Medfly eradication in California:

The impact of malathion-bait sprays (directed against medfly, Ceratitis capitata [Wiedemann]) on an endemic gall midge (Rhopalomyia californica Felt) and its parasitoids was investigated during 1982–83 in the south San Francisco Bay area of northern California. In a heavily sprayed area (Woodside), a population explosion of the midge was detected following 24 applications of malathion bait. The midge population reached levels ca. 90x greater than those observed in an adjacent unsprayed area (Jasper Ridge). In a moderately sprayed area (Portola Valley), the midge population increased as much as 5x that observed in the adjacent unsprayed area (Jasper Ridge), following 12 applications of malathion bait. In laboratory tests, the malathion bait was toxic to both the midge and its parasitoids. The major parasitoids were Torymus koebelei (Huber), Zatropis capitis Burks, Platygaster californica (Ashmead) and Mesopolobus sp. Population increases of the midge following malathion-bait sprays were attributed to destruction of parasitoids and other natural enemies of the midge. If the environmental impact of malathion-bait sprays is related to the number of applications (as suggested in this study), then it would be worthwhile to determine the appropriate bait-spray strategy for a given situation, so as to minimize adverse effects on nontarget species, yet insure suppression or eradication of medfly.

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Résumé L'impact des pièges tratiés au malathion (destinés à Ceratitis capitata Wiedem) sur Rhopalomyia californica Felt et ses parasitoïdes a été examiné en 1982–1983 dans le sud de la zone de la baie de San Francisco en Californie. Dans une zone fortement traitée (Woodside), une explosion de population a été décelée après 24 traitements. La population de R. californica a atteint des niveaux 90 fois supérieurs à ceux observés dans une zone contiguë non traitée (Jasper Ridge). Dans une zone modérément traitée (Portola Valley), avec 12 traitement, la population de R. californica a atteint jusqu'a 5 fois celle de Jasper Ridge. Au laboratoire, le piège à malathion a été toxique tant pour R. californica que pour ses parasitoïdes, dont les principaux étaient: Torymus koebelei (Huber), Zatropis capitis Burks, Platygaster californica(Ashmead) et Mesopolobus sp. L'accroissement de la population de C. capitata après traitement a été attribué à la destruction de parasitoïdes et d'autres ennemis naturels. Si l'effet su l'environnement du traitement est lié au nombre d'interventions (comme le suggère cette étude), alors cela vaudrait la peine de définir une stratégie de traitement appropriée à une situation donnée, de façon à minimiser les effets négatifs sur des espèces non visées, tout en assurant la suppression ou l'éradication de C. capitata.

     

Re-expression of proteins involved in cytokinesis during cardiac hypertrophy

Cardiomyocytes stop dividing after birth and postnatal heart growth is only achieved by increase in cell volume. In some species, cardiomyocytes undergo an additional incomplete mitosis in the first postnatal week, where karyokinesis takes place in the absence of cytokinesis, leading to binucleation. Proteins that regulate the formation of the actomyosin ring are known to be important for cytokinesis. Here we demonstrate for the first time that small GTPases like RhoA along with their downstream effectors like ROCK I, ROCK II and Citron Kinase show a developmental stage specific expression in heart, with high levels being expressed in cardiomyocytes only at stages when cytokinesis still occurs (i.e. embryonic and perinatal). This suggests that downregulation of many regulatory and cytoskeletal components involved in the formation of the actomyosin ring may be responsible for the uncoupling of cytokinesis from karyokinesis in rodent cardiomyocytes after birth. Interestingly, when the myocardium tries to adapt to the increased workload during pathological hypertrophy a re-expression of proteins involved in DNA synthesis and cytokinesis can be detected. Nevertheless, the adult cardiomyocytes do not appear to divide despite this upregulation of the cytokinetic machinery. The inability to undergo complete division could be due to the presence of stable, highly ordered and functional sarcomeres in the adult myocardium or could be because of the inefficiency of degradation pathways, which facilitate the division of differentiated embryonic cardiomyocytes by disintegrating myofibrils.     

TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible

The objective of this study was to investigate the incidence of overexpression of TP53 (formerly known as p53) in osteosarcomas occurring after treatment of rabbit mandibles with high-dose external-beam radiation. As part of a protocol investigating hyperbaric oxygen treatment for osteoradionecrosis, 102 female New Zealand-White rabbits underwent mandibular radiation treatments with a total dose of 64 Gy in 20 treatment fractions. Twelve animals died during irradiation, leaving 90 animals at risk for tumor development. These animals were divided into one control group and 12 other groups each treated with different schedules of postirradiation hyperbaric oxygen. All animals were sacrificed after the hyperbaric oxygen treatment, approximately 8 months after completion of irradiation. Seventeen of the 90 animals that survived after irradiation developed high-grade osteosarcomas, for a 19% incidence of malignancy. Tumor sizes ranged from 1-4 cm. Immunohistochemistry staining of the 17 tumors detected a 59% overall incidence of TP53 overexpression. There was no correlation between the intensity of hyperbaric oxygen treatment and development of osteosarcoma. The high incidence and short interval of development of osteosarcoma suggest that the study animals may have had a genetic predisposition to radiation-induced osteosarcoma. Additionally, our data provide further evidence that TP53 mutations may play an important role in radiation-induced osteosarcoma.     

