α-Tocopherol reduces fluorescent age pigment levels in heart and brain of young mice

Summary The levels of fluorometrically measured lipofuscin, or age pigment, were significantly lower in the brain and the heart of -tocopherol (vitamin E)-injected mice as compared to untreated control mice at 3 and at 5 months of age.     

Blocking of melatonin synthesis and MT1 receptor impairs the activation of Jurkat T cells

Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin’s role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT₁ receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT₁ antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT₁ cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.     

Structure of the insulin receptor ectodomain reveals a folded-over conformation

The insulin receptor is a phylogenetically ancient tyrosine kinase receptor found in organisms as primitive as cnidarians and insects. In higher organisms it is essential for glucose homeostasis, whereas the closely related insulin-like growth factor receptor (IGF-1R) is involved in normal growth and development. The insulin receptor is expressed in two isoforms, IR-A and IR-B; the former also functions as a high-affinity receptor for IGF-II and is implicated, along with IGF-1R, in malignant transformation. Here we present the crystal structure at 3.8 A resolution of the IR-A ectodomain dimer, complexed with four Fabs from the monoclonal antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a fragment of an insulin mimetic peptide. The structure reveals the domain arrangement in the disulphide-linked ectodomain dimer, showing that the insulin receptor adopts a folded-over conformation that places the ligand-binding regions in juxtaposition. This arrangement is very different from previous models. It shows that the two L1 domains are on opposite sides of the dimer, too far apart to allow insulin to bind both L1 domains simultaneously as previously proposed. Instead, the structure implicates the carboxy-terminal surface of the first fibronectin type III domain as the second binding site involved in high-affinity binding.     

Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells

Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.     

Field identification of Myotis yumanensis and Myotis lucifugus: a morphological evaluation

Myotis lucifigus and Myotis yumanensis are 2 species of bats subject to potentially high rates of misidentification because they are often difficult to differentiate in the hand under field conditions. We tested the utility of a suite of external morphological characteristics frequently cited in regional keys to differentiate the 2 species in the field. Forearm length, dorsal pelage sheen, ear color, and forehead slope were examined from 101 bats captured in central Oregon during 2002–2003. Post hoc genetic analysis was performed on tissue samples collected from the 101 bats to confirm identification. Forearm lengths overlapped considerably between species. Only 18% of M. yumanensis and 17% of M. lucifugus were correctly identified with probability ≥95% using forearm length alone. Pelage sheen, ear color, and forehead slope successfully identified 96%, 82%, and 77% of individual bats, respectively. When forearm length was considered together with other traits, identification rates ranged from 92% to 20%. Ability to correctly identify M. yumanensis was 2–6 times greater than for M. lucifugus. Pelage sheen was useful in our study; however, using this character required a subjective decision from the observer, and the result often contradicted other characters for species identification stated in regional keys. For these reasons, we recommend that morphological features be used judiciously and only as supportive criteria for field identification in combination with voucher echolocation calls and genetic confirmation.     

sRNA methylase activity of embryonic liver

Résumé Utilisant SAM-¹⁴CH₃ il a été démontré que le foie foetal a plus d'activité de sRNA methylase que le foie adulte.

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This investigation was supported in part by an allocation from a Public Health Service General Research Support Grant No. SO 1 FR-05545-03, and an American Cancer Society Grant No. IN 19F to The Jackson Laboratory, Bar Harbor, Maine, and by Public Health Service Research Grants No. HD-01496 from the National Institute of Child Health and Human Development and No. FR-00251 from the Division of Research Facilities and Resources.