Crystal structure of inhibitor of growth 4 (ING4) dimerization domain reveals functional organization of ING family of chromatin-binding proteins

The protein ING4 binds to histone H3 trimethylated at Lys-4 (H3K4me3) through its C-terminal plant homeodomain, thus recruiting the HBO1 histone acetyltransferase complex to target promoters. The structure of the plant homeodomain finger bound to an H3K4me3 peptide has been described, as well as the disorder and flexibility in the ING4 central region. We report the crystal structure of the ING4 N-terminal domain, which shows an antiparallel coiled-coil homodimer with each protomer folded into a helix-loop-helix structure. This arrangement suggests that ING4 can bind simultaneously two histone tails on the same or different nucleosomes. Dimerization has a direct impact on ING4 tumor suppressor activity because monomeric mutants lose the ability to induce apoptosis after genotoxic stress. Homology modeling based on the ING4 structure suggests that other ING dimers may also exist.     

Impact factor of Revista Iberoamericana de Micología

The impact factor is a bibliometric indicator published annually in the Journal Citation Reports, and widely regarded as a quality ranking of the journals included in this database. The problem with this indicator is that the impact factor of several journals not listed in the Science Citation Index database is largely unknown. The aim of this study was to analyze the 2001 national and international impact factor of Revista Iberoamericana de Micología. The National impact factor of Revista Iberoamericana de Micología was obtained by adding the number of cites in 2001 from a total of 87 Spanish medical journals of greater scientific quality. Also, bibliographical references from Spanish journals indexed in the 2001 Journal Citation reports database have been included to determine the international impact factor of this analyzed journal. Revista Iberoamericana de Micología received a total of 62 cites from published articles in 1999 to 2001, coming from 20 different journals, being their self-citation index 10.1%. The journal with the highest number of cites to Revista Iberoamericana de Micología was Journal of Clinical Microbiology, with 12 cites (19.3%). According to this findings the national and international impact factor of Revista Iberoamericana de Micología was 0.266 and 0.606, respectively. The impact factor of Revista Iberoamericana de Micología, although not included in the Science Citation Index database, was higher than other Journal Citation Reports. Moreover, Revista Iberoamericana de Micología received most of its citations from high impact factor journals included in the Journal Citation Reports database. These data support the international recognition of the scientific level of the journal.     

Staphylococcal self-loading helicases couple the staircase mechanism with inter domain high flexibility

Replication is a crucial cellular process. Replicative helicases unwind DNA providing the template strand to the polymerase and promoting replication fork progression. Helicases are multi-domain proteins which use an ATPase domain to couple ATP hydrolysis with translocation, however the role that the other domains might have during translocation remains elusive. Here, we studied the unexplored self-loading helicases called Reps, present in Staphylococcus aureus pathogenicity islands (SaPIs). Our cryoEM structures of the PriRep5 from SaPI5 (3.3 Å), the Rep1 from SaPI1 (3.9 Å) and Rep1–DNA complex (3.1Å) showed that in both Reps, the C-terminal domain (CTD) undergoes two distinct movements respect the ATPase domain. We experimentally demonstrate both in vitro and in vivo that SaPI-encoded Reps need key amino acids involved in the staircase mechanism of translocation. Additionally, we demonstrate that the CTD′s presence is necessary for the maintenance of full ATPase and helicase activities. We speculate that this high interdomain flexibility couples Rep′s activities as initiators and as helicases.     

Phosphatase activity of benthic marine algae. An overview

This review provides an account of the phosphatase activities of benthicmarine algae and is based on reports for more than a hundred species, includingcyanobacteria, red, brown and green algae. Particular emphasis is given to theuse of phosphomonoesterase activity as a rapid means of assessing thephosphorusstatus of the alga and thus indirectly that of the environment. Anunderstandingof the influence of environmental factors and the growth pattern of theparticular alga is important in carrying out assays. For instance, the responseto light differs markedly between species, especially in short-term assays,whenthe effect can be obvious or none. Considerations about the methodology formeasuring "alkaline phosphatase activity" are discussed, particularly whethertosimulate field conditions or to use optimum conditions. Recommendations aresuggested concerning the best methodology for routine use, followed by adiscussion of the future prospects for the method.     