The sensitive giant: the role of titin-based stretch sensing complexes in the heart

Every heart beat is not equal. As physiological demands of the cardiovascular system change, cardiac myocytes modulate contractile parameters including the rate and force of contraction. Adaptive responses require the sensing of biomechanical signals involving the interface between the contractile cytoskeleton (myofibrils) and the sarcolemma at specialized cell-cell junctions (intercalated discs) and cell-substrate adhesion complexes (costameres). Recent studies have shed insight into how protein complexes within cardiac myocytes sense biomechanical signals, processes required for normal adaptive or pathological responses. This new evidence suggests that complexes associated with the giant, myofibrillar protein titin sense myocyte stretch. Here, we discuss evidence supporting titin being an ideal biomechanical sensor.     

Intermediate filament-co-localized molecules with myosin heavy chain epitopes define distinct cellular domains in hair follicles and epidermis

Background  

Proteins linking intermediate filaments to other cytoskeletal components have important functions in maintaining tissue integrity and cell shape.     

Measles virus matrix protein specifies apical virus release and glycoprotein sorting in epithelial cells

In polarized epithelial cells measles virus (MV) is predominantly released at the apical cell surface, irrespective of the sorting of its two envelope glycoproteins F and H. It has been reported previously that the viral matrix (M) protein modulates the fusogenic capacity of the viral envelope glycoproteins. Here, extant MV mutants and chimeras were used to determine the role of M protein in the transport of viral glycoproteins and release of progeny virions in polarized epithelial CaCo2 cells. In the absence of M, envelope glycoproteins are sorted to the basolateral surface, suggesting that they possess intrinsic basolateral sorting signals. However, interactions of M with the glycoprotein cytoplasmic tails allow M-glycoprotein co-segregation to the apical surface, suggesting a vectorial function of M to retarget the glycoproteins for apical virion release. Whereas this may allow virus airway shedding, the intrinsic sorting of the glycoproteins to the basolateral surface may account for systemic host infection by allowing efficient cell-cell fusion.     

CD40 ligand trimer and IL-12 enhance peripheral blood mononuclear cells and CD4+ T cell proliferation and production of IFN-gamma in response to p24 antigen in HIV-infected individuals: potential contribution of anergy to HIV-specific unresponsiveness

It has been suggested that CD4+ T cell proliferative responses to HIV p24 Ag may be important in the control of HIV infection. However, these responses are minimal or absent in many HIV-infected individuals. Furthermore, while in vitro and in vivo responses to non-HIV recall Ags improve upon administration of highly active antiretroviral therapy, there does not appear to be a commensurate enhancement of HIV-specific immune responses. It is possible that CD4+ p24-specific T cells are deleted early in the course of infection. However, it is also possible that a discrete unresponsiveness, or anergy, contributes to the lack of proliferation to p24. To evaluate the possible contribution of unresponsiveness to the lack of CD4+ T cell proliferation to p24 in HIV-infected individuals, we attempted to overcome unresponsiveness. CD40 ligand trimer (CD40LT) and IL-12 significantly increased PBMC and CD4+ T cell proliferative responses to p24 Ag in HIV-infected, but not uninfected, individuals. No increase in proliferative response to CMV Ag was observed. CD40LT exerted its effect through B7-CD28-dependent and IL-12- and IL-15-independent mechanisms. Finally, the increase in proliferation with CD40LT and IL-12 was associated with an augmented production of IFN-gamma in most, but not all, individuals. These data suggest the possible contribution of HIV-specific unresponsiveness to the lack of CD4+ T cell proliferation to p24 Ag in HIV-infected individuals and that clonal deletion alone does not explain this phenomenon. They also indicate the potential for CD40LT and IL-12 as immune-based therapies for HIV infection.     

Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors

The virus-specific CD8+ T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low levels of plasma viral RNA and strong proliferative responses to HIV Ags. HIV-specific CD8+ T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular IFN-gamma in response to HIV-vaccinia recombinant-infected autologous B cells. Very high frequencies (0.8-18.0%) of circulating CD8+ T cells were found to be HIV specific. High frequencies of HIV-specific CD8+ T cells were not limited to long-term nonprogressors with restriction of plasma virus. No correlation was found between the frequency of HIV-specific CD8+ T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the majority of cases not contained within large monoclonal expansions. These data demonstrate that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8+ T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease.