The interscale skin of the intermandibular‐gular regions of Alligator mississippiensis serves as a distribution system for the conditioning secretion of the gular gland

The skin of alligators is covered by plate‐like, non‐imbricate and hard‐cornified scales that are separated by a network of soft‐cornified interscale skin. The width of the interscale skin is correlated with the local expansibility of the skin. In most of the intermandibular‐gular region, the skin needs to stretch significantly when large prey items are swallowed to allow for the expansion of the pharynx. The interscale skin is widest along the mandibular rami where it forms longitudinal folds and channels that radiate rostrally from the paired gular gland orifices. The surface of these interscale channels is studded with small scale bumps. These wide channels are interconnected by a network of smaller, stretchable channels, whose surface structures are regionally distinct. The structured surface of the channels may enhance capillary action of the oily gular gland secretion as it is massaged through the channels by movements of the intermandibular‐gular skin during deglutition. This configuration of the intermandibular‐gular skin suggests that the channels serve to distribute the oily secretion of the gular gland to condition the stretchable interscale skin so as to keep it pliable and elastic. In contrast, the unyielding interscale skin in the area that subtends the hyoid and larynx is very narrow and has a smooth surface structure.

Regulation of catecholamine biosynthetic enzymes by nitric oxide

The neurotransmitters/neurohormones catecholamines (CA) are involved in the sympathetic control of arterial blood pressure and cardiac function. Recent studies show that nitric oxide (NO) can regulate the release of CA from the adrenal medulla. The in vitro PC12 cell line was used to examine the effect of NO on the regulation of the CA biosynthetic enzymes: tyrosine hydroxylase (TH), dopamine‐β‐hydroxylase (DBH) and phenylethanolamine N‐methyltransferase (PNMT). Results obtained from drug treatments with the NO donor, sodium nitroprusside (SNP) constitute an assessment of its effects in PC12 cells. Treatment of cells with SNP for 6 hours significantly increased TH and PNMT mRNA levels. Combination drug studies with SNP and intracellular kinase activators (forskolin, PMA, 8‐Br‐cGMP) and inhibitors for PKA (H‐89), cGMP (6‐anilinoquinone) PKG (DT‐2) and PKC (GF109203X) were also conducted. Increases in transcript levels for TH and PNMT were obtained under combination drug treatments of SNP and activators of PKA and PKG (p<0.05). mRNA transcript levels of TH, DBH and PNMT showed significant decreases when cells were pre‐treated with PKA, PKC and PKG inhibitors. Furthermore, preliminary transfections showed activation of the PNMT promoter by SNP treatment. Results from this study suggest that NO is capable of regulating CA biosynthetic enzymes, TH and PNMT via activation of the PKA and PKG pathways.

Evolutionary conservation of Tino/Quaking interaction suggests its impact to cell polarity control in ontogenesis and oncogenesis

Loss of cell polarity is very common in invasive and metastatic tumours, but also in early stages of cancerogenesis. In C. elegans the conserved Par genes control several proteins transducing polarity cues in the embryo. One of these transducers is ceMex‐3, a translational regulator of cell fate during development. Its human ortholog is Tino, firstly identified in our lab as a post‐transcriptional regulator. The high conservation between ceMex‐3 and Tino suggests that also Tino could have an impact on mammalian embryogenesis, cell polarity and cancer. Par‐4 is a ceMex‐3 translational regulator, its human ortholog Lkb1 is responsible, if mutated, for the Peutz‐Jeghers cancer syndrome. Another liaison dangereuse co‐involves ceMex‐3 with Gld‐1 gene, whose mammal ortholog is Quaking (Qki). Both ceMex‐3 and Gld‐1 co‐regulate common targets and if mutated induce onset of teratomas during embryogenesis. Here we show that Qki contributes to the negative regulation of Tino, confirming our hypothesis of evolutive conservation of Tino pathway. Furthermore, identification of Tino's target mRNAs and their consensus reveals that 50% of these mRNAs contains also Qki consensus, underlying the possibility that Qki and Tino co‐regulate common targets.

Effects of aging on the cutaneous microcirculation evaluated by a novel neurovascular testing in humans

Aging alters vascular and nervous systems. Skin pressure‐induced vasodilation (PIV) relying on intact neurovascular interaction tests the capacity of the skin to resist to pressure‐induced ischemia. We hypothesized that PIV would be altered in older subjects because of the endothelial dysfunction and would be aggravated by a neuropathy. Subjects were divided according to their age (20‐35 or 60‐75 yrs) and the presence of peripheral neuropathy. In the skin microcirculation, PIV was reduced in non neuropathic older subjects (12±7%) compared to young subjects (62±4%) and was totally abolished in neuropathic older subjects (‐31±10%). The skin endothelium‐dependent responses to acetylcholine and local heating were likewise reduced in both groups of older subjects, showing a comparable endothelial dysfunction. The quantitative sensory tests showed an early C‐fiber dysfunction in non neuropathic older subjects, which was emphasized in neuropathic older subjects. Therefore, for a given endothelial dysfunction, the alteration of the neurovascular interaction was mild to severe according to the degree of the severity of the C fiber dysfunction in older subjects. The skin neurovascular interaction testing could discriminate subjects into subgroups presenting different capacities to resist against tissue ischemia with comparable endothelial dysfunction. Supported by PHRC 2005‐541 and MEDD 0000375.

