Relationships between BK virus lineages and human populations

BK polyomavirus (BKV) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney, in which it can cause nephropathy in renal transplant patients. BKV isolates are classified into four subtypes (I-IV) using serological or genotyping methods, and subtype I is further divided into four subgroups, Ia, Ib-1, Ib-2, and Ic, based on DNA sequence variations. To clarify whether there is an association between BK virus lineages and human populations, we examined BKV-positive urine samples collected from immunocompetent individuals at various locations in Europe, Africa, and Asia. Partial BKV DNA sequences (n=299) in these samples were determined and subjected to phylogenetic and single nucleotide polymorphism analysis to classify BKV isolates around the world. The validity of the classification was confirmed by analyses based on complete BKV DNA sequences. Subtype I was the major subtype throughout the studied regions, and subtype IV was prevalent only in Asia and Europe. Subtype-I subgroups showed close relationships to major geographical areas. It has recently been shown that JC virus (a human polyomavirus closely related to BKV) co-evolved with human populations, and the present study thus suggests that host-linked evolution is the general mode of polyomavirus evolution. Additionally, our results indicate certain unique aspects of the relationship between BKV and humans.     

Hypermetabolism of fat in V1a vasopressin receptor knockout mice

[Arg8]Vasopressin (AVP) has an antilipolytic action on adipocytes, but little is known about the mechanisms involved. Here, we examined the involvement of the V1a receptor in the antilipolytic effect of AVP using V1a receptor-deficient (V1aR-/-) mice. The levels of blood glycerol were increased in V1aR-/- mice. The levels of ketone bodies, such as acetoacetic acid and 3-hydroxybutyric acid, the products of the lipid metabolism, were increased in V1aR-/- mice under a fasting condition. Triacylglyceride and free fatty acid levels in blood were decreased in V1aR-/- mice. Furthermore, measurements with tandem mass spectrometry determined that carnitine and acylcarnitines in serum, the products of beta-oxidation, were increased in V1aR-/- mice. Most acylcarnitines were increased in V1aR-/- mice, especially in the case of 2-carbon (C2), C10:1, C10, C14:1, C16, C18:1, and hydroxy-18:1-carbon (OH-C18:1)-acylcarnitines under feeding rather than under fasting conditions. The analysis of tissue C2-acylcarnitine level showed that beta-oxidation was promoted in muscle under the feeding condition and in liver under the fasting condition. An in vitro assay using brown adipocytes showed that the cells of V1aR-/- mice were more sensitive to isoproterenol for lipolysis. These results suggest that the lipid metabolism is enhanced in V1aR-/- mice. The cAMP level was enhanced in V1aR-/- mice in response to isoproterenol. The phosphorylation of Akt by insulin stimulation was reduced in V1aR-/- mice. These results suggest that insulin signaling is suppressed in V1aR-/- mice. In addition, the total bile acid, taurine, and cholesterol levels in blood were increased, and an enlargement of the cholecyst was observed in V1aR-/- mice. These results indicated that the production of bile acid was enhanced by the increased level of cholesterol and taurine. Therefore, these results indicated that AVP could modulate the lipid metabolism by the antilipolytic action and the synthesis of bile acid via the V1a receptor.     

Role of humic acid fraction with higher aromaticity in enhancing the activity of a biomimetic catalyst, tetra(p-sulfonatophenyl)porphineiron(III)

To elucidate the structural features of humic acids (HAs) that potentially contribute to enhancing the activity of a tetra(p-sulfonatophenyl)porphineiron(III) (Fe(III)-TPPS) catalyst, the effects of the chemical properties of molecular weight fractionated HAs on the catalytic activity of Fe(III)-TPPS were investigated. Three fractions were obtained as the following order of molecular size: F3 < F2 < F1. The deactivation of Fe(III)-TPPS, which can be attributed to the self-degradation of Fe(III)-TPPS, was retarded in the presence of HAs, and the pseudo-first-order rate constant in the presence of F3 was the smallest of the three fractions. In addition, the highest catalytic activity, determined as the percent degradation of an organic substrate, was observed in the presence of F3. The enhanced catalytic activity of Fe(III)-TPPS was due to the formation of supramolecular complexes with HAs, and the formation constant for F3 was the largest. Thus, the F3 fraction was the most effective fraction. Solid-state CPMS 13C NMR spectra indicated that the aromaticity of F3 was the highest of all of the fractions. Thus, it can be concluded that aromatic moieties in HAs play an important role in the formation of supramolecular complexes with Fe(III)-TPPS, leading to an enhancement in catalytic activity.     

