On the definition and the computation of the type-reproduction number T for structured populations in heterogeneous environments

In the context of mathematical epidemiology, the type-reproduction number (TRN) for a specific host type is interpreted as the average number of secondary cases of that type produced by the primary cases of the same host type during the entire course of infection. Here, it must be noted that T takes into account not only the secondary cases directly transmitted from the specific host but also the cases indirectly transmitted by way of other types, who were infected from the primary cases of the specific host with no intermediate cases of the target host. Roberts and Heesterbeek (Proc R Soc Lond B 270:1359–1364, 2003) have shown that T is a useful measure when a particular single host type is targeted in the disease control effort in a community with various types of host, based on the fact that the sign relation sign(R ₀ ? 1) = sign(T ? 1) holds between the basic reproduction number R ₀ and T. In fact, T can be seen as an extension of R ₀ in a sense that the threshold condition of the total population growth can be formulated by the reproduction process of the target type only. However, the original formulation is limited to populations with discrete state space in constant environments. In this paper, based on a new perspective of R ₀ in heterogeneous environments (Inaba in J Math Biol 2011), we give a general definition of the TRN for continuously structured populations in heterogeneous environments and show some examples of its computation and applications.     

Expression of Myostatin in Neural Cells of the Olfactory System

Recent studies show that myostatin mRNA expression is found in some regions of the brain. However, the functional significance of this is currently unknown. We therefore investigated myostatin expression and function in the brain. In this study, we used immunohistochemistry, in situ hybridization, and RT-PCR analysis to reveal that myostatin is expressed in the mitral cells in the olfactory bulb (OB) and in neurons in the olfactory cortex (OC). Using 3D reconstruction, mitral cells positive for myostatin were positioned in the lateral and ventral regions of the OB. In contrast, myostatin-positive mitral cells were detected in mice at 2 weeks of age, but not on days 0 and 7 after birth. Activin receptor IIB, a myostatin receptor, was expressed in the OB, OC, hippocampus, and paraventricular thalamic nucleus. Moreover, c-Fos immunostaining in granule cells in the OB was augmented after intracerebroventricular injection of myostatin. These findings suggest that myostatin is localized in specific cells associated with the olfactory system of the brain and may act as a key inhibitor in cell and/or signal development of the olfactory system.     

Acylated dolabellane-type diterpenes from Nigella sativa seeds with triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells

Two new acylated dolabellane-type diterpenes, nigellamines B₃ (9) and D (10), were isolated from Nigella sativa (Ranunculaceae) seeds using column chromatography and preparative HPLC. Their structures were determined based on chemical and physicochemical evidence, and confirmed using previously isolated related compounds as reference. Of the seed constituents, nigellamines A₂ (2), A₃ (3), A₅ (5), B₁ (6), and B₂ (7) had in vitro triglyceride metabolism-promoting activities in the high glucose-pretreated human liver carcinoma cell line, HepG2.     

Inflammatory Cytokine Gene Expression in Mesenteric Adipose Tissue during Acute Experimental Colitis

Background

Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT.

Methods

Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water) for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF), and mesenteric lymph nodes.

Results

During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF.

Conclusions

Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.     

