Transient muscle paralysis degrades bone via rapid osteoclastogenesis

A unilateral injection of botulinum toxin A (BTxA) in the calf induces paralysis and profound loss of ipsalateral trabecular bone within days. However, the cellular mechanism underlying acute muscle paralysis-induced bone loss (MPIBL) is poorly understood. We hypothesized that MPIBL arises via rapid and extensive osteoclastogenesis. We performed a series of in vivo experiments to explore this thesis. First, we observed elevated levels of the proosteoclastogenic cytokine receptor activator for nuclear factor-κB ligand (RANKL) within the proximal tibia metaphysis at 7 d after muscle paralysis (+113%, P<0.02). Accordingly, osteoclast numbers were increased 122% compared with the contralateral limb at 5 d after paralysis (P=0.04) and MPIBL was completely blocked by treatment with human recombinant osteoprotegerin (hrOPG). Further, conditional deletion of nuclear factor of activated T-cells c1 (NFATc1), the master regulator of osteoclastogenesis, completely inhibited trabecular bone loss (-2.2±11.9%, P<0.01). All experiments included negative control assessments of contralateral limbs and/or within-animal pre- and postintervention imaging. In summary, transient muscle paralysis induced acute RANKL-mediated osteoclastogenesis resulting in profound local bone resorption. Elucidation of the pathways that initiate osteoclastogenesis after paralysis may identify novel targets to inhibit bone loss and prevent fractures.     

Second-order functions are the simplest correlations between flow cytometric light scatter and bacterial diameter

Second-order mathematical relationships between bacterial cell diameter determined by electric particle analyser and flow cytometric forward light scatter in axenic cultures are obtained and discussed. Since it is technically impossible today to obtain both measurements for each individual cell, standard regression techniques cannot be applied. To overcome this limitation, we assume that these two parameters are related by a monotone increasing function that enables their mathematical relationships to be studied. Our conclusion is that forward light scatter data cannot be linearly transformed into bacterial size values by an accurate and universal function. However, second-order relationships seem to be the simplest satisfactory relationships between cell diameter and forward light scatter in eubacteria.     

Enzymes of SPZ7 phage: Isolation and properties

Bacteriophage enzyme preparations exolysin and endolysin were studied. Exolysin (a phage-associated enzyme) was obtained from tail fraction and endolysin from phage-free cytoplasmic fraction of disintegrated Salmonella enteritidis cells. A new method for purification of these enzymes was developed, and their molecular masses were determined. The main catalytic properties of the studied enzymes (pH optimum and specificity to bacterial substrates) were found to be similar. Both enzymes lyse Escherichia coli cells like chicken egg lysozyme, but more efficiently lyse S. enteritidis cells and cannot lyse Micrococcus luteus, a good substrate for chicken egg lysozyme. Similar properties of exolysin and endolysin suggest that these enzymes are structurally similar or even identical.     

Dendritic Cells Loaded with Tumor Antigens and a Dual Immunostimulatory and Anti-Interleukin 10-Specific Small Interference RNA Prime T Lymphocytes against Leukemic Cells

Vaccines using dendritic cells (DCs) harboring leukemic antigens to stimulate T cells is a possible treatment of acute myeloid leukemia (AML). Limitations of breaking tolerance to leukemic cells and lack of specific activation of T cell-mediated cytotoxicity may explain the discouraging clinical results with this approach. To break self-tolerance against AML cells, we loaded DCs with AML antigens and a bifunctional small interference (si) RNA targeting interleukin (IL) 10 and simultaneously activating toll-like receptors (TLRs). In vitro, this active siRNA inhibited (P < .05) IL-10 production by silencing the IL-10 gene in DCs. The active siRNA stimulated production of tumor necrosis factor α, implying activation of TLRs. Vaccination in a nonimmunogenic rat model mimicking human AML with the loaded DCs induced a substantial and specific T-cell cytotoxicity. Leukemic rats treated with the active siRNA lived longer and had markedly less leukemic cell mass infiltrating their bone marrow compared with rats given inactive siRNA (P < .05). Furthermore, compared with inactive siRNA treatment, the active siRNA led to significantly less extramedullar leukemic dissemination, evidenced by reduced matrix metalloproteinase activity and smaller spleens. Our data demonstrate that this bifunctional siRNA may work as an immunomodulatory drug with antileukemic properties.     

