Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice. Level of α1-Syntrophin and α-Dystrobrevin in Skeletal Muscles of mdx Mice

Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for dystrophin expression in skeletal muscles. To overcome limited packaging capacity of AAV vectors (<5 kb), truncated recombinant microdystrophin genes with deletions of most of rod and carboxyl-terminal (CT) domains of dystrophin have been developed. We have previously shown the efficiency of mRNA sequence–optimized microdystrophin (ΔR4-23/ΔCT, called MD1) with deletion of spectrin-like repeat domain 4 to 23 and CT domain in ameliorating the pathology of dystrophic mdx mice. However, the CT domain of dystrophin is thought to recruit part of the dystrophin-associated protein complex, which acts as a mediator of signalling between extracellular matrix and cytoskeleton in muscle fibers. In this study, we extended the ΔR4-23/ΔCT microdystrophin by incorporating helix 1 of the coiled-coil motif in the CT domain of dystrophin (MD2), which contains the α1-syntrophin and α-dystrobrevin binding sites. Intramuscular injection of AAV2/9 expressing CT domain–extended microdystrophin showed efficient dystrophin expression in tibialis anterior muscles of mdx mice. The presence of the CT domain of dystrophin in MD2 increased the recruitment of α1-syntrophin and α-dystrobrevin at the sarcolemma and significantly improved the muscle resistance to lengthening contraction–induced muscle damage in the mdx mice compared with MD1. These results suggest that the incorporation of helix 1 of the coiled-coil motif in the CT domain of dystrophin to the microdystrophins will substantially improve their efficiency in restoring muscle function in patients with Duchenne muscular dystrophy.

Children’s physic: medical perceptions and treatment of sick children in early modern England, c. 1580-1720

Historians of medicine, childhood, and paediatrics, have often assumed that early modern doctors neither treated children, nor adapted their medicines to suit the peculiar temperaments of the young. Through an examination of medical textbooks and doctors’ casebooks, this article refutes these assumptions. It argues that medical authors and practising doctors regularly treated children, and were careful to tailor their remedies to complement the distinctive constitutions of children. Thus, this article proposes that a concept of ‘children’s physic’ existed in early modern England: this term refers to the notion that children were physiologically distinct, requiring special medical care. Children’s physic was rooted in the ancient traditions of Hippocratic and Galenic medicine: it was the child’s humoral makeup that underpinned all medical ideas about children’s bodies, minds, diseases, and treatments. Children abounded in the humour blood, which made them humid and weak, and in need of medicines of a particularly gentle nature.

Trophoblast phagocytic program: roles in different placental systems

Although not belonging to the class of professional phagocytes, in many species trophoblast cells exhibit intense phagocytic activity. The complete range of physiological functions of trophoblast phagocytosis has not yet been fully characterized. Close association between the trophoblast and nutrition was determined many years ago. Hubrecht (1889) when proposing for the first time the name trophoblast to the external layer of the blastocyst, directly established the nutritive significance of this embryonic layer. Indeed, histotrophic phagocytosis, i.e. the internalization of maternal cells and secreted materials, is considered an important function of the trophoblast before the completion of the placenta. Recently, however, unexpected characteristics of the trophoblast have significantly enhanced our understanding of this process. Roles in acquisition of space for embryo development, in tissue remodeling during implantation and placentation and in defense mechanisms are highlighting how this cellular activity may be relevant for the maternal-fetal relationship beyond its nutritional function.

Immunogenic properties of a recombinant fusion protein containing the C-terminal 19 kDa of Plasmodium falciparum merozoite surface protein-1 and the innate immunity agonist FliC flagellin of Salmonella Typhimurium

In a recent study, we demonstrated the immunogenic properties of a new malaria vaccine polypeptide based on a 19 kDa C-terminal fragment of the merozoite surface protein-1 (MSP1(19)) from Plasmodium vivax and an innate immunity agonist, the Salmonella enterica serovar Typhimurium flagellin (FliC). Herein, we tested whether the same strategy, based on the MSP1(19) component of the deadly malaria parasite Plasmodium falciparum, could also generate a fusion polypeptide with enhanced immunogenicity. The His(6)FliC-MSP1(19) fusion protein was expressed from a recombinant Escherichia coil and showed preserved in vitro TLR5-binding activity. In contrast to animals injected with His(6)MSP1(19), mice subcutaneously immunised with the recombinant His6FliC-MSP1(19) developed strong MSP1(19)-specific systemic antibody responses with a prevailing IgG1 subclass. Incorporation of other adjuvants, such as CpG ODN 1826, complete and incomplete Freund`s adjuvants or Quil-A, improved the IgG responses after the second, but not the third, immunising dose. It also resulted in a more balanced IgG subclass response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response, as determined by the detection of antigen-specific interferon-gamma secretion by immune spleen cells. MSP(19)-specific antibodies recognised not only the recombinant protein, but also the native protein expressed on the surface of P. falciparum parasites. Finally, sera from rabbits immunised with the fusion protein alone inhibited the in vitro growth of three different P. falciparum strains. In summary, these results extend our previous observations and further demonstrate that fusion of the innate immunity agonist FliC to Plasmodium antigens is a promising alternative to improve their immunogenicity. (c) 2010 Elsevier Ltd. All rights reserved.

