Acritarch-like Microorganisms from the 1.9 Ga Gunflint Chert, Canada.

Fossil evidence of eukaryotic life older than 1.8 Ga has long been debated because known fossils of that age usually lack cellular micro- and ultra-structures that bear strong affinities to eukaryotes. These include fossils of the ∼1.9 Ga Gunflint Chert microbiota that, despite being exceptionally well preserved, have suffered from cellular degradation, which poses challenges to studying their delicate cellular structures. In this study, we use an extended-focal-depth imaging technique, in combination with scanning electron microscopy, to document multiple types of large (10-35 µm diameter), cyst-like bodies based on distinctive details such as (1) radially arranged internal strands similar to those in some acritarchs and dinoflagellates; (2) regularly spaced long tubular processes, stubby pustules, and/or robust podia on the cell surface; (3) reticulate cell-wall sculpturing such as scale-like tubercles, pits, and ridges; and (4) internal bodies that may represent membrane-bound organelles. These micro- and ultra-structures provide strong morphological evidence for the presence of protists in the late Paleoproterozoic.

Interaction between PARP-1 and HIF-2α in the hypoxic response.

Hypoxia-inducible factors (HIFs) mediate the transcriptional adaptation of hypoxic cells. The extensive transcriptional programm regulated by HIFs involves the induction of genes controlling angiogenesis, cellular metabolism, cell growth, metastasis, apoptosis, extracellular matrix remodeling and others. HIF is a heterodimer of HIF-α and HIF-ß subunits. In addition to HIF-1α, HIF-2α has evolved as an isoform that contributes differently to the hypoxic adaptation by performing non-redundant functions. Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein involved in the control of DNA repair and gene transcription by modulating chromatin structure and acting as part of gene-specific enhancer/promoter-binding complexes. Previous results have shown that PARP-1 regulates HIF-1 activity. In this study, we focused on the cross-talk between HIF-2α and PARP-1. By using different approaches to suppress PARP-1, we show that HIF-2α mRNA expression, protein levels and HIF-2-dependent gene expression, such as ANGPTL4 and erythropoietin (EPO), are regulated by PARP-1. This regulation occurs at both the transcriptional and post-trancriptional level. We also show a complex formation between HIF-2α with PARP-1. This complex is sensitive to PARP inhibition and seems to protect against the von Hippel-Lindau-dependent HIF-2α degradation. Finally, we show that parp-1(-/-) mice display a significant reduction in the circulating hypoxia-induced EPO levels, number of red cells and hemoglobin concentration. Altogether, these results reveal a complex functional interaction between PARP-1 and the HIF system and suggest that PARP-1 is involved in the fine tuning of the HIF-mediated hypoxic response in vivo.

Poly(ADP-ribose)-dependent regulation of Snail1 protein stability.

Snail1 is a master regulator of the epithelial-mesenchymal transition (EMT) and has been implicated in key tumor biological processes such as invasion and metastasis. It has been previously shown that poly(ADP-ribose) polymerase-1 (PARP-1) knockdown, but not PARP inhibition, downregulates the expression of Snail1. In this study we have characterized a novel regulatory mechanism controlling Snail1 protein expression through poly(ADP-ribosyl)ation. The effect is not only limited to repression of Snail1 transcription but also to downregulated Snail1 protein stability. PARP-1 (but not PARP-2) poly(ADP) ribosylates Snail1, both in vivo and in vitro, and interacts with Snail1, an association that is sensitive to PARP inhibitors. PARP inhibition has also clear effects on EMT phenotype of different tumor cells, including Snail1 downregulation, E-cadherin upregulation, decreased cell elongation and invasiveness. Therefore, this study reveals a new regulatory mechanism of Snail1 activation through poly(ADP-ribosyl)ation with consequences in malignant transformation through EMT.

[Gestational disorders]. / Morbilidad gestacional.

We present the results of an interview of 375 pregnant women which explores their gestational risk diagnoses, the types and frequencies of complaints. Five groups of 75 patients each were formed from this random sample corresponding to 30, 32, 34, 36 and 38 weeks of pregnancy respectively. We too analyze the patients' opinions about their own morbidity, the repercussion on activities of daily life and self-medication. The interview included the actions taken on their own account to deal with complaints during pregnancy, as well as to establish the relationships between these actions and medical attention they received. A total of 1534 complaints were recorded from the entire group, the mean per patient were four with a range from one to six. The reported from the entire group, the mean per patient were four with a range from one to six. The reported complaints did not caused medical consultation and were totally different with the respective risk diagnoses. Our results show that patients almost always accept their symptoms as a normal part of pregnancy, even when arise from pathology. Almost 70% of the patients view their symptoms as normal despite the fact that they produce difficulties of daily life in 41%, and that they temporarily block these activities in 19%. Around 10% of the patients admit self-medication. Over 50 types of actions were self-initiated, 1371 for the entire group as a whole. Around 95% of the complaints considered abnormal received no medical attention. We presented a series of thoughts on the effectiveness of popular practices and the possibility of integrating some of them into medical practice.(ABSTRACT TRUNCATED AT 250 WORDS)