Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states

Skeletal muscle has the ability to achieve rapid repair in response to injury or disease. Many individuals with Marfan syndrome (MFS), caused by a deficiency of extracellular fibrillin-1, exhibit myopathy and often are unable to increase muscle mass despite physical exercise. Evidence suggests that selected manifestations of MFS reflect excessive signaling by transforming growth factor (TGF)-beta (refs. 2,3). TGF-beta is a known inhibitor of terminal differentiation of cultured myoblasts; however, the functional contribution of TGF-beta signaling to disease pathogenesis in various inherited myopathic states in vivo remains unknown. Here we show that increased TGF-beta activity leads to failed muscle regeneration in fibrillin-1-deficient mice. Systemic antagonism of TGF-beta through administration of TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor blocker losartan normalizes muscle architecture, repair and function in vivo. Moreover, we show TGF-beta-induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy.     

Management of early-instar Japanese beetle (Coleoptera: Searabaeidae) in field-grown nursery crops.

Numerous field studies were conducted in commercial nurseries in Tennessee from 1996 through 1999 to evaluate chemical and biological treatments, application timing and rates, and method of application for control of early instars of Japanese beetle, Popillia japonica Newman. Insecticide treatments included bifenthrin, bendiocarb, chlorpyrifos, carbaryl, fipronil, halofenozide, imidacloprid, permethrin, tefluthrin, thiamethoxam, and trichlorfon. Biological treatments included entomopathogenic nematodes (Heterorhabditis bacteriophora HP88 or H. marelatus, Bacillus thuringiensis Berliner subspecies japonensis Buibui strain, and Beauveria bassiana (Balsamo) Vuillemin. All treatments were applied on the soil surface or injected into the soil around the base of each tree. Tree type and size varied among and within tests, however, the sampling unit (61-cm-diameter root ball) remained the same throughout all tests. The biological treatments provided poor-to-moderate control (0-75%) of Japanese beetle larvae. Imidacloprid was the most frequently evaluated insecticide and achieved 91-100, 87-100, 83-100, and 41-100% control with applications in May, June, July, and August, respectively. Halofenozide treatments were not significantly different from imidacloprid treatments with one exception. Halofenozide provided 60-87, 85-100, and 82-92 control with applications made in June, July, and August, respectively. Fipronil and thiamethoxam were evaluated to a lesser extent but both performed similarly to imidacloprid. Most other insecticide treatments were less successful in reducing numbers of Japanese beetle larvae and with few exceptions achieved <50% control.     

Human IgG and Streptococcus mutans SR protein contain cross-reactive epitopes

Antigen B, a glycoprotein present on the cell surface of "mutans streptococci," mediates bacterial adherence to teeth surfaces and has been implicated in cross-reactivity with human heart components. Elevated levels of anti-IgG antibodies were generally found in sera of rabbits immunized with protein SR, a B-related protein from Streptococcus mutans serogroup f, or recombinant protein SR (rSR). These anti-IgG antibodies could be involved in the previously mentioned heart cross-reactivities. Results from immunoblots and ELISA analyses demonstrate that these anti-IgG antibodies recognize common epitopes on SR, rSR, and human IgG2 and IgG4 probably located on the Fab region. Furthermore, control experiments with biotinylated human IgG show that the cross-reactions between IgG and SR were not mediated by an FcR mechanism. Direct competition between rSR and human IgG in binding to anti-IgG or anti-SR antibodies confirm that S. mutans SR protein possesses Ag mimicry with human IgG. Our studies provide some evidence that S. mutans SR protein and human IgG H chains share autoimmune epitopes which could play a role in the induction of anti-IgG antibodies and therefore could explain the enhancement of anti-IgG antibody levels observed in rabbits immunized with either S. mutans whole cells or purified B-related Ag.     

P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics

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Relationship between Photoconvertible and Nonphotoconvertible Protochlorophyllides

Two forms of protochlorophyllide are found in dark-grown bean (Phaseolus vulgaris, var. Black Velentine) leaves, one (protochlorophyllide₆₅₀) which is directly photoconvertible to chlorophyllide and another (protochlorophyllide₆₃₂) which is not. Dark-grown leaves placed in solutions of δ-aminolevulinic acid accumulate protochlorophyllide₆₃₂. Protochlorophyllide₆₅₀ and protochlorophyllide₆₃₂ can be partially separated on sucrose density gradients. A nitrogen atmosphere blocks chlorophyll synthesis in light or the regeneration of protochlorophyllide₆₅₀ in the dark, even in the presence of excess δ-aminolevulinic acid, except when a stockpile of protochlorophyllide₆₃₂ is present in the leaf. Under the latter conditions chlorophyll synthesis or protochlorophyllide₆₅₀ regeneration is accompanied by a decrease in protochlorophyllide₆₃₂. These experiments suggest that protochlorophyllide₆₃₂ may be converted to protochlorophyllide₆₅₀.     