Demonstration of Closed Circuit TV by filming Wiliam C. H. Meyer in an Automotive classroom at the New York Trade School

Depiction of closed circuit TV students at the New York Trade School filming a voltage regulator check performed by William C. H. Meyer. Original caption reads, "Closed-circuit TV takes a class at the New York Trade School into the Automotive Shop where William C. H. Meyer, head of the Automotive Department, demonstrates a voltage-regulator check. Students Robert Niefeld (left) and Denis Mahoney serve as cameramen." Black and white photograph part of series of four photographs accompanying a press release of the New York Trade School announcing the demonstration of a new technique in closed-circuit TV developed at the New York Trade School.

Effect of Usnic Acid on Candida orthopsilosis and C. parapsilosis

The activity of usnic acid against Candida orthopsilosis and Candida parapsilosis on planktonic and biofilm conditions was investigated by using a broth microdilution and microplate methods. Potent in vitro activities against different Candida species were obtained. The metabolic activity of sessile cells of C. parapsilosis complex was reduced by 80% at four times the 80% inhibitory concentration. The in vitro studies support further efforts to determine whether usnic acid can be used clinically to cure patients with Candida infections.

Incidência de ascite em frangos de corte alimentados com rações comerciais de alto nível energético

O trabalho objetivou avaliar os efeitos de diferentes rações comerciais com alto nível energético na incidência de ascite em frangos de corte. Foram utilizadas 1.200 aves de uma mesma linhagem comercial (Hubbard), distribuídas em 12 boxes, segundo um delineamento inteiramente ao acaso, com quatro tratamentos e três repetições de 100 aves cada. Os tratamentos foram constituídos por três diferentes rações comerciais trituradas (B, C e D) comparadas com o controle, uma ração farelada inicial (A), do primeiro ao 39º dia de idade. Não houve diferenças entre os tratamentos quanto ao consumo, peso e ganho de peso das aves. em relação à conversão alimentar, o tratamento C apresentou resultado significativamente melhor; entretanto, foi observada neste mesmo tratamento, a maior taxa de mortalidade. O maior motivo dos óbitos registrados foi a síndrome ascítica. Conclui-se que existe um favorecimento de surto de ascite pelas rações com melhor conversão alimentar nas aves.

Lemongrass and citral effect on cytokines production by murine macrophages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study of the combined radial post-feeding dispersion of the blowflies Chrysomya megacephala (Fabricius) and C. albiceps (Wiedemann) (Diptera, Calliphoridae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Palavra do corpo: confluência de linguagens em Night Journey

Trata-se de um exercício de leitura da coreografia Night Journey (1947), de Martha Graham, como reinvenção do texto de Édipo rei (século IV a. C.), de Sófocles. Pretende-se esboçar um estudo em que se evidenciem os processos interartísticos entre literatura e dança.

Physiological responses of Nile tilapia, Oreochromis niloticus, fed vitamin C- and lipid-supplemented diets and submitted to low-temperature stress

Water temperature alterations can determine harmful physiological modifications in fish, which should be prepared to cope with this, and nutrition strategies seem to be essential. This study evaluated the effects of different levels of vitamin C and lipids on physiological responses of Nile tilapia, Oreochromis niloticus, submitted to temperature stress. There were two phases: Phase I - preparing fish to store vitamin C and lipid at appropriate temperature, and Phase II - evaluating the contributions these reserves make to fish physiology under low-temperature stress. The experiment used a 3 x 2 factorial design with three vitamin C levels (300, 600, and 1200 mg/kg diet) and two lipid levels (8.0 and 12.0%), plus absence of nutrient test and a diet of 6.0% lipids and 125.0 mg/kg vitamin C. In Phase I, 192 fish were kept at 26.0 +/- 1.0 C for 112 d, and in Phase II, 48 fish were kept at 18.0 +/- 0.5 C for 32 d and at 15.0 +/- 0.5 C for 11 d. Fish fed C0L0 diet showed lower erythrocytes values in both phases; higher vitamin C supplement determined higher red blood cell (RBC) number and higher hematocrit (Htc) (Phase II); Htc was significantly lower in Phase II; after temperature stress, fish fed C0L0 diet had higher mean corpuscular volume, lower hemoglobin corpuscular concentration, and significantly lower vitamin C concentration in the liver; and higher supplementation determined a higher concentration in the liver (Phases I and II). Higher plasmatic cortisol concentration was seen in fish fed C0L0 diet. In conclusion, our results show that the absence of vitamin C in diets impairs RBC formation and does not enable fish to cope with stress; excess vitamin C is efficient in mitigating stress and 600 mg/kg diet is economic and physiologically sufficient to prepare fish for coping with low-temperature stress. Lipid supplementation does not determine alterations in stress biochemical parameters.

Amperometric differential determination of ascorbic acid in beverages and vitamin C tablets using a flow cell containing an array of gold microelectrodes modified with palladium

A simple and attractive method for quantification of ascorbic acid (AA) in beers, soda, natural juices and commercial vitamin C tablets was achieved by combining Bow injection analysis and amperometric detection. An array of gold microelectrodes electrochemically modified by deposition of palladium was employed as working electrode which was almost unaffected by fouling effects. Ascorbic acid was quantified in beverages and vitamin tablets using amperometric differential measurements. This method is based on three steps involving the flow injection of: 1) the sample plus a standard addition of AA, 2) the pure sample, and 3) the enzymatically-treated sample. The enzymatic treatment was carried out with Cucumis sativus tissue, which is a rich source of ascorbate oxidase, at pH 7. The calibration plots for freshly prepared ascorbic acid standards were very linear in the concentration range of 0.18-1.8 mg L-1 with a relative standard deviation (RSD) < 1%, while for real samples the deviations were between 2.7% to 8.9%.