Cell Surface Glycosaminoglycans As Receptors for Adhesion of Candida Spp. To Corneal Cells

The most common causal agents of fungal keratitis are yeasts of the Candida genus. Adhesion constitutes the first stage of pathogenesis. Previous studies have shown that glycosaminoglycans from the corneal cell surface play an essential role in bacterial keratitis, although little is known about their role in fungal infections. The objective of this work is to analyze the role that glycosaminoglycans (GAGs) play in the adhesion of fungi of the Candida genus to corneal epithelial cells. The participation of GAGs in the adhesion of fungi was studied through the specific inhibition of the synthesis of these molecules by enzymatic digestion using specific lyases and the silencing of various genes involved in heparan sulfate sulfation. The results seem to indicate that glycosaminoglycans act to some extent as receptors for this fungus, although there are differences between fungal species. Treatment with inhibitors partially reduced the adherence of fungal species. Digestion of cell surface heparan sulfate further reduced the adherence of Candida albicans and Candida glabrata compared to chondroitin sulfate, indicating that the binding is preferentially mediated by heparan sulfate. Degradation of both heparan sulfate and chondroitin sulfate produced similar effects on the adherence of Candida parapsilosis. However, adhesion of C. albicans hyphae is not dependent on GAGs, suggesting the expression of other adhesins and the recognition of other receptors present in corneal cells. Our results open the door to new strategies for stopping the adhesion of pathogenic fungi, and their subsequent invasion of the cornea; thus, reducing the probability of the keratitis development.     

Multiresistant Enterobacteriaceae in yellow‐legged gull chicks in their first weeks of life

Wild animal species living in anthropogenic areas are commonly carriers of antimicrobial‐resistant bacteria (AMRB), but their role in the epidemiology of these bacteria is unclear. Several studies on AMRB in wildlife have been cross‐sectional in design and sampled individual animals at only one point in time. To further understand the role of wildlife in maintaining and potentially transmitting these bacteria to humans and livestock, longitudinal studies are needed in which samples are collected from individual animals over multiple time periods. In Europe, free‐ranging yellow‐legged gulls (Larus michahellis) commonly live in industrialized areas, forage in landfills, and have been found to carry AMRB in their feces. Using bacterial metagenomics and antimicrobial resistance characterization, we investigated the spatial and temporal patterns of AMRB in a nesting colony of yellow‐legged gulls from an industrialized area in southern France. We collected 54 cloacal swabs from 31 yellow‐legged gull chicks in 20 nests on three dates in 2016. We found that AMRB in chicks increased over time and was not spatially structured within the gull colony. This study highlights the complex occurrence of AMRB in a free‐ranging wildlife species and contributes to our understanding of the public health risks and implications associated with ARMB‐carrying gulls living in anthropogenic areas.     

Ulcerative Colitis Seems to Imply Oral Microbiome Dysbiosis

Ulcerative colitis (UC) is a recurrent pathology of complex etiology that has been occasionally associated with oral lesions, but the overall composition of the oral microbiome in UC patients and its role in the pathogenesis of the disease are still poorly understood. In this study, the oral microbiome of UC patients and healthy individuals was compared to ascertain the possible changes in the oral microbial communities associated with UC. For this, the salivary microbiota of 10 patients diagnosed with an active phase of UC and 11 healthy controls was analyzed by 16S rRNA gene sequencing (trial ref. ISRCTN39987). Metataxonomic analysis revealed a decrease in the alpha diversity and an imbalance in the relative proportions of some key members of the oral core microbiome in UC patients. Additionally, Staphylococcus members and four differential species or phylotypes were only present in UC patients, not being detected in healthy subjects. This study provides a global snapshot of the existence of oral dysbiosis associated with UC, and the possible presence of potential oral biomarkers.     

Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging

Several human progerias, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by the accumulation at the nuclear envelope of farnesylated forms of truncated prelamin A, a protein that is also altered during normal aging. Previous studies in cells from individuals with HGPS have shown that farnesyltransferase inhibitors (FTIs) improve nuclear abnormalities associated with prelamin A accumulation, suggesting that these compounds could represent a therapeutic approach for this devastating progeroid syndrome. We show herein that both prelamin A and its truncated form progerin/LADelta50 undergo alternative prenylation by geranylgeranyltransferase in the setting of farnesyltransferase inhibition, which could explain the low efficiency of FTIs in ameliorating the phenotypes of progeroid mouse models. We also show that a combination of statins and aminobisphosphonates efficiently inhibits both farnesylation and geranylgeranylation of progerin and prelamin A and markedly improves the aging-like phenotypes of mice deficient in the metalloproteinase Zmpste24, including growth retardation, loss of weight, lipodystrophy, hair loss and bone defects. Likewise, the longevity of these mice is substantially extended. These findings open a new therapeutic approach for human progeroid syndromes associated with nuclear-envelope abnormalities.     

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.     

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.     

Classical swine fever virus p7 protein is a viroporin involved in virulence in swine

The nonstructural protein p7 of classical swine fever virus (CSFV) is a small hydrophobic polypeptide with an apparent molecular mass of 6 to 7 kDa. The protein contains two hydrophobic stretches of amino acids interrupted by a short charged segment that are predicted to form transmembrane helices and a cytosolic loop, respectively. Using reverse genetics, partial in-frame deletions of p7 were deleterious for virus growth, demonstrating that CSFV p7 function is critical for virus production in cell cultures. A panel of recombinant mutant CSFVs was created using alanine scanning mutagenesis of the p7 gene harboring sequential three- to six-amino-acid residue substitutions spanning the entire protein. These recombinant viruses allowed the identification of the regions within p7 that are critical for virus production in vitro. In vivo, some of these viruses were partially or completely attenuated in swine relative to the highly virulent parental CSFV Brescia strain, indicating a significant role of p7 in CSFV virulence. Structure-function analyses in model membranes emulating the endoplasmic reticulum lipid composition confirmed that CSFV p7 is a pore-forming protein, and that pore-forming activity resides in the C-terminal transmembrane helix. Therefore, p7 is a viroporin which is clearly involved in the process of CSFV virulence in swine.     

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.