Synovial perlecan is required for osteophyte formation in knee osteoarthritis

The osteophyte associated with osteoarthritis (OA) is a bony outgrowth formed at the margins of the affected joint through endochondral ossification-like processes. However, the mechanism of osteophyte formation and its pathogenesis are unclear. Perlecan (Hspg2), a heparan sulfate proteoglycan, is expressed in many extracellular tissues and plays critical roles in skeletal development and diseases. The aim of the present study is to identify the role of synovial perlecan in osteophyte formation using perinatal lethality rescued perlecan-knockout mice (Hspg2^?/?-Tg) wherein perlecan expression is lacking in the synovial and other tissues, except for cartilage. We analyzed the development of osteophytes in joints of Hspg2^?/?-Tg mice in two different animal models: the surgical OA model, in which the medial collateral ligament was transected and the medial meniscus was resected, and the TGF-β-induced osteophyte formation model. In the surgical OA model, the osteophyte size and maturation were significantly reduced in the OA joints of Hspg2^?/?-Tg mice compared with control mice, while OA developed on the medial side of the knee joints with no differences in the cartilage degradation score or synovitis score between control and Hspg2^?/?-Tg mice. The reduced osteophyte formation in Hspg2^?/?-Tg mice was associated with reduced cell proliferation and chondrogenesis. In the TGF-β model, the osteophyte size and maturation were also significantly reduced in Hspg2^?/?-Tg mice compared with control mice. Our findings suggest that synovial perlecan plays an important role in osteophyte development in OA, and they provide insights that may facilitate the development of OA therapy.     

Two-dimensional NMR Investigation of Solanascone

2-n-Heptyl-4-hydroxyquinoline-N-oxide (KF8940), isolated from Pseudomonas methanica, was a potent and selective inhibitor of the arachidonate 5-lipoxygenase of rat basophilic leukemia (RBL-1) cells. Kinetic analysis indicated that the inhibitory mode was non competitive. The Ki value was 3.5 × 10^?7 m. KF8940 also inhibited 12-lipoxygenase of bovine platelets in a non-competitive manner, but with a Ki value of 7 × 10^?5M. Ionophore A23187-stimulated SRS generation from rat peritoneal cells and antigen-stimulated SRS-A generation from sensitized rat lung were significantly inhibited by KF8940. KF8940 at a dose of 10 mg/kg (p.o.) suppressed the passive anaphylactic bronchoconstriction in guinea pigs.     

An Easy Synthesis of (E)-9-Oxo-2-decenoic Acid,the Queen Substance of the Honey Bee,and (Z)-6-Heneicosen-ll-one,the Sex Pheromone of the Douglas Fir Tussock Moth†

We investigated the effect of dietary phospholipid (PL) concentrate from bovine milk on the epidermis. Thirteen-week-old hairless male and female mice (Hos:HR-1) were separated into two experimental groups, each fed two experimental diets: the control group and the PL group. The mice were given the experimental diets for 6 weeks. Stratum corneum hydration and transepidermal water loss (TEWL) were measured using Corneometer CM825 and Tewameter TM300 (Courage and Khazaka Electronics, Cologne, Germany) at 3 weeks and 6 weeks. After the feeding period, ceramides in stratum corneum were analyzed. We found that stratum corneum hydration and ceramides in the PL group were significantly higher than those in the control group and that TEWL in the PL group tended to decrease.

These results indicate that dietary PL concentrate improves epidermal function by increasing the amount of ceramides, resulting in higher hydration.     

Phenol Ethers and Terpenes of Six Heterotropa Species Distributed in the Ryukyu Islands and Formosa

A new intracellular peptidase, which we call “d-peptidase S,” was purified from Nocardia orientalis IFO 12806 (ISP 5040). The purified enzyme was homogeneous on disc gel electrophoresis. The molecular weight and the isoelectric point were estimated to be 52,000 and 4.9, respectively. The optimum pH for the hydrolysis of d-leucyl-d-leucine was 8.0 to 8.1, and the optimum temperature was 36°C. The purified enzyme usually hydrolyzed the peptide bonds preceding the hydrophobic D-amino acids of dipeptides. Tri- and tetra-peptides extending to the amino terminus of such peptides were also hydrolyzed. Therefore, the enzyme is a carboxylpeptidase-like peptidase specific to d-amino acid peptides. The Km values for d-leucyl-d-leucine and l-leucyl-d-leucine were 0.21 × 10^-3 and 0.44 × 10^-3 m respectively. The activity was inhibited by several sulfhydryl reagents and two chelators, 8-hydroxyquinoline and o-phenanthroline.