Quantitative patterns in the clinical manifestations of radiation sickness in large laboratory animals exposed to radiation at superlethal doses. The quantitative patterns in the manifestations of radiation sickness in dogs

Radiation sickness manifestations have been studied in dogs exposed to electrons (electron energy 25 MeV) and gamma-neutron radiation (neutron energies of 0.37 and 1.2 MeV) in a wide dose range. Dose-response relationships have been calculated for mortality and some clinical manifestations of the intestinal and cerebral forms of radiation sickness. With regard to mortality, the highest effect has been observed for gamma-neutron radiation with a neutron energy of 1.2 MeV. For equal physical doses and for those equally effective in relation to mortality, clinical manifestations of damage are more prominent following exposure to electrons.     

Bovine ovarian non-genomic progesterone binding sites: presence in follicular and luteal cell membranes

We have shown recently that the bovine corpus luteum (CL) possesses specific luteal cell surface membrane binding sites for progesterone. We have now confirmed and extended these observations to compare the subcellular distribution of these binding sites in developing, mature and regressing CL. The median buoyant densities of luteal progesterone binding sites from early-, mid- and late-luteal phase CL were similar (though three of five density profiles for late-luteal phase CL showed association of steroid binding with a fraction with a lower density), and clearly resolved from nuclear, mitochondrial, lysosomal, peroxisomal, Golgi-endoplasmic reticulum-lysosomal and smooth endoplasmic reticulum markers. Specific binding of [3H]progesterone overlapped with the distributions of 5'-nucleotidase and luteinizing hormone receptor (luteal cell surface membrane markers) in both control and digitonin-treated gradients at all stages of the luteal phase. Since steroidogenic 'large luteal' and 'small luteal' cells of the CL are derived from the granulosa cells (GC) and theca of the preovulatory follicle, we also investigated whether similar receptors were present in the follicle, and describe for the first time specific membrane binding sites for progesterone in purified GC and thecal membranes from healthy bovine follicles of different sizes. Specific binding increased linearly with GC and thecal membrane protein concentration; however, it was detectable only when digitonin was included in the binding incubation. Binding sites were specific for progesterone; unlabelled progesterone competed for [3H]progesterone binding at low concentrations (IC50, 35 and 31 nmol/l) compared with testosterone (IC50, 905 and 870 nmol/l) and delta4-androstenedione (IC50, 1050 and 660 nmol/l) for GC and thecal receptors respectively. In contrast, oestradiol, oestrone, pregnenolone, cortisol, cholesterol, and a genomic progesterone receptor antagonist, RU486, competed poorly. Steroid binding was present in GC and thecal membranes of follicles of all sizes, but [3H]progesterone binding to GC membranes decreased significantly with increasing follicle size (P<0.02), perhaps indicating developmental regulation of GC membrane non-genomic progesterone receptors in the preovulatory bovine follicle. We suggest that these membrane steroid receptors may be involved in the autocrine/paracrine regulation of follicular function by progesterone.     

Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade

Developmental neurotoxicity caused by chlorpyrifos exposure is generally thought to target cholinesterase but chlorpyrifos may also act on cellular intermediates, such as adenylyl cyclase, that serve global functions in the coordination of cell development. In the current study, neonatal rats were exposed to apparently subtoxic doses of chlorpyrifos (no weight loss, no mortality) either on Postnatal Days 1-4 or on Postnatal Days 11-14, and the effects on components of the adenylyl cyclase cascade were evaluated in brain regions that are enriched (forebrain) or sparse (cerebellum) in cholinergic innervation, as well as in a nonneural tissue (heart). In all three, chlorpyrifos evoked deficits in multiple components of the adenylyl cyclase cascade: expression and activity of adenylyl cyclase itself, functioning of G-proteins that link neurotransmitter and hormone receptors to cyclase activity, and expression of neurotransmitter receptors that act through this cascade. Disruption of signaling function was not restricted to transduction of cholinergic signals but rather extended to adrenergic signals as well. In most cases, the adverse effects were not evident during the immediate period of chlorpyrifos administration, but appeared after a delay of several days. These results suggest that chlorpyrifos can affect cell development by altering the activity and reactivity of the adenylyl cyclase signaling cascade, a major control point for trophic regulation of cell differentiation. The effects are not restricted to cholinergic targets, nor even to the central nervous system. Hence, disruption of cell development by chlorpyrifos is likely to be more widespread than previously thought.     