Important role for AMPKαl in limiting skeletal muscle cell hypertrophy

Activation of AMP‐activated protein kinase (AMPK) inhibits protein synthesis through the suppression of the mammalian target of rapamycin complex 1 (mTORCl), a critical regulator of muscle growth. The purpose of this investigation was to determine the role of the AMPKα1 catalytic subunit on muscle cell size control and adaptation to muscle hypertrophy. We found that AMPKα1(—/—) primary cultured myotubes and myofibers exhibit larger cell size compared with control cells in response to chronic Akt activation. We next subjected the plantaris muscle of AMPKα1(—/—) and control mice to mechanical overloading to induce muscle hypertrophy. We observed significant elevations of AMPKαl activity in the control muscle at days 7 and 21 after the overload. Overloading‐induced muscle hypertrophy was significantly accelerated in AMPKα1(—/—) mice than in control mice [+32 vs . +53% at day 7 and +57 vs . +76% at day 21 in control vs . AMPKα1(—/—) mice, respectively]. This enhanced growth of AMPKα1‐deficient muscle was accompanied by increased phosphorylation of mTOR signaling downstream targets and decreased phosphorylation of eukaryotic elongation factor 2. These results demonstrate that AMPKα1 plays an important role in limiting skeletal muscle overgrowth during hypertrophy through inhibition of the mTOR‐signaling pathway.—Mounier, R., Louise Lantier, Leclerc, J., Sotiropoulos, A., Pende, M., Daegelen, D., Sakamoto, K., Foretz, M., Viollet, B. Important role for AMPKa1 in limiting skeletal muscle cell hypertrophy. FASEBJ. 23, 2264–2273 (2009)

Targeting adrenomedullin receptors with systemic delivery of neutralizing antibodies inhibits tumor angiogenesis and suppresses growth of human tumor xenografts in mice

Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor‐like receptor/receptor activity modifying protein‐2 and ‐3 (CLR/RAMP2 and CLR/ RAMP3). Previously, we reported on the development of an anti‐AM antibody that potently inhibits tumor cell proliferation in vitro and tumor growth in vivo . Here, we report the effect of anti‐AM receptor antibodies (αAMRs) on angiogenesis and tumor growth. We demonstrate that αAMRs decrease in a dose‐dependent manner the growth of U87 glioblastoma cells and HT‐29 colorectal cancer cells, but not A549 lung cancer cells, in vitro. In vivo , AM in Matrigel plugs induces angiogenesis by promoting recruitment of endothelial cells, pericytes, myeloid precursor cells, and macrophages and by promoting channel formation. Remarkably, systemic administration of αAMRs every 3 d markedly reduced neovascularization of Matrigel plugs in a dosedependent fashion, as demonstrated by reduced numbers of the recruited cells and vessel structures. Several human tumor xenografts in athymic mice were used to examine the effect of αAMR treatment on tumor angiogenesis and growth. αAMR treatment significantly suppressed the growth of glioblastoma, lung, and colon tumors. Histological examination of αAMR‐treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial and pericyte cells, and increased tumor cell apoptosis. These findings support the conclusion that αAMR treatment inhibits tumor growth by suppression of angiogenesis and tumor growth and suggest that AMRs may be useful therapeutic targets.—Kaafarani, I., Fernandez‐Sauze, S., Berenguer, C., Chinot, O., Delfino, C., Dussert, C., Metellus, P., Boudouresque, F., Mabrouk, K., Grisoli, F., Figarella‐Branger, D., Martin, P.‐M., Ouafik, L. H. Targeting adrenomedullin receptors with systemic delivery of neutralizing antibodies inhibits tumor angiogenesis and suppresses growth of human tumor xenografts in mice. FASEB J . 23, 3424–3435 (2009). www.fasebj.org

Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues

Staphylococcus aureus infections are associated with abscess formation and bacterial persistence; however, the genes that enable this lifestyle are not known. We show here that following intravenous infection of mice, S. aureus disseminates rapidly into organ tissues and elicits abscess lesions that develop over weeks but cannot be cleared by the host. Staphylococci grow as communities at the center of abscess lesions and are enclosed by pseudocapsules, separating the pathogen from immune cells. By testing insertional variants in genes for cell wall‐anchored surface proteins, we are able to infer the stage at which these molecules function. Fibrinogen‐binding proteins ClfA and ClfB are required during the early phase of staphylococcal dissemination. The heme scavenging factors IsdA and IsdB, as well as SdrD and protein A, are necessary for abscess formation. Envelope‐associated proteins, Emp and Eap, are either required for abscess formation or contribute to persistence. Fluorescence microscopy revealed Eap deposition within the pseudocapsule, whereas Emp was localized within staphylococcal abscess communities. Antibodies directed against envelope‐associated proteins generated vaccine protection against staphylococcal abscess formation. Thus, staphylococci employ envelope proteins at discrete stages of a developmental program that enables abscess formation and bacterial persistence in host tissues.—Cheng, A. G., Kim, H. K., Burts, M. L., Krausz, T., Schneewind, O., Missiakas, D. M. Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J . 23, 3393–3404 (2009). www.fasebj.org

Pregnancy desires, and contraceptive knowledge and use among prevention of mother-to-child transmission clients in Rwanda

To understand pregnancy intentions and contraception knowledge and use among HIV-positive and negative women in the national prevention of mother-to-child transmission (PMTCT) program in Rwanda.

Projected Changes in Reportable Enteric Disease Incidence in New Brunswick, Canada in Response to Changes in Temperature, Precipitation and Snow Depth

Quantification of Short Term Effects of Pollen Counts and Sentinel Botanic Garden Observations on Pollinosis Symptoms: A French Panel Study