Fecal steroid metabolites and reproductive monitoring in a female Tsushima leopard cat (Prionailurus bengalensis euptilurus)

Although the Tsushima leopard cat (Prionailurus bengalensis euptilurus) is one of the most endangered mammals in Japan, its reproductive physiology and endocrinology have been not elucidated. The objective was to establish the non-invasive monitoring of reproductive endocrinology in a female Tsushima leopard cat and to identify the types of fecal reproductive steroid metabolites in this species. Fecal concentrations of estrogen and progestin were determined by enzyme immunoassays, from 60 d before to 60 d after the last copulation, during three pregnancies. Fecal estrogen metabolite concentrations were increased before/around the mating period and after mid-pregnancy. Fecal progestin metabolite concentrations increased after the last copulation and remained high during pregnancy. The gestation period was 65.0 ± 0.6 d (mean ± SD). Fecal extracts were separated by high-performance liquid chromatography for identification of fecal metabolites. Fecal estrogens were identified as estradiol-17β and estrone. Fecal progestins during pregnancy contained 5α-reduced pregnanes: 5α-pregnan-3α-ol-20-one, 5α-pregnan-3β-ol-20-one and 5α-pregnan-3,20-dione, and nonmetabolized progesterone was barely detected in feces. In conclusion, measurement of fecal estrogen and progestin metabolites was effective for noninvasive reproductive monitoring in the Tsushima leopard cat. An immunoassay for fecal estradiol-17β concentrations seemed useful to monitor follicular activity, whereas an immunoassay with high cross reactivity for 5α-reduced pregnanes was useful to monitor ovarian luteal activity and pregnancy.     

Do female tamarins use visual cues to detect fruit rewards more successfully than do males?

Primates are unique among eutherian mammals for possessing trichromatic colour vision. It is generally proposed that trichromacy evolved to aid detection of ripe fruits against mature foliage. However, while trichromacy is routine in all Old World monkeys and apes (the catarrhines), a cone opsin polymorphism in New World monkeys (the platyrrhines) results in foraging groups with mixed capacities for chromatic distinction. Although 50-66% of female platyrrhines are trichromatic, all males are dichromatic. Here, we test the hypothesis that trichromatic platyrrhines use visual cues to detect fruit rewards more successfully than do males. Specifically, we ask whether female emperor tamarins, Saguinus imperator imperator, and saddleback tamarins, S. fuscicollis weddelli, are the first members of their foraging group to locate food patches; and, furthermore, whether they are more successful than males in using colour, shape and size cues to discriminate between sham and reward feeding sites. Our results show that females and males do not differ in their ability to locate or discriminate between feeding sites. We conclude that trichromatic vision in female tamarins does not confer an advantage for detecting yellow fruit rewards against mature foliage. Copyright 2003 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.      

Weight decline in body,carcass, organs,and “gut fill” of sheep during the long dry seasons of the sub-Saharan West Africa

Data were collected from 188 indigenous (92 Uda and 96 Yankasa) breeds of sheep slaughtered at Maiduguri abbatoir from November 1983 to May 1984 to study decline in weight of body, carcass, organs, and gut fill in animals during the long dry seasons of the sub-Saharan West Africa. There was a highly significant (P<0.001) decline in all traits, which was most rapid by March–May (the hottest season), which is also the end of the long dry spell. From December to May the skin suffered greatest decline (about 58%), followed by the intestine (about 48%), liver, and stomach (about 44% respectively), and the head (about 41%). Total decline was 32% and 30% for body and carcass weights respectively. The Uda, which is the larger breed, apparently suffered greater overall depreciation. Both the absolute and relative weights of the liver seem larger in tropical- than in temperate-type sheep. However, liveweight, empty body, carcass, skin weights obtained herein are comparable with data from lambs of only 2-to 16-week old temperate sheep. Also the highest gut fill (3.91 kg, about 11% of body weight) recorded for these adult tropical sheep was far inferior to the 6.58 kg or 17% of body weight recorded for 16-week old lambs of temperate sheep. These may be forms of physiological responses to warm tropical environments, or simply, a very good reflection of the nutritional differences existing between animals of the tropical world on one hand and those of the temperate countries on the other. Studies on these topics would prove invaluable for successful livestock improvement programmes here.