Exploration of Pericyte-Derived Factors Implicated in Lung Cancer Brain Metastasis Protection: A Pilot Messenger RNA Sequencing Using the Blood–Brain Barrier In Vitro Model

Cellular and Molecular Neurobiology - Metastatic brain tumors have poor prognoses and pose unmet clinical problems for the patients. The blood–brain barrier (BBB) implication is supposed to...     

The status of donor cancer tissues affects the fate of patient-derived colorectal cancer xenografts in NOG mice

Patient-derived xenografts (PDXs) of tumors are increasingly becoming important tools for translational research in oncology. The NOD.Cg-Prkdc^scid Il2rg^tm1Sug/Jic (NOG) mouse is an efficient host for PDXs. Thus as a basis for future development of methods to obtain PDXs from various disease types, we have studied the factors that affect the outcome of transplantation of human colorectal cancer in NOG mice. Of the original donor cases examined, 73% had successful engraftment. The outcome of donor-matched tissues was consistent in most cases, and was thought to show that the condition of the host did not affect engraftment. Next we analyzed the tumor aggressiveness in terms of histology grade of the original tumor and found that they were related to engraftment. Detailed histopathological examination of the transplanted tissues strongly indicated that lymphocytes engrafted with the tumor cells affect engraftment. As a factor related to transplantation of lymphocytes, we studied the human IgG concentration in the serum of tumor-bearing mice, but there was no tendency for higher concentrations to result in unsuccessful engraftment. Finally, we studied the type, density and location of T cells in the original donor tissue to determine the immune contexture and found that the unsuccessful engraftment cases tended to have an adequate or coordinated immune contexture compared to successful engraftment cases. From these results, we concluded that the aggressiveness and the T cell infiltration of the original tumor affect the outcome of transplantation in the NOG mouse.     

Effect of hypochlorous acid solution on the eradication and prevention of Pseudomonas aeruginosa infection,serum biochemical variables,and cecum microbiota in rats

In this study, hypochlorous acid solution, a weak acid, provided as drinking water to rats, was evaluated for its ability to eradicate and prevent Pseudomonas aeruginosa infection, while monitoring its simultaneous effect on serum biochemical variables and microbiota in the rat cecum. The results suggest that the solution could not eliminate the bacteria in the experimentally infected rats; however, the administration of a 10-parts-per-million (ppm) hypochlorous acid solution as drinking water was effective in inhibiting horizontal spread of P. aeruginosa infection among cage mates. Additionally, exposure to hypochlorous solution did not have any effect on serum biochemical variables of the rat including levels of total cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, total bilirubin, lipase, amylase, urea nitrogen, total protein, calcium (Ca), phosphorus (P), sodium (Na), chlorine (Cl), except for potassium (K) levels. The most frequently isolated bacteria in the rat cecum included species belonging to Bacteroidales, Lactobacillus, Clostridiales, Erysipelotrichaceae, Akkermansia, Coriobacteriales, and Firmicutes. The ratio of the terminal restriction fragment length polymorphism (T-RFLP) peaks did not differ across rats administered with 5 and 10 ppm weak acid solution as compared to the control group for any of the bacteria, except for Erysipelotrichaceae and Firmicutes, where the ratio of T-RFLP peaks was higher in the 5 ppm group for Erysipelotrichaceae and in the 10 ppm group for Firmicutes than that in the control group (P<0.01). The results suggest that the weak acid hypochlorous solution could not eradicate P. aeruginosa completely from rats. The solution was effective in preventing infection without affecting serum biochemical variables; however, some of bacterial microbiota may have changed due to administration of the solution.     

Potential of carotenoids in aquatic yeasts as a phylogenetically reliable marker and natural colorant for aquaculture

Apart from Xanthophyllomyces dendrorhous, pink colony-forming yeasts have not been examined as a pigmentation source in captive animals. In this study, aquatic yeasts were screened with a view to abundances of carotenoids. Phylogenetic analyses of these caroetnoid-rich yeasts based on large subunit ribosomal RNA gene (LSU rDNA) partial sequences showed that all belonged to the order Sporidiobolales. Both the qualitative and the quantitative differences in carotenoids between the yeasts appeared to be consistent with their phylogenetic affiliations. This information might be useful in the selection of pigment-rich yeasts containing specific carotenoids from a large number of strains. We also found, for the first time, the potential of a pigment-rich Rhodotorula strain as a colorant for aquaculture. The integuments of tilapia and carp fed the alkali-treated cells of strain Rhodotorula dairenensis Sag 17 were pigmented after 3 months of cultivation. The fish integuments retained the yeast carotenes shortly after the start of feeding, and were converted to the fish-specific xanthophylls in vivo.