Alterations in the expression of antioxidant genes and the levels of transcription factor NF-kappa B in relation to diabetic embryopathy in the Cohen diabetic rat model

BACKGROUND: We have previously shown that oxidative stress is important in the pathogenesis of diabetes-induced anomalies in Cohen Diabetic sensitive (CDs) rat embryos and seems to interplay with genetic factors. We investigated the role of genetic factors related to the antioxidant defense mechanism in CDs rat embryos. METHODS: We studied 11.5- and 12.5-day embryos of Cohen Diabetic resistant (CDr) and CDs rats that were fed a regular diet (RD), and hence not diabetic, compared to rats fed a high-sucrose low-copper diet (HSD) where only the CDs animals became diabetic. Embryos were monitored for growth and congenital anomalies. mRNA of catalase (CAT), glutathione peroxidase (GSHpx), CuZn-SOD (SOD-superoxide dismutase), and Mn-SOD and the extent of nuclear factor kappa B (NF-kappaB) activation were assessed. RESULTS: Embryos of CDs dams fed RD were significantly smaller and had an increased rate of NTDs compared to embryos of CDr dams fed RD. When CDs dams were fed HSD, >50% of the CDs embryos were dead and 44% of the live embryos had NTDs. Live 11.5-day old embryos of CDs dams fed RD had a statistically significant increase in CAT, CuZn-SOD, and GSHpx mRNA levels compared with the levels in the CDr embryos from dams fed RD. CDs embryos from dams fed HSD showed significant overactivation of NF-kappaB compared with CDr embryos from dams fed HSD (in which activation was decreased), without any increase in the expression of SOD, CAT, and GSHpx. CONCLUSIONS: This study demonstrates that one of the genetic differences between the CDr and CDs strains fed RD is an increased expression of genes encoding for antioxidant enzymes in the CDs but inability for upregulation in diabetes. In addition, while activation of NF-kappaB is decreased in CDr on HSD, it is increased in the CDs. These differences may play a role in the increased sensitivity of the CDs embryos to diabetic-induced teratogenicity.     

RF nonlinear interactions in living cells-I: nonequilibrium thermodynamic theory

Some biological experiments report effects that depend on low frequency modulation of a radiofrequency (RF) carrier. Such effects require nonlinear responses in biological preparations, which we show could be observed with great generality by the unique frequency signatures that would appear in the scattered RF energy. Following Illinger [Illinger (1982): Bioelectromagnetics 3:9-16], we considered a two part physical system. The greater part, dominated by the properties of water, interacts linearly with the RF field and is described by equilibrium thermodynamics. However, another, much smaller part, e.g., certain biological molecules and molecular subgroups, supports nonlinear interactions and is described by nonequilibrium thermodynamics. For example, a nonlinear interaction might result from scattering of RF photons from oscillators located in a region of strong field gradients, such as at membrane surfaces. A second nonlinear mechanism could appear if stress (elastic) waves were launched within the confines of the exposure vessel by RF heating. Amplitude modulation at angular frequency Omega of a carrier wave with angular frequency omega (omega < omega) produces two peaks in elastic stress in the cell structure during each period; that is, there is "full-wave demodulation." As a result of coherent nonlinear charge motion, modulation products could appear at frequencies omega +/- 2 omega and, in general, at omega +/- n 2 omega (n = 1, 2, em leader ) if vibrational harmonics at 2 n omega also are excited. Although in principle microwaves can alter the stability of a thermodynamic system by pumping a chemical transition, the degree of nonlinear coupling required for an observable instability is so great that its probability is effectively zero, unless field intensity is extremely high. A companion paper suggests an extremely sensitive method and the related instrumentation for detection of the spectrum scattered by living cells during exposure to amplitude modulated RF energy.     

Casein kinase 2 specifically binds to and phosphorylates the carboxy termini of ENaC subunits.

A number of findings have suggested the involvement of protein phosphorylation in the regulation of the epithelial Na+ channel (ENaC). A recent study has demonstrated that the C tails of the beta and gamma subunits of ENaC are subject to phosphorylation by at least three protein kinases [Shi, H., Asher, C., Chigaev, A., Yung, Y., Reuveny, E., Seger, R. & Garty, H. (2002) J. Biol. Chem. 277, 13539-13547]. One of them was identified as ERK which phosphorylates betaT613 and gammaT623 and affects the channel interaction with Nedd4. The current study identifies a second protein kinase as casein kinase 2 (CK2), or CK-2-like kinase. It phosphorylates betaS631, a well-conserved serine on the beta subunit. Such phosphorylation is observed both in vitro using glutathione-S-transferase-ENaC fusion proteins and in vivo in ENaC-expressing Xenopus oocytes. The gamma subunit is weakly phosphorylated by this protein kinase on another residue (gammaT599), and the C tail of alpha is not significantly phosphorylated by this kinase. Thus, CK2 may be involved in the regulation of the epithelial Na+ channel.     

