Bone Morphogenetic Protein 7 (BMP-7) Influences Tendon-Bone Integration In Vitro

IntroductionSuccessful graft ingrowth following reconstruction of the anterior cruciate ligament is governed by complex biological processes at the tendon-bone interface. The aim of this study was to investigate in an in vitro study the effects of bone morphogenetic protein 7 (BMP-7) on tendon-bone integration.ResultsIn both models, positive effects of BMP-7 on ALP enzyme activity were observed (p<0.001). Additionally, similar results were noted for LDH activity and lactate concentration. BMP-7 stimulation led to a significant increase in OCN expression. Whereas the effects of BMP-7 on tendon monoculture peaked during an early phase of the experiment (p<0.001), the cocultures showed a maximal increase during the later stages (p<0.001). The histological analysis showed a stimulating effect of BMP-7 on extracellular matrix formation. Organized ossification zones and calcium carbonate-like structures were only observed in the BMP-stimulated cell cultures.DiscussionThis study showed the positive effects of BMP-7 on the biological process of tendon-bone integration in vitro. Histological signs of improved mineralization were paralleled by increased rates of osteoblast-specific protein levels in primary bovine osteoblasts and fibroblasts.ConclusionOur findings indicated a role for BMP-7 as an adjuvant therapeutic agent in the treatment of ligamentous injuries, and they emphasized the importance of the transdifferentiation process of tendinous fibroblasts at the tendon-bone interface.     

Testicular metamorphosis rates in European Starlings maintained under short daily photophases

Juvenile male European Starlings(Sturnus vulgaris) were maintained under discrete fixed daily photophases ranging from 1 to 11 h in duration. Treatment began on 20 December when all birds were reproductively quiescent, and continued until 14 June of the following year.In situ measurements of left testis widths at monthly intervals documented testicular width increases to levels associated with complete spermatogenesis in birds under all photoperiod regimens. Starlings maintained under the shortest and longest photoperiods required fewer days of treatment to achieve spermatogenic testes than did those under intermediate-length photoperiods. Data are consistent with the hypothesis that prolonged daily periods of darkness result in oscillations of a circadian timing system stimulating increased gonadotropin secretion and consequent testicular metamorphosis.     

β-Amyloid (Aβ) Oligomers Impair Brain-derived Neurotrophic Factor Retrograde Trafficking by Down-regulating Ubiquitin C-terminal Hydrolase,UCH-L1

We previously found that BDNF-dependent retrograde trafficking is impaired in AD transgenic mouse neurons. Utilizing a novel microfluidic culture chamber, we demonstrate that Aβ oligomers compromise BDNF-mediated retrograde transport by impairing endosomal vesicle velocities, resulting in impaired downstream signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation. Our data suggest that a key mechanism mediating the deficit involves ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin. Aβ-induced deficits in BDNF trafficking and signaling are mimicked by LDN (an inhibitor of UCH-L1) and can be reversed by increasing cellular UCH-L1 levels, demonstrated here using a transducible TAT-UCH-L1 strategy. Finally, our data reveal that UCH-L1 mRNA levels are decreased in the hippocampi of AD brains. Taken together, our data implicate that UCH-L1 is important for regulating neurotrophin receptor sorting to signaling endosomes and supporting retrograde transport. Further, our results support the idea that in AD, Aβ may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival.     

Biologic and molecular characterization of two newly isolated ras-containing murine leukemia viruses.

A murine sarcoma virus (MSV) was recovered from an (NFS X NS.C58v-1) F1 mouse which developed splenic sarcoma and erythroleukemia 6 months after inoculation with a mink cell focus-inducing murine leukemia virus (MuLV) isolated from an NFS mouse infected with a wild mouse ecotropic MuLV. The MSV, designated NS.C58 MSV-1, induced foci of transformation in mouse and rat fibroblasts, and inoculation of mice of various strains 2 weeks of age or younger resulted in erythroleukemia and sarcomatous lesions in spleen, lymph node, and brain. The MSV provirus was molecularly cloned from a genomic library prepared from transformed non-producer rat cells. The 8.8-kilobase proviral DNA contained a 1.0-kilobase p21 ras coding segment which replaced most of the gp70-encoding portion of an MuLV, most likely the endogenous C58v-1 ecotropic virus. The ras oncogene is closely related to v-Ha-ras by hybridization, expression of p21 protein, and nucleotide sequence. It is nearly identical in sequence to v-bas, the only previously described transduced, activated mouse c-ras. At position 12 in the p21 coding region, arginine is substituted for the naturally occurring glycine present in c-ras. A second MSV isolate is described which is similar to NS.C58 MSV-1 except for a 100- to 200-base-pair deletion in the noncoding region of the ras-containing insert.     

