Free-Ranging Frigates (Fregata magnificens) of the Southeast Coast of Brazil Harbor Extraintestinal Pathogenic Escherichia coli Resistant to Antimicrobials

Seabirds may be responsible for the spread of pathogenic/resistant organisms over great distances, playing a relevant role within the context of the One World, One Health concept. Diarrheagenic E. coli strains, known as STEC (shiga toxin-producing E. coli), and the extraintestinal pathogenic E. coli (ExPEC and the subpathotype APEC), are among the E. coli pathotypes with zoonotic potential associated with the birds. In order to identify health threats carried by frigates and to evaluate the anthropic influence on the southern coast of Brazil, the aim of this work was to characterize E. coli isolated from free-ranging frigates in relation to virulence genotypes, serotypes, phylogenetic groups and antimicrobial resistance. Cloacal and choanal swabs were sampled from 38 Fregata magnificens from two oceanic islands and one rescue center. Forty-three E. coli strains were recovered from 33 out of the 38 birds (86.8%); 88.4% of strains showed some of the virulence genes (VGs) searched, 48.8% contained three or more VGs. None of the strains presented VGs related to EPEC/STEC. Some of the isolates showed virulence genotypes, phylogenetic groups and serotypes of classical human ExPEC or APEC (O2:H7, O1:H6, ONT:H7, O25:H4). Regarding antimicrobial susceptibility, 62.8% showed resistance, and 11.6% (5/43) were multidrug-resistant. The E. coli present in the intestines of the frigates may reflect the environmental human impact on southeast coast of Brazil; they may also represent an unexplored threat for seabird species, especially considering the overlap of pathogenic potential and antimicrobial resistance present in these strains.     

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF

Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.     

Error-threshold exists in fitness landscapes with lethal mutants

Background  

One of the important insights of quasi-species theory is an error-threshold. The error-threshold is the error rate of replication above which the sudden onset of the population delocalization from the fittest genotype occurs despite Darwinian selection; i.e., the break down of evolutionary optimization. However, a recent article by Wilke in this journal, after reviewing the previous studies on the error-threshold, concluded that the error-threshold does not exist if lethal mutants are taken into account in a fitness landscape. Since lethal mutants obviously exist in reality, this has a significant implication about biological evolution. However, the study of Wagner and Krall on which Wilke's conclusion was based considered mutation-selection dynamics in one-dimensional genotype space with the assumption that a genotype can mutate only to an adjoining genotype in the genotype space. In this article, we study whether the above conclusion holds in high-dimensional genotype space without the assumption of the adjacency of mutations, where the consequences of mutation-selection dynamics can be qualitatively different.     

Time lag of the response on the otolith strontium/calcium ratios of the Japanese eel, <Emphasis Type="Italic">Anguilla japonica</Emphasis> to changes in strontium/calcium ratios of ambient water

We conducted a laboratory experiment to validate the relationship between the otolith strontium/calcium (Sr/Ca) ratio of Japanese eels (Anguilla japonica) and water Sr/Ca ratio when the ratio in water was changed. A linear and additive mixed modeling approach was used to assess otolith Sr/Ca ratio for elver-juvenile Japanese eels when ambient water was changed from seawater to freshwater. There was a significant difference between otolith Sr/Ca ratios of eels reared in freshwater and in seawater (freshwater: 1.3–2.3; seawater: 7.0–7.8 mmol/mol). The response of otolith Sr/Ca ratios of eels was not detected until after 10 d and models suggested that it might not be completed until at least 30–60 d. This study indicated the detailed ability of otolith Sr/Ca ratio to be used as a proxy for reconstructing the individual environmental history of Japanese eels. These findings can provide some assurances for future otolith Sr/Ca studies of eels in this system or in other areas that have similar environmental conditions.     

Deficiency of macrophage migration inhibitory factor gene delays healing of the medial collateral ligament: a biomechanical and biological study

The role played by macrophage migration inhibitory factor (MIF) in the process of wound healing is controversial. Besides, there have been no reports that investigated the expression or the role of MIF in the repair process after ligament injury. In this study, we hypothesized that the deficiency in MIF gene might delay ligament healing in mice. The aim of this study was to clarify this hypothesis using MIF gene-deficient mice (MIFKO) and murine model of injury to the medial collateral ligament (MCL). Biomechanical testing showed that the levels of mechanical properties were significantly lower in MIFKO than in wild-type mice (WT) on day 28 after injury. Levels of matrix metalloproteinase (MMP)-2 and -13 mRNA in the healing tissue were significantly lower in MIFKO than in WT on day 28 and on day 7, respectively. Histologically, healing tissues in MIFKO exhibited prolonged hypertrophy, poor vascularity, and prolonged increase in cell number compared with those in WT. Taken together, it was suggested that MIFKO exhibited delayed healing of the MCL, which might be caused by lower mRNA expression of MMP-2 and -13.