Novel cytokine release inhibitors. Part III: Truncated analogs of tripterine

Truncated analogs of tripterine as cytokine (IL-1, IL-1β, TNF-, IL-6, and IL-8) release inhibitors are discussed.     

Ion complexation in nonactin,monactin, and dinactin: A Raman spectroscopic study

The ability of the macrotetrolide nactins to complex selectivity with a wide variety of cations makes these ionophorous antibiotics important model systems for the study of biologic ionic transport. We report a Raman spectroscopic investigation of the Na⁺, K⁺, Rb⁺, Cs⁺, Tl⁺, NH₄⁺, NH₃OH⁺, C(NH₂)₃⁺, and Ba⁺⁺ complexes of nonactin, monactin, and dinactin in 4:1 (v/v) CH₃OH/CHCl₃ and in the solid state. The nactins display characteristic spectral changes upon complexation, some of which are specific for a given cation. In the K⁺, Rb⁺, Cs⁺, NH₃OH⁺, and C(NH₂)₃⁺ complexes, which are apparently isosteric, the ester carbonyl stretch frequency is found to be linearly proportional to the cation–carbonyl electrostatic interaction energy, as calculated from a simplified model. Deviations for the Na⁺, NH₄⁺, Tl⁺, and Ba⁺⁺ complexes are interpreted as arising from additional nonelectrostatic interactions. Additional information is obtained from other spectral regions and from measurements of depolarization ratios. Spectra of the nactin complexes differ from each other more in the solid state than in solution, reflecting the effects of crystalline contact forces.     

Alignment and defect structures in oriented phosphatidylcholine multilayers.

The alignment of dilauryl-, dimyristoyl-, and dipalmitoylphosphatidylcholine at various water concentrations into large oriented monodomain multilayers by annealing at elevated temperatures (Powers and Clark, 1975, Proc. Natl. Acad. Sci. U.S.A. 72:840; Powers and Pershan. 1977. Biophys. J. 20:137) is accompanied by the formation and subsequent dissolution of various defect structures. Some of these defects appear similar to those observed in thermotropic and other lyotropic liquid crystals, reflecting the lamellar structure of these materials. The formation and evolution of defects during the alignment of the lipids into the defect-free, monodomain, multilamellar geometry is studied using polarized microscopy. A combination of polarized and dark-field microscopy facilitated characterization of the defects; specific structural models are proposed. A new alignment technique involving compression and dilation of the lipid, which effects sample alignment at temperatures that are lower than those required by the Powers technique, is described. Lower temperature alignment avoids thermal decomposition that will sometimes occur if the lipid is maintained at elevated temperatures for prolonged periods. With this technique, samples (80 micrometer thick) of dilaurylphosphatidylcholine with 20% water by weight were aligned at room temperature.     

Morphological diversity of anatomical strepsirrhinism and the evolution of the lemuriform toothcomb

The hypothesis that the vomeronasal organ has an important functional relationship with, and led to the evolution of, the prosimian toothcomb has not been well tested. This paper examines the diversity of anatomical strepsirrhinism across several mammalian taxa to determine if fossil and living strepsirrhine primates exhibit any derived characters that may highlight the functional link between the vomeronasal organ and the toothcomb, and to examine the potential importance of anatomical strepsirrhinism to toothcomb origins. Results indicate that extant gregarious lemuriforms are derived in having a relatively wide interincisal gap, providing an unobstructed line of communication between the vomeronasal organ and anterior rostral structures such as the toothcomb. This finding is consistent with the proposal that anatomical strepsirrhinism is functionally related to use of the toothcomb in grooming. However, the importance of the vomeronasal organ to toothcomb origins is less clear. If the morphology of adapiforms and non-gregarious lemuriforms is representative of the morphology of basal lemuriforms, then it can be inferred that early lemuriforms did not possess the wide-gap autapomorphy; hence, anatomical evidence discussed here cannot be used to rule out non-social hypotheses of toothcomb origins. Am J Phys Anthropol 105:355–367, 1998. © 1998 Wiley-Liss, Inc.