CB947804. 2007CB947900) and Guangzhou Science and Technology Development Funds (Grant No. 2008A1-E4011)     

The coconut pathosystem: weed hosts of nymphs of the American palm Cixiid Haplaxius crudus (Hemiptera: Fulgoroidea)

Lethal yellowing (LY) of coconut palm (Cocos nucifera L., Arecaceae) is a disease of economic importance that is caused by the phytoplasma ‘Candidatus Phytoplasma palmae’ and is transmitted by the planthopper Haplaxius crudus (Van Duzee) (Hemiptera: Cixiidae). This study explores the weeds used by H. crudus nymphs and other Cixiidae in a coconut pathosystem in southern Mexico. Nymphs were collected directly from the root system of each weed by hand or with the help of a vacuum after carefully opening the culm. This study included 11 species of weeds: nine Poaceae [Brachiaria decumbens Stapf, B. humidicola (Rendle) Schweick, B. mutica (Forssk.) Stapf, Digitaria abyssinica (Hochst. Ex A. Rich.) Stapf, Eustachys petraea (Sw.) Desv., Leersia hexandra Sw., Panicum laxum Sw., P. maximum Jacq., Paspalum notatum Flüggé]; one Cyperaceae [Cyperus ligularis L.], and one Portulacaceae: [Portulaca pilosa L.]. Brachiaria mutica, E. petraea, B. humidicola, P. maximum were identified as the principal host species for H. crudus nymphs. Brachiaria decumbens, D. abyssinica, and C. ligularis are new host records for the nymphs of H. crudus. Additionally, it was found that H. crudus may coexist with its cogeners H. skarphion Kramer (Cixiidae) and H. caldwelli Kramer (Cixiidae), on B. mutica. On C. ligularis, H. crudus may coexist with Oecleus snowi Ball (Cixiidae) nymphs. These results suggest that in the coconut pathosystem there is a complex of multitrophic interactions that should be considered in integrated management of LY.