The influence of prenatal and postnatal fraternity size on reproduction in mice

Effects of prenatal and postnatal fraternity size (size of litter in which an individual is reared) on age at vaginal opening, growth, and subsequent litter production were examined by rearing mice in standardized prenatal and postnatal fraternities in a 3 X 3 factorial design. Prenatal fraternity size was standardized by reducing litters of 14 or more to either 14, 10, or 6 fetuses on Day 9 of gestation. Postnatal fraternity size was standardized by assigning pups randomly to nurse in litters of 5, 10, or 15 pups within 24 h of birth. Both prenatal and postnatal fraternity size affected growth of the mice (p = 0.02 and p less than 0.01, respectively) with mice reared in small fraternities attaining greater weights throughout the study. Prenatal fraternity size had a negative linear effect on litter size at second parity and tended to have a positive linear effect on age at vaginal opening. Postnatal fraternity size affected age at vaginal opening (p less than 0.01), litter size at first parity (p less than 0.01), and litter size at second parity (p = 0.03). These effects were positive and linear for age at vaginal opening (p less than 0.01; small fraternity size associated with younger age at vaginal opening) and negative and linear for litter size at first and second parity (p less than 0.01 and p = 0.10, respectively; smaller fraternity size associated with larger litter size). There was no interaction between prenatal and postnatal fraternity size effects on age at vaginal opening or litter size (p greater than 0.20).     

Intra-tree foraging behavior of Ceratitis capitata flies in relation to host fruit density and quality

We examined the intra-tree foraging behavior of individually-released, wild-population Mediterranean fruit flies (medflies), Ceratitis capitata (Wiedemann), on field-caged host trees bearing each of three different densities (0, 3, or 12 per tree) of non-infested host fruit (kumquat) or each of two levels of fruit quality (12 non-infested fruit or 12 fruit infested with eggs and covered with host marking pheromone). With increasing density of non-infested fruit, medflies tended to remain longer in trees, visit more fruit before leaving, oviposit more often, accept a proportionately smaller number of fruit visited, and emigrate sooner after the last egg was laid (i.e. have a shorter Giving-Up-Time). Medflies spent much less time, oviposited much less often, and exhibited a longer Giving-Up-Time on trees harboring pheromone-marked fruit than non-infested fruit. Variation in temperature within the range at which experiments were conducted (25–36°C) had little detectable influence on foraging behavior. We compare our findings with published findings on the intra-tree foraging behavior of another tephritid fly, Rhagoletis pomonella (Walsh), and with current foraging behavior theory. We discuss implications of our findings with respect to medfly management strategies, particularly fruit stripping in eradication programs and use of synthetic marking pheromone for control.

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Résumé Nous avons étudié le comportement de prospection dans un arbre, de femelles d'une population sauvage de C. capitata, libérées individuellement à l'intérieur de cages contenant des Eriobotrya japonica (kumquat), portant chacun 3 densités différentes de fruits no contaminés (0, 3, 12 par arbre) et chacun 2 niveaux de qualité de fruits: 12 fruits non infestés ou 12 fruits contaminés par des oeufs et recouverts de phéromone de marquage de l'hôte. C. capitata avait terndance à rester plus longtemps dans les arbres, à visiter plus de fruits avant le quitter, à pondre plus souvent, à accepter proportionnellement un nombre plus réduit de fruits déjà visités, à émigrer plus tôt après la ponte du dernier oeuf (c'est-à-dire à présenter un temps d'abandon plus bref), quand la densité des fruits non contaminés augmentait. C. capitata a dépensé beaucoup moins de temps, pondu beaucoup moins souvent, et présenté un temps d'abandon plus long sur les arbres portant des fruits marqués par la phéromone que sur ceux ayant des fruits non contaminés. Les variations de température dans la gamme de cells où les observations ont eu lieu (23–36°C) n'ont eu qu'une faible influence décelable sur le comportement de prospection. Nous avons comparé nos résultats avec ceux publiés sur la prospection à l'intérieur de l'arbre par une autre téphritide (Rhagoletis pomonella) et avec la théorie dominante sur le comportement de prospection. Nous discutons les conséquences de nos résultats sur les stratégies de lutte contre C. capitata, en particulier l'élimination des fruits dans les plans d'erradication et l'utilisation de phéromone synthétique de marquage.

     

Ca2+ channels in chick neural retina cells characterized by 1,4-dihydropyridine antagonists and activators

The voltage-sensitive calcium channel in cultured chick neural retina cells was characterized by the actions of the enantiomers of Bay K 8644 and 202-791 and other 1,4-dihydropyridines. These cells showed time- and voltage-dependent Ca2+ uptake that was stimulated by K+ depolarization and blocked by the inorganic calcium channel blockers Cd2+ and Co2+. A small fraction only (15% maximum) of the uptake was inactivated by predepolarization of the cells with 80 mM K+. Ca2+ uptake was sensitive to the 1,4-dihydropyridine calcium channel antagonists and activators. (S)-Bay K 8644 and (S)-202-791 stimulated the Ca2+ uptake, and (R)-Bay K 8644 and (R)-202-791 as well as nitrendipine and PN 200-110 inhibited Ca2+ uptake stimulated by K+ depolarization or channel activators. The K+ depolarization-stimulated uptake was inhibited by 90%, but the activator-stimulated uptake was completely blocked by the 1,4-dihydropyridine antagonists. The potencies of these agents as inhibitors of Ca2+ uptake were significantly lower than the binding affinities in membrane preparations from the same cells or their binding and pharmacologic affinities in vascular smooth muscle. K+ depolarization or (S)-Bay K 8644 induced 45Ca2+ uptake was not observed in a glial cell culture. [3H]Nitrendipine and [3H]PN 200-110 bound to membrane preparations of the cells consistent with the presence of a single type of high affinity binding site.(ABSTRACT TRUNCATED AT 250 WORDS)