Changes in the content of progesterone receptor isoforms and estrogen receptor alpha in the chick brain during embryonic development

Progesterone and estradiol participate in the regulation of several reproductive functions through interaction with intracellular progesterone receptors (PR) and estrogen receptors (ER), respectively. In this work, we determined PR and ER-alpha isoforms content in the brain of chicks of both sexes on days 8 and 13 of embryonic development as well as on the day of hatching by Western blot analysis. PR isoforms protein content increased during embryonic development in both female and male chick brain. The highest PR isoforms content was observed on the day of hatching in both sexes. Interestingly, PR-A content was higher in the brain of chick males than in that of females on day 8 of embryonic development. PR-A/PR-B ratio was higher in the brain of males than in that of females at all ages. We found two ER-alpha isoforms of 66 and 52 kDa; the content of both isoforms was higher in the brain of females than in that of males on days 8 and 13 of embryonic development. An opposite pattern of ER-alpha isoforms content was observed. In males, ER-alpha content increased during embryonic development whereas in the females it decreased during this process. These results indicate that the content of PR and ER-alpha isoforms is related to the degree of brain development in chicks, and suggest that PR and ER-alpha isoforms should exhibit sexual dimorphism in the brain of chicks during embryonic development.     

Identification of the Lipodepsipeptide MDN-0066, a Novel Inhibitor of VHL/HIF Pathway Produced by a New Pseudomonas Species

Throughout recent history, metabolites of microbial origin have had an extraordinary impact on the welfare of humanity. In fact, natural products have largely been –and still are– considered an exceedingly valuable platform for the discovery of new drugs against diverse pathologies. Such value is partly due to their higher complexity and chemical diversity as compared to those of synthetic and combinatorial compounds. Mutations in the Von Hippel-Lindau (vhl) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types. The primary cause of morbidity and mortality for these patients arises from progression of Renal Cell Carcinoma (RCC) or end-stage renal disease. Inactivation of the Von Hippel-Lindau (vhl) tumor suppressor gene arises in the majority of Renal Cell Carcinoma (RCC) as well as in other types of cancer and is associated with a high degree of vascularization and poor prognosis. Loss of pVHL function thus represents a pathognomonic molecular defect for therapeutic exploitation. In this study, renal carcinoma cell lines with naturally occurring vhl mutations (RCC4 VA) and their genetically matched wild-type vhl (RCC4 VHL) counterparts were seeded onto 96-well plates and treated with a collection of 1,040 organic extracts obtained from 130 bacterial strains belonging to at least 25 genera of the phyla Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes. This strategy allowed us to identify several extracts obtained from bacterial strain F-278,770^T, the type strain of the recently proposed new species Pseudomonas granadensis, showing biological activities not associated with previously known bioactive metabolites. The fractionation and structural elucidation of one of these extracts led to the discovery of a new lipodepsipeptide (MDN-0066) with specific toxicity in pVHL deficient cells that is not detectable in cells with pVHL expression rescue. This specific toxicity is associated with apoptosis induction in VHL deficient cell line as demonstrated with PARP activation and Annexin V staining. Our study demonstrated the feasibility of selectively targeting the loss of the vhl tumor suppressor gene for potential clinical benefit. Our results may have great impact on the development of new targeted therapies from natural products for the treatment of cancer and other genetic diseases.     

Conformation of Single and Interacting Lipopolysaccharide Surfaces Bearing O-Side Chains

The outer surfaces of Gram-negative bacteria are composed of lipopolysaccharide (LPS) molecules exposing oligo- and polysaccharides to the aqueous environment. This unique, structurally complex biological interface is of great scientific interest as it mediates the interaction of bacteria with antimicrobial agents as well as with neighboring bacteria in colonies and biofilms. Structural studies on LPS surfaces, however, have so far dealt almost exclusively with rough mutant LPS of reduced molecular complexity and limited biological relevance. Here, by using neutron reflectometry, we structurally characterize planar monolayers of wild-type LPS from Escherichia coli O55:B5 featuring strain-specific O-side chains in the presence and absence of divalent cations and under controlled interaction conditions. The model used for the reflectivity analysis is self-consistent and based on the volume fraction profiles of all chemical components. The saccharide profiles are found to be bimodal, with dense inner oligosaccharides and more dilute, extended O-side chains. For interacting LPS monolayers, we establish the pressure-distance curve and determine the distance-dependent saccharide conformation.