Heme oxygenase 1 is required for mammalian iron reutilization

Stressed mammalian cells up-regulate heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells from mice lacking functional Hmox1 to oxidative challenges. Cultured Hmox1(-/-) embryonic fibroblasts demonstrated high oxygen free radical production when exposed to hemin, hydrogen peroxide, paraquat, or cadmium chloride, and they were hypersensitive to cytotoxicity caused by hemin and hydrogen peroxide. Furthermore, young adult Hmox1(-/-) mice were vulnerable to mortality and hepatic necrosis when challenged with endotoxin. Our in vitro and in vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.     

Neurochemical studies of schizophrenia in Japan

Neurobiological research in schizophrenia has been hampered by several confounding factors such as the heterogeneity of the illness and the paucity of biological markers. Recent progress in research methods, however, has enabled the improvement in our understanding its pathophysiology. This paper reviews recent neurochemical investigations of schizophrenia and its animal models which were conducted in Japan in the last decade. The research areas reviewed are (i) monoamine and their metabolites in body fluids, (ii) phospholipids and prostaglandins, (iii) neurochemistry in autopsy brains, (iv) immunological measures, (v) magnetic resonance spectroscopy, (vi) regional cerebral blood flows (rCBF), (vii) molecular genetics, and (viii) animal models. It is worth noting that there exist abnormalities of amino acidergic (glutamatergic and GABAergic) neurotransmission as well as monoaminergic (dopaminergic and serotonergic) one in postmortem schizophrenic brains. These abnormalities and also the findings of altered rCBF indicate the existence of disturbed neuronal circuits that contribute to the diverse symptoms of schizophrenia. Also, dysfunction of membrane phospholipids derived from studies on magnetic resonance spectroscopy may underlie negative symptoms in schizophrenia. Given that schizophrenia is considered to comprise a group of disorders with a diverse heterogeneity of etiologies, research in the next decade is expected to identify putative genes that are involved in vulnerability to schizophrenic phenotype.     

Certain nonlinear partially observable stochastic optimal controlproblems with explicit control laws equivalent to LEQG/LQG problems

This paper is concerned with partially observed stochastic optimal control problems when nonlinearities enter the dynamics of the unobservable state and the observations as gradients of potential functions. Explicit representations for the information state are derived in terms of a finite number of sufficient statistics. Consequently, the partially observed problem is recast as one of complete information with a new state generated by a modified version of the Kalman filter. When the terminal cost is quadratic in the unobservable state and includes the integral of the nonlinearities, the optimal control laws are explicitly computed, similar to linear-exponential-quadratic-Gaussian (LEQG) and linear-quadratic-Gaussian (LQG) tracking problems. The results are applicable to filtering and control of Hamiltonian systems     

Estimating the viewing parameters of random, noisy projections ofasymmetric objects for tomographic reconstruction

The ability to determine the viewing parameters of objects from their projections has enabled well established tomographic techniques to be employed in the 3D reconstruction of objects from images obtained via modalities where the orientation of the objects cannot be controlled. A method is described for the determination of the viewing parameters of randomly acquired projections of asymmetric objects. It extends upon the common lines algorithm by determining the relative orientation of projections from the location of lines of intersection among the Fourier transforms of the projections in 3D Fourier space. A new technique for finding the lines of intersection in the presence of translational displacement, and for subsequently finding the translational displacement, is presented. The complete algorithm is described and its efficacy is demonstrated using real data. A new technique for dealing with noise is also discussed     

On a large-gain theorem

The aim of this paper is to give a general quantitative requirement which the loop gain must satisfy in order to stabilize a given unstable (possibly nonlinear and time-varying) plant, namely that the gain must exceed one.     

Stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug

This review is written to evaluate the stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug. This discussion will be useful in the development of knowledge about stereoselective cutaneous hydrolysis and its influence on stereoselective transdermal transport of many other chiral prodrugs and drugs. Propranolol prodrugs undergo stereoselective hydrolysis in hairless mouse skin homogenate and in excised skin samples during permeation; the stereoselectivity is markedly biased towards hydrolysis of the (R) isomer. Unlike the liver, the esterase activity of the skin is high in its cytosolic fraction. Most of the lipophilic propranolol prodrugs cause stereoselective permeation across hairless mouse skin. A mechanism of stereoselective permeation of propranolol prodrug across the skin has been proposed, which indicates that the stereoselectivity in permeation is resulted from the stereoselective hydrolysis of lipophilic prodrug during permeation.     

Histochemical evaluation of placental dipeptidyl peptidase IV (CD26) in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational hypertensive disorders

Nitric oxide (NO) acts as a modulator of neuronal transmission in mature neuronal systems, including the retina. Recently, NO has also been suggested to have a trophic function during development. We examined immunocytochemically the distribution of NO-producing cells in developing and transplanted rabbit retinas. An antibody detecting the neuronal isoform of its biosynthetic enzyme, nitric oxide synthase (NOS), was used on normal developing retinas [starting at embryonic day (E) 15] and on rabbit retinal transplants after various survival times (1-139 days after surgery). Weakly stained cell bodies were first observed in the proximal margin of the neuroblastic layer at E 29. Stained processes projecting towards a developing inner plexiform layer were also visible at this time point. Immunoreactive cells were located at later stages in the innermost part of the inner nuclear layer and in the ganglion cell layer, and are likely to correspond mainly to amacrine cells. NOS-labelled cells were also found in retinal transplants. The first NOS-labelled cells appeared, as in normal developing retinas, in ages corresponding to E 29 and were still detected in transplants corresponding to postnatal day 123. NOS-labelled cells were seen in areas between rosettes, where amacrine cells are located. NOS-labelled processes were at times seen to project for long distances, forming very distinct plexuses. NOS-containing amacrine cells thus appear both in the transplants and in developing retinas in the embryonic stages, long before synaptic function involving these cells can be expected, suggesting a role for NO not only in neuromodulation but also in retinal development.     

Imprudent linking weaves a tangled Web

Hypertext linking is often embraced uncritically by Web authors eager to explore the power of hypertext without first considering its effects on their readers' comprehension. Hypertext linking is not a substitute for thought-we think with ideas, not with dissociated snippets of raw information. Even the most germane bits of information cannot become ideas, regardless of how cleverly they are stacked, listed or linked. Ideas define relevance, provide context and establish patterns. With patterns, most concepts become intelligible, and we need continuity and stability of theme and context to recognize patterns. So, like most powerful technologies, hypertext links are a mixed blessing. Used improperly, they can be detrimental to Web sites. “Loose links” can drive away an audience, dilute the site's message, confuse the reader with irrelevant digressions and become a continuing maintenance headache for site authors and Webmasters