Uptake and fate of IAA in apple callus tissues: metabolism of IAA-2-14C

Young and old apple callus tissues were incubated in light ordarkness with IAA-2-¹⁴C. A large portion of the IAA disappearedfrom the medium with both young and old calluses. Whereas withold calluses the loss was mainly due to IAA destruction, youngcalluses accumulated IAA to a level which exceeded the externalconcentration and, in addition, seemed to protect it from breakdown.After 24 hr the level of IAA-2-¹⁴C in the medium dropped to50% with old calluses both in the dark and light, and with youngcalluses to 20% in the light and 50% in the dark. Chromatographyand scanning of the media and calluses showed that IAA was convertedinto two compounds (comp. A and comp. B). The amounts and proportionsof these metabolites in the medium and tissue were dependenton the different treatments and callus age. The breakdown ofIAA by old tissue gave rise to a higher level of comp. B bothin the tissue and medium, particularly after 6 hr of incubation.In the medium of young tissues the level of comp. A was higherthan comp. B while equal amounts of the two compounds were detectedin the tissue, itself. The origin of the IAA products in thetissue was probably endogenous and not via absorption from themedium. The IAA metabolism of apple callus tissues seems toproceed via the oxindole pathway and it is proposed that compoundsA and B are 3-hydroxymethyloxindole and 3-methylene oxindole,respectively. ¹ Contribution from the Agricultural Research Origanization,The Volcani Center, Bet Dagan, Israel. 1973 Series No. 275-E. (Received May 30, 1974; )     

Suppressed in vitro blastogenic responsiveness of rat spleen cells after continuous infusion of endotoxin by an implanted osmotic pump

Continuous infusion of a gram-negative bacterial endotoxin in relatively small doses into rats by means of an implanted osmotic pump was studied. The model system was designed to examine the effects of endotoxin on the blastogenic response of spleen cells to the endotoxin itself and to a nonspecific T-cell mitogen, concanavalin A (Con A). Rats were implanted with an osmotic pump which delivered saline for the first 42 hr to provide postsurgical recovery before the onset of endotoxin infusion. Previous studies had shown that during the first 1-4 days after administration of endotoxin marked alterations of metabolism and some changes in physiologic parameters such as blood pressure and in vitro myocardial performance occurred. In the present study the blastogenic responsiveness of spleen cells to endotoxin itself as well as to the nonspecific T-cell mitogen Con A was markedly decreased after several days of continuous administration of endotoxin. Control animals receiving only saline for the same period of time showed a similar depression of blastogenic responsiveness to the lipopolysaccharide (LPS), as well as to Con A, however, with a delay of 2-4 days before comparable levels of suppression became evident. These results indicate that marked alterations of immune competence as measured by blastogenesis of spleen cells to Escherichia coli LPS and to a mitogen such as Con A may occur after implantation of an osmotic pump, with or without continuous infusion of endotoxin. Further studies seem warranted to determine the role of the foreign body reaction to the osmotic pump as well as to the endotoxin administered by the pump.     

Identification of genomic regions that affect grain-mould incidence and other traits of agronomic importance in sorghum

Grain-mould is a major problem in grain sorghum utilization as mouldy grain has a reduced quality due to the deterioration of the endosperm and reduced embryo viability. Here, our objective was to use genome mapping to improve knowledge of genetic variation and co-variation for grain-mould incidence and other inter-related agronomic traits. Grain-mould incidence, kernel-milling hardness, grain density, plant height, panicle peduncle length, foliar-disease incidence, and plant color were measured on 125 F₅ genotypes derived from a cross of Sureño and RTx430. Quantitative trait loci were detected by means of 130 mapped markers (44 microsatellites, 85 AFLPs, one morphological-trait locus) distributed among ten linkage groups covering 970 cM. One to five QTLs affected each trait, with the exception of grain density for which no QTLs were detected. Grain-mould incidence was affected by five QTLs each accounting for between 10 and 23% of the phenotypic variance. The effects and relative positions of QTLs for grain-mould incidence were in accordance with the QTL distribution of several inter-related agronomic traits (e.g., plant height, peduncle length) and with the correlation between these phenotypic traits and grain-mould incidence. The detection of QTLs for grain-mould incidence was dependent on the environment, which is consistent with heritibility estimates that show strong environmental and genotype × environment effects. Several genomic regions affected multiple traits including one region that affected grain-mould incidence, plant height, panicle peduncle length, and grain-milling hardness, and a second region that influenced grain-mould (in four environments) and plant height. One genomic region, which harbors loci for plant color, influenced the severity of foliar disease symptoms and the incidence of grain-mould in one environment. Collectively QTLs detected in the present population explained between 10% and 55% of the phenotypic variance observed for a given trait.     

ANALYSIS OF PORPHYRA RBC L DEMONSTRATES MULTIPLE MIGRATIONS OCCURRED BETWEEN THE NORTH ATLANTIC AND NORTH PACIFIC.

Ground level ultraviolet-B (UV-B; 290–320 nm) fluxes in Antarctica have been increasing due to stratospheric ozone depletion. Although mat-forming cyanobacteria are major component of freshwater algal biomass in Antarctica, little is known about their response to increasing ultraviolet radiation (UVR). The present study evaluated the sensitivity to UVR of two strains of mat-forming cyanobacteria with different cell size, Phormidium murrayi (6.0 x 3.2 μm) and Schizothrix calcicola (2.2 x 2.3 μm). Cyanobacterial photosynthesis was measured under different UV spectral quality and quantity achieved by polychromatic filters with different cutoff wavelengths and neutral density screens. The productivity and irradiance data were used to generate biological weighting functions (BWF) for the assessment of UV inhibition on photosynthesis. The kinetics of UV inhibition, as determined by PAM fluorometry, differed between the two species so that inhibition of P. murrayi and S. calcicola were modeled based on UV-irradiance and cumulative exposure, respectively. After a one hour exposure, BWF's did not differ between the two isolates of cyanobacteria despite their differences in cell size. To evaluate the negative impact of increased UV-B exposure due to ozone depletion on cyanobacteria, the BWF's were applied to two solar spectra obtained from McMurdo Station, one on a day when the ozone hole was prominent (O₃ = 170 Dobson units; DU = 10-3 cm O₃), and the other on a day with high ozone concentration (O₃ = 328 DU). The decrease in ozone level would reduce productivity by 3–8%. Seasonal variation of UVR has a bigger impact on cyanobacterial productivity than ozone depletion.