Rapid identification of protein phosphatase 1-binding proteins by mixed peptide sequencing and data base searching. Characterization of a novel holoenzymic form of protein phosphatase 1

Microcystin-affinity chromatography was used to purify 15 protein phosphatase 1 (PP1)-binding proteins from the myofibrillar fraction of rabbit skeletal muscle. To reduce the time and amount of material required to identify these proteins, proteome analysis by mixed peptide sequencing was developed. Proteins are resolved by SDS-polyacrylamide gel electrophoresis, electroblotted to polyvinylidene fluoride membrane, and stained. Bands are sliced from the membrane, cleaved briefly with CnBr, and applied without further purification to an automated Edman sequencer. The mixed peptide sequences generated are sorted and matched against the GenBank using two new programs, FASTF and TFASTF. This technology offers a simple alternative to mass spectrometry for the subpicomolar identification of proteins in polyacrylamide gels. Using this technology, all 15 proteins recovered in PP-1C affinity chromatography were sequenced. One of the proteins, PP-1bp55, was homologous to human myosin phosphatase, MYPT2. A second, PP-1bp80, identified in the EST data bases, contained a putative PP-1C binding site and a nucleotide binding motif. Further affinity purification over ATP-Sepharose isolated PP-1bp80 in a quaternary complex with PP-1C and two other proteins, PP-1bp29 and human p20. Recombinant PP-1bp80 also bound PP-1C and suppressed its activity toward a variety of substrates, suggesting that the protein is a novel regulatory subunit of PP-1.     

Simulation and experimental analyses of electromagnetic transients behaviors of lightning surge on vertical conductors

Simulation of very fast surge phenomena in a three-dimensional (3-D) structure requires a method based on Maxwell's equations, such as the finite-difference time-domain (FDTD) method or the method of moments, because circuit-equation-based methods cannot handle the phenomena. This paper uses a method of thin-wire representation of the vertical conductor system for the FDTD method which is suitable for the 3-D surge simulation. The thin-wire representation is indispensable to simulate electromagnetic surges on wires or steel frames in which the radius is smaller than a discretized space step used in the FDTD simulation. In this paper, a general surge analysis program named the virtual surge test lab based on the Maxwell's equations formulated by the FDTD method, is used to simulate the surge phenomena of a vertical conductor, including the effects of horizontal wave incidence and vertical wave incidence. Experimental results on the reduced scale model have been presented in order to compare among the simulation results by the FDTD method and the results using numerical electromagnetic code based on the MoM.     

The functional reanimation of paralyzed limbs.

The functional reanimation of paralyzed limbs has been a longstanding goal of neural prosthetic research, but clinically successful applications have been elusive. Natural voluntary limb movement requires four major elements: actuators (i.e., motor units), sensors (i.e., somatosensory afferents), commands (i.e., cerebral cortical activity), and control (i.e., integration of the previous three elements at various levels of the neuraxis). Prosthetic equivalents of each of these elements are, as yet, primitive and often cumbersome to deploy, but new technologies promise substantial improvements for all. This article focuses on one such technology, bionic neuon (BION) modular microimplants, and its relationship to alternative and complementary technologies. The challenge remains to select and integrate them into systems that can be tailored efficiently to the widely disparate needs of patients with various patterns of weakness and paralysis.     

Sexual orientation-related differences in prepulse inhibition of the human startle response.

Prepulse inhibition (PPI) refers to a reduction in the startle response to a strong sensory stimulus when this stimulus is preceded by a weaker stimulus--the prepulse. PPI reflects a nonlearned sensorimotor gating mechanism and also shows a robust gender difference, with women exhibiting lower PPI than men. The present study examined the eyeblink startle responses to acoustic stimuli of 59 healthy heterosexual and homosexual men and women. Homosexual women showed significantly masculinized PPI compared with heterosexual women, whereas no difference was observed in PPI between homosexual and heterosexual men. These data provide the first evidence for within-gender differences in basic sensorimotor gating mechanisms and implicate the known neural substrates of PPI in human sexual orientation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)